KR20120112538A - Emulsion-type liquid composition for oral cavity, and process for production thereof - Google Patents

Abstract

(A) A liquid oral composition containing isopropylmethylphenol and substantially free of ethanol, comprising (B) E.O. 40 to 100 moles of polyoxyethylene hardened castor oil, (C) (C-1) decaglycerin monofatty acid ester and (C-2) trifatty acid glyceryl, (D) glycerin, propylene glycol, average molecular weight of 190 to 630 A polyhydric alcohol selected from polyethylene glycol is blended, and the mass ratio of {(B) and (C-1)} / {(C-2)} is 0.77 to 1.87, and the blending amount of (D) is 5 to 15 mass%. The present invention provides a composition for penetrating and disinfecting periodontal pathogenic biofilms containing glycerin at least 0.003% by mass and having high oral retention in isopropylmethylphenol, having good appearance stability and hypoallergenic emulsifying liquid oral cavity. Moreover, the method of manufacturing the said composition which adds (C) component as an emulsion after mix | blending (A), (B) and (D) component is also provided.

Description

Emulsified liquid composition for oral cavity and its manufacturing method {EMULSION-TYPE LIQUID COMPOSITION FOR ORAL CAVITY, AND PROCESS FOR PRODUCTION THEREOF}

The present invention is formulated with no ethanol, and formulated with a specific emulsion, which enhances the oral retention of medicinal components and exhibits a high penetration and sterilizing effect against periodontal pathogenic biofilms. And a non-alcohol-type emulsified liquid oral composition containing isopropylmethylphenol, which has good external appearance stability at low temperature storage and is also mild in use, and a method for producing the same.

It is considered that the cause of caries and bad breath is not only caused by periodontal disease, but also caused by various bacteria in biofilm, and as an effective means for the prevention and improvement of oral diseases, sterilization of biofilm bacteria is important for the prevention of oral diseases. Therefore, nonionic fungicides and cationic fungicides have been formulated into oral care products. In particular, nonionic fungicides such as isopropylmethylphenol among the fungicides formulated for oral care products have a characteristic that the antimicrobial spectrum tends to be broader than that of cationic fungicides. , On the market. Among them, isopropylmethylphenol is an important component in preventing periodontal disease because it has an excellent effect of penetrating and sterilizing the genus of periodontal pathogenic biofilm, which is not present in other sterilizing components. In addition, it is more important to keep these fungicides and medicinal components having an effect of promoting anti-inflammatory, blood circulation, and antioxidant in the oral cavity for a long time, to prevent oral diseases.

Conventionally, liquid oral compositions, such as mouthwashes, contain ethanol for the purpose of improving the refreshing feeling and improving stickiness. see. Moreover, in recent years, the oral cavity, such as dry mouth, dries severely, and there is an increasing number of people who are very sensitive to stimulation, or those who are sensitive to ethanol-specific stimulation even if they are not dry mouth. For those who are sensitive to such dry mouth and ethanol, opportunities for using a mouthwash are increasing in terms of simplicity and effectiveness at the time of use, but there is a tendency to avoid ethanol-containing formulations.

In such a situation, in recent years, ethanol-free liquid oral compositions have been widespread, but in such a product, a feeling of cooling and bad breath prevention is inferior to liquid oral compositions such as ethanol-containing mouthwashes. have. In addition, since nonionic bactericidal components such as isopropylmethylphenol as described above are useful, in order to stably blend the liquid oral composition without blending ethanol, a larger amount of surfactant is required than the ethanol blend composition. This makes it difficult to achieve compatibility between the appearance stability at low temperature and high temperature storage and the biofilm sterilizing power, and there is a problem such as a sudden irritation when using a mouthwash with a surfactant.

On the other hand, the applicant proposed a technique of mitigating the stimulation peculiar to ethanol and keeping the drug in the oral cavity for a long time by blending the emulsion with a formulation containing ethanol (see Patent Document 1). However, this technique relates to an ethanol-containing composition, and somewhat relieves the stimulus after washing and discharging, but the user, especially the mouth dryer as described above, stays in the mouth and feels ethanol-specific stimulation in washing mouth. Also, in view of the image of ethanol blending, the formulation tends to be light in use. Furthermore, in this Patent Document 1, by emulsifying the oil-soluble active ingredient together, the emulsion stays in the oral mucosa and the retention property of the active ingredient is improved. However, since the active ingredient is contained in the emulsion, the bactericidal effect is sufficiently exhibited. It was difficult to say that the sterilization power to the biofilm was lowered and the caries, periodontal disease and bad breath prevention effects were sufficiently exhibited. In addition, also in appearance stability, an emulsion tends to collapse in high temperature long-term storage and low temperature long-term storage (freezing preservation), and it is still hard to satisfy also about the appearance stability of a formulation, and there exists room for improvement in this point.

From the above problems, it is desirable to develop a non-alcoholic liquid oral composition having a high preventive effect such as periodontal disease, a low mouthwash irritation and good external appearance stability even when used by an oral dryer.

Patent Document 1: Japanese Patent Application Laid-Open No. 2005-179231 Patent Document 2: International Publication No. 07/148551

The present invention has been made in view of the above circumstances, exhibits a high penetration and sterilizing effect on periodontal pathogenic biofilms, has high retention in the oral cavity of drugs, and also has good appearance stability in high temperature storage and low temperature (freezing) storage. An object of the present invention is to provide a non-alcohol-type liquid oral composition containing isopropylmethylphenol, which is hypoallergenic, and a method for producing the same.

MEANS TO SOLVE THE PROBLEM As a result of earnestly examining, the present inventors found that the average added mole number of (B) ethylene oxide is 40 to the liquid composition for oral cavity which contains (A) isopropylmethylphenol as a sterilization component and does not contain ethanol substantially. 100 mol polyoxyethylene hardened castor oil, (C) (C-1) decaglycerol monofatty acid ester and (C-2) trifatty acid glyceryl, (D) glycerin, propylene glycol, polyethylene having an average molecular weight of 190 to 630 (C-1) decaglycerol monofatty acid ester in (C-1) polyoxyethylene hardened castor oil which is a compound (B) which is 1 type, or 2 or more types of polyhydric alcohols chosen from glycol, and is a nonionic surfactant The mass ratio of the total amount of to and the amount of the (C-2) trifatty acid glyceryl in the component (C), which is an oily component, is set to an appropriate ratio, and the blending amount of the polyhydric alcohol of the component (D) is appropriate. Let's do it, write A serine has been found that, the above object can be achieved by as containing not less than 0.003 mass%.

Moreover, in the manufacturing method of the liquid oral composition which contains isopropylmethylphenol and does not contain ethanol substantially, after mix | blending said (A), (B) and (D) components suitably, (C) As the component, an emulsion consisting of the above (C-1) component, (C-2) component, (C-3) glycerin and water is added, and the {total amount of (B) component and (C-1) component} / {( It was found that the emulsified liquid oral composition can be produced by appropriately mass ratio of C-2) component amount}.

According to the present invention, high penetration and sterilization ability to the periodontal pathogenic biofilm is exhibited, the oral retention property of isopropylmethylphenol as a medicinal component is also high, and the appearance stability is good even when stored at high temperature or low temperature, and irritation in the oral cavity The hypoallergenic emulsified liquid oral composition which hardly feels irritation even when used by a sensitive person can be obtained.

Applicant is a technology that balances biofilm sterilization power and appearance stability, and is selected from a specific anionic surfactant, polyoxyethylene hardened castor oil, and polyoxyethylene alkyl ether in a liquid oral composition containing isopropylmethylphenol. A liquid oral composition is proposed in which a soluble surfactant and a polyhydric alcohol are blended, and the water content in the composition is 70% by mass or more (see Patent Document 2). Still felt the stimulation of Segu City, and there was room for improvement in the oral retention of medicinal components.

Then, the present inventors further examined the non-alcohol type liquid oral composition which contains isopropylmethylphenol and does not contain ethanol substantially. As a result, the said liquid oral composition mix | blends specific polyoxyethylene hardened castor oil as a solubilizer, and said (C) component as an emulsifier, and mix | blends as an emulsion of the specific average particle diameter which prepared (C) component previously, By blending so that the ratio of the total amount of the nonionic surfactant in the two components and the oil component contained in the emulsion is appropriate, and by appropriately blending a specific polyhydric alcohol, the emulsion is stably compounded and the above problem is solved by periodontal It has been found that the pathogenic biofilm sterilizing power and appearance stability are both compatible and hypoallergenic. In the present invention, the texture of the action is not clear, but isopropyl methylphenol is completely emulsified by post-adding the emulsion, unlike emulsifying and blending oil-soluble isopropylmethylphenol from the beginning. It is guessed that it is mix | blended stably in a formulation, without being accepted in the inside. For this reason, the fall of the sterilizing power of the oral biofilm derived from isopropylmethylphenol can be suppressed, and high sterilizing power is exhibited, and even if it is preserve | saved for 3 months at high temperature or low temperature, emulsion remains stable and thereby emulsifies It is considered that the color tone becomes unstable, the color tone of the formulation is not faded, or the oily component separates and the liquid is not separated, and it is excellent in the appearance stability of the formulation. Moreover, the stimulation by surfactant can also be suppressed by mix | blending (D) component suitably. In addition, in the present invention, since ethanol is not blended and a large amount of the surfactant may not be blended again, a hypoallergenic agent may be used at the time of use, for example, in mouthwashing.

Moreover, in this invention, the effect of this invention is achieved by combining suitably the said (C) component with (B) component, and also (D) component, and even if it mixes an inappropriate emulsion, or the said Even if it lacks any of the essential requirements, the object of the present invention is not achieved.

The liquid oral composition of the present invention is easy to use even for those who are sensitive to irritation in the oral cavity, such as those with severe dryness in the oral cavity, such as dry mouth, or those who are very sensitive to stimulation, or those who are sensitive to ethanol, and such as periodontal disease. Effective for the prevention or improvement of diseases in the oral cavity.

Therefore, this invention provides the following emulsified liquid oral composition.

Claim 1:

(A) To a liquid oral composition containing isopropylmethylphenol and substantially free of ethanol,

(B) polyoxyethylene hardened castor oil having an average added mole number of ethylene oxide of 40 to 100 moles,

(C) (C-1) decaglycerin monofatty acid ester and (C-2) trifatty acid glyceryl,

(D) At least one polyhydric alcohol selected from glycerin, propylene glycol and polyethylene glycol having an average molecular weight of 190 to 630 is blended, and the total amount of the decaglycerol monofatty acid ester of {(B) component and (C-1) component } / {Mass ratio of triglyceride glyceryl which is (C-2) component} is 0.77-1.87, the compounding quantity of (D) component is 5-15 mass%, and 0.003 mass% of glycerin Emulsion-type liquid oral composition comprising the above.

Claim 2:

Claim (C) A component is mix | blended as an emulsion of the average particle diameter of 50-500 nm which consists of (C-1) decaglycerol monofatty acid ester, (C-2) trifatty acid glyceryl, (C-3) glycerin, and water. Emulsion type liquid oral composition of 1 description.

[Claim 3]

Emulsion type liquid oral composition of Claim 1 or 2 whose total compounding quantity of polyoxyethylene hardened castor oil which is (B) component and decaglycerol monofatty acid ester which is (C-1) component is 0.18-0.49 mass% of the whole composition. .

Claim 4:

Emulsion type of Claim 1, 2 or 3 whose carbon number of fatty acids of the decaglycerol monofatty acid ester which is (C-1) component is 12-16, and carbon number of fatty acids of glyceryl trifatty acid is 6-12. Liquid oral composition.

[Claim 5]

The composition for emulsified liquid oral cavity of any one of Claims 1-4 whose component (D) is glycerin and polyethyleneglycol 400, or a combination of glycerin, propylene glycol, and polyethyleneglycol 400.

[Claim 6]

Emulsion type liquid oral composition of any one of Claims 1-5 whose ethanol content in a composition is 100 ppm or less.

[Claim 7]

Moreover, the composition for emulsified liquid oral cavity of any one of Claims 1-6 which mix | blended (E) vitamin E.

Claim 8:

The emulsion type liquid oral composition of Claim 7 which mix | blended 0.05-0.2 mass% of (E) component.

Claim 9:

A method for producing a liquid oral composition containing isopropylmethylphenol and containing substantially no ethanol,

(A) isopropylmethylphenol,

(B) polyoxyethylene hardened castor oil having an average added mole number of ethylene oxide of 40 to 100 moles, and

(D) 5 to 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, an emulsion having an average particle diameter of 50 to 500 nm consisting of (C) (C-1) decaglycerin monofatty acid ester, (C-2) trifatty acid glyceryl, (C-3) glycerin and water was added, and { Emulsion type characterized in that the mass ratio of the total amount of the component (B) and the decaglycerol monofatty acid ester as the component (C-1)} / {the amount of the triglyceride glyceryl as the component (C-2)} is 0.77 to 1.87 Method for producing a liquid oral composition.

According to the present invention, in the liquid oral composition containing isopropylmethylphenol and having no ethanol blend, a high penetration sterilization effect is exhibited against the periodontal pathogenic biofilm, and the oral retention of isopropylmethylphenol is increased. The hypoallergenic emulsified liquid oral composition having good visual stability over time at low temperature and high temperature storage and having little oral irritation at the time of mouth can be obtained. Therefore, the composition of the present invention is effective for the prevention or suppression of periodontal disease, especially for a user who is sensitive to stimulation in the oral cavity that the oral cavity dries severely or is sensitive to ethanol-specific stimulation due to dry mouth symptoms and the like.

EMBODIMENT OF THE INVENTION Hereinafter, when this invention is demonstrated in more detail, the emulsified liquid oral composition of this invention is soluble in the liquid oral composition which contains (A) isopropylmethylphenol as a sterilization component, and does not contain ethanol substantially. Polyoxyethylene hardened castor oil having an average added mole number of ethylene oxide (B) of 40 to 100 moles as the agent, (C) (C-1) decaglycerin monofatty acid ester and (C-2) trifatty acid glyceryl, polyhydric acid as an emulsifier As alcohol, it mix | blends at least 1 sort (s) chosen from (D) glycerin, propylene glycol, and polyethyleneglycol of average molecular weights 190-630. In this case, (C) component is mix | blended as an emulsion of the average particle diameters 50-500 nm which consist of (C-1) decaglycerol 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 compounding amount of (A) isopropylmethylphenol is not particularly limited, but is 0.01 to 0.1% of the whole composition in terms of the penetration sterilization effect and appearance stability to the periodontal pathogenic biofilm. (Mass%, likewise below), Especially 0.03 to 0.08% is preferable. If the blending amount is less than 0.01%, satisfactory penetration sterilization power may not be exhibited with respect to the oral biofilm, and if it exceeds 0.1%, the appearance stability may be impaired.

The polyoxyethylene hardened castor oil which is (B) component is 40-100 mol, Preferably it is 60-100 mol of ethylene oxide. When the average added mole number is less than 40 mol, it precipitates at the time of low temperature storage, and what exceeds 100 mol is generally not marketed.

As for the compounding quantity of (B) component, 0.15-0.40%, especially 0.20-0.30% of the whole composition are preferable at the point of solubilization of (A) component, the germicidal power to a periodontal pathogenic biofilm, and appearance stability. If the blending amount is less than 0.15%, the appearance stability may be inferior. If the blending amount exceeds 0.40%, the sterilizing power to the periodontal pathogenic biofilm may be impaired.

(C) component is (C-1) decaglycerol monofatty acid ester and (C-2) trifatty acid glyceryl, (C-1) decaglycerol monofatty acid ester, (C-2) trifatty acid glyceryl, ( C-3) It can mix | blend as an emulsion of 50-500 nm of average particle diameters which consist of glycerin and water. The oily component is trifatty acid glyceryl, glycerin, the aqueous component is water, and mixed using a decaglycerol monofatty acid ester which is a nonionic surfactant, to prepare an emulsion.

In addition, in this invention, isopropylmethylphenol which is (A) component is mix | blended as an oil-based component in a composition, and is not contained at the time of the said emulsion adjustment.

In the said emulsion, as decaglycerol monofatty acid ester, the thing of 12-16 carbon atoms of a fatty acid is suitable, For example, monomyristin decaglyceryl, monolauric acid decaglyceryl, etc. are mentioned.

The compounding quantity of decaglycerol monofatty acid ester can be normally used as 5 to 15% in an emulsion. If it is less than 5%, the oily component separates, and if it exceeds 15%, gelation may occur.

Moreover, as trifatty acid glyceryl in an emulsion, the thing of carbon chain length 6-12 is suitable, For example, a tricaprylic acid glyceryl, a tricaprylic acid glyceryl, a tri (capuryl capric acid) glyceryl, etc. are mentioned. Can be mentioned.

1 type (s) or 2 or more types are used for a trifatty acid glyceryl, and the compounding quantity can be 40 to 60% normally in an emulsion. If it is less than 40%, an emulsion cannot be formed, and if it exceeds 60%, an oily component may isolate | separate and may damage external appearance stability.

In addition, content of the glycerin in an emulsion can be 1 to 30%, especially 10 to 20%. If it is less than 1%, the homogeneous dissolution of surfactant will become complicated, and if it exceeds 30%, an oily component may isolate | separate.

The average particle diameter of the emulsion is 50 to 500 nm, particularly preferably 100 to 300 nm. If average particle diameter is out of the said range, external appearance stability may be inferior and the objective of this 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 emulsion is of O / W type. The preparation method is, for example, after stirring a predetermined amount of decaglycerin monofatty acid ester, glycerin and a half amount of water with a homomixer, trifatty acid glyceryl is added, an emulsion is formed, and finally the remaining water is added I can prepare it. Then, the method of adjusting an average particle diameter using the high pressure homogenizer which created the emulsion can be employ | adopted preferably. The desired oral composition can be obtained by adding a predetermined amount of the emulsion thus prepared to the liquid oral composition.

Moreover, as this emulsion, a commercial item, for example, NET-TE-50 by Nikko Chemicals, etc. can be used.

As for the compounding quantity of the emulsion of (C) component, 0.3-0.9% of the whole composition, especially 0.4-0.7% are preferable. If the blending amount is less than 0.3%, the color tone of the composition may be discolored (transparent) at high temperature storage, and the appearance stability may be impaired. .

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

Moreover, it is preferable that the total compounding quantity of the polyoxyethylene hardened castor oil which is (B) component, and the decaglycerol monofatty acid ester which is (C) component is 0.18 to 0.49%, especially 0.2 to 0.37% of the whole composition. It is more effective to make a total compounding quantity into the said range, the high permeability and sterilization power to a periodontal pathogenic biofilm are exhibited, and also the composition which is favorable in external appearance stability is preserve | saved even at high temperature or low temperature. If the amount is less than 0.18%, the oil may separate and impair the appearance stability at low temperature (freezing) preservation, and if it exceeds 0.49%, the sterilizing power to the periodontal pathogenic biofilm may be impaired.

As the polyhydric alcohol as the component (D), one selected from glycerin, propylene glycol and polyethylene glycol having an average molecular weight of 190 to 630 is used alone or in combination of two or more thereof.

In addition, the above-mentioned average molecular weight shows the average molecular weight of the quasi drug raw material specification 2006, and this is the average molecular weight measured by making it react with phthalic anhydride in pyridine, making it a phthalic acid ester, and titrating with sodium hydroxide.

Examples of polyethylene glycols having an average molecular weight of 190 to 630 include polyethylene glycol 200 (average molecular weights 190 to 210), polyethylene glycol 300 (average molecular weights 290 to 310), polyethylene glycol 400 (average molecular weights 390 to 410), and polyethylene glycol 600 (590 to 610). This corresponds. Depending on the product, like polyethylene glycol 200, # may be added between polyethylene glycol and a numerical value.

Moreover, it is preferable to use 2 or more types of compounded species of (D) component from the point of the irritation and external stability at the time of use, and it is more preferable to use 3 or more types. As a combination of 2 types, a combination of glycerin, propylene glycol, and polyethylene glycol 400 is preferable as a combination of 3 types of glycerin and polyethylene glycol.

The total compounding quantity of (D) component is 5 to 15% of the whole composition, Especially 6 to 13% is preferable at the point of the appearance stability at low temperature and high temperature, and the stimulation at the time of use. If the blending amount is less than 5%, it is difficult to maintain the appearance stability at low temperature and high temperature, and the stimulus derived from the surfactant may not be suppressed. If the amount exceeds 15%, the color tone fades and impairs the appearance stability. There is.

When formulated as 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 glycol having an average molecular weight of 190 to 630 It is preferable to mix | blend 1% or more of.

In addition, content in the composition of glycerin is 0.003 mass% or more.

It is preferable to mix | blend the vitamin E (E) further with the liquid composition for oral cavity of this invention, and by doing this, it is possible to improve the blood circulation promoting effect while achieving the said outstanding characteristic. As vitamin E in this invention, tocopherol ester derivatives, such as a tocopherol, a tocotrienol, a tocopherol acetate ester, and a tocopherol nicotinic acid ester, are mentioned, 1 type, or 2 or more types selected from these can be used. As for the compounding quantity of (E) component, 0.05-0.2% of the whole composition, especially 0.05-0.15% are preferable, When the compounding quantity is less than 0.05%, blood circulation promoting effect is not obtained satisfactorily, and when it exceeds 0.2%, a preparation isolates The 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, particularly preferably 10 ppm or less, and the lower limit is 0 ppm with respect to the whole composition. In addition, although the composition for oral liquids of this invention mix | blends ethanol free, since the trace amount of ethanol derived from a raw material may be contained in the pharmaceutical compound mix | blended in a composition, the ethanol contained in trace amount etc. in a medicine etc. is considered. In addition, it does not contain ethanol.

The liquid oral composition of the present invention can be formulated and applied as a mouthwash, a liquid skirt, or the like, and in accordance with the dosage form, other appropriate known ingredients are added to the above components in a range that does not interfere with the effects of the present invention. can do. For example, a solvent, a wetting agent other than the polyhydric alcohol which is (D) component, a thickener, surfactant other than surfactant of (B) component, and (C) component, a solvent, If necessary, pH adjuster, preservative, sweetener, It can contain an active ingredient, coloring agents, etc. other than a coloring agent, (A) component, and (E) component.

As a humectant, things other than the polyhydric alcohol which is (D) component, for example, sugar alcohols, such as sorbitol, xylite, maltite, and lactite, ethylene glycol, etc. are mentioned. When mix | blending these humectants, the range in which the compounding quantity containing the polyhydric alcohol which is (D) component becomes 5 to 15% is preferable.

As the thickener, xanthan rubber, 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 amount of the compound is usually 0 to 5%, and in the case of blending, 0.01 to 5%).

As the pH adjuster, one or two or more of phthalic acid, phosphoric acid, citric acid, succinic acid, acetic acid, fumaric acid, malic acid and carbonic acid and their potassium salts, sodium and ammonium salts, ribo nucleic acids and their salts, and sodium hydroxide can be used. In particular, a combination of phosphoric acid, citric acid and their sodium salt is preferable. In particular, in the liquid oral composition of the present invention, the pH at 25 ° C. is preferably adjusted to 5.5 to 7.5, and sodium dihydrogen phosphate and sodium isophosphate as a pH adjuster in the vicinity are combined with citric acid and sodium citrate. It is preferable to use what was made.

As the solvent, purified water is usually used. The compounding quantity of a solvent is 60 to 94.49% normally.

As a preservative, paraoxybenzoic acid esters, such as sodium benzoate, methyl paraben, ethyl paraben, propyl paraben, and butyl paraben, alkyldiaminoethylglycine hydrochloride, potassium sorbate, etc. can be contained.

As the sweetening agent, saccharin sodium, stevioside, sucralose, reduced palatinose, erythritol and the like can be contained.

Natural ingredients such as peppermint oil, spearmint oil, eucalyptus oil, winter green oil, clove oil, thyme oil, sage oil, cardamom oil, rosemary oil, marjoram oil, lemon oil, nutmeg oil, lavender oil and paracrese oil Essential oils, and l-carbon, 1,8-cineol, methylsalicylate, eugenol, thymol, linalool, limonene, menton, menthyl acetate, citral, camphor, borneol, pinene, spytolhol and the like The pharmaceutical components contained in the natural essential oils of the above, further, ethyl acetate, ethyl butyrate, isoamyl acetate, hexanal, hexenal, methyl anthranilate, ethyl methyl phenyl glycidate, benzaldehyde, vanillin, ethyl vanillin, praneol, Pharmaceutical components such as maltol, ethyl maltol gamma / delta decaractone, gamma / deltown decaractone, N-ethyl-p-mentan-3-carboxamide, menthyllactate, and ethylene glycol-1-mentylcarbonate; Some ingredients or natural ingredients Of combination flavors such as apple, banana, strawberry, blueberry, melon, peach, pineapple, grape, muscat, wine, cherry, squash, coffee, brandy, yogurt, etc. One type or two types or more can be used in 0.00001 to 3% in the composition of this invention in the range which does not prevent the effect of this invention.

As surfactant other than the nonionic surfactant as said (B) component and (C) component, an alkyl sulfate (for example, sodium lauryl sulfate, potassium lauryl sulfate, sodium myristyl sulfate, potassium myristyl sulfate) is used, for example. Alkali metal salts of alkyl sulfuric acid having 12 to 16 alkyl groups), N-acylamino acid alkali metal salt having 12 to 16 carbon atoms of acyl group, lauroylmethyltaurine, acylamino acid salt, sodium dodecylbenzenesulfonate, α-sulfo Anionic surfactants such as fatty acid alkyl esters, sodium and alkyl phosphate ester salts, acetic acid betaine type amphoteric surfactants such as alkyldimethylaminoacetic acid betaine and fatty acid amidepropyldimethylaminoacetic acid betaine, N-fatty acid acyl-N-carboxymethyl Amino acid type surfactant, such as imidazoline type amphoteric surfactant, such as -N-hydroxyethylethylenediamine salt, and N-fatty acid acyl-L-alginate salt Amphoteric surfactants, etc. are mentioned, It can mix | blend 1 type individually or in combination of 2 or more types in the range which does not prevent the effect of this invention. In addition, in this invention, surfactant other than the nonionic surfactant as said (B) component and (C) component, especially nonionic surfactant may not mix | blend and 0% may be sufficient, but when mix | blending, 0.01 to 1% is preferred.

As an active ingredient, in addition to isopropylmethylphenol and also tocopherol acetate ester, other components, for example, antiseptics such as triclosan and cetylpyridinium chloride, anti-inflammatory agents such as trinexamic acid and epsilon-aminocaproic acid, dextranase , Amylase, protease, mutanase, lysozyme, lytic enzymes, enzymes such as lytecenzyme, fluorides such as sodium fluoride, sodium monofluorophosphate, stannous fluoride, aluminum chloride hydroxyalantoin, allantoin, azulene, lysozyme chloride , Vitamin C such as ascorbic acid, dihydrocholesterol, glycyrrhetirine, glycyrrhetinic acid, hydrocholesterol, chlorophyll, copper chlorophyllin sodium, thyme, golden, sperm, hamamelis and other plant extracts, gluconic acid Copper, Carofeptide, Sodium Polyphosphate, Water Soluble Inorganic Phosphate, Polyvinylpyrrolidone, Lauroyl Salcosine Sodium, it may be added to a tartar agent, a plaque inhibitor, potassium nitrate, aluminum lactate and the like. In addition, the compounding quantity of these active ingredients can be contained in the range which does not prevent the effect of this invention.

As the coloring agent, water-soluble pigments having high safety such as blue No. 1, green No. 3, yellow No. 4 and red No. 105 can be added.

Although PET (polyethylene terephthalate), glass, polypropylene, and polyethylene can be used as a container, the use of PET and glass is preferable at the point of suppressing the adsorption of a nonionic fungicide and a chemical | medical agent.

Example

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

In preparation of the composition for liquid oral cavity of each case, isopropylmethylphenol (made by Osaka Chemical Co., Ltd.), polyoxyethylene (60) hardened castor oil (made by Nikko Chemicals Corporation), polyoxyethylene (80) hardened castor oil (made by Nikko Chemicals Corporation) ), Emulsion (average particle diameter 200nm, NET-TE50, Nikko Chemicals Corporation), glycerin (100%, manufactured by Sakamoto Pharmaceutical Co., Ltd.), propylene glycol (manufactured by Asahi Glass Co., Ltd.), polyethylene glycol 400 (manufactured by Lion Chemical Corporation), tocopherol acetate ester (Manufactured by DSM Nutri Japan Co., Ltd.), citric acid (manufactured by Fuso Chemical Co., Ltd.), and sodium citrate (manufactured by Fuso Chemical Co., Ltd.) were used. In addition, triclosan (made by Chiba-Specialty Chemicals Co., Ltd.), polyoxyethylene (30) hardened castor oil (made by Nikko Chemicals Co., Ltd.), emulsion (comparative emulsion, average particle diameter 10nm, Nikko Chemicals Co., Ltd.), ethanol (Japanese alcohol sales Company) was used in the comparative example. In addition, POE in a table | surface represents polyoxyethylene and the% shown below means the mass% as long as there is no notice in particular. In addition, the composition of the said emulsion is shown below.

[Composition of Emulsion (average particle diameter 200 nm)]

10% decaglyceryl monomyristin

Tri (Caprylyl-Capric Acid) Glyceryl 50

Glycerin 15

Water 25

100% in total

[Composition and preparation method of comparative emulsion (average particle diameter 10 nm)]

10% decaglyceryl monolauric acid

Olive oil 50

Glycerin 15

Water 25

100% in total

Glycerin, half the water, and decaglyceryl monolauric acid were preliminarily stirred, then olive oil was added, stirred with a homomixer, and finally the remaining water was added to prepare.

The average particle diameter of the emulsion was measured by the following method.

[Measurement method of average particle diameter]

Using dynamic light scattering photometer N5, manufactured by BECKMAN COULTER, the emulsion was diluted 100 times with purified water and placed in a cell to measure an average particle diameter at 25 ° C.

Experimental Example 1

The liquid oral composition (washing agent) of the composition shown to Tables 1-5 was prepared by a daily method, the emulsion was disperse | distributed last, and the following evaluation was performed. The results are shown in Tables 1-5.

Evaluation of Appearance Stability:

The liquid oral composition of the sample was filled with 450 ml of a 450 ml PET container (polyethylene terephthalate container manufactured by Yoshino Kogyo Co., Ltd.), and stored in a 50 ° C. thermostat for 3 months or 3 in a -10 ° C. thermostat. The stability after months storage was visually determined according to the following criteria in comparison with the control product (initial product of Example 3).

Evaluation standard of appearance stability (50 degrees Celsius, three months)

(Double-circle): A change is not recognized by the hue of a formulation.

(Circle): Although the fading of the hue of a preparation advances slightly, it is a level without a problem.

(Triangle | delta): The fading of the hue of the preparation is advanced.

X: The color tone of a preparation remarkably fades even if it does not compare with a control.

And in the said evaluation and the following evaluation, fading progresses that the color tone immediately after preparation of the preparation was white, and it is a state which fades transparently. The cause is not clear, but the free surfactant in a preparation is not clear. It is considered to be solubilization by.

Evaluation standard of appearance stability (-10 degrees Celsius, three months)

(Double-circle): A change is not recognized.

(Circle): Very little separation is seen but it is a level without a problem.

(Triangle | delta): Separation is advanced.

X: Substantial separation is recognized, and the fading of the color tone of a preparation is also advanced.

Experimental Example 2

About the liquid oral composition shown in Tables 1-5, the periodontal pathogenic biofilm penetration sterilization power was evaluated by the following method. The results are shown in Tables 1-5.

Evaluation of Biofilm Penetrating Sterilization:

(1) Production method of model periodontal pathogenic biofilm

A hydroxyapatite (HA) plate (manufactured by Asahi Optical Co., Ltd.) having a diameter of 7 mm and a thickness of 3.5 mm was treated with human non-irritating saliva filtered with a 0.45 μm filter for 4 hours using a carrier for producing a model biofilm. As the culture solution, 5 mg of hemin (manufactured by Sigma) and 0.5 mg of menadione (manufactured by Sigma) were added to a solution in which 30 g of trythicase soy broth (manufactured by Difco) was dissolved in 1 liter of purified water. In order to produce a model biofilm, Streptococcus gordon ATC51656 strain and Actinomyces naeslundi ATCC51655 strain as the oral supernatant bacteria, and Porphyromonas Jinjivalis ATCC33277 strain as the pathogenic bacterium were used. Was used. Each of these three species was inoculated in the culture medium described above to be 2 × 10 ⁷ cfu / ml (cfu: colony forming units), and at 37 ° C. under anaerobic conditions (5 vol% carbon dioxide, 95 volumes, together with saliva-treated HA carrier). % Nitrogen) was continuously cultured for 2 weeks (replacement rate of the culture solution was set to 10% by volume) to form a model biofilm of three species mixed on the HA surface.

(2) Penetrating sterilization effect on model biofilm

The formed model biofilm was immersed in 2 ml of the sample (composition for liquid oral cavity) 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 ultrasonication (200 μs, 10 seconds) with 4 ml of sterile saline solution, and 10% cotton destained blood trychicase soy agar plate (manufactured by Difco) and kanamycin sulfate (200 mg / L: Sigma Co., Ltd.) Trypticase Soy was plated 50 µl on agar plate, and cultured under anaerobic conditions. The grown colonies were measured, and the number of viable bacteria (cfu) of the remaining porphyromonas jinjivalis bacteria was determined and determined according to the following criteria.

Criteria

◎: less than 10 ⁶

○: 10 ⁶ or more but less than 10 ⁷

△: 10 ⁷ or more but less than 10 ⁸

×: 10 ⁸ or more

Experimental Example 3

About the liquid oral composition shown in Tables 1-5, the oral | survival rate of isopropylmethylphenol was evaluated by the following method. The results are shown in Tables 1-5.

In addition, the composition for oral cavity shown in Table 4 was used as a sample, and the intraoral residual rate of the tocopherol acetate ester was evaluated by the following method. The experimental method and the calculation method of a residual rate are the same as that of isopropylmethylphenol. The results are shown in Table 4.

Intraoral Survival Rate of Isopropylmethylphenol:

With 10 ml of the sample (liquid oral composition) shown in the table in the mouth, the isopropyl methyl phenol concentration contained in the discharge liquid rinsed for 30 seconds was measured by the liquid chromatograph method, and the obtained isopropyl methyl phenol concentration was combined. The residual ratio in the oral cavity was calculated from the concentration and the discharge liquid amount.

The liquid chromatograph measurement sample accurately weighed the discharge liquid, and dissolved 0.3 g of pallaoxybenzoic acid isoamyl (manufactured by Tokyo Chemical Industry Co., Ltd.) in 200 ml of 60% ethanol (99.5) (Kanto Chemical Co., Ltd.) aqueous solution as an internal standard. After adding 1 ml, it was measured by liquid chromatography (sample injection amount 20 ml) to quantify the amount of isopropylmethylphenol. The mobile phase of liquid chromatography uses a mixture of methanol, purified water, and phosphate (volume ratio 1300: 700: 1), and pump: PU-980, Nippon Spectroscopy Co., Ltd., AS-950, Nippon Spectroscopy Co., Ltd., Japan Spectrophotometer UV-970 (measurement wavelength is set to 280 nm), recording device: System Instrument Chromatocorder21J, column high temperature bath: Nippon Spectroscopy CO-966 (set to 50 ° C), column: Kanto Chemical ( Note) Mightysil RP-18 GP (5 μm) was used. From the peak area ratio of isopropylmethylphenol / internal standard substance, the isopropylmethylphenol residual ratio in the oral cavity was computed using the following formula, and the residual ratio was evaluated by the following criteria.

formula;

Isopropylmethylphenol oral residual rate (%) =

[((Detergent dosage × isopropylmethylphenol concentration)-(Isopropylmethylphenol concentration in the amount of discharged liquid × discharge)) ÷ (Detergent dose × isopropylmethylphenol compounded concentration)] × 100

Of isopropylmethylphenol  Criteria for determination of oral residual rate

◎: 20% or more

○: 15% or more but less than 20%

△: 12% or more but less than 15%

×: less than 12%

Oral Residual Rate of Tocopherol Acetic Acid Ester:

The liquid chromatograph measurement sample accurately weighed the discharge liquid, and after adding 2 ml of a liquid in which 0.02 g of ergocalciferol (manufactured by Kanto KK) was dissolved in 200 ml of methanol (manufactured by Kanto KK) as an internal standard substance, It measured by liquid chromatography (sample injection amount 20 ml), and the quantity of tocopherol acetate ester was quantified. Methanol is used as the mobile phase of the liquid chromatography, and the pump: Nippon Ikebukki Co., Ltd. PU-980, the sample introduction part: Nippon Ikeshi Co., Ltd. AS-950, the detector: Nippon Ikeshi Co., Ltd., UV-970 (measuring wavelength 284 nm) Setting), recording device: System Instrument Chromatocorder21J, column high temperature tank: Japan Spectrometer CO-966 (set at 50 ° C), column: Nakaraitesuku COSMOSIL 5C18 Waters (4.6 mmφ x 150 mm) Used. From the peak area ratio of the tocopherol acetate ester / internal standard substance, the tocopherol acetate ester residual ratio in the oral cavity was computed using the above calculation formula, and the residual ratio was evaluated by the above criteria.

Experimental Example 4

About the liquid oral composition shown in Tables 1-5, the stimulation of mouthwash was evaluated by the following method. The results are shown in Tables 1-5.

Evaluation of irritation in segusi:

Ten subjects who felt dry mouth were rinsed for 10 seconds with 10 ml of the sample (liquid oral composition) in their mouths, and then evaluated for stimulation at the time of washing, with Comparative Example 6 as a control, and evaluated in the following three steps. The average score of ten people was determined according to the following criteria.

Segu  pepper

3: hardly felt irritation.

2: Although the reduction of the stimulus was recognized slightly, the slight stimulus was still recognized.

1: The stimulus more than equivalent was recognized.

Stimulus evaluation criteria

○: 2.0 points or more

(Triangle | delta): An average score 1.5 or more and less than 2.0 points

×: average score 1.0 or more and less than 1.5

Experimental Example 5

About the liquid oral composition shown in Table 4, the blood circulation promoting force was measured by the following method, and the blood circulation promoting effect was evaluated. The results are shown in Table 4.

Evaluation of the effect of promoting blood circulation:

In 10 subjects, the blood volume of the upper jaw gum after measuring the sample shown in Table 4 in 10 ml mouth for 30 seconds was measured. The measurement was carried out blood flow measurement by laser doppler method (moorLDI by Monte System Co., Ltd.) after 30 minutes of fine workmanship and three mouths. The average value of the increase rate of 10 people was determined based on the following criteria as a relative blood flow with the pre-nucleated blood flow.

Blood flow growth rate

○: 15% or more

△: 10% or more but less than 15%

×: less than 10%

[Table 1]

*: The total amount of POE cured castor oil which is a nonionic surfactant and decaglycerol monofatty acid ester contained in the emulsion (hereinafter, the same).

**: Triglyceride amount of glyceryl contained in the total amount / emulsion of nonionic surfactant of * (hereinafter, the same).

[Table 2]

[Table 3]

[Table 4]

[Table 5]

Claims (9)

(A) To a liquid oral composition containing isopropylmethylphenol and substantially free of ethanol,
(B) polyoxyethylene hardened castor oil having an average added mole number of ethylene oxide of 40 to 100 moles,
(C) (C-1) decaglycerin monofatty acid ester and (C-2) trifatty acid glyceryl,
(D) at least one polyhydric alcohol selected from glycerin, propylene glycol and polyethylene glycol with an average molecular weight of 190 to 630
The mass ratio of {the total amount of the decaglycerol monofatty acid ester which is (B) component and (C-1) component} / {triglyceride amount of trifatty acid which is (C-2) component}} to 0.77-1.87, Moreover, the compounding quantity of (D) component is 5-15 mass%, and contains 0.003 mass% or more of glycerin, The composition for emulsified liquid oral cavity characterized by the above-mentioned. The method of claim 1,
(C) component is mix | blended as an emulsion of the average particle diameter of 50-500 nm which consists of (C-1) decaglycerol mono fatty acid ester, (C-2) trifatty acid glyceryl, (C-3) glycerin, and water, It is characterized by the above-mentioned. Emulsified liquid oral composition to be. 3. The method according to claim 1 or 2,
The total compounding quantity of the polyoxyethylene hardened castor oil which is (B) component, and the decaglycerol monofatty acid ester which is (C-1) component is 0.18-0.49 mass% of the whole composition, The composition for emulsified liquid oral cavity. The method according to claim 1, 2 or 3,
Emulsion-type liquid oral composition characterized in that the carbon number of the fatty acid of the decaglycerol monofatty acid ester as the component (C-1) is 12 to 16, and the carbon number of the fatty acid of (C-2) trifatty acid glyceryl is 6 to 12 . The method according to any one of claims 1 to 4,
(D) Component is glycerin and polyethyleneglycol 400, or a combination of glycerin, propylene glycol, and polyethyleneglycol 400, The composition for emulsified liquid oral cavity characterized by the above-mentioned. The method according to any one of claims 1 to 5,
The ethanol content in a composition is 100 ppm or less, The emulsified liquid oral composition characterized by the above-mentioned. 7. The method according to any one of claims 1 to 6,
Moreover, (E) the composition for emulsified liquid oral cavity which mix | blended vitamin E. 8. The method of claim 7,
0.05-0.2 mass% of (E) component were mix | blended, The composition for emulsified liquid oral cavity characterized by the above-mentioned. A method for producing a liquid oral composition containing isopropylmethylphenol and containing substantially no ethanol,
(A) isopropylmethylphenol,
(B) polyoxyethylene hardened castor oil having an average added mole number of ethylene oxide of 40 to 100 moles, and
(D) 5 to 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, an emulsion having an average particle diameter of 50 to 500 nm consisting of (C) (C-1) decaglycerin monofatty acid ester, (C-2) trifatty acid glyceryl, (C-3) glycerin and water was added, and { Emulsion type characterized in that the mass ratio of the total amount of the component (B) and the decaglycerol monofatty acid ester as the component (C-1)} / {the amount of the triglyceride glyceryl as the component (C-2)} is 0.77 to 1.87 Method for producing a liquid oral composition.