JP4985905B2 - Liquid oral composition and l-menthol precipitation prevention method - Google Patents

Description

  The present invention relates to a liquid oral composition having a non-alcohol or low alcohol composition that exhibits bactericidal activity against oral bacteria, has good appearance stability, and is less irritating. The present invention also relates to a method for preventing the precipitation of l-menthol in a liquid oral composition having such a non-alcohol or low alcohol composition.

In the past, sterilization of oral bacteria, which has been the cause of caries, gingivitis, periodontal disease, bad breath, etc., is important for the prevention of oral diseases. Has been included. However, these bactericides have a problem that the active site of the bactericide is inactivated by a nonionic surfactant contained mainly to solubilize the fragrance, and the effect is halved. Therefore, when the surfactant content is reduced to improve the bactericidal activity, l-menthol, which mainly imparts a refreshing sensation with the main component of the fragrance, is precipitated, especially in low temperature storage, and the appearance stability of the composition is remarkably increased There was a problem of being damaged. Therefore, it is possible to increase the amount of ethanol to prevent the precipitation of l-menthol. However, in the low alcohol mild type mouthwash and non-alcohol mouthwash that have been spreading in recent years, the precipitation of l-menthol is not possible. It was difficult to prevent.
Accordingly, there has been a demand for the development of a liquid oral composition having good appearance stability and low irritation even when stored at low temperatures while exerting sterilizing power.

  So far, techniques for preventing oral diseases by using a cationic fungicide together (Patent Document 1: Japanese Patent Laid-Open No. 5-931, Patent Document 2: Japanese Patent Laid-Open No. 7-25734, Patent Document 3: Japanese Patent Laid-Open No. 8). -133969, Patent Document 4: JP-A-8-259428, Patent Document 5: JP-A-8-268850, Patent Document 6: JP-A-11-12142, Patent Document 7: JP-A 2000-53546. Patent Document 8: Japanese Patent Application Laid-Open No. 2000-178154, Patent Document 9: Japanese Patent Application Laid-Open No. 2001-81019, Japanese Patent Application Laid-Open No. 2001-151690, and Japanese Patent Application Laid-Open No. 2001-294536. Patent Document 12: Japanese Patent Application Laid-Open No. 2002-284657 and Patent Document 13: Japanese Patent Application Laid-Open No. 2003-12484). However, in order to ensure good appearance stability, the content of nonionic surfactant is large, and sufficient bactericidal power cannot be exhibited, or 5% or more of ethanol is contained, and it is a highly irritating type for oral use The composition was unavoidable. Conversely, if the amount of the active agent is reduced with a low alcohol composition that emphasizes bactericidal activity, 1-menthol, which is an essential component for imparting a refreshing sensation to the composition when stored at a low temperature, is not problematic at room temperature. As a result, there was a problem that good appearance stability could not be maintained.

Japanese Patent Laid-Open No. 5-931 JP 7-25734 A JP-A-8-133969 JP-A-8-259428 JP-A-8-268850 Japanese Patent Laid-Open No. 11-12142 JP 2000-53546 A JP 2000-178154 A JP 2001-81019 A JP 2001-151690 A JP 2001-294536 A JP 2002-284657 A JP 2003-12484 A

  The present invention has been made in view of the above circumstances, and exhibits a bactericidal power against oral bacteria, a good appearance stability, a liquid non-alcohol or low alcohol composition with low irritation, and such a liquid oral cavity. It aims at providing the method of preventing precipitation of 1-menthol in a composition.

As a result of intensive studies to achieve the above object, the present inventor contains a cationic bactericide such as cetylpyridinium chloride as a bactericidal component, and also contains l-menthol as a fragrance, and has an ethanol content. A specific polyoxyethylene hydrogenated castor oil or polyoxyethylene alkyl ether as a nonionic surfactant is added to a low-alcohol or non-alcohol liquid oral composition that is 3% (% by mass or less) of the whole product. Combined, and in combination with methyl paraoxybenzoate and ethyl paraoxybenzoate , these ingredients are combined appropriately to exert bactericidal activity against oral bacteria, and at low alcohol composition with low irritation, low temperature Liquid oral composition with good appearance stability without l-menthol precipitation even after storage Was found that to obtain, the present invention has been accomplished.

  As a mechanism of action to prevent the precipitation of l-menthol at low temperature by the combined use of methyl paraoxybenzoate and ethyl paraoxybenzoate, the combined system of these paraoxybenzoate esters interacts with l-menthol in a hydrophobic manner, It seems that the solubility of l-menthol is improved and crystallization is suppressed. In this case, even if methyl paraoxybenzoate or ethyl paraoxybenzoate is used alone, such an effect is not exerted, and propyl paraoxybenzoate or butyl paraoxybenzoate is not combined with methyl paraoxybenzoate or ethyl paraoxybenzoate. Even if they are used in combination, the above effect is not exhibited, and only the combined system of methyl paraoxybenzoate and ethyl paraoxybenzoate gives the above effect specifically.

Therefore, the present invention
(A) A composition for a liquid oral cavity containing 0.01 to 0.10% by mass of a cationic fungicide and (D) 1-menthol and having an ethanol content of 3% by mass or less of the whole composition. And (B) 0.05 to 0.4% by mass using (B) methyl paraoxybenzoate and ethyl paraoxybenzoate in a mass ratio of 1/1 to 3/1 , and (C) an average addition mole of ethylene oxide 0.1 to 1.0 mass% of polyoxyethylene hydrogenated castor oil having a number of 40 to 100 mol or polyoxyethylene alkyl ether having a carbon chain length of 16 to 18 and an average added mole number of ethylene oxide of 10 to 50 mol And (D) 1-menthol content is 0.001 to 0.15% by mass .

The present invention also provides:
(A) A composition for a liquid oral cavity containing 0.01 to 0.10% by mass of a cationic fungicide and (D) 1-menthol and having an ethanol content of 3% by mass or less of the whole composition. And (B) 0.05 to 0.4% by mass using (B) methyl paraoxybenzoate and ethyl paraoxybenzoate in a mass ratio of 1/1 to 3/1 , and (C) an average addition mole of ethylene oxide 0.1 to 1.0 mass% of polyoxyethylene hydrogenated castor oil having a number of 40 to 100 mol or polyoxyethylene alkyl ether having a carbon chain length of 16 to 18 and an average added mole number of ethylene oxide of 10 to 50 mol blended bets, and the content of (D) l- menthol, characterized in that a 0.001 to 0.15 wt%, to provide a deposition method for preventing l- menthol in the liquid oral composition .

  The liquid oral composition of the present invention is a liquid oral composition that exhibits bactericidal effects against oral bacteria, has good appearance stability, and is less irritating.

  The liquid oral composition of the present invention contains (A) a cationic bactericidal agent as a bactericidal component, (B) a combination of methyl paraoxybenzoate and ethyl paraoxybenzoate as a paraoxybenzoic acid ester, It contains a specific polyoxyethylene hydrogenated castor oil or polyoxyethylene alkyl ether as an ionic surfactant, further contains (D) 1-menthol, and (E) has an ethanol content of 3% or less. And

Examples of the component (A) cationic fungicide used in the present invention include cetylpyridinium chloride, benzethonium chloride, benzalkonium chloride, chlorhexidine hydrochloride, chlorhexidine gluconate, and one or more of them may be used. it can. The blending amount is preferably 0.01 to 0.10%, more preferably 0.02 to 0.05% of the whole composition in terms of exerting bactericidal power against oral bacteria. If it is too small, can not be exhibited the sterilizing power against the oral bacteria, and too much stimulation is strong, Ru impaired is a feeling of use.

The total blending amount of component (B) methyl paraoxybenzoate and ethyl paraoxybenzoate used in the present invention is 0.05 to 0.00% of the total composition in terms of preventing precipitation of 1-menthol during low-temperature storage . 4% , more preferably 0.15 to 0.25%. Too little, can not prevent the deposition of l- menthol in cryopreservation, is too large, irritation is strong, Ru is impaired feeling. The mass ratio (Me / Et) between methyl paraoxybenzoate (Me) and ethyl paraoxybenzoate (Et) is 1/1 to 3/1, particularly 2/1, and the effect of the present invention is achieved. Preferred to achieve.

As the component (C) nonionic surfactant 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 length of 16 to 18 carbon chain length And an average added mole number of ethylene oxide of 10 to 50 moles. Among them, polyoxyethylene hydrogenated castor oil having an average added mole number of ethylene oxide of 60 to 100 moles and an alkyl chain length of 16 to 18 carbon chains in terms of bactericidal power against oral bacteria and solubilization of fragrances. Polyoxyethylene alkyl ether having an average addition mole number of ethylene oxide of 20 to 50 mol is preferred. The amount thereof in terms of solubilization of sterilizing power and flavors for oral bacteria, and 0.1 to 1.0%, preferably 0.2 to 0.7%. Too little, it is difficult to prevent l- menthol precipitation at low temperature, while when too large, Ru impaired bactericidal power against oral bacteria.

  In addition, the mass ratio of component (C) nonionic surfactant / (A) cationic fungicide used in the present invention is 4 to 20 in the case of cetylpyridinium chloride, chlorhexidine hydrochloride or chlorhexidine gluconate, More preferably, it is 4 to 12 in terms of exhibiting bactericidal power against oral bacteria. If the mass ratio of (C) / (A) is less than 4, it may be difficult to prevent the precipitation of l-menthol at low temperatures, and the mass ratio of (C) / (A) exceeds 20. And the bactericidal power against oral bacteria may be impaired. Further, the mass ratio of (C) nonionic surfactant / (A) cationic fungicide is 10 to 80 in the case of benzethonium chloride and benzalkonium chloride, and exerts bactericidal power against oral bacteria. More preferably, it is 10-60. If the mass ratio of (C) / (A) is less than 10, it may be difficult to prevent precipitation of l-menthol at low temperatures, and the mass ratio of (C) / (A) exceeds 80. And the bactericidal power against oral bacteria may be impaired.

Component (D) 1-menthol used in the present invention may be used alone, or may be used as peppermint oil or Japanese mint oil containing l-menthol, or both may be used in combination. Good. Their total amount is in that to ensure freshness, 0.001 to 0.15%, more preferably from 0.005 to 0.10%. Too little, it is difficult to secure a cooling sensation, is too large, it is difficult to prevent l- menthol precipitation at low temperatures, appearance stability Ru impaired.

  The component (E) ethanol used in the present invention may be used alone, ethanol in a perfume may be used, or both may be used in combination. The total blending amount is preferably 3% or less, particularly 2% or less in terms of ensuring low irritation, and if it exceeds 3%, the irritation is strong and the usability may be impaired. Moreover, the lower limit ethanol value of the oral composition of the present invention is 0%, and it can be prepared as a non-alcohol-type oral composition substantially free of ethanol.

  As the container, PET (polyethylene terephthalate), glass, polypropylene, and polyethylene can be used, but use of PET or glass is preferable from the viewpoint of suppression of adsorption of the cationic bactericide and the fragrance.

  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 according to the dosage form, and include, for example, wetting agents, thickeners, pH adjusters, preservatives, sweeteners, fragrances, surfactants, active ingredients, coloring agents, etc. it can.

  As the wetting agent, glycerin, sorbitol, propylene glycol, ethylene glycol, polyethylene glycol, xylite, maltite, lactit and the like can be contained. As a thickener, xanthan gum, carrageenan, hydroxymethylcellulose, sodium alginate, polyvinyl alcohol, etc., and as a pH adjuster, phthalic acid, phosphoric acid, citric acid, succinic acid, acetic acid, fumaric acid, malic acid and carbonic acid and their One or two or more of potassium salt, sodium salt and ammonium salt, ribonucleic acid and salts thereof, and sodium hydroxide can be used. In particular, a combination of phosphoric acid, citric acid and their sodium salt is preferable. .

  In particular, the liquid oral composition of the present invention preferably adjusts the pH at 25 ° C. to 5.5 to 7.5, and sodium dihydrogen phosphate and sodium monohydrogen phosphate or A combination of citric acid and sodium citrate can be used.

  As a preservative, sodium benzoate, alkyldiaminoethylglycine hydrochloride, potassium sorbate and the like can be contained in addition to the above-mentioned paraoxybenzoic acid ester.

  In addition, saccharin sodium, steviosite and the like can be contained as sweeteners.

  As perfumes, natural essential oils such as 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 oil, and Fragrance components contained in the above natural essential oils such as l-carvone, 1,8-cineole, methyl salicylate, eugenol, thymol, linalool, limonene, menthone, menthyl acetate, citral, camphor, borneol, pinene, spirantol, etc. Acetate, ethyl butyrate, isoamyl acetate, hexanal, hexenal, methyl anthranilate, ethyl methyl phenylglycidate, benzaldehyde, vanillin, ethyl vanillin, furaneol, maltol, ethyl malto , Gamma / delta decalactone, gamma / deltown decalactone, N-ethyl-p-menthane-3-carboxamide, menthyl lactate, ethylene glycol 1-menthyl carbonate, and some other perfume ingredients Use one or more flavors of apple, banana, strawberry, blueberry, melon, peach, pineapple, grape, muscat, wine, cherry, squash, coffee, brandy, yogurt, etc. In the composition of the present invention, it can be used within a range that does not interfere with the effects of the present invention at a blending amount of 0.00001 to 3%.

  As surfactants other than polyoxyethylene hydrogenated castor oil or polyoxyethylene alkyl ether, myristyl sodium sulfate, N-lauroyl sarcosinate, lauroyl methyl taurine, acylamino acid salt, sodium dodecylbenzenesulfonate, α-sulfo fatty acid alkyl ester Anionic surfactants such as sodium and alkyl phosphate ester salts, betaine acetate type amphoteric surfactants such as alkyldimethylaminoacetic acid betaine, fatty acid amidopropyldimethylaminoacetic acid betaine, N-fatty acid acyl-N-carboxymethyl-N An imidazoline type amphoteric surfactant such as hydroxyethylethylenediamine salt and an amino acid type surfactant such as N-fatty acid acyl-L-alginate salt can be used alone or in combination. Can be can be 0.01 to 1% used within a range which does not impair the effects of the present invention.

  Active ingredients include fungicides such as triclosan and isopropylmethylphenol, anti-inflammatory agents such as tranexamic acid and epsilon-aminocaproic acid, enzymes such as dextranase, amylase, protease, mutanase, lysozyme, lytic enzyme, lytechenzyme, and fluoride Sodium, sodium monofluorophosphate, fluoride such as stannous fluoride, vitamin C such as aluminum chlorohydroxy allantoin, allantoin, azulene, lysozyme chloride, ascorbic acid, dihydrocholesterol, glycyrrhetin salts, glycyrrhetinic acid, hydrocholesterol, Chlorophyll, copper chlorophyllin sodium, thyme, hornon, clove, hamamelis and other plant extracts, copper gluconate, caropeptide, sodium polyphosphate, water-soluble Machine phosphoric acid compound, polyethylene glycol, polyvinyl pyrrolidone, sodium lauroyl sarcosinate, anti-tartar agents, anti-plaque agents, potassium nitrate, may be added to aluminum lactate and the like. In addition, the compounding quantity of these active ingredients can be contained in the range which does not disturb the effect of this invention.

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

  EXAMPLES Hereinafter, although this invention is demonstrated in detail based on an Example and a comparative example, this invention is not restrict | limited by these Examples. In addition, all the% shown below means the mass%.

[Experiment 1]
Bactericidal effect on oral bacteria For the bacterial count measurement test, Dentocult-SM (manufactured by Orion Diagnostics, Finland) which is a simple bacterial count kit for mutans in saliva was used. In advance, the number of bacteria in saliva was evaluated according to the method of using Dentocult-SM, and 10 people with 2 or more points were targeted according to the following criteria. The measurement was carried out by rinsing with 10 mL of the mouthwash having the composition shown in Tables 1 and 2 in the mouth for 30 seconds, and the number of mutans bacteria in saliva after 3 hours was similarly shown using Denocult-SM. Evaluation was made according to the criteria described, and the average score of 10 people was calculated.
Judgment standard 3: The number of mutans bacteria is 10 ⁶ or more 2: The number of mutans bacteria is 10 ⁵ or more and less than 10 ⁶ 1: The number of mutans bacteria is less than 10 ⁵

[Experiment 2]
Appearance stability 450 mL of the sample shown in Tables 1 and 2 was filled in a 500 mL PET container, and the appearance stability after 1 month storage in a -5 ° C thermostatic bath was visually determined according to the following criteria.
Appearance stability evaluation criteria A : There is no difference from the initial product, and no precipitation of needle crystals is observed.
○: A very small amount of orientation is observed.
Δ: Precipitation of a small amount of crystals is observed.
X: Precipitation of acicular crystals is observed.

[Experiment 3]
Usability Evaluation After the sample 10 mL shown in Tables 1 and 2 was included in the mouth and rinsed for 30 seconds, the absence of irritation after mouthwash and the refreshing feeling were evaluated in the following three stages, and the average score of 10 persons was calculated.
No irritation after mouthwash 3: No irritation 2: Slight irritation 1: Irritation was observed
A refreshing feeling after mouthwash 3: A refreshing feeling was recognized 2: A slightly refreshing feeling was recognized 1: A refreshing feeling was not recognized

[Example 11] Mouthwash A Benzethonium chloride 0.01%
Benzalkonium chloride 0.01
B methyl paraoxybenzoate 0.1
Ethyl paraoxybenzoate 0.1
C polyoxyethylene (60) hydrogenated castor oil 0.3
D Fragrance A (1-menthol: 23% contained) 0.4
Ethanol * 2.8
Sodium fluoride 0.05
Ascorbic acid 0.01
Cationized cellulose 0.05
Acetic acid dl-α-tocophenol 0.05
Glycerin 7
Xylitol 3
Citric acid 0.03
Sodium citrate 0.3
Water remaining
Total 100.0%
l-Menthol total amount 0.09%
*: Since the amount of ethanol in the fragrance was very small, the second decimal place was rounded off to indicate the total amount.

[Example 12] Mouthwash A cetylpyridinium chloride 0.05%
B methyl paraoxybenzoate 0.1
Ethyl paraoxybenzoate 0.05
C Polyoxyethylene (100) hydrogenated castor oil 0.6
D Fragrance B (1-Menthol: 21% contained) 0.05
Isopropylmethylphenol 0.03
Triclosan 0.02
Propylene glycol 3
Glycerin 5
Xylitol 2
Saccharin sodium 0.006
ε-aminocaproic acid 0.02
Citric acid 0.03
Sodium citrate 0.25
Water remaining
Total 100.0%
l-Menthol total amount 0.01%

[Example 13] Mouthwash A Benzalkonium chloride 0.02%
B Methyl paraoxybenzoate 0.2
Ethyl paraoxybenzoate 0.1
C polyoxyethylene (20) cetyl ether 0.2
D l-Menthol 0.04
Fragrance C (1-Menthol: 19% contained) 0.2
Ethanol * 2
Sodium fluoride 0.05
Dextranase 0.2
Copper chlorophyllin sodium 0.01
Sodium monohydrogen phosphate 0.2
Sodium disodium phosphate 0.1
Aspartame 0.02
Xylitol 5
Glycine 0.2
Water remaining
Total 100.0%
l-Menthol total amount 0.08%
*: Since the amount of ethanol in the fragrance was very small, the second decimal place was rounded off to indicate the total amount.

[Example 14] Mouthwash A cetylpyridinium chloride 0.05%
B methyl paraoxybenzoate 0.1
Ethyl paraoxybenzoate 0.05
C Polyoxyethylene (100) hydrogenated castor oil 0.6
D l-Menthol 0.02
Fragrance D (1-Menthol: 19% contained) 0.4
Ethanol * 2.2
Sodium pyrophosphate 0.2
Polyethylene glycol 600 0.5
Tranexamic acid 0.03
Glycerin 2
Saccharin sodium 0.002
Citric acid 0.03
Sodium citrate 0.25
Water remaining
Total 100.0%
l-Menthol total amount 0.1%
*: Since the amount of ethanol in the fragrance was very small, the second decimal place was rounded off to indicate the total amount.

[Example 15] Mouthwash A chlorhexidine hydrochloride 0.05%
B Methyl paraoxybenzoate 0.2
Ethyl paraoxybenzoate 0.1
C polyoxyethylene (30) stearyl ether 0.4
D l-Menthol 0.06
Fragrance E (1-menthol: containing 8%) 0.5
Ethanol * 1
Polyvinylpyrrolidone 0.05
Sodium polyphosphate 0.02
Sodium fluoride 0.02
Propylene glycol 2
Glycerin 2
Citric acid 0.03
Sodium citrate 0.3
Water remaining
Total 100.0%
l-Menthol total amount 0.1%
*: Since the amount of ethanol in the fragrance was very small, the second decimal place was rounded off to indicate the total amount.

[Example 16] Mouthwash A cetylpyridinium chloride 0.05%
B methyl paraoxybenzoate 0.1
Ethyl paraoxybenzoate 0.05
C Polyoxyethylene (60) hydrogenated castor oil 0.5
Fragrance F (1-Menthol: 18% contained) 0.1
Lysozyme chloride 0.5
Propylene glycol 4
Polyethylene glycol 600 3
Citric acid 0.06
Sodium citrate 0.5
Saccharin sodium 0.005
Water remaining
Total 100.0%
l-Menthol total amount 0.02%

注）上記表において、部は質量部である（以下、同様）。

Note) In the above table, parts are parts by mass (the same applies hereinafter).

Claims (7)

(A) A composition for a liquid oral cavity containing 0.01 to 0.10% by mass of a cationic fungicide and (D) 1-menthol and having an ethanol content of 3% by mass or less of the whole composition. And (B) 0.05 to 0.4% by mass using (B) methyl paraoxybenzoate and ethyl paraoxybenzoate in a mass ratio of 1/1 to 3/1 , and (C) an average addition mole of ethylene oxide 0.1 to 1.0 mass% of polyoxyethylene hydrogenated castor oil having a number of 40 to 100 mol or polyoxyethylene alkyl ether having a carbon chain length of 16 to 18 and an average added mole number of ethylene oxide of 10 to 50 mol And (D) 1-menthol content is 0.001 to 0.15% by mass .   The liquid oral composition according to claim 1, wherein (A) the cationic bactericidal agent is cetylpyridinium chloride, chlorhexidine hydrochloride or chlorhexidine gluconate, and the mass ratio of (C) / (A) is 4 to 20.   The liquid oral composition according to claim 1, wherein (A) the cationic bactericidal agent is benzethonium chloride or benzalkonium chloride, and the mass ratio of (C) / (A) is 10 to 80.   The composition for liquid oral cavity according to claim 1, 2 or 3, wherein the components (B) and (C) are blended as a precipitation inhibitor for l-menthol. The composition for liquid oral cavity according to any one of claims 1 to 4, which is prepared as a mouthwash. (A) A composition for a liquid oral cavity containing 0.01 to 0.10% by mass of a cationic fungicide and (D) 1-menthol and having an ethanol content of 3% by mass or less of the whole composition. And (B) 0.05 to 0.4% by mass using (B) methyl paraoxybenzoate and ethyl paraoxybenzoate in a mass ratio of 1/1 to 3/1 , and (C) an average addition mole of ethylene oxide 0.1 to 1.0 mass% of polyoxyethylene hydrogenated castor oil having a number of 40 to 100 mol or polyoxyethylene alkyl ether having a carbon chain length of 16 to 18 and an average added mole number of ethylene oxide of 10 to 50 mol preparative blended, and (D) l- content of menthol, characterized in that a 0.001 to 0.15 mass%, the precipitation preventing method of l- menthol in the liquid oral composition. The method according to claim 6, wherein the liquid oral composition is a mouthwash composition.