WO2007148551A1

WO2007148551A1 - Liquid oral composition containing isopropylmethylphenol

Info

Publication number: WO2007148551A1
Application number: PCT/JP2007/061701
Authority: WO
Inventors: Yasuo Nomura; Kazuo Mukasa
Original assignee: Lion Corporation
Priority date: 2006-06-23
Filing date: 2007-06-11
Publication date: 2007-12-27
Also published as: KR101380508B1; KR20090023577A; JPWO2007148551A1; JP5136797B2

Abstract

A liquid oral composition containing isopropylmethylphenol, which comprises: (A) an anionic surfactant selected from an sodium alkyl sulfate and an N-acylsarcosine sodium; (B) a nonionic surfactant selected from a polyoxyethylene hydrogenated castor oil having an average molar number of an ethyleneoxide unit added of 40 to 100 moles and a polyoxyethylene alkyl ether having 16 to 18 carbon atoms in the carbon chain and having an average molar number of an ethyleneoxide unit added of 10 to 40 moles; and (C) a wetting agent selected from glycerin, propylene glycol, butylene glycol and a polyethylene glycol having an average molecular weight of 190 to 630 in an amount of 5 to 15% by mass relative to the total amount of the composition, which has a moisture content of 70% by mass or more, and which contains substantially no ethanol. It becomes possible to provide a liquid oral composition having a high permeating/bactericidal effect against a periodontopathic biofilm, a good appearance stability, a reduced sticky feeling in the oral cavity during and after use, and a low irritation.

Description

Specification

Isopropylmethylphenol-containing liquid oral composition

Technical field

[0001] The present invention exhibits a high penetrating and bactericidal effect on periodontopathic biofilms, has good appearance stability over time during storage at low and high temperatures, and is used in the oral cavity after use and after use. The present invention relates to a liquid oral composition containing isopropylmethylphenol, characterized by being substantially free of ethanol with low irritation and low irritation. Background art

[0002] Conventionally, the causes of caries, gingivitis, periodontitis and bad breath are thought to be caused by various bacteria in plaque. Plaque control, that is, effective means for prevention and improvement of oral diseases, It is said that it is useful to keep the oral bacteria count at a low level.

[0003] As a means for reducing the number of pathogenic bacteria in the oral cavity, it is an effective means to add a nonionic fungicide or a cationic fungicide to an oral care product. In particular, among the germicides used in oral care products, nonionic germicides such as isopropylmethylphenol have characteristics that tend to have a broader antibacterial spectrum than cationic germicides. It is blended into products and marketed.

[0004] However, these nonionic fungicides are oil-soluble compounds and are almost insoluble in water as they are, so they are solubilized by blending various surfactants and solvents such as ethanol. However, since the surfactant inactivates the active site of the bactericidal agent, sufficient bactericidal power is not expressed when the blending amount increases, and the blending amount of the surfactant for improving the bactericidal power. If the amount is reduced, the liquid becomes clouded with time at low and high temperatures, and the appearance stability of the composition is impaired.

[0005] On the other hand, since the blending of ethanol used as a solubilizing solvent causes a crisp and irritating feeling when using oral compositions, non-alcohol detergents that do not contain ethanol have been widely used in recent years. . However, liquid oral compositions that contain no ethanol and contain nonionic fungicides require more solubilizing power than surfactants when combined with ethanol. Appearance stability over time It was more difficult to achieve both.

[0006] Isopropylmethylphenol is a nonionic fungicide that is attracting attention as a bactericidal preparation with a high penetration bactericidal effect on periodontopathic biofilms. Until now, isopropylmethylphenol has been solubilized with low-concentration polyoxyethylene hydrogenated castor oil in the technology for preventing oral disease using isopropinolemethylphenol (Japanese Patent Laid-Open No. 62-24010, JP-A-1-305021, JP-A-7-48237, JP-A-10-330230: refer to Patent Documents 1 to 4), and these compositions all contain ethanol and thus have a high irritation potential. there were.

[0007] In addition, a high-concentration wetting agent is blended so that the water content in the preparation is 40% or less (see JP-A-11-322554: Patent Document 5), or the moisture content is less than half of the blended amount of polyols. It has been proposed to ensure the aging stability and bactericidal activity of isopropylinomethylphenol by adjusting and blending (see JP 2001-199854 A: Patent Document 6). However, these techniques have the disadvantage that the water content is low and the composition has a high viscosity and is not suitable for mouthwashing, or the stickiness in the oral cavity after use is extremely poor.

[0008] Patent Document 1: Japanese Patent Laid-Open No. 62-24010

Patent Document 2: JP-A-1 305021

Patent Document 3: Japanese Patent Laid-Open No. 7-48237

Patent Document 4: JP-A-10-330230

Patent Document 5: Japanese Patent Laid-Open No. 11 322554

Patent Document 6: Japanese Unexamined Patent Publication No. 2001-199854

Disclosure of the invention

Problems to be solved by the invention

[0009] The present invention has been made in view of the above circumstances, exhibits a high penetrating and bactericidal effect on periodontopathic biofilms, has good appearance stability over time during storage at low and high temperatures, and is used. It is an object of the present invention to provide a liquid oral composition containing isopropylenomethylphenol and containing substantially no ethanol, which has a low irritation with low stickiness in the oral cavity after use.

Means for solving the problem [0010] As a result of intensive studies to achieve the above object, the inventors of the present invention have developed a liquid oral composition containing isopropylmethylphenol as a bactericidal component, into sodium alkyl sulfate and N-acyl sarcosine sodium. At least one anionic surfactant selected from the group consisting of polyoxyethylene hydrogenated castor oil with an average addition mole number of ethylene oxide of 40 to 100 moles and an average addition mole number of ethylene oxide of 16 to 18 Is blended with at least one nonionic surfactant selected from 10 to 40 mol of polyoxyethylene alkyl ether, and further selected from glycerin, propylene glycol, butylene glycol, and polyethylene glycol having an average molecular weight of 190 to 630. At least one wetting agent is used in combination with 5 to 15% by weight of the total composition. By making the water content in the composition 70% by mass or more, a high osmotic sterilization effect on periodontopathic biofilms is exhibited, appearance stability is good even at high and low temperature storage, and it is used during use. A liquid oral composition substantially free of ethanol with a low irritation with a low stickiness in the later oral cavity is obtained, and by adding triclosan to the liquid oral composition, It discovered that the bactericidal effect with respect to an airborne microbe improved.

[0011] According to the present invention, in the liquid oral composition containing isopropylmethylphenol, the composition containing substantially no ethanol in the periodontal pathogenic biofilm is formulated by combining the specific components described above. Excellent bactericidal activity against oral bacteria such as periodontal disease bacteria, excellent appearance stability over time during storage at low and high temperatures, and low stickiness in the mouth during and after mouthwashing It has been found that a high-quality liquid composition for oral cavity can be obtained which has a feeling of use and is excellent in preventing and improving oral diseases.

Therefore, the present invention provides

[I] A liquid oral composition containing isopropylmethylphenol,

(A) at least one anionic surfactant selected from sodium alkyl sulfate and sodium N-acyl sarcosine,

(B) Polyoxyethylene hydrogenated castor oil having an average addition mole number of ethylene oxide of 40 to 100 moles and a polyoxyethylene alkyl having a carbon chain length of 16 to 18 and an average addition mole number of ethylene oxide of 10 to 40 moles At least one non-io selected from ethers Surfactant,

(C) at least one wetting agent selected from glycerin, propylene glycol, butylene glycol, and polyethylene glycol having an average molecular weight of 190 to 630 is 5 to 15% by mass of the total composition

And a liquid oral composition characterized by having a water content in the composition of 70% by mass or more and substantially not containing ethanol.

[II] Component (A) is at least one selected from sodium alkyl sulfate having a carbon chain length of 12 to 14 and sodium N-acyl sarcosine, and component (B) has an average added mole number of ethylene oxide. 60 to 100 moles of polyoxyethylene hydrogenated castor oil and a polyoxyethylene alkyl ether power having an alkyl chain with a carbon chain length of 16 to 18 and an average added mole number of ethylene oxide of 20 to 40 moles are selected. The liquid oral composition according to [I], which is at least one kind

[III] The composition for liquid oral cavity according to [I] or [II], further comprising (D) triclosan

I will provide a.

The invention's effect

[0013] The liquid oral composition of the present invention exhibits an osmotic and bactericidal effect on periodontopathic biofilms and has good appearance stability over time during storage at low and high temperatures. It is hypoallergenic with low stickiness.

BEST MODE FOR CARRYING OUT THE INVENTION

Hereinafter, the present invention will be described in more detail. The liquid oral composition of the present invention contains isopropylmethylphenol as a bactericidal component, and (A) sodium alkyl sulfate and N-a as an anionic surfactant. At least one selected from sodium silsarcosine, (B) polyoxyethylene hydrogenated castor oil having an average addition mole number of ethylene oxide of 40 to 100 moles as a nonionic surfactant and a carbon chain length of 16 to 18 At least one selected from polyoxyethylene alkyl ethers having an average added mole number of ethylene oxide of 10 to 40 moles, and selected from (C) glycerin, propylene glycol, butylene glycolol as a wetting agent, and polyethylene glycol having an average molecular weight of 190 to 630 Little It is characterized in that at least one kind is contained in 5 to 15% by mass of the whole composition, the water content in the composition is 70% by mass or more, and substantially no ethanol is contained.

[0015] The anionic surfactant of component (A) used in the present invention includes sodium alkyl sulfate, N_acyl sarcosine sodium, from the viewpoint of osmotic bactericidal activity against periodontopathic biofilm, taste and irritation. Use at least one selected from Among these, it is selected from sodium alkyl sulfate and sodium N-acyl sarcosine having a carbon chain length of 12 to 14 in terms of osmotic bactericidal activity against periodontal pathogenic biofilms and solubilization of isopropylmethylphenol. In particular, sodium lauryl sulfate and sodium lauryl sarcosine are preferably used.

[0016] The total amount of component (A) is preferably from 0.05 to 1.0% of the total composition in terms of penetrating bactericidal activity against periodontal pathogenic biofilms and solubilizing isopropylmethylphenol. % By mass, the same shall apply hereinafter), and more preferably 0.05 to 0.5%. If the blending amount is less than 0.05%, it may become cloudy and the appearance stability at high temperature may be impaired.If it exceeds 1.0%, it may precipitate over time during storage at low temperature, cause irritation, and taste may deteriorate. It may get worse.

[0017] As the nonionic surfactant of component (B) used in the present invention, the average number of calories of ethylene oxide with respect to periodontopathic biofilm and the number of calories with an average of ethylene oxide ¾0 ~ Use at least one selected from 100 mol polyoxyethylene hydrogenated castor oil and polyoxyethylene alkyl ether having an alkyl chain with a carbon chain length of 16 to 18 and an average added mole number of ethylene oxide of 10 to 40 mol To do. As polyoxyethylene alkyl ethers, those having an average added mole number of 10 to 40 moles, such as point power of stimulation, are used. Among these, polyoxyethylene hydrogenated castor oil with an average number of caromoles of ethylene oxide of 60 to 100 mol and carbon chain length in terms of osmotic bactericidal power against periodontopathic biofilm and solubilization of isopropylmethylphenol. Polyoxyethylene alkyl ethers having an alkyl chain of 16 to 18 and an average addition mole number of ethylene oxide of 20 to 40 mol are preferably used. Furthermore, from the viewpoint of low irritation, polyoxyethylene hydrogenated castor oil having an average addition mole number of ethylene oxide of 60 to 100 mol is particularly preferably used. If the average number of moles of ethylene oxide added to polyoxyethylene hydrogenated castor oil is less than 40 moles, it will precipitate during storage at low temperatures, Those that exceed are generally not on the market. When the average number of added moles of polyoxyethylene alkyl ether is less than 10 moles, those which are precipitated during low-temperature storage as described above and are strongly irritating more than 40 moles are generally not commercially available. In the above polyoxyethylene alkyl ether, when the alkyl chain length is less than 16, the bitterness and irritation are more than 18 and the appearance stability at low or high temperature is inferior.

[0018] The total amount of component (B) is preferably from 0.1 to 1.0 in the entire composition in terms of osmotic bactericidal activity against periodontal pathogenic biofilm and solubilization of isopropylmethylphenol. %, More preferably 0.2 to 0.7%. If the blending amount is less than 0.1%, it may be difficult to maintain appearance stability at low and high temperatures, and if it exceeds 1.0%, the bactericidal activity may be impaired. When polyoxyethylene alkyl ether is used as component (B), irritation may occur if the compounding amount exceeds 1.0%.

As the wetting agent of component (C) used in the present invention, at least one selected from glycerin, propylene glycol, butylene glycol, and polyethylene glycol having an average molecular weight of 190 to 630 is used.

[0020] The above-mentioned average molecular weight indicates the average molecular weight described in Cosmetic Raw Material Standards (2nd edition comment), and polyethylene glycol having an average molecular weight of 190 to 630 is polyethylene glycol 200 (average molecular weight 190 to 210). Polyethylene glycol 300 (average molecular weight 280 to 320), polyethylene glycol 400 (average molecular weight 380 to 420), and polyethylene glycol 600 (average molecular weight 570 to 630). Depending on the product, there may be a # bracket between the polyethylene glycol and the number, for example, polyethylene glycol # 200.

[0021] Furthermore, it is preferable to use two or more kinds of component (C) from the viewpoint of appearance stability at low temperature and taste at the time of use. It is preferable to use three or more kinds from the viewpoint of appearance stability at higher temperature. More preferred. Preferred combinations of the two are glycerin and propylene glycol, glycerin and butylene glycol, and glycerin and polyethylene glycol (especially polyethylene glycol # 400). As the three combinations, a combination of glycerin, propylene glycol and polyethylene glycol, or a combination of glycerin, propylene glycol and butylene glycol is preferred. [0022] The total blending amount of component (C) is 5 to 15% of the total composition, in terms of appearance stability at low and high temperatures, and stickiness in the oral cavity after use during use. 6 to: 13% is preferable. If the blending amount is less than 5%, it may become cloudy, which makes it difficult to maintain appearance stability at high and low temperatures. If it exceeds 15%, an anionic surfactant may precipitate during storage at low temperatures, or stickiness after use may occur during use.

[0023] Furthermore, as component (C), when blending glycerin, 0.5% or more of the whole composition, and when blending propylene glycol, blend 1% or more of butylene glycol with the whole composition. In this case, it is preferable that 1% or more of the whole composition and polyethylene glycol having an average molecular weight of 190 to 630 are blended by 1% or more of the whole composition.

[0024] The amount of isopropylmethylphenol used in the present invention is 0.01 to 0.1% of the total composition, particularly 0.02 in terms of exerting the osmotic bactericidal effect of the periodontopathic biofilm. -0.08% power S is preferable. If the blending amount is less than 0.01%, the biofilm may not be sterilized. If it exceeds 0.1%, white turbidity and appearance stability may be reduced. It may be damaged.

[0025] In the liquid oral composition of the present invention, the water content is preferably 70% or more of the total amount of the composition from the viewpoint of usability and taste, and more preferably 80% or more from the viewpoint of the feeling of use. The upper limit of the amount of water is preferably such that the sum of the lower component amounts of components (A) to (C) and isopropylmethylphenol is 100%, ie 94.84%.

[0026] Furthermore, (D) triclosan can be blended in the liquid oral composition of the present invention for the purpose of improving the bactericidal power against airborne bacteria. The blending amount should be 0 · 01-0.1% of the total composition, especially 0.02 to 0.08%. S is preferable. If the blending amount is less than 0.01%, The sterilizing power may not be exhibited, and if it exceeds 0.1%, it may become cloudy and the appearance stability may be impaired.

[0027] 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 lOOppm or less, more preferably 50ppm or less, particularly preferably lOppm or less with respect to the whole composition. The lower limit is Oppm. In addition, the liquid oral composition of the present invention is an ethanol derived from a raw material in a fragrance compounded in a power composition containing no ethanol. Therefore, in consideration of these reasons, ethanol is not included in addition to ethanol contained in trace amounts in perfumes.

[0028] The liquid oral composition of the present invention can be prepared and applied as a mouthwash, liquid dentifrice, etc., but the liquid oral composition of the present invention has a dosage form other than the above components. Appropriate optional components can be blended depending on the situation, for example, wetting agents other than the above components, thickeners, pH adjusters, preservatives, sweeteners, fragrances, surfactants, active ingredients, coloring agents, etc. Can be contained.

[0029] As the wetting agent other than the component (C) described above, sorbitol, ethylene glycol, xylite, maltite, lactit and the like can be contained. The blending amount of the moistening agent other than these components (C) is preferably 0 to 6% based on the entire composition.

[0030] As the thickening agent, xanthan gum, sodium alginate, polybulal alcohol, hydroxychetyl cellulose, carrageenan, sodium carboxymethyl cellulose and the like can be used as long as the effects of the present invention are not hindered.

[0031] pH adjusters include phthalic acid, phosphoric acid, citrate, succinic acid, acetic acid, fumaric acid, malic acid and carbonic acid and their potassium, sodium and ammonium salts, ribonucleic acid and its salts, and water. At least one kind such as sodium oxide can be used, and in particular, a combination of phosphoric acid and citrate and their sodium salts is preferable.

In particular, the liquid oral composition of the present invention preferably has sodium dihydrogen phosphate and sodium monohydrogen phosphate as pH adjusting agents, preferably adjusting the pH at 25 ° C. to 5.5 · 7.5. Alternatively, it is preferable to use a combination of citrate and sodium citrate.

As the preservative, sodium benzoate, methylparaben, ethylparaben, propylparaben, butylparaben, cetylpyridinium hydrochloride, alkyldiaminoethyldaricin hydrochloride, potassium sorbate and the like can be contained.

[0033] As the sweetening agent, saccharin sodium, stepiosite, sucralose, reduced palatinose, erythritol and the like can be contained.

[0034] As the fragrance, 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, paracres Natural essential oils such as oil, and 1_carvone, 1,8—cineole, methyl salicylate, eugenol, thymol, linalool, limonene, Perfume ingredients contained in the above-mentioned natural essential oils such as n-tone, menthyl acetate, citral, camphor, borneol, pinene, spirantol, etc. Nile, Ethylmethylphenyldaricidate, Benzaldehyde, Vanillin, Ethylvanillin, Furanonore, Manoletonore, Ethinoremanoletonore, Gamma or Tenoletakacalactone, Gamma or Deltown Decalactone, N _P Menthane _ 3 _ Carboxamide, menthyl lactate, ethylene glycol _1_ Perfume ingredients such as menthyl carbonate, les, some fragrance ingredients and natural essential oils in combination, Apple, Banana, Belle Berri , Melon, peach, pineapple, grape, muscat, wine, cheri, squash, coffee, brandy, yogurt, etc. Can be used so that it does not substantially contain ethanol. The blending amount of the fragrance is preferably 0.00001 -3% of the entire composition.

[0035] Examples of surfactants other than the above components (A) and (B) include anions such as lauroylmethyl taurine, isyl amino acid salt, sodium dodecylbenzenesulfonate, sodium α-sulfo fatty acid alkyl ester, alkyl phosphate ester salt, etc. Surfactants, amphoteric surfactants such as alkyl dimethylamino amino acid betaine and fatty acid amidopropyldimethylamino amino acid betaine, Ν fatty acid acyl カルボキシ carboxymethyl ヒ hydroxetyl ethylenediamine salt An imidazoline type amphoteric surfactant, an amino acid type surfactant such as Ν fatty acid acyl-L-alginate salt, etc. can be used alone or in combination as long as the effects of the present invention are not impaired. When a surfactant other than the above components (Α) and (Β) is blended, the blending amount is preferably 0.01 to 5% of the entire composition.

[0036] Active ingredients other than isopropylmethylphenol and triclosan include anti-inflammatory agents such as tranexamic acid and epsilon monoaminocaproic acid, dextranase, amylase, protease, mutanase, lysozyme, lytic enzyme, ritechenzyme Enzymes such as sodium fluoride, sodium monofluorophosphate, stannous fluoride, aluminum chlorohydroxy allantoin, allantoin, azulene, lysozyme chloride, ascorbine Vitamin c such as acid, dihydrocholesterol, glycyrrhetin salts, glycyrrhetinic acid, hydrocholesterol, chlorophyll, copper chlorophyllin sodium, thyme, argon, tiyodi, hamamelis, etc. plant extracts, copper dalconate, caropeptide, sodium polyphosphate Sulfur, water-soluble inorganic phosphate compound, polyvinyl pyrrolidone, anticalculus agent, anti-plaque agent, potassium nitrate, aluminum lactate and the like can be added. The blending amount of these active ingredients can be an effective amount as long as the effects of the present invention are not hindered.

[0037] As the coloring agent, a water-soluble coloring matter having high safety such as Blue No. 1, Green No. 3, Yellow No. 4, Red No. 105 can be added.

[0038] As a container for storing the liquid oral composition of the present invention, PET (polyethylene terephthalate), glass, polypropylene, and polyethylene can be used. From the viewpoint of suppressing adsorption of nonionic disinfectant and fragrance. And the use of glass is preferred.

Example

[0039] Hereinafter, the present invention will be described in more detail based on experimental examples, examples, and comparative examples. However, the present invention is not limited to these examples.

Preparation of these liquid oral compositions includes isopropylmethylphenol (Osaka Kasei), sodium lauryl sulfate (Toho Chemical Industries), myristyl sulfate (Nikko Chemicals), cetyl sulfate (Nikko Chemicals). ), Lauroyl sarcosine sodium (manufactured by Kawaken Fine Chemical Co., Ltd.), myristoyl sarcosine sodium (manufactured by Nikko Chemicals), palmitoyl sarcosine sodium (manufactured by Nikko Chemicals), polyoxyethylene (40) hydrogenated castor oil (manufactured by Nikko Chemicals) , Polyoxyethylene (60) hydrogenated castor oil (Nikko Chemicals), polyoxyethylene (100) hydrogenated castor oil (Nikko Chemicals), polyoxyethylene (40) stearyl ether (Nihon Emulsion), polyoxyethylene Tylene (40) (Made by Nippon Emulsion), polyoxyethylene (20) cetyl ether (made by Nippon Emulsion), polyoxyethylene (10) cetyl ether (made by Nikko Chemicals), glycerin (85%, made by Sakamoto Pharmaceutical Co., Ltd.) , Propylene glycol (manufactured by Asahi Glass Co., Ltd.), butylene glycol (manufactured by Daicel Chemical Industries, Ltd.), polyethylene glycol # 200 (macro gonorre 200, manufactured by Sanyo Chemical Co., Ltd.), polyethylene glycol # 400 (manufactured by Lion Chemical), polyethylene glycol # 600 ( Lion Chemical), Triclosan (Ciba's Special) Culty's (manufactured by Fuso Chemical Co., Ltd.), kuenic acid (manufactured by Fuso Chemical Co., Ltd.), and sodium quenate (manufactured by Fuso Chemical Co., Ltd.) Also, sodium lauryl phosphate (manufactured by Nikko Chemicals), polyoxyethylene (2) sodium lauryl ether sulfate (manufactured by Nikko Chemicals), polyoxyethylene (30) hydrogenated castor oil (manufactured by Nikko Chemicals), polyoxyethylene (7 Cetyl etherenore (manufactured by Nihon Emarjiyon Co., Ltd.) and ethanolanol (manufactured by Nippon Alcohol Sales Co., Ltd.) were used as comparative examples. In the table, P0E represents polyoxyethylene, PEG represents polyethylene glycol, and the percentages shown below mean mass% unless otherwise specified.

[Experiment 1]

Tables: A liquid oral composition having the composition shown in! ~ 6 was prepared by a conventional method, and the penetration sterilization effect on the model biofilm was evaluated by the following method. The results are shown in Tables:! -6.

(1) Preparation method of model periodontopathic biofilm

A model biofilm carrier prepared by treating a hydroxyapatite (HA) plate (made by Asahi Optical Co., Ltd.) (diameter 7mm x thickness 3.5mm) with human unstimulated saliva filtered through a 0.45 / im filter for 4 hours. Used for. The culture solution was prepared by adding 5 mg of hemin (manufactured by Sigma) and 0.5 mg of menadione (manufactured by Sigma) to a solution obtained by dissolving 30 g of trypticase soy broth (manufactured by Difco) in 1 L of purified water. In order to prepare a model biofilm, Streptococcus gordonii ATC51656 and Actinomyces naeslandi ATCC51655 were used as oral resident bacteria, and Borfiromonas gingivalis ATCC 33277 was used as a pathogenic bacterium. These 3 bacterial species were inoculated into the above culture solution to 2 x 10 ⁷ cfu / mL (cfu: colony for mining units), respectively, and 37 ° C with saliva-treated HA carrier under anaerobic conditions (5% carbonic acid). Gas and 95% nitrogen) were continuously cultured for 2 weeks (the replacement rate of the culture medium was 10 Vol%) to form a model biofilm with a mixture of three bacterial species on the HA surface.

[0041] (2) Osmotic sterilization effect on model biofilm

The formed model biofilm was immersed in 2 mL of the samples shown in Tables 1 to 3 for 3 minutes and washed 6 times with 1 mL of sterile physiological saline. The model biofilm is then dispersed by sonication (200 μΑ, 10 seconds) with 4 mL of sterile physiological saline, a tripty case soy agar plate (made by Dif co) containing 10% sheep defibrillating blood, and kanamycin sulfate (200 mg / L). (Manufactured by Sigma): 50 μL of the triptycase soy blood agar plate was smeared and cultured under anaerobic conditions. The grown colonies were counted, and the number of remaining B. gingivalis bacteria (cfu) was determined and determined according to the following criteria.

A: Viable count is less than 10 ⁶

○: Viable count is 10 ⁶ or more and less than 10 ⁷

Δ: Viable count is 10 ⁷ or more and less than 10 ⁸

X: More than 10 ⁸ viable bacteria

[Experiment 2]

Tables: Appearance stability of the liquid oral compositions having the compositions shown in Tables! To 6 was evaluated by the following method. The results are shown in Tables:! -6.

(1) Appearance stability

Table: Samples shown in! ~ 6 were filled into 450 mL PET containers with 450 mL injection volume, and the appearance stability after 1 month storage in a 5 ° C or 50 ° C constant temperature bath was visually judged according to the following criteria. .

[0043] Appearance stability evaluation criteria

A: No change is observed compared to the initial product.

〇: Very slight orientation is recognized but problematic.

Δ: Slight turbidity is observed.

X: Considerable cloudiness or precipitate is observed.

[Experiment 3]

About the liquid oral composition of the composition shown to Tables 1-6, the usability was evaluated by the following method. The results are shown in Tables:! -6.

(1) Usability evaluation

10 mL of the sample shown in Tables 1 to 6 is included in the mouth, rinsed for 30 seconds, and after the mouthwash, there was no irritation and stickiness in the following 4 levels compared to the control product (Comparative Example 6 or 9) The average score of 10 people is shown in the table according to the following criteria: ◎, ○, △, X.

◎: Average point over 3.0 point and below 4.0 point

〇: Average point 2. Over 0 point and below 3.0 point : Average point 1.5 or more 2. 0 or less

X: Average point 1.0 or higher 1. Less than 5

[0045] No irritation after mouth-rinsing (needle shine: Comparative Example 6)

4: The irritation was significantly lower than that of the control product.

3: Slightly lower irritation compared to the stimulation of the control product.

2: Stimulation equivalent to that of the control product was observed.

1: Stimulation was observed compared to the control product.

'7 no motto: t m9)

4: No stickiness was observed compared to the stickiness of the control product.

3: Compared with the stickiness of the control product, the stickiness was not recognized and the level was problematic.

2: Stickiness equivalent to that of the control product was observed.

1: Stickiness was recognized in comparison with the stickiness of the control product.

[Experiment 4]

The liquid oral composition having the composition shown in Table 6 was evaluated for the bactericidal effect against airborne bacteria by the following method. The results are shown in Table 6.

(1) Bactericidal effect against airborne bacteria

Bacterial solution used was 30ml Trypticase Soy Broth (Difco) dissolved in 1L of purified water as a culture solution, and Actinomyces naesrandi ATCC 51655 was used as an oral resident bacterium at 37 ° C, anaerobic It was prepared by adding physiological saline so that the permeability at 550 nm of the liquid cultured for 1 day under the conditions (5% carbon dioxide gas, 95% nitrogen) was 20. Samples shown in Table 5 2. Add 0.3 mL of bacterial solution to 7 mL, stir, react at 37 ° C for 1 minute, stir again, and then add a tube containing 2.7 mL of the culture solution in advance. Five tubes were prepared and 0.3 mL was added to the first test tube and stirred. 0.3 mL of this solution was collected, added to the second test tube, and stirred. This operation was repeated in the same way for the third to fifth test tubes. After stirring the culture solution in the 1st, 3rd, and 5th test tubes, 50 μL was smeared on a 10% cotton defibrinated blood-containing trypticase soy agar plate (Difco) and cultured under anaerobic conditions. The grown colonies were counted, and the number of remaining bacteria (cfu) of Actinomyces naeslandi was determined and judged according to the following criteria. Judgment standard of bactericidal effect against koji mold

○: Viable count is less than 10 ³

Δ: Viable count is 10 ³ or more and less than 10 ⁴

X: More than 10 ⁴ viable bacteria

[table 1]

[Table 2] Example m (%)

8 9 10 11 12 13 14

W Pyrmethylphenol 0.05 0.02 0.05 0.01 0.1 0.05 0.05 Sodium lauryl sulfate 1 0.05 0.1 Sodium myristyl sulfate 0.05 t Sodium sulfate

A

Lai; Yushin sodium 0.05 0.05 Myristoylucosin sodium 0.5

C. Lumitoyl sarcosine sodium 0.1 0.1

POE (60) hydrogenated castor oil 0.3 0.1 0.8 0.5 0.2

ΡΟΕ (ΙΟΟ) hydrogenated castor oil 0.2

B

POE (40) Cetyl ether 0.2

POE (20) Cetyl ether 0.4 0.4 0.2 Darine lysine (85%) 2 4 2.35 5.88 2 1 pylene; Π call 2 5 2 3 5 3

C

PEG # 200 2 3

PEG # 400 2 5

PEG # 600 2 3

Total amount of component C 9.7 5 9.4 5 15 7.7 6.85 Cuenic acid 0.05 0.05 0.05 0.05 0.05 0.05 0.05 Sodium taenoate 0.3 0.3 0.3 0.3 0.3 0.3 0.3 Purified water Residue Residual Residual Residual Residual Total 100 100 100 100 100 100 100 Total moisture Amount 89.3 93.83 89.6 93.54 83.7 91.25 91.75 Periodontopathogenic

Yes

Osmotic sterilization power ◎ O ○ ○ © O Rating Appearance -5 ° C ○ ○ ◎ ○ ○ ◎ ◎ Stability 50 ° C © ○ ○ ○ © © © Value

No irritation 〇

Usability ◎ ○ ○ ◎ ◎ o No stickiness ◎ ○ ◎ ◎ Table 3]

Example Composition (%)

15 16 17 w ° Lohi. Rumethylphenol 0.05 0.05 0.05 Sodium lauryl sulfate 0.1 0.1 0.1 Sodium myristyl sulfate

Sodium cetyl sulfate

A

Lauroy Lukocin Sodium

Myristoyl sarcosine sodium

C. Lumitoyl sarcosine sodium

FOE (40) hydrogenated castor oil 0.3

B POE (IO) cetyl ether 0.3

FOE (40) Stearyl Gel 0.3 'Reserine (85%) 2 2 2 Lohi 'renk' recall 4 4 4

C

PEG # 200

PEG # 400 5 5 5

PEG # 600

Total amount of component C 10.7 10.7 10.7 Cuenic acid 0.05 0.05 0.05 Sodium taenoate 0.3 0.3 0.3 Purified water Residual residual Total 100 100 100 Total water content 88.5 88.5 88.5 Periodontal pathogenicity

©

Penetrating sterilization power ◎ ◎ Review Appearance-5. C ○ ◎ Stability 50 ° C

◎ ◎ ◎ No irritation © 〇〇 Feeling of use

No stickiness ◎ ◎ 4] Comparative example

Composition (%)

1 2 3 4 5 6 Isof. Methyl pyrmethylphenol 0.05 0.05 0.05 0.05 0.05 0.05 Sodium lauryl sulfate

A

Lauroyl sarcosine sodium 0.1 0.1 ratio Sodium lauryl phosphate 0.2

Comparison

POE (2) Sodium lauryl ether sulfate 0.2

P0E (60) hydrogenated castor oil 0.3 0.3 0.3

B

FOE (40)

Ratio P0E (30) hydrogenated castor oil 0.5

FOE (7) Cetylol 0.5 product

"Liserin (85%) 2 2 2 2 2 2

C Lopirenta "! I call 4 4 4 4 4 4

PEGS400 5 5 5 5 5 5

Total amount of component C 10.7 10.7 10.7 10.7 10.7 10.7 Ratio

Comparison Ethanol

B ΡΠ

Titanic acid 0.05 0.05 0.05 0.05 0.05 0.05 Sodium titanate 0.3 0.3 0.3 0.3 0.3 0.3 Purified water Residue Residue Residual Residual Residual Total 100 100 100 100 100 100 Total moisture 88.6 88.4 88.4 88.8 88.3 88.4 Periodontal pathogenicity ' of

X Δ Δ X X X

Osmotic sterilization power

Review 舰-5. C X Δ Δ X X X Stability 50 ° C X X X X Δ Δ

No irritation

Usability ◎ Δ Δ ◎ ◎ Δ No stickiness ◎ ◎ ◎ ◎ ◎ © 5] Comparative example

Composition (%)

7 8 9 10 11 Isof. Methyl pyrmethylphenol 0.05 0.05 0.05 0.05 0.05 Sodium lauryl sulfate 0.1 0.1 0.1 0.1 0.1

A

Lauroyl sarcosine sodium

Ratio Sodium lauryl phosphate

Comparison

POE (2) Sodium lauryl ether sulfate

P0E (60) hydrogenated castor oil 0.3 0.3 0.3 0.3 0.3

B

FOE (40)

Ratio P0E (30) hydrogenated castor oil

Comparison

FOE (7)

Goods

"Liserin (85%) 4.7 2 20 2

C Lopirenta "! I call 4 10 4

PEGS400 10 10 5

Total amount of component C 0 4.0 15.7 37 10.7 Ratio

Comparison Ethanol 5

B ΡΠ

Titanic acid 0.05 0.05 0.05 0.05 0.05 Sodium titer 0.3 0.3 0.3 0.3 0.3 Purified water residue Residue residue Residual total 100 100 100 100 100 Total water content 99.2 95.2 83.5 62.2 83.5 Periodontal pathogenicity ', "

X X ○ ○ Penetration sterilization power ◎ Review Appearance-5. C X X X Δ

Stability 50 ° C X Δ

◎ ◎ ◎ No stimulation 〇

Usability ◎ 〇〇 X No stickiness ◎ ◎ Δ X © 6] Example

Composition (° / »)

18 19 20 21

Iso, P-pyrmethylphenol 0. 05 0. 05 0. 08 0. 03

Sodium lauryl sulfate 0. 1 0. 1

A

Lauroyl sarcosine sodium 0. 1 0. 1

P0E (60) Hardened castor oil 0. 3 0. 4

B

POE (40) Cetyl ether 0. 3 0. 3

"Liserin (85%) 2 2 2 2

C Fu Lopirenta! I call 4 4 4 4

PEGS400 5 5 5 5

c Total amount of ingredients 10. 7 10. 7 10. 7 10. 7

D Tritalosan 0. 02 0. 02 0. 03 0. 04

Acid 0. 05 0. 05 0. 05 0. 05

Sodium titanate 0. 3 0. 3 0. 3 0. 3

Purified water residue residue residue residue

Total 100 100 100 100 Total moisture 88. 48 88. 48 88. 44 88. 38

Periodontal pathogenicity / "to the film

-5 ° C

Appearance ◎ ◎ ◎

Stability 50 ° C ◎ ◎ ◎ 〇

No stimulation

Usability ◎ ◎ ◎

Next, the liquid oral compositions of the following examples were prepared by conventional methods and evaluated in the same manner as described above. It had floating fungicidal ability (evaluated only in Examples 22 and 23 having a composition containing triclosan), appearance stability, and feeling of use. In addition, the fragrance | flavor of the composition shown in following Table 7 was used for the fragrance | flavor.

[Example 22] Mouthwash

Isopropyl methyl phenol

A Sodium lauryl sulfate

B Polyoxyethylene (60) hydrogenated castor oil

C Glycerin

Propylene glycol

PEG # 400 D Triclosan 0 · 05 Tranexamic acid 0.04 Dipotassium glycyrrhizinate 0.06 Cenoic acid 0.06 Sodium citrate 0.5 0.5 Methyl paraoxybenzoate 0.1 Sodium saccharin 0. 01 Fragrance A 0. 2

_ _ Total 100. 0%

[Example 23] Mouthwash

Isopropyl methyl phenol 0. 05%

A Lauroyl sarcosine sodium 0.1

B Polyoxyethylene (60) hydrogenated castor oil 0.3

C Glycerin 2

Propylene glycolate 4

PEG # 400 5

D Triclosan 0 · 02 Xylitol 5 ε-aminocaproic acid 0 · 03 Sodium benzoate 0.3 Crenoic acid 0.03 Sodium citrate 0.225 Fragrance Β 0.2

B _ Total 100. 0%

[Example 24] Mouthwash

Isopropyl methyl phenol 0. 05% A Lauroyl sarcosine sodium 0 · 1

B Polyoxyethylene (100) hydrogenated castor oil 0.3

C Glycerin 3

Propylene glycol 4 Butylene glycol 5 Xylitol 4

Acetic acid dl_ α-Tocophenolol 0.05 Sodium fluoride 0.1 Quenic acid 0.03 Sodium quenate 0.25 Fragrance C 0.3

Remaining

Total 100.0% [Example 25] Mouthwash

Isopropylmethylphenol 0.1%

A Sodium myristyl sulfate 0.2

B Polyoxyethylene (80) hydrogenated castor oil 0.5

C Glycerin 3

Propylene glycol 4 Xylitol 4

Aspartame 0.02 Sodium pyrophosphate 0.17 Sodium polyphosphate 0.02 Cenoic acid 0.1 Sodium citrate 0.8 Perfume D 0.4

Remaining

Total 100. 0% [Example 26] Mouthwash

Isopropylmethylphenol 0 ・ 06%

A Myristoyl sarcosine sodium 0 · 2

B Polyoxyethylene (20) cetyl ether 0.4 C Glycerin 3

Propylene glycolol 4 PEG # 600 5 Saccharin 0. 01 Aspartame 0. 02 Copper black mouth fin sodium 0. 01 Dextranase 0. 02 Fasco / sodium levate 0. 03 Quenic acid 0.06 Sodium quenate 0 · 5 Fragrance E 0. 2

Remaining

Total 100. 0%

[Example 27] Mouthwash

Isopropyl methylphenol 0 · 6%

A Lauroyl sarcosine sodium 0-15

B Polyoxyethylene (40) stearyl ether 0 · 5

C Glycerin 2

Propylene glycol 4 PEG # 400 3 Xylitol 2

Sorbitol 1

Allantoin 0.01 Quenic acid 0.03 Sodium quenate 0 · 5 Fragrance F 0. 2

_ Total 100. 0%

[0060] [Table 7]

[0061] [Table 8] Flavor i composition

Lemon oil 1 part Lemon oil front part 95% strength 1 part Lime oil 1 part Mandarin oil 1 part Grapefruit oil 1 part Sweety 1 oil 1 part Boiled oil 1 part Citra 1 Norre 1 part Triacetin 2 parts Total 1 part The parts are parts by mass (the same shall apply hereinafter) Table 9]

Flavor 2 composition

U-power oil 1 part Clove oil 1 part thyme oil 1 part sage oil 1 part force Noredamon oil 1 part coriander oil 1 part rosemary oil 1 part laurel oil 1 part camo minole oil 1 part carayu oil 1 part nojinole 1 part propyleneda Ricohone 1

Η 1 1 2 parts Table 10] Flavor 3 composition

[0064] [Table 11]

Flavor 4 composition

[0065] [Table 12] Flavor 5 composition

13]

Flavor 6 composition

Cis-3-hexenol 1 part Trans-2-hexenal 1 part Ethyl butyrate 1 part Undecalactone 1 part Decalataton 1 part Isoamyl acetate 1 part Benzaldehyde 1 part Hexinole acetate 1 part Ethyl-2-methylbutyrate 1 part Benzinore Anoleconol 1 part α-Terbinol 1 part Linalyl acetate 1 part Phenylethyl glycidate 1 part Ferreethyl alcohol 1 part Carylhexanoate 1 part Octanol 1 part Methylcinnamate 1 part Methyl heptine Carbonate 1 part Nonon 1 part Ethyl-Methyl thiopone 1 part Cis-6-Noneno / Le 1 part Carrone 1 part Methino rejasmonate 1 part Propylene dalicorone 1 part a at 2 4 parts

Claims

The scope of the claims

[1] A liquid oral composition containing isopropylmethylphenol,

(B) Polyoxyethylene hydrogenated castor oil having an average addition mole number of ethylene oxide of 40 to 100 moles and a polyoxyethylene alkyl having a carbon chain length of 16 to 18 and an average addition mole number of ethylene oxide of 10 to 40 moles Ether power at least one nonionic surfactant chosen,

And an isopropylmethylphenol-containing liquid oral composition characterized by containing a water content of 70% by mass or more and containing substantially no ethanol.

[2] Component (A) is at least one selected from sodium alkyl sulfate and sodium N-acyl sarcosine having a carbon chain length of 12 to: 14, and component (B) has an average added mole number of ethylene oxide. 60 to 100 mol of polyoxyethylene hydrogenated castor oil and at least 1 selected from polyoxyethylene alkyl ethers having an alkyl chain with a carbon chain length of 16 to 18 and an average added mole number of ethylene oxide of 20 to 40 mol The liquid oral composition according to claim 1, which is a seed.

[3] The liquid oral composition according to claim 1 or 2, further comprising (D) triclosan.