JP4591680B2 - Liquid oral composition - Google Patents

Description

  The present invention is a liquid oral composition that exhibits osmotic sterilizing power on periodontopathic biofilms, improves the retention of non-cationic bactericides by thickening, and has a good appearance stability of the composition About.

  Conventionally, bactericides have been incorporated into oral compositions for the purpose of preventing oral diseases caused by bacteria such as caries, gingivitis, periodontal disease and bad breath. Among them, an oil-soluble non-cationic fungicide, triclosan, is incorporated as a fungicide to replace the cationic fungicide for the purpose of suppressing plaque (see Patent Document 1: Japanese Patent Laid-Open No. 60-239410). As a technique for improving its function, a technique for retaining a bactericide by adding a specific amphoteric surfactant (see Patent Document 2: Japanese Patent Laid-Open No. 5-124943) has been proposed.

  However, since these oil-soluble disinfectants are hardly soluble in water as they are, various surfactants are blended and solubilized for solubilization. Therefore, the active site of the bactericidal agent is inactivated by the surfactant and cannot fully exert the bactericidal power, and if the blending amount of the surfactant is reduced to improve the bactericidal power, the liquid becomes cloudy over time and the composition There existed a subject that the external appearance stability of a thing was remarkably impaired.

  On the other hand, in order to improve the retention of non-cationic bactericides in the oral cavity, various polymer substances have been tried (Patent Documents 3 to 7: Japanese Patent No. 2860331, Japanese Patent Laid-Open Publication No. 11). -116450 gazette, patent 3031004 gazette, patent 3189549 gazette, and patent 3479822 gazette), when blended into a liquid oral composition, the polymer substance itself is cloudy or insoluble unless water solubility is high. It is difficult to maintain a clear appearance. Among them, an oral composition having an example of blending an emulsion composition composed of a silicone oil, a surfactant, a preservative and a specific high water-soluble polymer substance in anticipation of antifoaming properties (Patent Document 8: Special) In the Kaihei 8-325126 publication), a clear appearance cannot be maintained in the same manner because the emulsion composition is blended.

JP 60-239410 A JP-A-5-124943 Japanese Patent No. 2880631 Japanese Patent Laid-Open No. 11-116450 Japanese Patent No. 3031004 Japanese Patent No. 3189549 Japanese Patent No. 3479822 JP-A-8-325126

  The present invention has been made in view of the above circumstances, and in a liquid oral composition containing a non-cationic bactericidal agent as a bactericidal component, while improving the high penetrating bactericidal power and the bactericide retentivity with respect to biofilms. An object of the present invention is to provide a liquid oral composition having good appearance stability.

As a result of intensive studies to achieve the above object, the present inventors have found that carboxymethylcellulose sodium having a degree of etherification of 2.0 to 2.8 is included in a liquid oral composition containing a non-cationic bactericide as a bactericidal component. It was found that when the non-cationic fungicide was blended at a mass ratio of 0.01 to 0.5, the retention in the oral cavity of the non-cationic fungicide was improved. As described above, it is difficult to maintain a good appearance when a water-soluble polymer substance is added to a liquid oral composition, but the above-mentioned sodium carboxymethyl cellulose having a degree of etherification of 2.0 to 2.8 is It has been found that a liquid oral composition having good appearance stability can be obtained, and that when ethanol is contained, the appearance of white turbidity and precipitate after high-temperature storage is not observed, and a good appearance can be maintained.
Furthermore, it has been found that when sodium lauryl sulfate is added to this liquid oral composition, the penetration bactericidal power to periodontal pathogenic biofilm is improved, and the present invention has been made.

Therefore, the present invention
(A) A liquid oral composition containing 0.001 to 0.10% by mass of at least one selected from non-cationic fungicides ,
(B) 0.05 to 3 mass% of carboxymethylcellulose sodium having a degree of etherification of 2.0 to 2.8 is blended, and the mass ratio of (A) non-cationic fungicide / (B) sodium carboxymethylcellulose is set. Provided is a liquid oral composition characterized by having 0.01 to 0.5 and (C) a nonionic surfactant and (D) ethanol. In this case, it is preferable to blend (E) sodium lauryl sulfate.

  The liquid oral cavity composition of the present invention improves the osmotic sterilizing power and the retention of the bactericide with respect to periodontopathic biofilms, and has good appearance stability.

  The liquid oral composition of the present invention comprises (A) a liquid oral solution containing a non-cationic bactericide, (B) sodium carboxymethylcellulose having a degree of etherification of 2.0 to 2.8, (C) non It is characterized by containing an ionic surfactant and (D) ethanol, more preferably (E) sodium lauryl sulfate.

  As the non-cationic fungicide of the component (A) used in the present invention, one selected from halogenated diphenyl ether, halogenated carboanilide, benzoic acid ester and phenolic compound is preferable. Examples of the halogenated diphenyl ether include triclosan, 2,2′-dihydroxy-5,5′-dibromo-diphenyl ether, and examples of the halogenated salicylanilide include 4 ′, 5-dibromosalicylanilide and 3,4 ′, 5-trichlorosalicylanilide. 2,3,3 ′, 5-tetrachlorosalicylanilide, 3 ′, 5-dibromo-3′-trifluoromethylsalicylanilide, and halogenated carboanilide include 3-trifluoromethyl-4,4′-dichloro Examples of carboanilide and phenolic compounds include isopropylmethylphenol, and one or more of them can be used. Among them, a combination of triclosan and isopropylmethylphenol is particularly suitable in that it exerts the sterilizing power for periodontopathic biofilm.

  The blending amount of these non-cationic bactericides is 0.001 to 0.10% (mass%, the same shall apply hereinafter) of the whole composition in terms of exerting penetrating bactericidal power to periodontal pathogenic biofilms. It is preferably 0.04 to 0.10%, and if it is less than 0.001%, it cannot exert bactericidal activity against periodontopathic biofilms, and if it exceeds 0.10%, it becomes cloudy and the appearance is stable. Detract from sex.

  In this case, when triclosan and isopropylmethylphenol are used in combination as non-cationic fungicides, the blending amount is 0.02 to 0.08% of the total composition of triclosan and 0.02 to 0.08% of isopropylmethylphenol. It is preferable to set it as 08%.

  Component (B) sodium carboxymethylcellulose used in the present invention has a degree of etherification of 2.0 to 2.8, particularly preferably 2.2 to 2.6, such as Daicel Chemical Industries ( Ernest gum FDM manufactured by Co., Ltd. is used. The amount of carboxymethylcellulose sodium having a degree of etherification of 2.0 to 2.8 is 0.05 to 3% of the total composition in terms of improving the retention of the bactericide, and particularly 0.1 to 1%. Preferably, if it is less than 0.05%, the retention of the bactericidal agent is impaired, and if it exceeds 3%, the viscosity is high and the usability as a liquid oral composition is significantly impaired.

  Moreover, the mass ratio of non-cationic fungicide / sodium carboxymethylcellulose is 0.01 to 0.5, and more preferably 0.02 to 0.25 from the viewpoint of retention of the fungicide. If the mass ratio of the non-cationic fungicide / sodium carboxymethylcellulose is less than 0.01, the bactericidal power cannot be exerted on the periodontopathic biofilm, and the mass ratio of the non-cationic fungicide / sodium carboxymethylcellulose is 0. If it exceeds .5, the retention of the disinfectant is impaired.

  As the nonionic surfactant of component (C) used in the present invention, polyoxyethylene hydrogenated castor oil having an average addition mole number of ethylene oxide of 40 to 100 mol, an alkyl chain having a carbon chain length of 16 to 18 is used. Long polyoxyethylene alkyl ether having an average addition mole number of ethylene oxide of 10 to 50 mol, polyoxyethylene having an average addition mole number of ethylene oxide of 30 to 300 mol, and an average addition mole number of propylene oxide of 30 to 70 mol Polyoxypropylene glycol is preferred. Among them, polyoxyethylene hydrogenated castor oil having an average addition mole number of ethylene oxide of 60 to 100 moles and a carbon chain length of 16 to 18 in terms of solubilization of a non-cationic fungicide and improvement in appearance stability. Polyoxyethylene alkyl ethers having an alkyl chain length and an average added mole number of ethylene oxide of 20 to 50 mol are particularly preferred. The blending amount is preferably 0.1 to 5%, particularly preferably 0.2 to 2% in terms of solubilization of the non-cationic fungicide and improvement in appearance stability. It is difficult to maintain the properties, and if it exceeds 5%, the taste is bad and the usability may be significantly impaired.

  The blending amount of the component (D) ethanol used in the present invention is preferably 3 to 20%, particularly preferably 5 to 15% in terms of improving the appearance stability, and if it is less than 3%, the appearance stability is maintained. When it exceeds 20%, irritation is strong and the feeling of use is significantly impaired.

  Furthermore, (E) sodium lauryl sulfate can be mix | blended with the liquid oral cavity composition of this invention in order to improve the osmotic | sterilizing power of a noncationic disinfectant. The blending amount is preferably 0.05 to 1% of the entire composition, particularly preferably 0.1 to 0.5%, and if it is less than 0.05%, the disinfectant to the periodontopathic biofilm The penetrating and sterilizing effect is small, and if it exceeds 1%, the liquid oral composition has a bad taste and the usability may be significantly impaired.

  The liquid oral composition of the present invention can be prepared and applied as a mouthwash, mouth freshener, concentrated mouthwash, etc., but the liquid oral composition of the present invention, in addition to the above components, Appropriate optional components can be blended depending on the dosage form, for example, wetting agents, thickeners, pH adjusters, preservatives, sweeteners, fragrances, surfactants, active ingredients, cleaning aids, coloring A material can be blended.

  As the wetting agent, sorbitol, propylene glycol, ethylene glycol, polyethylene glycol, xylitol, maltite, lactit and the like can be blended.

  As the thickener, xanthan gum, carrageenan, hydroxyethyl cellulose, sodium alginate, polyvinyl alcohol and the like can be blended in addition to the above sodium carboxymethyl cellulose.

  Examples of preservatives include sodium benzoate, methyl paraben, ethyl paraben, propyl paraben, butyl paraben, cetyl pyridinium chloride, potassium sorbate and the like.

  Moreover, as a sweetening agent, saccharin sodium, stevioside, etc. can be mix | blended.

  Perfumes include peppermint oil, spearmint oil, anise oil, eucalyptus oil, winter green oil, cassia oil, cinnamon oil, clove oil, thyme oil, sage oil, cardamom oil, rosemary oil, marjoram oil, lemon oil, orange oil , Natural essential oils such as fennel oil, nutmeg oil, lavender oil, paracres oil, and l-menthol, l-carvone, anethole, 1,8-cineole, methyl salicylate, eugenol, thymol, linalool, limonene, menthone, menthyl acetate , Citral, camphor, borneol, pinene, spirantol, and other fragrance ingredients contained in the above natural essential oils, ethyl acetate, ethyl butyrate, isoamyl acetate, hexanal, hexenal, methyl anthranilate, ethyl methyl Phenylglycidate, benzaldehyde, vanillin, ethyl vanillin, furaneol, maltol, ethyl maltol, gamma / delta decalactone, gamma / deltown decalactone, N-ethyl-p-menthane-3-carboxamide, menthyl lactate, ethylene glycol- Perfume ingredients such as l-menthyl carbonate, and some perfume ingredients and natural essential oils, apple, banana, strawberry, blueberry, melon, peach, pineapple, grape, muscat, wine, cherry, squash, coffee One or two or more kinds of blended flavors such as brandy and yogurt can be used in the range of 0.00001 to 3% in the composition of the present invention without impairing the effects of the present invention.

  Surfactants other than those described above include sodium myristyl sulfate, N-lauroyl sarcosinate, lauroyl methyl taurine, acylamino acid salt, sodium dodecylbenzenesulfonate, α-sulfo fatty acid alkyl ester / sodium, alkyl phosphate ester salt, etc. Anionic surfactants, betaine acetate type amphoteric surfactants such as alkyldimethylaminoacetic acid betaine, fatty acid amidopropyldimethylaminoacetic acid betaine, imidazoline type such as N-fatty acid acyl-N-carboxymethyl-N-hydroxyethylethylenediamine salt Amino acid surfactants such as amphoteric surfactants and N-fatty acid acyl-L-alginate salts can be used alone or in combination, and the blending amount can be used as 0 to 5%.

  Further, as active ingredients other than the above bactericides, anti-inflammatory agents such as tranexamic acid, epsilon-aminocaproic acid, enzymes such as dextranase, amylase, protease, mutanase, lysozyme, lytic enzyme, lytechenzyme, sodium fluoride, mono Fluorides such as sodium fluorophosphate, stannous fluoride, aluminum chlorohydroxy allantoin, allantoin, azulene, lysozyme chloride, ascorbic acid and other vitamin C, dihydrocholesterol, glycyrrhetin salts, glycyrrhetinic acid, hydrocholesterol, chlorophyll, copper Chlorophyllin sodium, Thyme, Ogon, Clove, Hamamelis and other plant extracts, copper gluconate, caropeptide, sodium polyphosphate, water-soluble inorganic phosphate compound, polyethylene glycol Lumpur, polyvinylpyrrolidone, sodium lauroyl sarcosinate, anti-tartar agents, anti-plaque agents, potassium nitrate, may be added to aluminum lactate and the like. In addition, the addition amount of these active ingredients can be made into the range which does not prevent the effect of this invention.

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

  Examples of pH adjusters include phthalic acid, phosphoric acid, citric acid, succinic acid, acetic acid, fumaric acid, malic acid and carbonic acid and their potassium, sodium and ammonium salts, ribonucleic acid and its salts, and sodium hydroxide. Or a combination of phosphoric acid, citric acid and their sodium salts is particularly preferred. In this case, the liquid oral composition of the present invention preferably adjusts the pH at 25 ° C. to 5.5 to 8.5, and sodium dihydrogen phosphate and monophosphate as pH adjusters near this neutrality. Sodium hydrogen or a combination of citric acid and sodium citrate can be used.

  As the container, PET (polyethylene terephthalate), glass, polypropylene, and polyethylene can be used, but the use of PET or glass is preferable from the viewpoint of suppressing adsorption of non-cationic bactericides and fragrances.

EXAMPLES Hereinafter, although this invention is demonstrated in detail based on an experiment example, an Example, and a comparative example, this invention is not restrict | limited by these Examples. For preparation of these liquid oral compositions, isopropylmethylphenol (Osaka Kasei), triclosan (Ciba Specialty Chemicals), CMC (Daicel Chemical Industries), polyoxyethylene (60) hydrogenated castor oil (Nikko) Chemicals), polyoxyethylene (20) cetyl ether (manufactured by Nippon Emulsion), ethanol (manufactured by Nippon Alcohol Sales), sodium lauryl sulfate (manufactured by Toho Chemical), citric acid (manufactured by Fuso Chemical), sodium citrate (manufactured by Fuso Chemical) ) Was used.
In addition, unless otherwise indicated,% shown below means the mass%, and a part means a mass part. Moreover, pH in a table | surface measured using the pH meter (model number HM-30S) by Toa Denpa Kogyo immediately after adjustment, and showed the value after 25 degreeC and 3 minutes.

[Experimental Example 1]
(1) Model plaque preparation method 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 unstimulated saliva filtered through a 0.45 μm filter for 4 hours. Used as a model plaque carrier, the culture solution is 30 mg of trypticase soy broth (Difco) dissolved in 1 L of purified water, 5 mg of hemin (Sigma), 0.5 mg of menadione (Sigma) The one to which was added was used. In order to prepare model plaques, Streptococcus gordonii ATCC 51656 strain and Actinomyces naeslandi ATCC 51655 strain were used as oral resident bacteria, and Porphyromonas gingivalis ATCC 33277 strain was used as a pathogenic bacterium. These three bacterial species were inoculated into the above-mentioned culture solution so as to be 2 × 10 ⁷ cfu / mL (cfu: colony forming units), respectively, at 37 ° C. under anaerobic conditions (5% carbon dioxide gas, 95% nitrogen) was continuously cultured for 2 weeks (the replacement rate of the culture medium was 10 Vol%), and model plaques mixed with 3 bacterial species were formed on the HA surface.

(2) Bactericidal effect on model plaque (biofilm) The formed model plaque was immersed in 2 mL of the sample shown in Table 1 for 3 minutes and washed 6 times with 1 mL of sterile physiological saline. Then, model plaques are dispersed by ultrasonic treatment (200 μA, 10 seconds) with 4 mL of sterile physiological saline, and 50 μL is smeared on a 10% cotton defibrillated blood-containing trypticase soy agar plate (Difco), and anaerobic Cultured under conditions. The grown colonies were counted, and the number of remaining Porphyromonas gingivalis bacteria (cfu) was determined and determined according to the following criteria.
Judgment standard ◎: Viable count is less than 10 ⁶ ○: Viable count is 10 ⁶ or more and less than 10 ⁷ △: Viable count is 10 ⁷ or more and less than 10 ⁸ ×: Viable count is 10 ⁸ or more

[Experiment 2]
After mouthwashing with 20 mL of the sample shown in Table 1 for 30 seconds, it was discharged and about 1 mL of saliva was collected after 5 minutes. Of these, 0.5 g was weighed, 1 mL of an internal standard (ethanol solution of n-hexyl paraoxybenzoate (0.3 g / 200 mL)) was added, and the volume was made up to 10 mL with 60% ethanol to obtain a sample for liquid chromatography. . The measurement was carried out using an HPLC apparatus (model number PU-980, AS-950, UV-970, CO-966) manufactured by JASCO Corporation, and a mobile phase of acetonitrile / water / acetic acid mixture (600 mL / 400 mL / 10 mL) was set to 0.00. Run a YMC column (ODS-A A-303 (4.6 mm × 250 mm)) at a constant temperature of 45 ° C. from each peak area of 285 nm to reduce the amount of isopropylmethylphenol and / or triclosan retained. Calculated and judged according to the following criteria.
Judgment criteria ◎: Retention amount after 5 minutes is 15% or more ○: Retention amount after 5 minutes is 10% or more and less than 15% △: Retention amount after 5 minutes is 5% or more and less than 10% ×: 5 minutes Less than 5% retention after

[Experiment 3]
450 mL of the sample shown in Table 1 was filled into a 500 mL filled PET container, and the appearance stability after 1 month storage in a 50 ° C. constant temperature bath was visually determined according to the following criteria.
Appearance stability evaluation standard ○: There is no cloudiness or precipitation, and it is transparent.
Δ: Slight turbidity or orientation is observed.
X: Considerable white turbidity or precipitate is observed.

[Example 6] Mouthwash A isopropylmethylphenol 0.05%
A Triclosan 0.05
B Carboxymethylcellulose sodium 1
(Degree of etherification: 2.4)
C Polyoxyethylene (60) hydrogenated castor oil 0.5
D Ethanol 5
E Sodium lauryl sulfate 0.2
Propylene glycol 2
Tranexamic acid 0.04
Dipotassium glycyrrhizinate 0.05
Glycerin 5
Citric acid 0.06
Sodium citrate 0.5
Saccharin sodium 0.01
Fragrance A 0.5
Water remaining
Total 100.0%
pH 6.4

[Example 7] Mouthwash A isopropylmethylphenol 0.05%
A Triclosan 0.02
B Sodium carboxymethylcellulose 0.75
(Degree of etherification: 2.2)
C polyoxyethylene (60) hydrogenated castor oil 0.3
D ethanol 10
E Sodium lauryl sulfate 0.1
ε-aminocaproic acid 0.03
Propylene glycol 2
Glycerin 2
Citric acid 0.03
Sodium citrate 0.25
Xylitol 4
Fragrance B 0.5
Water remaining
Total 100.0%
pH 6.4

[Example 8] Mouthwash A isopropylmethylphenol 0.1%
B Sodium carboxymethylcellulose 1.5
(Degree of etherification: 2.6)
C Polyoxyethylene (100) hydrogenated castor oil 1
D Ethanol 7
E Sodium lauryl sulfate 0.5
Lauroyl sarcosine sodium 0.1
Propylene glycol 3
Cationized cellulose 0.05
Acetic acid dl-α-tocophenol 0.05
Glycerin 5
Citric acid 0.03
Sodium citrate 0.3
Sodium fluoride 0.05
Xylitol 4
Sodium benzoate 0.3
Fragrance C 0.4
Water remaining
Total 100.0%
pH 6.7

[Example 9] Mouthwash A Triclosan 0.05%
B Sodium carboxymethylcellulose 0.3
(Degree of etherification: 2.0)
C polyoxyethylene (20) cetyl ether 0.3
D ethanol 12
Propylene glycol 1
Sodium pyrophosphate 0.02
Sodium polyphosphate 0.08
Citric acid 0.03
Sodium citrate 0.3
Sorbitol 1
Fragrance D 0.4
Water remaining
Total 100.0%
pH 6.7

[Example 10] Mouthwash A Triclosan 0.1%
B Sodium carboxymethylcellulose 0.6
(Degree of etherification: 2.3)
C Polyoxyethylene (60) hydrogenated castor oil 2
D Ethanol 18
Propylene glycol 2
Copper chlorophyllin sodium 0.01
Citric acid 0.03
Sodium citrate 0.5
Aspartame 0.02
Trehalose 3
Dextranase 0.2
DL-alanine 0.3
Fragrance E 0.2
Water remaining
Total 100.0%
pH 6.7

[Example 11] Mouthwash A 2,2'-dihydroxy-5,5'-dibromo-0.03%
Diphenyl ether B sodium carboxymethyl cellulose 0.7
(Degree of etherification: 2.1)
C Polyoxyethylene (300) Polyoxypropylene (55) 0.5
Glycol D Ethanol 5
E Sodium lauryl sulfate 0.05
Propylene glycol 2
Lysozyme chloride 1
Polyethylene glycol 600 3
Citric acid 0.03
Sodium citrate 0.5
Saccharin sodium 0.005
Methyl paraoxybenzoate 0.1
Ethyl paraoxybenzoate 0.05
Fragrance F 0.2
Water remaining
Total 100.0%
pH 6.6

In addition, about the fragrance | flavor, the fragrance | flavor AF shown in Table 2 was created and mix | blended.

なお、表中の部はいずれも質量部である（以下、同様）。

In addition, all the parts in the table are parts by mass (the same applies hereinafter).

Claims (5)

(A) A liquid oral composition containing 0.001 to 0.10% by mass of at least one selected from non-cationic fungicides ,
(B) 0.05 to 3 mass% of carboxymethylcellulose sodium having a degree of etherification of 2.0 to 2.8 is blended, and the mass ratio of (A) non-cationic fungicide / (B) sodium carboxymethylcellulose is set. and 0.01 to 0.5, and (C) a nonionic surfactant and (D) a liquid oral composition, characterized in that blended with ethanol. The content of the component (A) is 0.04 to 0.10% by mass, the component (B) is blended 0.1 to 3% by mass, and the component (C) is 0.2 to 5% by mass, ( The composition for oral cavity of Claim 1 which mix | blended 3-15 mass% of D) component. The liquid oral composition according to claim 1 or 2 , further comprising (E) sodium lauryl sulfate. The composition for liquid oral cavity according to claim 1 , 2 or 3, wherein isopropylmethylphenol and triclosan are used in combination as component (A). As a nonionic surfactant, an average addition mole number of ethylene oxide with polyoxyethylene hydrogenated castor oil having an average addition mole number of ethylene oxide of 40 to 100 moles and / or an alkyl chain length of carbon chain length of 16 to 18 is used. The liquid oral composition of any one of Claims 1 thru | or 4 which mix | blended 10-50 mol polyoxyethylene alkyl ether.