JP6939096B2 - Liquid oral composition - Google Patents

Description

The present invention relates to a liquid oral composition containing p-menthane-3-carboxamides, which gives a high refreshing feeling in the oral cavity and has excellent appearance stability.

In liquid oral compositions, especially mouthwashes used for the purpose of preventing bad breath, giving a feeling of use that makes the oral cavity feel refreshed after use is to improve the feeling of use and effect. It is meaningful. On the other hand, since the mouthwash may be prepared clearly, it is important in terms of quality to maintain the appearance of the formulation in a stable manner without gargles or the like even after storage. .. However, it is difficult for a liquid oral composition such as a mouthwash to give a satisfactory feeling of use and at the same time maintain a stable appearance of the formulation over time.

In the liquid oral composition, l-menthol is generally blended as a fragrance that gives a refreshing sensation in order to improve the feeling of use, and various studies have been conducted to enhance the refreshing sensation. By using p-menthol-3-carboxamides, which are agents, techniques for enhancing a refreshing feeling and a refreshing feeling and enhancing their sustainability have been proposed (Patent Documents 1 to 6).

Japanese Unexamined Patent Publication No. 2014-125440 Japanese Unexamined Patent Publication No. 2015-182983 Japanese Unexamined Patent Publication No. 2016-102076 Japanese Patent Publication No. 2014-507440 Special Table 2012-508741 Special Table 2011-520925

The present invention has been made in view of the above circumstances, and is a liquid oral composition containing p-menthane-3-carboxamides, which gives a high refreshing feeling in the oral cavity, suppresses stagnation over time, and has excellent appearance stability. The purpose is to provide.

As a result of diligent studies to achieve the above object, the present inventors have added a nonionic surfactant, glycerin and / or / or a nonionic surfactant to a liquid oral composition containing specific p-menthane-3-carboxamides. When propylene glycol and sugar alcohol are properly combined, it gives a high refreshing feeling that makes the oral cavity feel refreshed after use, and also suppresses the occurrence of nigiri over time, resulting in a stable formulation appearance. It was found that it can be maintained. That is, in the present invention, (B) a nonionic surfactant is added to a liquid oral composition containing (A) N- (2- (2-pyridinyl) ethyl) -2-isopropyl-5-methylcyclohexanecarboxamide. By blending (C) glycerin and / or propylene glycol and (D) sugar alcohol in specific amounts and the mass ratio of (C) / (D) within a specific range, a high refreshing feeling is given in the oral cavity. The present invention has been made by finding that a liquid oral composition having excellent appearance stability can be obtained while giving it and suppressing squeaking even with time.

More specifically, the cooling agent p-menthane-3-carboxamides may have a stronger irritation feeling as the amount is increased. Therefore, it is necessary to suppress the irritation when sufficiently giving a refreshing feeling. In addition, the solubility differs depending on the substance, and in particular, the solubility of N- (2- (2-pyridinyl) ethyl) -2-isopropyl-5-methylcyclohexanecarboxamide in water is relatively low. However, in the present invention, when the component (A) is used as the p-menthane-3-carboxamides and the components (B), (C) and (D) are combined with the component (A), (C) / (D) is mass. When the ratio is 4.5 or more, the component (B) and the components (C) and (D) interact with the component (A) to improve the effect of imparting a refreshing feeling and to improve the effect of the component (A). The occurrence is suppressed and the appearance of the formulation is stabilized, and both are compatible. Therefore, as shown in Examples described later, in the present invention, it is possible to give a high refreshing feeling in the oral cavity and give an excellent feeling of use. Moreover, in the present invention, although the solubility of the component (A) in water is relatively low as described above, the generation of gargling by the component (A) is under low temperature and harsh conditions as in the freeze restoration test. It is suppressed even after storage underneath, and excellent appearance stability can be imparted even with a mouthwash having a clear appearance.
In the present invention, a special action and effect are exhibited only by appropriately combining the components (B), (C) and (D) with the component (A), and inappropriately, a surfactant, a polyhydric alcohol and the like. When sugar alcohol is used, the action and effect of the present invention are inferior. As shown in the comparative example described later, when the (C) / (D) ratio is too small, the oral cavity is less refreshing, and when the amount of the (B), (C) or (D) component is inappropriate, it is refreshing. Poor sensation or freeze-restorability (appearance stability after performing freeze-restoration test in which storage is performed alternately at −20 ° C. and room temperature three times for two days).

Therefore, the present invention provides the following liquid oral compositions.
[1]
(A) A liquid oral composition containing N- (2- (2-pyridinyl) ethyl) -2-isopropyl-5-methylcyclohexanecarboxamide, and further.
(B) Nonionic surfactant 0.1 to 1% by mass,
(C) Glycerin and / or Propylene Glycol 3 to 20% by mass,
And (D) sugar alcohol 0.3-4% by mass
A liquid oral composition containing (C) / (D) having a mass ratio of 4.5 or more.
[2]
(B) The nonionic surfactant is a polyoxyethylene hydrogenated castor oil having an average addition molar number of ethylene oxide of 60 to 100 mol, a polyglycerin fatty acid ester having a fatty acid carbon number of 10 to 18, and a fatty acid carbon number. The liquid oral composition according to [1], which is one or more selected from sucrose fatty acid esters having a value of 10 to 22.
[3]
(D) The liquid oral composition according to [1] or [2], wherein the sugar alcohol is xylitol and / or erythritol.
[4]
The liquid oral composition according to any one of [1] to [3], wherein the content of the component (A) is 0.00000001 to 0.01% by mass.
[5]
The liquid oral composition according to any one of [1] to [4], which is a mouthwash, a liquid toothpaste, or a mouthwash.

According to the present invention, it is possible to provide a liquid oral composition containing p-menthane-3-carboxamides, which gives a high refreshing feeling in the oral cavity, suppresses stagnation over time, and has excellent appearance stability.

Hereinafter, the present invention will be described in more detail. The liquid oral composition of the present invention contains (A) N- (2- (2-pyridinyl) ethyl) -2-isopropyl-5-methylcyclohexanecarboxamide as p-menthane-3-carboxamides and ( It contains B) a nonionic surfactant, (C) glycerin and / or propylene glycol, and (D) a sugar alcohol.

(A) N- (2- (2-pyridinyl) ethyl) -2-isopropyl-5-methylcyclohexanecarboxamide is a refreshing agent. Specifically, a commercially available product such as that manufactured by Givaudan Japan Co., Ltd. can be used.
The blending amount of the component (A) is preferably 0.00000001 to 0.01% (mass%, the same applies hereinafter) of the entire composition, and more preferably 0.00000005 to 0.005%. Within this range, a sufficiently refreshing feeling can be imparted, and the stimulation of itself can be sufficiently suppressed. In addition, sufficient freeze-restorability can be obtained.

(B) As the nonionic surfactant, one or more selected from polyoxyethylene hydrogenated castor oil, polyglycerin fatty acid ester and sucrose fatty acid ester are preferable, and polyoxy is particularly effective in suppressing irritation. Polyethylene hydrogenated castor oil is more preferred.

From the viewpoint of usability and solubilization, the polyoxyethylene hydrogenated castor oil preferably has an average addition mole number (EO) of ethylene oxide of 60 to 100 moles.
The polyglycerin fatty acid ester preferably has 10 or more carbon atoms, particularly 12 or more carbon atoms, and more preferably 18 or less, particularly 14 or less, from the viewpoint of usability and solubilization. be.
From the viewpoint of usability and solubilization, the sucrose fatty acid ester preferably has 10 or more carbon atoms, particularly 12 or more carbon atoms, and more preferably 22 or less, particularly 18 or less carbon atoms. be.
Commercially available products can be used as such nonionic surfactants. Specifically, polyoxyethylene hydrogenated castor oil (manufactured by Nippon Emulsion Co., Ltd.), sucrose stearic acid ester (DK ester SS, manufactured by Daiichi Kogyo Seiyaku Co., Ltd.), polyglyceryl myristate (Sunsoft Q-14Y-) C, manufactured by Taiyo Kagaku Co., Ltd.) and the like.

The blending amount of the (B) nonionic surfactant is 0.1 to 1%, preferably 0.3 to 0.8% of the total composition. Within this range, the effect of imparting a refreshing feeling and the freeze-restoring property are excellent, and the feeling of irritation is suppressed. If it is less than 0.1%, the freeze-restorability is poor. If it exceeds 1%, the feeling of cleanliness decreases.

(C) Glycerin and / or propylene glycol may be used alone or in combination of two.

The blending amount of the component (C) is 3 to 20%, preferably 5 to 15% of the total composition. Within this range, the feeling of cleanliness does not decrease, the feeling of irritation is suppressed, and a high effect on freeze stability can be obtained. If it is less than 3%, the freeze-restorability is inferior even if the components (B) and (D) are appropriately blended, and the irritation sensation is not suppressed. If it exceeds 20%, the stickiness due to the component (C) becomes strong and the refreshing feeling is lowered.

The sugar alcohol (D) is preferably xylitol and / or erythritol, and can be used alone or in combination of two.
The blending amount of the sugar alcohol (D) is 0.3 to 4%, preferably 1 to 3% of the total composition. Within this range, the feeling of cleanliness is high and the feeling of irritation is suppressed. Even if the components (B) and (C) are properly blended, the refreshing feeling is inferior when the content is less than 0.3%, and the irritation feeling due to the component (A) is not suppressed, and when the content exceeds 4%, the refreshing feeling is poor. Decreases.

In the present invention, (C) / (D) indicating the blending ratio of the component (C) and the component (D) is 4.5 or more as a mass ratio. If the (C) / (D) ratio is less than 4.5, the effect of imparting a refreshing feeling is reduced. The (C) / (D) ratio is preferably 5.0 or more from the viewpoint of suppressing stimulation, and the upper limit is not particularly limited, but 40 or less is more preferable, and 15 or less is further preferable. ..

The liquid oral composition of the present invention can further contain a bactericidal agent as an active ingredient.
Examples of the disinfectant include cationic disinfectants such as cetylpyridinium chloride and benzethonium chloride, and nonionic disinfectants such as isopropylmethylphenol. Among them, cationic disinfectants, particularly cetylpyridinium chloride, are preferable. The blending amount of the disinfectant is preferably 0.001 to 0.1%, particularly 0.01 to 0.05% of the total composition.
Further, as an active ingredient, other known ingredients such as a fluorine-containing compound, an anti-inflammatory agent such as tranexamic acid, an enzyme such as dextranase, vitamins and the like may be blended, if necessary. An effective amount of these active ingredients can be added as long as the effects of the present invention are not impaired.

The liquid oral composition of the present invention can be prepared and applied as a mouthwash, a liquid toothpaste, a mouthwash, and the like, but a mouthwash is particularly preferable. In addition to the above-mentioned components, an appropriate known component can be blended as necessary according to the dosage form, purpose of use, and the like. Specifically, surfactants other than the component (B), wetting agents other than the components (C) and (D), thickeners, preservatives, sweeteners, colorants, fragrances, pH adjusters, solvents, etc. It is compounded. It is preferable that the liquid oral composition, particularly the mouthwash, does not usually contain a solid component that is not solubilized, such as an abrasive, and does not contain an abrasive.

Surfactants include alkyl sulfates such as sodium lauryl sulfate and sodium myristyl sulfate, N-lauroyl sarcosinate, lauroyl methyl taurine, acyl amino acid salts, sodium dodecylbenzene sulfonate, α-sulfo, as anionic surfactants. Examples thereof include fatty acid alkyl ester sodium and alkyl phosphate ester salt. Examples of the amphoteric tenside include a betaine type acetate such as alkyldimethylaminoacetic acid betaine and an imidazoline type such as N-fatty acid acyl-N-carboxymethyl-N-hydroxyethylethylenediamine salt.
The blending amount of the surfactant other than the component (B) is preferably 0 to 0.2%, particularly preferably 0.01 to 0.1%.
The liquid oral composition of the present invention, particularly the mouthwash, does not need to contain a surfactant other than the component (B), and among them, an anionic surfactant, particularly an alkyl sulfate such as sodium lauryl sulfate. Is preferably not blended because it affects the usability due to the occurrence of foam residue, but when blended, it is preferably 0.1% or less, particularly 0.05% or less.

As the wetting agent, since the components (C) and (D) also act as wetting agents, it is not necessary to add other than these, but ethylene glycol, polyethylene glycol and the like may be added if necessary. .. When these wetting agents are blended, the blending amount is preferably 5% or less, particularly 3% or less, and may be 0%.

Examples of the thickener include xanthan gum, carrageenan, hydroxyethyl cellulose, sodium alginate, polyvinyl alcohol, carboxymethyl cellulose and the like (usually, the blending amount is 0 to 1%).

Examples of the preservative include paraoxybenzoic acid ester, benzoic acid or a sodium salt thereof.
Examples of the sweetener include sodium saccharin, stebioside and the like.
Examples of the colorant include highly safe water-soluble dyes such as Blue No. 1, Green No. 3, Yellow No. 4, and Red No. 105.

Natural fragrances include peppermint oil, sparemint oil, eucalyptus oil, winter green oil, clove oil, thyme oil, sage oil, cardamon oil, rosemary oil, majorum oil, lemon oil, nutmeg oil, lavender oil, paracress oil, etc. Essential oils and l-menthol, l-carboxylic, synamic aldehyde, orange oil, anetol, 1,8-cineole, methylsalicylate, eugenol, timole, linalol, limonene, menthon, menthyl acetate, citral, camphor, borneol, pinen, Fragrance components contained in the above natural essential oils such as spirantol, ethyl acetate, ethyl butyrate, isoamyl acetate, hexanal, hexenal, methyl anthranilate, ethyl methyl phenyl glycidate, benzaldehyde, vanillin, ethyl vanillin, flaneol, Fragrance components such as maltor, ethyl maltor, gamma / delta decalactone, gamma / deltown decalactone, N-ethyl-p-menthan-3-carboxamide, mentyl lactate, ethylene glycol-l-mentyl carbonate, and some One or two blended flavors of apple, banana, strawberry, blueberry, melon, peach, pineapple, grape, muscat, wine, cherry, squash, coffee, brandy, yogurt, etc. The above can be used in the composition of the present invention at 0.000001 to 3% within a range that does not interfere with the effects of the present invention.
The fragrance containing the component (A) can be used within the above-mentioned blending amount of the component (A).

The amount of menthol blended as a fragrance is preferably 0.001 to 0.15%, particularly 0.005 to 0.10%, but may be 0% without blending. According to the present invention, even if the blending amount of menthol is small, a high refreshing feeling can be imparted and the action and effect are excellent.

In the liquid oral composition of the present invention, the pH at 25 ° C. is preferably adjusted to 5.5 to 8.0, and sodium dihydrogen phosphate and sodium monohydrogen phosphate are used as pH adjusting agents in the vicinity. Alternatively, a combination of citric acid and sodium citrate can be added.

Purified water is generally used as the solvent. Further, a lower monohydric alcohol such as ethanol may be blended, and particularly when ethanol is added, the amount added is preferably 30% or less, particularly 4 to 20% of the entire composition. The addition of the lower monohydric alcohol is suitable for imparting a refreshing feeling, but when the content exceeds 30%, the irritation becomes strong and the usability may deteriorate. Further, a lower monohydric alcohol, particularly a preparation that does not substantially contain ethanol (the content of ethanol is 0.2% or less of the total composition) is suitable as a hypoallergenic type preparation. In the present invention, even such a liquid oral composition containing substantially no ethanol is excellent in the action and effect of the present invention.

Hereinafter, the present invention will be specifically described with reference to Examples and Comparative Examples, but the present invention is not limited to the following Examples. In the following examples,% indicates mass% unless otherwise specified.

[Examples, comparative examples]
Using the raw materials shown below and the fragrance composition having the composition shown in Table 1, a liquid oral composition (mouthwash) having the composition shown in Tables 2 to 4 was prepared by a conventional method, and these were used as samples. It was evaluated by the method shown below. The results are also shown in the table.

The details of the raw materials used are shown below.
(A) N- (2- (2-pyridinyl) ethyl) -2-isopropyl-5-methylcyclohexanecarboxamide; Evacour, manufactured by Givaudan Japan (B) polyoxyethylene (100) cured castor oil;
E. O. 100, Nippon Emulsion Co., Ltd. (B) Polyoxyethylene (60) Hardened castor oil;
E. O. 60, Nippon Emulsion Co., Ltd. (B) polyglycerin fatty acid ester;
Sunsoft Q-14Y-C (polyglyceryl myristate), Taiyo Kagaku Co., Ltd. (B) sucrose fatty acid ester;
DK ester SS (sucrose stearic acid ester), Daiichi Kogyo Seiyaku Co., Ltd. (C) glycerin; Sakamoto Yakuhin Kogyo Co., Ltd. (C) propylene glycol; Asahi Glass Co., Ltd. (D) xylitol; Rocket Japan ( Made by (D) Erythritol Co., Ltd .; Made by Mitsubishi Chemical Foods Co., Ltd.

(1) Evaluation method of refreshing feeling After containing 20 mL of the sample in the mouth and rinsing for 20 seconds, the refreshing feeling immediately after use is judged in 4 stages according to the following evaluation criteria, and the average score of 10 people is calculated and according to the following evaluation criteria. evaluated.
Rating criteria 4 points: Highly refreshing feeling 3 points: Refreshing feeling 2 points: Not very refreshing feeling 1 point: No refreshing feeling at all Evaluation criteria ◎: 3.5 points or more ○: 3.0 points or more 3 .Less than 5 points ×: Less than 3.0 points

(2) Evaluation method of irritation (no irritation) 20 mL of the sample was put in the mouth, rinsed for 20 seconds, and the no irritation during the use of the mouthwash was judged on a 4-point scale according to the following scoring criteria, and the average score of 10 people was calculated. It was calculated and evaluated according to the following evaluation criteria.
Rating criteria 4 points: No stimulus 3 points: Almost no stimulus 2 points: Stimulation is felt 1 point: Very stimulus is felt Evaluation criteria ◎: 3.5 points or more and 4.0 points or less ○: 3.0 Points or more and less than 3.5 points ×: Less than 3.0 points

(3) Evaluation method of freeze-restorability 450 mL of each sample was filled in a PET (polyethylene terephthalate) container having a full injection volume of 500 mL. Next, the cycle of storing these in a constant temperature bath at −20 ° C. for 2 days and then storing them at room temperature for 1 day was repeated three times. Then, the appearance of the pharmaceutical product of the sample at room temperature was evaluated by comparing with the initial product (the product immediately after preparation before storage, the appearance was clear) according to the following evaluation criteria.
Evaluation Criteria ◎: There is no difference from the initial product, and no squeak is observed.
◯: Very slight nigori is observed.
×: Nigori is recognized.

Claims (4)

(A) A liquid oral composition containing N- (2- (2-pyridinyl) ethyl) -2-isopropyl-5-methylcyclohexanecarboxamide, and further.
(B) Polyoxyethylene hydrogenated castor oil having an average added molar number of ethylene oxide of 60 to 100 mol, polyglycerin fatty acid ester having a fatty acid having a carbon number of 10 to 18, and a salt having a fatty acid having a carbon number of 10 to 22. One or more nonionic surfactants selected from glycofatty acid esters 0.1 to 1% by mass,
(C) Glycerin and / or Propylene Glycol 3 to 20% by mass,
And (D) sugar alcohol 0.3-4% by mass
A liquid oral composition containing (C) / (D) having a mass ratio of 4.5 or more. (D) a sugar alcohol, xylitol and / or erythritol in a claim 1 Liquid oral composition. The liquid oral composition according to claim 1 or 2 , wherein the content of the component (A) is 0.00000001 to 0.01% by mass. The liquid oral composition according to any one of claims 1 to 3 , which is a mouthwash, a liquid toothpaste or a mouthwash.