JP5690744B2 - Emulsified liquid oral composition and method for producing the same - Google Patents

Description

  The present invention eliminates ethanol and blends a specific emulsion to increase the retention of medicinal components in the oral cavity and to exhibit a high osmotic bactericidal effect on periodontopathic biofilms. The present invention relates to a non-alcohol-type emulsified liquid oral composition containing isopropylmethylphenol, which has good appearance stability at the time and is less irritating during use, and a method for producing the same.

  Not only periodontal disease, but also the causes of touch and bad breath are thought to be due to various bacteria in the biofilm, and biofilm bacteria sterilization is an effective means for the prevention and improvement of oral diseases to prevent oral diseases Therefore, nonionic and cationic fungicides have been incorporated into oral care products. In particular, non-ionic disinfectants such as isopropylmethylphenol among disinfectants blended in oral care products have characteristics that tend to have a broad antibacterial spectrum compared to cationic disinfectants. It is blended and marketed in oral compositions. Among them, isopropylmethylphenol is an important component in preventing periodontal disease because it has an excellent action of penetrating and sterilizing the periodontopathic biofilm, which is not found in other sterilizing components. In addition, it is more important for preventing oral diseases that these bactericides and medicinal components having the effects of anti-inflammation, blood circulation promotion, and antioxidant are retained in the oral cavity for a long time.

  Conventionally, liquid oral compositions such as mouthwashes have been blended with ethanol for the purpose of assisting in refreshing and improving stickiness. Many users do this. In recent years, the oral cavity such as xerostomia is severely thirsty, and there are an increasing number of people who are very sensitive to irritation and those who are not xerostomia and sensitive to irritation peculiar to ethanol. For those who are sensitive to xerostomia and ethanol, there are increasing opportunities to use a mouthwash from the viewpoint of convenience and effect during use, but there is a tendency to avoid preparations containing ethanol.

  Under such circumstances, in recent years, liquid oral compositions containing no ethanol have become widespread, but in such products, a refreshing feeling and a sense of bad breath prevention are inevitably used as liquid oral compositions such as a mouthwash containing ethanol. It was inferior when compared. In addition, since nonionic bactericidal components such as isopropylmethylphenol are oil-soluble as described above, a larger amount of surface activity than ethanol-blended composition is required to stably blend in liquid oral compositions without blending ethanol. It is difficult to achieve both the stability of appearance and biofilm sterilization power during storage at low and high temperatures, and there is a problem of spicy irritation when using a mouthwash with a surfactant. was there.

  On the other hand, the applicant has proposed a technique for alleviating the irritation peculiar to ethanol and retaining the drug in the oral cavity for a long time by blending an emulsion with a preparation blended with ethanol (see Patent Document 1). However, this technique is related to an ethanol-containing composition and is moderated to some extent in the stimulation after mouthwashing and exhaling. The irritation peculiar to ethanol was felt, and the use of the above preparation tended to be avoided from the viewpoint of the image of ethanol blending. Furthermore, in this patent document 1, the oil-soluble active ingredient is emulsified together, whereby the emulsion stays in the oral mucosa and the retention of the active ingredient is improved. However, the active ingredient is contained in the emulsion. Therefore, the bactericidal effect is not sufficiently exerted, the bactericidal power on the biofilm is reduced, and it is difficult to say that the effect of preventing touch, periodontal disease and bad breath is sufficiently exerted. Further, in terms of appearance stability, the emulsion is easily disintegrated during long-term storage at high temperature or long-term storage at low temperature (freezing storage), and the appearance stability of the preparation is still unsatisfactory, and there is room for improvement in these respects.

  Because of the above problems, non-alcohol type liquid oral cavity is highly effective in preventing oral diseases such as periodontal disease, low irritation at mouthwash even when used by dry mouth, and good appearance stability Development of a composition is desired.

JP 2005-179231 A International Publication No. 07/148551 pamphlet

  The present invention has been made in view of the above circumstances, exhibits a high penetrating and bactericidal effect on periodontopathic biofilms, has a high retention in the oral cavity of the drug, and also has an appearance stability in high-temperature storage and low-temperature (frozen) storage. An object is to provide a non-alcohol-type liquid oral composition containing isopropylmethylphenol, which is good and less irritating, and a method for producing the same.

As a result of intensive studies, the inventors of the present invention have added (A) isopropylmethylphenol as a bactericidal component and (B) an average added mole number of ethylene oxide to a liquid oral composition substantially free of ethanol. 40 to 100 mol of polyoxyethylene hydrogenated castor oil, (C) (C-1) decaglycerin monofatty acid ester and (C-2) trifatty acid glyceryl, (D) glycerin, propylene glycol, average molecular weight 190 to One or two or more polyhydric alcohols selected from polyethylene glycol of 630 is blended, and (B) component polyoxyethylene hydrogenated castor oil which is a nonionic surfactant and (C) -1) Total amount of decaglycerin monofatty acid ester and (C-2) tri-fatty acid glycerin in component (C) which is oil component Amounts as appropriate ratio mass ratio of, has adequate amount of the polyhydric alcohol of the component (D), by containing glycerin or 0.003 wt% has been found that the object can be achieved.
Moreover, in the manufacturing method of the composition for liquid oral cavity which contains isopropylmethylphenol and does not contain ethanol substantially, after blending said (A), (B) and (D) component appropriately, (C) component And (C-1) component, (C-2) component, (C-3) glycerin and water emulsion are added, and {total amount of (B) component and (C-1) component} / { It was found that the emulsified liquid composition for oral cavity can be produced by appropriately adjusting the mass ratio of (C-2) component amount}.
According to the present invention, high penetrating and bactericidal power to periodontopathic biofilm is exhibited, isopropylmethylphenol, which is a medicinal component, is highly retained in the oral cavity, and appearance stability even when stored at high and low temperatures Is obtained, and a hypoallergenic emulsified liquid oral composition is obtained that hardly feels irritation even when used by a person who is sensitive to irritation in the oral cavity.

  As a technology that achieves both biofilm sterilization power and appearance stability, the applicant has applied a specific anionic surfactant, polyoxyethylene hydrogenated castor oil, polyoxyethylene alkyl to a liquid oral composition containing isopropylmethylphenol. A liquid oral composition was proposed in which a nonionic surfactant selected from ether and a polyhydric alcohol were blended, the water content in the composition was 70% by mass or more, and no ethanol was blended (see Patent Document 2). However, with this technique, when used by a dry mouth person, there is still room for improvement in the oral retention of the medicinal component, as well as irritation during mouthwashing.

Accordingly, the present inventors have further investigated a non-alcohol-type liquid oral composition containing isopropylmethylphenol and substantially free of ethanol. As a result, the above-mentioned liquid oral composition was used in combination with a specific polyoxyethylene hydrogenated castor oil as a solubilizer and the above component (C) as an emulsifier, and in particular, the specific average particle prepared in advance with the component (C) Blended as an emulsion of diameter, blended so that the ratio of the total amount of nonionic surfactant in both components and the oily component contained in the emulsion is appropriate, and properly blended with specific polyhydric alcohol Thus, it was found that the above emulsion is stably blended, solves the above-mentioned problems, achieves both periodontopathic biofilm bactericidal power and appearance stability, and is hypoallergenic. In the present invention, the mechanism of its action is unknown, but unlike the case where oil-soluble isopropylmethylphenol is emulsified from the beginning, the isopropylmethylphenol is completely added by post-adding the emulsion. Is presumed to be stably incorporated in the preparation without being incorporated into the emulsion. For this reason, the bactericidal power reduction of the oral biofilm derived from isopropylmethylphenol can be suppressed and high bactericidal power is exhibited, and even when stored at high or low temperature for 3 months, the emulsion is stably maintained. The emulsification becomes unstable and the color tone of the preparation does not fade, or the oily component is not separated and liquid-separated, and it is considered that the appearance stability of the preparation is excellent. Furthermore, the irritation | stimulation by surfactant can also be suppressed by mix | blending (D) component appropriately. In addition, in the present invention, ethanol is not blended and a large amount of surfactant does not have to be blended, so that it can be a hypoallergenic preparation at the time of use, for example, mouthwash.
In the present invention, the above-mentioned component (C) is combined with the component (B) and further the component (D), and the effects of the present invention can be achieved by appropriately blending the components. Even if it mix | blends or it lacks either of the said essential requirements, the objective of this invention is not achieved.
The liquid oral composition of the present invention can be used for people who are extremely sensitive to irritation in the oral cavity such as xerostomia, those who are severely thirsty, those who are very sensitive to irritation, those who are sensitive to ethanol, etc. It is easy to use and is effective in preventing or improving oral diseases such as periodontal disease.

  Accordingly, the present invention provides the following emulsified liquid oral compositionAnd its manufacturing methodI will provide a.
[1]
  (A) A liquid oral composition containing isopropylmethylphenol and substantially free of ethanol,
(B) polyoxyethylene hydrogenated castor oil having an average added mole number of ethylene oxide of 40 to 100 moles,
(C) (C-1) Decaglycerin monofatty acid ester,(C-2) Tri-fatty acid glyceryl (C-3) An emulsion having an average particle size of 50 to 500 nm, consisting of glycerin and water,
(D) At least one polyhydric alcohol selected from glycerin, propylene glycol, and polyethylene glycol having an average molecular weight of 190 to 630
And a mass ratio of {total amount of (B) component and (C-1) component decaglycerin monofatty acid ester} / {(C-2) component trifatty acid glyceryl} is 0.77 to 1 The emulsified liquid oral composition is characterized by comprising .87, and the blending amount of component (D) is 5 to 15% by mass, and glycerin is contained in an amount of 0.003% by mass or more.
[2]
  The total amount of (B) component polyoxyethylene hydrogenated castor oil and (C-1) component decaglycerin monofatty acid ester is 0.18 to 0.49 mass% of the entire composition.[1]The emulsified liquid oral composition as described.
[3]
  The carbon number of the fatty acid of (C-1) component decaglycerin monofatty acid ester is 12-16, and the carbon number of the fatty acid of (C-2) trifatty acid glyceryl is 6-12.[1]Or[ 2]The emulsified liquid oral composition as described.
[4]
  The content of the component (C-1) in the emulsion of the component (C) is 5 to 15% by mass, (C-2) The content of the component is 40 to 60% by mass, and the content of the component (C-3) is 1 to 30% by mass [1. ] The emulsion type liquid oral cavity composition of [2] or [3] description.
[5]
  The blending amount of the emulsion of component (C) is 0.3 to 0.9% by mass of the entire composition [1 ] The emulsified liquid oral cavity composition in any one of-[4].
[6]
  The component (D) is a combination of glycerin and polyethylene glycol 400, or a combination of glycerin, propylene glycol, and polyethylene glycol 400.[1] ~ [5]EitherInThe emulsified liquid oral composition as described.
[7]
  (A) Emulsification in any one of [1]-[6] which contains 0.01-0.1 mass% of component. Type liquid oral composition.
[8]
  The ethanol content in the composition is 100 ppm or less[1] ~ [7]EitherInThe emulsified liquid oral composition as described.
[9]
  Furthermore, (E) Vitamin E0.05-0.2% by massBlended[1] ~ [8]EitherInThe emulsified liquid oral composition as described.
[10]
  A method for producing a liquid oral composition containing isopropylmethylphenol and substantially free of ethanol,
(A) isopropylmethylphenol,
(B) polyoxyethylene hydrogenated castor oil having an average added mole number of ethylene oxide of 40 to 100 moles, and
(D) 5-15% by mass of at least one polyhydric alcohol selected from glycerin, propylene glycol, and polyethylene glycol having an average molecular weight of 190 to 630
After blending, (C) (C-1) decaglycerin monofatty acid ester, (C-2) trifatty acid glyceryl, (C-3) glycerin,And an emulsion having an average particle size of 50 to 500 nm comprising water and {total amount of (B) component and decaglycerin monofatty acid ester of component (C-1)} / {trifatty acid of component (C-2) The mass ratio of glyceryl} is 0.77 to 1.87, and the method for producing an emulsified liquid oral composition is characterized by the following.

  According to the present invention, in a liquid oral composition containing isopropylmethylphenol and containing no ethanol, a high osmotic bactericidal effect is exerted on periodontopathic biofilms, and the retention of isopropylmethylphenol in the oral cavity is high. In addition, it is possible to obtain a low-irritant emulsified liquid oral composition having good appearance stability over time during storage at low and high temperatures and almost no irritation in the mouth during mouthwashing. Therefore, the composition of the present invention is extremely sensitive to oral irritation such as that the oral cavity is severely dry due to dry mouth symptoms or sensitive to ethanol-specific irritation, for the prevention or suppression of periodontal disease. It is also effective for new users.

  Hereinafter, the present invention will be described in more detail. The emulsified liquid oral composition of the present invention contains (A) isopropylmethylphenol as a bactericidal component and is substantially free of ethanol. (B) Polyoxyethylene hydrogenated castor oil having an average added mole number of ethylene oxide of 40 to 100 mol as a solubilizer, (C) (C-1) decaglycerin monofatty acid ester and (C-2) trifatty acid as emulsifiers As glyceryl and polyhydric alcohol, (D) glycerin, propylene glycol, and at least one selected from polyethylene glycol having an average molecular weight of 190 to 630 are blended. In this case, the component (C) is blended as an emulsion having an average particle size of 50 to 500 nm comprising (C-1) decaglycerin monofatty acid ester, (C-2) trifatty acid glyceryl, (C-3) glycerin and water. It is preferable.

  In the emulsified liquid oral composition of the present invention, the blending amount of (A) isopropylmethylphenol is not particularly limited, but in terms of penetrating bactericidal effect on periodontopathic biofilm and appearance stability, 0.01 to 0.1% (mass%, the same applies hereinafter), particularly 0.03 to 0.08% is preferable. If the blending amount is less than 0.01%, satisfactory penetrating and bactericidal power may not be exhibited for the oral biofilm, and if it exceeds 0.1%, appearance stability may be impaired.

  The (B) component polyoxyethylene hydrogenated castor oil has an average added mole number of ethylene oxide of 40 to 100 mol, preferably 60 to 100 mol. If the average number of added moles is less than 40 moles, it will precipitate during low-temperature storage, and those exceeding 100 moles are generally not commercially available.

  The blending amount of the component (B) is 0.15 to 0.40% of the total composition in terms of solubilization of the component (A), bactericidal power to periodontal pathogenic biofilm, and appearance stability, 0.20 to 0.30% is preferable. If the blending amount is less than 0.15%, the appearance stability may be inferior, and if it exceeds 0.40%, the bactericidal power to the periodontopathic biofilm may be impaired.

(C) component is (C-1) decaglycerin monofatty acid ester and (C-2) trifatty acid glyceryl, (C-1) decaglycerin monofatty acid ester, (C-2) trifatty acid glyceryl, (C -3) It can mix | blend as an emulsion with an average particle diameter of 50-500 nm which consists of glycerol and water. An oily component is trifatty acid glyceryl and glycerin, an aqueous component is water, and mixing can be performed using decaglycerin monofatty acid ester which is a nonionic surfactant, and an emulsion can be prepared.
In the present invention, the component (A), isopropylmethylphenol, is blended as an oily component in the composition and is not contained during the emulsion preparation.

In the above emulsion, as decaglycerin monofatty acid ester, fatty acid having 12 to 16 carbon atoms is suitable, and examples thereof include decaglyceryl monomyristate and decaglyceryl monolaurate.
The blending amount of decaglycerin monofatty acid ester can be usually used as 5 to 15% in the emulsion. If it is less than 5%, the oily component is separated, and if it exceeds 15%, gelation may occur.

Further, as the tri fatty acid glyceryl in the emulsion, those having a carbon chain length of 6 to 12 are preferable, and examples thereof include glyceryl tricaprylate, glyceryl tricaprate, glyceryl tri (capryl / caprate).
1 type (s) or 2 or more types are used for tri fatty acid glyceryl, and the compounding quantity can be normally made into 40 to 60% in an emulsion. If it is less than 40%, an emulsion cannot be formed, and if it exceeds 60%, the oily component may be separated and the appearance stability may be impaired.

  Furthermore, the glycerin content in the emulsion can be 1-30%, in particular 10-20%. If it is less than 1%, uniform dissolution of the surfactant becomes complicated, and if it exceeds 30%, the oil component may be separated.

  The average particle size of the emulsion is 50 to 500 nm, and particularly preferably 100 to 300 nm. If the average particle size is outside the above range, the appearance stability is poor and the object of the present invention may not be achieved. In addition, the measuring method of the average particle diameter of an emulsion is based on the method as described in an Example.

The form of the emulsion is O / W type. For example, a predetermined amount of decaglycerin monofatty acid ester, glycerin and half amount of water are stirred with a homomixer, then trifatty acid glyceryl is added to form an emulsion, and finally the remaining water is added. it can. Thereafter, a method of adjusting the average particle diameter of the prepared emulsion using a high-pressure homogenizer can be preferably employed. The target oral composition can be obtained by adding a predetermined amount of the emulsion thus prepared to the liquid oral composition.
A commercially available product such as NET-TE-50 manufactured by Nikko Chemicals can be used as the emulsion.

  The blending amount of the emulsion of component (C) is preferably 0.3 to 0.9%, particularly 0.4 to 0.7% of the whole composition. If the blending amount is less than 0.3%, the color tone of the composition may fade (clear) during high-temperature storage, which may impair the appearance stability. If it exceeds 0.9%, sterilization to periodontopathic biofilms It may impair strength and appearance stability.

  In the composition of the present invention, the total amount of (C-1) decaglycerin monofatty acid ester contained in the (B) component polyoxyethylene hydrogenated castor oil and (C) component which is a nonionic surfactant, and (C ) Ratio of (C-2) tri-fatty acid glyceryl contained in the component, that is, {total amount of (C-1) decaglycerin monofatty acid ester in (B) component and (C) component} / { The mass ratio of (C-2) tri-fatty acid glyceryl amount in component (C) is 0.77 to 1.87, preferably 1.00 to 1.20. If the ratio is less than 0.77, the emulsion may collapse in low temperature (frozen) storage, oil may separate and impair appearance stability, and if it exceeds 1.87, the color tone fades in high temperature storage, Appearance stability may be impaired.

  Furthermore, the total amount of the (B) component polyoxyethylene hydrogenated castor oil and the (C) component decaglycerin monofatty acid ester is 0.18 to 0.49%, particularly 0.2 to 0% of the total composition. .37% is preferable. By making the total blending amount within the above range, it is more effective to obtain a composition that exhibits high penetrating and bactericidal power to periodontal pathogenic biofilms and has good appearance stability even when stored at high and low temperatures. It is. If the blending amount is less than 0.18%, the oil may separate in the low temperature (frozen) storage and impair the appearance stability. If it exceeds 0.49%, the bactericidal power to periodontopathic biofilms It may damage.

  (D) As a polyhydric alcohol of a component, what is chosen from glycerin, propylene glycol, and polyethyleneglycol with an average molecular weight of 190-630 is used individually by 1 type or in combination of 2 or more types.

In addition, the average molecular weight mentioned above shows the average molecular weight described in the Quasi-drug Raw Material Standard 2006, which is an average measured by reacting with phthalic anhydride in pyridine to form a phthalic acid ester and titrating with sodium hydroxide. Molecular weight.
Examples of polyethylene glycol having an average molecular weight of 190 to 630 include polyethylene glycol 200 (average molecular weight 190 to 210), polyethylene glycol 300 (average molecular weight 290 to 310), polyethylene glycol 400 (average molecular weight 390 to 410), and polyethylene glycol 600 (590 to 610). ) Is applicable. Depending on the product, there may be a # between the polyethylene glycol and the numerical value, such as polyethylene glycol # 200.

  Furthermore, it is preferable to use 2 or more types of component (D) from the viewpoint of irritation at the time of use and appearance stability, and more preferably 3 or more types. As a combination of two kinds, a combination of glycerin, propylene glycol and polyethylene glycol 400 is preferable as a combination of three kinds of glycerin and polyethylene glycol 400.

  The total amount of component (D) is 5 to 15% of the entire composition, and 6 to 13% is particularly preferred in terms of appearance stability at low and high temperatures and irritation during use. If the blending amount is less than 5%, it is difficult to maintain the appearance stability at low and high temperatures, and the stimulus derived from the surfactant may not be suppressed, and if it exceeds 15%, the color tone fades and the appearance It may impair stability.

When blended as the component (D), glycerin is 0.5% or more of the whole composition, propylene glycol is 1% or more of the whole composition, butylene glycol is 1% or more of the whole composition, and polyethylene having an average molecular weight of 190 to 630. Glycol is preferably blended in an amount of 1% or more of the entire composition.
In addition, content in the composition of glycerol is 0.003 mass% or more.

  The liquid oral composition of the present invention preferably further contains (E) vitamin E, thereby exhibiting the above excellent characteristics and improving the blood circulation promoting effect. In the present invention, vitamin E includes tocopherol, tocotriere, tocopherol ester derivatives such as tocopherol acetate and tocopherol nicotinate, and one or more selected from these can be used. Component (E) is preferably added in an amount of 0.05 to 0.2%, more preferably 0.05 to 0.15% of the entire composition. However, if it exceeds 0.2%, the preparation may be separated and appearance stability may be impaired.

  The liquid oral composition of the present invention is substantially free of ethanol. Here, “substantially free of ethanol” means that the amount of ethanol in the composition is preferably 100 ppm or less, more preferably 50 ppm or less, and particularly preferably 10 ppm or less with respect to the entire composition. Is 0 ppm. The liquid oral composition of the present invention contains no ethanol, but there are cases where a small amount of raw material-derived ethanol is contained in the fragrance compounded in the composition. In addition, it contains no ethanol other than a small amount of ethanol contained in the perfume.

  The liquid oral cavity composition of the present invention can be prepared and applied as a mouthwash, liquid dentifrice, etc., depending on its dosage form, in addition to the above components, in addition to the above components Appropriate known components can be blended. For example, a solvent, a wetting agent other than the polyhydric alcohol of component (D), a thickener, a surfactant other than the surfactants of component (B) and component (C), a solvent, and if necessary, a pH adjuster, Preservatives, sweeteners, fragrances, active ingredients other than the components (A) and (E), coloring agents, and the like can be contained.

  Examples of the wetting agent include those other than the polyhydric alcohol of component (D), for example, sugar alcohols such as sorbitol, xylit, malt, lactit, ethylene glycol, and the like. When mix | blending these wetting agents, the range which the compounding quantity including the polyhydric alcohol of (D) component becomes 5 to 15% is desirable.

  As a thickener, xanthan gum, sodium alginate, polyvinyl alcohol and the like can be contained within a range that does not interfere with the effects of the present invention (the blending amount is usually 0 to 5%, and 0.01 to 5% when blended). .)

Examples of pH adjusters include phthalic acid, phosphoric acid, citric acid, succinic acid, acetic acid, fumaric acid, malic acid and carbonic acid and their potassium, sodium and ammonium salts, ribonucleic acid and its salts, and sodium hydroxide. Or a combination of phosphoric acid, citric acid and their sodium salts is particularly preferred. In particular, the liquid oral composition of the present invention preferably adjusts the pH at 25 ° C. to 5.5 to 7.5, and sodium dihydrogen phosphate and sodium monohydrogen phosphate as pH adjusters in the vicinity thereof, Alternatively, it is preferable to use a combination of citric acid and sodium citrate.
As the solvent, purified water is usually used. The amount of the solvent is usually 60 to 94.49%.

  Examples of the preservative may include paraoxybenzoic acid esters such as sodium benzoate, methylparaben, ethylparaben, propylparaben, and butylparaben, alkyldiaminoethylglycine hydrochloride, potassium sorbate, and the like.

  The sweetener may contain saccharin sodium, steviosite, sucralose, reduced palatinose, erythritol and the like.

  Natural flavors such as peppermint oil, spearmint oil, eucalyptus oil, wintergreen oil, clove oil, thyme oil, sage oil, cardamom oil, rosemary oil, marjoram oil, lemon oil, nutmeg oil, lavender oil, paracres oil, etc. Essential oils, and perfume ingredients contained in the above natural essential oils such as l-carvone, 1,8-cineole, methyl salicylate, eugenol, thymol, linalool, limonene, menthone, menthyl acetate, citral, camphor, borneol, pinene, spirantol, etc. Ethyl acetate, ethyl butyrate, isoamyl acetate, hexanal, hexenal, methyl anthranilate, ethyl methyl phenylglycidate, benzaldehyde, vanillin, ethyl vanillin, furaneol, maltol Perfume ingredients such as ethyl maltol, gamma / delta decalactone, gamma / deltown decalactone, N-ethyl-p-menthane-3-carboxamide, menthyl lactate, ethylene glycol-l-menthyl carbonate, A combination of flavoring ingredients and natural essential oils (without ethanol), including flavors such as apple, banana, strawberry, blueberry, melon, peach, pineapple, grape, muscat, wine, cherry, squash, coffee, brandy, yogurt 1 type (s) or 2 or more types can be used in the range of 0.00001 to 3% in the composition of this invention, and the range which does not prevent the effect of this invention.

  Examples of the surfactants other than the nonionic surfactants as the component (B) and the component (C) include alkyl sulfates (eg, alkyl sulfates such as sodium lauryl sulfate, potassium lauryl sulfate, sodium myristyl sulfate, and potassium myristyl sulfate). Alkali metal salt of alkyl sulfate having 12 to 16 groups), N-acyl amino acid alkali metal salt having 12 to 16 carbon atoms of acyl group, lauroylmethyl taurine, acyl amino acid salt, sodium dodecylbenzenesulfonate, α-sulfo fatty acid Anionic surfactants such as alkyl ester sodium and alkyl phosphate ester salts, betaine acetate type amphoteric surfactants such as alkyldimethylaminoacetic acid betaine, fatty acid amidopropyldimethylaminoacetic acid betaine, N-fatty acid acyl-N-carboxymethyl − -Amphoteric surfactants such as imidazoline-type amphoteric surfactants such as hydroxyethylethylenediamine salt and amino acid-type surfactants such as N-fatty acid acyl-L-alginate salts, etc. 1 type can be mix | blended individually or in combination of 2 or more types. In the present invention, the surfactant other than the nonionic surfactant as the component (B) and the component (C), particularly the nonionic surfactant, may not be blended and may be 0%. When mix | blending, 0.01 to 1% of the whole composition is desirable.

  As an active ingredient, in addition to isopropylmethylphenol and further tocopherol acetate, other ingredients such as fungicides such as triclosan and cetylpyridinium chloride, anti-inflammatory agents such as tranexamic acid and epsilon-aminocaproic acid, dextranase, Enzymes such as amylase, protease, mutanase, lysozyme, lytic enzyme, lytechenzyme, fluorides such as sodium fluoride, sodium monofluorophosphate, stannous fluoride, aluminum chlorohydroxy allantoin, allantoin, azulene, lysozyme chloride, ascorbine Vitamin C such as acids, dihydrocholesterol, glycyrrhetin salts, glycyrrhetinic acids, hydrocholesterol, chlorophyll, copper chlorophyllin sodium, thyme, ougon, clove Add plant extracts such as hamamelis, copper gluconate, caropeptide, sodium polyphosphate, water-soluble inorganic phosphate compound, polyvinylpyrrolidone, sodium lauroyl sarcosine, anticalculus, anti-plaque, potassium nitrate, aluminum lactate, etc. it can. In addition, the compounding quantity of these active ingredients can be contained in the range which does not disturb the effect of this invention.

  As a colorant, a highly safe water-soluble pigment such as Blue No. 1, Green No. 3, Yellow No. 4, Red No. 105 can be added.

  As the container, PET (polyethylene terephthalate), glass, polypropylene, and polyethylene can be used, but the use of PET and glass is preferable from the viewpoint of suppressing adsorption of nonionic fungicides and fragrances.

  EXAMPLES Hereinafter, although an experimental example, an Example, and a comparative example are shown and this invention is demonstrated concretely, this invention is not restrict | limited to the following Example.

  For preparation of the liquid oral composition of each example, isopropylmethylphenol (Osaka Kasei Co., Ltd.), polyoxyethylene (60) hydrogenated castor oil (Nikko Chemicals), polyoxyethylene (80) hydrogenated castor oil (Nikko) Chemicals), emulsion (average particle size 200 nm, NET-TE50, Nikko Chemicals), glycerin (100%, Sakamoto Yakuhin Kogyo), propylene glycol (Asahi Glass), polyethylene glycol # 400 (Lion Chemical) Manufactured), tocopherol acetate ester (manufactured by DSM Nutri Japan), citric acid (manufactured by Fuso Chemical), and sodium citrate (manufactured by Fuso Chemical). Triclosan (Ciba Specialty Chemicals), polyoxyethylene (30) hydrogenated castor oil (Nikko Chemicals), emulsion (comparative emulsion, average particle size 10 nm, Nikko Chemicals), ethanol (Nihon Alcohol Sales) Used in the comparative example. In the table, POE represents polyoxyethylene, and the percentages shown below mean mass% unless otherwise specified. The composition of the emulsion is shown below.

[Composition of emulsion (average particle size 200 nm)]
Decaglyceryl monomyristate 10%
Tri (Capryl / Capric Acid) Glyceryl 50
Glycerin 15
Water 25
Total 100%

[Composition and preparation method of comparative emulsion (average particle size 10 nm)]
Decaglyceryl monolaurate 10%
Olive oil 50
Glycerin 15
Water 25
Total 100%
After pre-stirring glycerin, half amount of water and decaglyceryl monolaurate, olive oil was added and stirred with a homomixer, and finally the remaining water was added.

The average particle size of the emulsion was measured by the following method.
[Measurement method of average particle diameter]
Using a dynamic light scattering photometer N5 manufactured by BECKMAN COULTER, the emulsion was diluted 100 times with purified water, placed in a cell, and the average particle size at 25 ° C. was measured.

[Experimental Example 1]
Liquid oral compositions (mouthwashes) having the compositions shown in Tables 1 to 5 were prepared by a conventional method, and finally the emulsion was dispersed, and the following evaluation was performed. The results are shown in Tables 1-5.

Appearance stability evaluation:
Fill the sample liquid oral composition into a 450 mL PET container (polyethylene terephthalate container, manufactured by Yoshino Kogyo) and store in a 50 ° C. thermostatic bath for 3 months, or after storing in a −10 ° C. thermostatic bath for 3 months The stability was evaluated visually according to the following criteria in comparison with a control product (initial product of Example 3).
Evaluation criteria for appearance stability (50 ° C., 3 months) A : No change is observed in the color tone of the preparation.
○: Although the fading of the color tone of the preparation is progressing slightly, it is a level at which there is no problem.
Δ: Fading of the color tone of the preparation is progressing.
X: The color tone of the preparation is remarkably faded without comparison with the control product.
In the above evaluation and the following evaluation, fading progresses is a state in which the color tone immediately after preparation of the preparation is white, and the color fades transparently. This is considered to be solubilized by a free surfactant.
Evaluation criteria for appearance stability (−10 ° C., 3 months) A : No change is observed.
○: Slight separation is observed, but there is no problem.
Δ: Separation is progressing.
X: Considerable separation is observed, and the color tone of the preparation is also fading.

[Experimental example 2]
About the composition for liquid oral cavity shown in Tables 1-5, periodontopathic biofilm penetration bactericidal power was evaluated by the following method. The results are shown in Tables 1-5.
Evaluation of biofilm penetration sterilization power:
(1) Method for producing model periodontopathic biofilm 4 hours with human unstimulated saliva obtained by filtering a hydroxyapatite (HA) plate (manufactured by Asahi Optical Co., Ltd.) having a diameter of 7 mm and a thickness of 3.5 mm with a 0.45 μm filter. The treated solution is used as a model biofilm carrier, and the culture solution is 30 mg of trypticase soy broth (Difco) dissolved in 1 L of purified water, 5 mg of hemin (Sigma), menadione (Sigma) (Product) 0.5 mg added was used. In order to produce a model biofilm, Streptococcus gordonii ATC 51656 strain and Actinomyces naeslandi ATCC 51655 strain were used as oral resident bacteria, and Porphyromonas gingivalis ATCC 33277 strain was used as a pathogenic bacterium. These three bacterial species were inoculated into the above-mentioned culture solution so as to be 2 × 10 ⁷ cfu / mL (cfu: colony forming units), respectively, and the saliva-treated HA carrier at 37 ° C. under anaerobic conditions (5% carbon dioxide gas). , 95 volume% nitrogen) for 2 weeks (the replacement rate of the culture medium was set to 10 volume%) to form a model biofilm mixed with three bacterial species on the HA surface.

(2) Osmotic sterilization effect on model biofilm The model biofilm formed was immersed in 2 mL of the sample (liquid oral composition) shown in the table for 3 minutes and washed 6 times with 1 mL of sterile physiological saline. Thereafter, the model biofilm was dispersed by sonication (200 μA, 10 seconds) with 4 mL of sterilized physiological saline, a 10% cotton defibrinated blood-containing trypticase soy agar plate (manufactured by Difco) and kanamycin sulfate (200 mg / L). (Manufactured by Sigma Co., Ltd.) containing 50 μL of trypticase soy blood agar plate and cultured under anaerobic conditions. The grown colonies were counted, and the viable count (cfu) of the remaining Porphyromonas gingivalis was determined and determined according to the following criteria.
Criteria ◎: Less than 10 ⁶ ○: 10 ⁶ or more and less than 10 ⁷ △: 10 ⁷ or more and less than 10 ⁸ ×: 10 ⁸ or more

[Experimental Example 3]
About the liquid oral cavity composition shown in Tables 1-5, the intraoral residual rate of isopropylmethylphenol was evaluated by the following method. The results are shown in Tables 1-5.
Moreover, the liquid oral composition shown in Table 4 was used as a sample, and the intraoral residual rate of tocopherol acetate was evaluated by the following method. The experimental method and the calculation method of the residual rate are the same as those of isopropylmethylphenol. The results are shown in Table 4.

Intraoral residual rate of isopropylmethylphenol:
Measure the isopropylmethylphenol concentration in the discharge liquid containing 10 mL of the sample (liquid oral composition) shown in the table in the mouth and rinse for 30 seconds, and mix with the resulting isopropylmethylphenol concentration The residual ratio in the oral cavity was calculated from the concentration and the amount of discharged liquid.
The liquid chromatograph measurement sample accurately measures the discharge liquid, and 0.3 g of isoamyl paraoxybenzoate (manufactured by Tokyo Chemical Industry Co., Ltd.) as an internal standard substance is added to 200 mL of 60% ethanol (99.5) (manufactured by Kanto Chemical Co., Inc.). After adding 1 mL of the dissolved solution, the amount of isopropylmethylphenol was determined by liquid chromatography (sample injection amount 20 μL). The mobile phase of liquid chromatography is methanol / purified water / phosphoric acid mixed solution (volume ratio 1300: 700: 1), pump: JASCO PU-980, sample introduction part: JASCO AS-950 , Detector: JASCO Corporation UV-970 (set to a measurement wavelength of 280 nm), Recording device: System Instrument Co., Ltd. Chromatocoder 21J, Column Hot Bath: JASCO Corporation CO-966 (set to 50 ° C.) Column: Kanto Chemical Co., Ltd. Mightysil RP-18 GP (5 μm) was used. From the peak area ratio of isopropylmethylphenol / internal standard substance, the residual ratio of isopropylmethylphenol in the oral cavity was calculated using the following formula, and the residual ratio was evaluated according to the following criteria.
a formula;
Isopropylmethylphenol remaining in the oral cavity (%) =
[((Mouthwash dosage x isopropylmethylphenol blending concentration)-(Discharge liquid volume x isopropylmethylphenol concentration in the ejection liquid)) ÷ (Mouthwash dosage x isopropylmethylphenol blending concentration)] x 100

Judgment criteria for intraoral residual rate of isopropylmethylphenol ◎: 20% or more ○: 15% or more and less than 20% △: 12% or more and less than 15% ×: Less than 12%

Tocopherol acetate residual rate in the oral cavity:
For the liquid chromatograph measurement sample, the discharge liquid was accurately measured, and 2 mL of a solution obtained by dissolving 0.02 g of ergocalciferol (manufactured by Kanto Chemical Co., Ltd.) in 200 mL of methanol (manufactured by Kanto Chemical Industry Co., Ltd.) was added as an internal standard substance. Thereafter, the amount of tocopherol acetate was determined by liquid chromatography (sample injection amount 20 μL). The mobile phase of liquid chromatography uses methanol, pump: JASCO Corporation PU-980, sample introduction part: JASCO Corporation AS-950, detector: JASCO Corporation UV-970 (measurement wavelength 284 nm) Recording apparatus: System Instruments Co., Ltd. Chromatocoder 21J, column high-temperature bath: JASCO Corporation CO-966 (set to 50 ° C.), column: Nacalai Tesque COSMOSIL 5C18 Waters (4.6 mmφ × 150 mm) used. From the peak area ratio of tocopherol acetate / internal standard substance, the residual ratio of tocopherol acetate in the oral cavity was calculated using the same calculation formula as above, and the residual ratio was evaluated based on the same criteria as described above.

[Experimental Example 4]
About the liquid oral cavity composition shown to Tables 1-5, the irritation | stimulation at the time of mouthwash was evaluated by the following method. The results are shown in Tables 1-5.
Evaluation of irritation during mouthwash:
10 subjects who feel dry mouth, 10 mL of sample (composition for liquid oral cavity) was rinsed for 30 seconds, and the mouth-rinsing stimulus was compared with Comparative Example 6 and evaluated in the following three stages. Then, the average score of 10 people was determined according to the following criteria.
Irritation at mouthwash 3: Almost no irritation was felt.
2: A slight reduction in irritation was observed, but some irritation was still observed.
1: Stimulation equal to or greater than that was observed.
Stimulus evaluation criteria ○: Average score of 2.0 or higher △: Average score of 1.5 or higher and lower than 2.0 × ×: Average score of 1.0 or higher and lower than 1.5

[Experimental Example 5]
About the composition for liquid oral cavity shown in Table 4, the blood circulation promotion power was measured with the following method, and the blood circulation promotion effect was evaluated. The results are shown in Table 4.
Evaluation of blood circulation promotion effect:
The blood flow rate of the maxillary postcard was measured after 10 subjects included the sample shown in Table 4 in a 10 mL mouth and rinsed for 30 seconds. The blood flow was measured by a laser Doppler method (MoorLDI, manufactured by Monte System Co., Ltd.) before mouthwash and after 30 minutes after mouthwash. The average increase rate of 10 persons was determined according to the following criteria as a relative blood flow with the blood flow before mouthwash.
Blood flow increase rate ○: 15% or more △: 10% or more and less than 15% ×: less than 10%

＊ ：ノニオン性界面活性剤であるＰＯＥ硬化ヒマシ油とエマルジョン中に
含まれるデカグリセリンモノ脂肪酸エステルとの合計量（以下、同様
）。
＊＊：＊のノニオン性界面活性剤の総量／エマルジョン中に含まれるトリ脂
肪酸グリセリル量（以下、同様）。

*: Total amount of POE hydrogenated castor oil, which is a nonionic surfactant, and decaglycerin monofatty acid ester contained in the emulsion (hereinafter the same).
**: Total amount of nonionic surfactant of * / Amount of glyceryl trifatrate contained in the emulsion (hereinafter the same).

Claims (10)

  (A) A liquid oral composition containing isopropylmethylphenol and substantially free of ethanol,
(B) polyoxyethylene hydrogenated castor oil having an average added mole number of ethylene oxide of 40 to 100 moles,
(C) (C-1) Decaglycerin monofatty acid ester,(C-2) Tri-fatty acid glyceryl (C-3) An emulsion having an average particle size of 50 to 500 nm, consisting of glycerin and water,
(D) At least one polyhydric alcohol selected from glycerin, propylene glycol, and polyethylene glycol having an average molecular weight of 190 to 630
And a mass ratio of {total amount of (B) component and (C-1) component decaglycerin monofatty acid ester} / {(C-2) component trifatty acid glyceryl} is 0.77 to 1 The emulsified liquid oral composition is characterized by comprising .87, and the blending amount of component (D) is 5 to 15% by mass, and glycerin is contained in an amount of 0.003% by mass or more. (B) a polyoxyethylene hydrogenated castor oil component the component (C-1) of the total amount of the decaglycerin fatty acid ester of claim 1 which is from 0.18 to 0.49% by weight of the total composition An emulsified liquid oral composition. (C-1) number of carbon atoms in the fatty acid decaglycerin fatty acid ester component is 12~16, (C-2) number of carbon atoms in the fatty acid tri fatty acid glyceryl according to claim 1 or 2, wherein 6 to 12 An emulsified liquid oral composition. The content of the component (C-1) in the emulsion of the component (C) is 5 to 15% by mass, (C-2) The content of the component is 40 to 60% by mass, and the content of the component (C-3) is 1 to 30% by mass. Item 4. The emulsified liquid oral composition according to item 1, 2 or 3. The blending amount of the emulsion of component (C) is 0.3 to 0.9% by mass of the whole composition. Item 5. The emulsified liquid oral composition according to any one of Items 1 to 4.
The emulsion liquid oral composition according to any one of claims 1 to 5 , wherein the component (D) is a combination of glycerin and polyethylene glycol 400, or glycerin, propylene glycol, and polyethylene glycol 400. The milk according to any one of claims 1 to 6, comprising 0.01 to 0.1% by mass of component (A). Liquid oral composition. The emulsified liquid oral composition according to any one of claims 1 to 7 , wherein the ethanol content in the composition is 100 ppm or less. The emulsified liquid oral composition according to any one of claims 1 to 8 , further comprising (E) 0.05 to 0.2 mass% of vitamin E. A method for producing a liquid oral composition containing isopropylmethylphenol and substantially free of ethanol,
(A) isopropylmethylphenol,
(B) at least one polyhydric alcohol selected from polyoxyethylene hydrogenated castor oil having an average added mole number of ethylene oxide of 40 to 100 moles, and (D) glycerin, propylene glycol, and polyethylene glycol having an average molecular weight of 190 to 630 5 to 15% by mass
After blending, (C) (C-1) decaglycerin monofatty acid ester, (C-2) trifatty acid glyceryl, (C-3) glycerin , and an emulsion having an average particle size of 50 to 500 nm are added, {Mass ratio of (B) component and (C-1) component decaglycerin monofatty acid ester} / {(C-2) component tri-fatty acid glyceryl amount} was 0.77 to 1.87. A method for producing an emulsified liquid oral composition.