JP3219995B2 - Refreshing agent - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a refreshing sensation improver. More specifically, the present invention relates to a compound which gives an excellent cooling sensation or cooling sensation to human skin and mucous membranes. For example, the present invention relates to a refreshing sensation improver that enhances its durability and suppresses irritation.

[0002]

2. Description of the Related Art (1R, 2S, 5R) -5-methyl-2
-(1-Methylethyl) cyclohexyl alcohol (hereinafter, referred to as "l-menthol") has a strong light odor with a cooling sensation and is used as a fragrance,
It is known that d-menthol, which is an optical antipode, has a slightly refreshing flavor and a slightly sweet flavor (Genichi Indo,
"Actual knowledge of spices" (March 25, 1975, Toyo Keizai Shimpo, p. 79).

[0003] l-menthol has a wide variety of uses as a flavoring agent that gives a refreshing feeling, such as foods, toothpastes, chewing gums,
It is used as a mouthwash, cataplasm, cosmetics, shaving cream and tobacco flavor. Such useful l-menthol also has two disadvantages which have been pointed out so far. One is that l-menthol has the property of sublimation, and the second is a strong peppermint odor.
The former volatilizes in the air and causes a lack of coolness. The latter irritates the eyes and nostrils, and the smell spreads around, and it is desired to improve these drawbacks.

[0004] 3-{(1R, 2S, 5R)-[5-methyl-2, which has one less methyl group than the refreshing agent of the present invention.
-(1-Methylethyl) cyclohexyl] oxy} propane-1,2-diol (hereinafter referred to as "3-1-menthoxypropane-1,2-diol") is disclosed in
It is a known compound described in -48813. According to the publication, this compound is obtained by converting l-menthol into a sodium salt with metallic sodium or sodium hydride, and then reacting the salt with allyl halide to obtain 3-l-menthoxypropan-1-ene. This is obtained by oxidizing this with an organic peracid to form an oxide, followed by hydrolysis.

According to the same publication, 3-l-menthoxypropane-1,2-diol has a cooling sensation, but does not have an odor unlike l-menthol. For the purpose of imparting a cooling effect without affecting the fragrance imparted to the product at all, compositions for oral use such as powdered toothpaste, toothpaste, toothpaste, chewing gum, sherbet, and hard candy Such as foods and beverages, and cosmetics (Japanese Patent Laid-Open No. 60-2590).
No. 8, JP-A-63-208505), cosmetics such as eye packs (JP-A-62-96403), hair cosmetics (JP-A-62-29212), and other anti-inflammatory analgesics. Aerosol composition (Japanese Patent Application Laid-Open No. 63-26)
No. 4522) has been proposed.

[0006] However, 3
There is no description about the use of -l-menthoxypropane-1,2-diol with other compounds, and this optically active compound (2S) -3-{(1R, 2S, 5)
R)-[5-Methyl-2- (1-methylethyl) cyclohexyl] oxypropane-1,2-diol is also disclosed in JP-A-7-82200. Only compositions, foods and beverages, and cosmetics are disclosed.

On the other hand, with respect to the refreshing agent of the present invention,
Substitution of a methyl group at the 1- or 2-position of the glycerin moiety (propane) of 3-menthoxypropane-1,2-diol adds a strong bitter taste to the cooling sensation (Takasago Times No.11)
8,12,1995), and compounds of the type in which a methyl group was introduced into the glycerin moiety of 3-menthoxypropane-1,2-diol (1) were excluded because of increased bitterness at any position ( Although it is described in the Japan Skin Association Journal, Vol. 9, NO17, 77, 1986), there is no report on the improvement of cooling sensation, and only the description that it is not preferable to use it.

[0008]

SUMMARY OF THE INVENTION The present invention relates to a cooling sensation agent which gives a cooling sensation or a refreshing sensation, particularly l-, a typical compound thereof.
It is an object of the present invention to provide a refreshing sensation improving agent that enhances the sustainability of menthol's cooling sensation or cooling sensation and further suppresses irritation.

[0009]

DISCLOSURE OF THE INVENTION The present inventors have conducted intensive studies to solve the disadvantage of 2-methyl-3-l-menthoxypropane-1,2-diol, that is, bitterness,
It has been found that the compound improves the sustainability and irritation of its action by being added to a cooling sensation agent such as l-menthol, menthol, isopulegol, menthyl acetate, sabinene hydrate and the like. Reached.

For the bitterness of 2-methyl-3- (1-menthoxy) propane-1,2-diol, a concentration of 0.0
When evaluated with a 01 to 1% aqueous solution, it was found that bitterness was rapidly reduced at a concentration of 0.1% or less. Also l-
Many panelists felt that bitterness was further reduced when used in combination with menthol. In other words, it was determined that the bitter effect was weakly assigned to ancillary properties as compared to the strong cooling effect of 2-methyl-3- (1-menthoxy) propane-1,2-diol.

In addition, by using 2-methyl-3- (1-menthoxy) propane-1,2-diol in combination with a cooling compound, the bitterness of the product is hardly obstructed at the concentration in the product, and the toothpaste is used. And chewing gums, and other oral compositions, foods and drinks, and cosmetics, and the like.

That is, the present invention relates to 2-methyl-3-
Provided are a refreshing sensation improver comprising (l-menthoxy) propane-1,2-diol, and an oral composition, a food or drink or a cosmetic containing the cool sensation improver.

[0013]

BEST MODE FOR CARRYING OUT THE INVENTION The refreshing agent of the present invention, 2-
Methyl-3- (1-menthoxy) propane-1,2-diol, i.e., 2-methyl-3-{(1R, 2S,
5R)-[5-Methyl-2- (1-methylethyl) cyclohexyl] oxy} propane-1,2-diol (represented by 1 in the following reaction formula) is synthesized by a method represented by the following reaction formula. be able to.

[0014]

Embedded image That is, l-menthol (2) is converted into a sodium salt with sodium hydride in toluene or xylene, and
-Methylpropenyl halide (3) to give 3-l
-Mentoxy-2-methyl-1-propene (4) was prepared, oxidized with an organic peracid, and then hydrolyzed to give 2-methyl-3- (1-menthoxy) propane-1,
2-diol (1) is obtained.

As the starting compounds, 2-methylpropenyl halide (3) and 1-menthol (2), commercially available products can be used as they are. The synthesis method will be described in detail below. The method of the addition reaction is not particularly limited. For example, a solution of l-menthol (2) in a suitable solvent such as toluene or xylene is mixed with a suitable metal hydride such as sodium hydride or sodium. Or the like, and a solution obtained by dissolving 2-methylpropenyl halide (3) (chloride, bromide, etc.) in a suitable solvent may be dropped and reacted.

The amount of 2-methylpropenyl halide (3) used is preferably about 1 to 1-menthol (2).
The equivalent is preferably 2 to 2 equivalents, particularly preferably about 1.1 to 1.5 equivalents. The amount of the alkali metal or hydride metal used may be the amount used in a usual addition reaction, and is preferably 1-
The equivalent is preferably about 1 to 1.1 times equivalent to menthol (2). Sodium hydride and potassium hydride are used as the metal hydride used in the present invention, and sodium is used as the alkali metal. Particularly preferably, sodium hydride is used. In addition, as a reaction solvent,
Toluene, xylene, petroleum ether, tetrahydrofuran and the like can be mentioned, and toluene is particularly preferably used.

The reaction temperature of the addition reaction is preferably refluxed at the boiling point of each reaction solvent, and particularly preferably, it is heated to around the boiling point of toluene at 110 to 111 ° C., and the temperature is maintained at about 0.5 to The reaction is preferably performed for 3 hours.

The thus obtained 2-methyl-3- (l-
Mentoxy) -1-propene (4) can be subjected to the next oxidation reaction without purification.

Oxidation is carried out by adding a substrate and a solvent of an organic acid such as formic acid or acetic acid 1.5 to 5 times the weight of the substrate to a reaction temperature of 5 to 5 times.
The reaction is carried out by maintaining the temperature at 0 to 70 ° C. and dropping 1.2% to 1.5 times equivalent of 35% hydrogen peroxide to the substrate, followed by further reacting for 1 to 5 hours.

After the reaction, the reaction solution is cooled to room temperature, the unreacted peracid is decomposed, water is added, the product is extracted with an organic solvent such as toluene, the extract is washed with water, and the solvent is recovered. Obtain the oxide. This crude oxide is heated and refluxed for 1 to 5 hours in a dilute aqueous alkali solution such as 15 to 30% by weight of caustic soda or potassium hydroxide to give 2-methyl-3- (1-menthoxy) propane-1,2-diol. Obtain (1).

As described above, the refreshing agent of the present invention,
-Methyl-3- (1-menthoxypropane) -1,2-
The diol (1) can be synthesized using easily available raw materials and a simple reaction operation.

The thus synthesized 2-methyl-
3-l-menthoxypropane-1,2-diol (1)
Can be appropriately blended with a known cooling sensation compound and used in a wide range without any particular limitation. That is, the cooling sensation improving agent of the present invention can maintain or enhance, for example, a refreshing and cool cooling sensation or a cooling sensation, can suppress irritation, and make it mellow. It can be added to foods, foods and drinks, cosmetics and the like to increase its commercial value.

The mixing ratio to the cooling sensation compound is not particularly limited depending on the intended effect of improvement, but generally it may be used in the range of 10 to 80% by weight.

Examples of the oral composition containing the refreshing agent of the present invention include various forms such as dentifrices such as powder toothpaste, lubricating toothpaste, toothpaste, gargle, chewing gum and the like. In such an oral composition, the cooling sensation compound is generally added in an amount of 0.1 to 4.0% by weight, but the cooling sensation improving agent of the present invention, 2-methyl-3- (1-menthoxy) propane- The amount of the 1,2-diol varies depending on the form, but it is preferably about 0.01 to 3% by weight, preferably 0.1 to 2% by weight.

In such an oral composition, in addition to the above-mentioned refreshing sensation improver, as a cooling sensation compound, usually, peppermint oil, spearmint oil, 1-menthol, carvone, mentone, anethole, camphor, 1,8- Although a fragrance such as cineol is used, an arbitrary component according to the purpose of use can be blended as other components. For example, in the case of chewing gum, in addition to the gum base, sweeteners such as sugar and stevioside, and active ingredients such as flavonoids can be appropriately compounded according to a conventional method. Similarly, in dentifrices, gargles and the like, components according to the type of product can be appropriately compounded.

Examples of the food or drink containing the refreshing agent include ice cream, sherbet, jelly, hard candy, refreshing drink and the like. In such foods and drinks, the cooling sensation compound is 0.01% in total.
The amount of 2-methyl-3-l-menthoxypropane-1,2-diol (1) varies depending on the form, but is about 0.01 to 3% by weight, preferably 0 to 3% by weight. 0.1 to 2% by weight.

In such foods and drinks, in addition to the above-mentioned refreshing sensation improver, as a cooling sensation compound, peppermint oil, spearmint oil, eucalyptus oil, l-menthol, menthon, 1,8-cineole and the like are used. Compounds such as peppermint oil and l-menthol are blended in carbonated beverages, but any other components can be used according to the intended use as other components. For example, in the case of a hard candy, in addition to a base such as granulated sugar, starch syrup, and water, a fragrance such as a cider fragrance and the like can be appropriately compounded according to a conventional method. Similarly, in ice cream, sherbet, jelly, soft drinks, and the like, components according to the type of product can be appropriately compounded.

Examples of the cosmetics of the present invention include various lotions such as astringent lotion, various lotions such as aftershave lotion, emulsions, various creams such as massage creams and nutritional creams, eye packs and paste-like rinses. Various packs such as packs, hair tonics, pomades, shampoos, rinses, treatments, and hair cosmetics such as hair creams, as well as facial cleansers, other soaps, antiperspirants, deodorants and the like can be mentioned.

In such cosmetics, as the cooling sensation compound, peppermint oil, spearmint oil, l-menthol, menthon, 1,8-cineole and the like are used.
The compounding amount is usually 0.01 to 5% by weight of the whole, but 2-methyl-3-l-menthoxypropane-
The amount of the 1,2-diol varies depending on the form, but is 0.01 to 5% by weight, preferably 0.7 to 3% by weight.
% By weight.

As the other components, any components can be used according to the purpose of use. For example, in the case of a cream, other than an emulsifier, a fragrance, a preservative, and a pigment, if necessary, a nutrient, a humectant, an ultraviolet ray inhibitor and the like can be appropriately compounded according to a conventional method. Similarly, lotions, lotions,
In milky lotions, packs, hair cosmetics, soaps, antiperspirants, deodorants, etc., components according to the types of products can be appropriately compounded.

Further, the compound of the present invention is expected to be incorporated into pharmaceuticals. For example, it is expected to be incorporated into external preparations such as aerosol preparations, cataplasms, and ointments.

[0032]

EXAMPLES Next, the present invention will be described specifically with reference to examples, but the present invention is not limited to these examples.

The analysis in the examples was performed using the following analytical equipment. Gas chromatogram: 5890-A (manufactured by Hewlett-Packard) Column: Chemical bonded column OV-1 25 mm × 0.25 mm, ID 0.15 mm (manufactured by GL Sciences Inc.) Temperature: 70 to 220 ° C. (heating at 4 ° C./min) Optical rotation: DIP-370 type (JASCO Corporation) Proton nuclear magnetic resonance spectrum (1H-NMR): AM-40
Type 0 (400MHz) (Brucker)

Synthesis Example 1 2-Methyl-3- (l-menthoxy) -1,2-dio
1) Synthesis of 2-methyl-3- (1-menthoxy) -1-propene (4) To a solution of 2000 ml of toluene and 168 g (4.2 mol) of sodium hydride (containing 62% by weight in paraffin) A solution of 624 g (4 mol) of l-menthol (2) and 800 ml of toluene is added dropwise over 1.5 hours under reflux of toluene (if xylene is used instead of toluene, keep the temperature in the range of 110 to 120 ° C. Drip). After reacting at the same temperature for 30 minutes after the dropwise addition, 400 g (4.4 mol) of 2-methylpropenyl chloride (3) is added dropwise over 30 minutes while maintaining the temperature at 105 to 110 ° C., and then the reaction is carried out at the same temperature for 4 hours. After the reaction, the solution was cooled to room temperature, 30 ml of methanol was added and stirred to quench excess sodium hydride, and 800 ml of water was added.
Stir for 0 minutes, allow to stand, separate the toluene layer and separate.
Then, the toluene solution is distilled under a low vacuum to recover toluene to obtain 990 g of crude 2-methyl-3- (1-menthoxy) -1-propene (4). Distill this under high vacuum, boiling point
2-methyl-3- (l-menthoxy) -1-purified at 76 ° C / 2mmHg
781.2 g (93 theoretical%) of propene (4) are obtained.

[Α] _D ²⁵ = −100.2 ° (c = 1, EtOH) IR (NaCl, cm ⁻² ): 3075,1800,1655,1455,1370,1340,132
0,1235,1180,1110,1055,1005,975 MS (m / z, 20 eV): M ⁺ = 210 (0), 154,139,138,125,97,95,
83,81,57,43 NMR (CDCl _3, δppm): 0.77 (d, 3H, J = 7.0), 0.79-1.02 (m, 3
H), 0.89, 0.92 (dd, 6H, J = 7.0), 1.26 (m, 1H), 1.34 (m, 1
H), 1.75 (s, 3H), 1.59-1.67 (m, 2H), 1.75 (s, 3H), 2.07-
2.13 (m, 1H), 2.22-2.30 (dq, 1H.J = 7.0), 3.03-3.10 (dt, 1
H, J = 10.7), 3.76,4.01 (d, 2H), 4.84,4.96 (s, 2H)

2) 2-methyl-3- (1-menthoxy)
Synthesis of propane-1,2-diol (1) 1.05 kg (5 mol) of 2-methyl-3- (1-menthoxy) propene (4) obtained in 1) and 1.15 kg (25% by weight) of formic acid
Mol) 35% by weight aqueous hydrogen peroxide solution at 50 ° C
g (6 mol) is added dropwise over 4 hours, and after the addition, the reaction is continued at the same temperature for 2 hours. After the reaction, add 2,000 ml of cold water, stir, let stand, and separate and separate the oil layer. 100m of separated oil layer
After washing with 1 l of cold water, the solution is added to a solution of 504 g (12.6 mol) of sodium hydroxide and 2500 ml of water, and heated under reflux for 2 hours to hydrolyze. After cooling, extract the oil layer with toluene and wash with water,
The toluene was recovered by distillation under low vacuum and the crude 2-methyl-3
-(l-3-menthoxy) propane-1,2-diol (1) 1.15
gain kg. This was distilled under high vacuum to obtain 650 g (53 theoretical%) of 2-methyl-3- (1-menthoxy) propane-1,2-diol (1) purified at a boiling point of 125 ° C./0.9 mmHg.

[Α] _D ²⁵ = −77 ° (c = 1, EtOH) d ₂₀ ²⁰ = 0.981, n _D ²⁰ = 1.471 IR (NaCl, cm ⁻¹ ): 3400,1460,1390,1375,1115,1096 , 106
0,1015,923,850 MS (m / e, 20eV): M ⁺ = 244,139,138,97,95,85,75 (100), 7
1,69,57,55 CI-MS M ⁺ + 1 = 245 NMR (CDCl _3, δ ppm): 0.76-0.79 (dd, 3H, J = 7.0), 0.81-
1.03 (m, 3H), 0.89-0.92 (dd, 6H, J = 7.0), 1.12,1.13 (ds, 3
H), 1.21-1.27 (m, 1H), 1.35 (m, 1H), 1.59-1.69 (m, 2H),
1.75 (s, 3H), 2.05-2.18 (m, 2H), 2.50,2.59 (dq, 1H), 2.7
8, 2.87 (ds, 1H), 3.02-3.10 (m, 1H), 3.22, 3.33, 3.55,
3.68 (m, 2H), 3.40-3.46,3.58-3.64 (m, 2H)

[Example 1, Comparative Example 1] Preparation and evaluation of an aqueous solution of l-menthol 9.95 ppm + 2-methyl-3- (l-menthoxy) propane-1,2-diol 10.05 ppm l-menthol 0.995 g and 2- 100 ml of 1.005 g of methyl-3- (1-menthoxy) propane-1,2-diol
Take in a volumetric flask and dissolve in
And 1 ml of the solution was placed in a 1000 ml volumetric flask and made up to 1000 ml with distilled water.

Ten expert panelists who had experienced for more than 10 years contained 10 ml of the above-mentioned aqueous solution in their mouth, and this time was set to 0 second, and the strongest strength (coolness, irritation) was evaluated on a five-point scale. The average of 10 panelists was taken as the evaluation value. The result is shown in FIG.

For comparison, 1 g of l-menthol was added to 100 ml
Take in a volumetric flask, dissolve in
Fill up to prepare a 1% solution, and add 1 ml of the solution
Take in a 1000 ml volumetric flask and make up to 1000 ml with distilled water.
A ppm aqueous solution was prepared, and similarly, a sensory test was conducted by 10 panelists (Comparative Example 1). The results are shown in FIG.

Example 2 Hand cream 2-ml prepared separately from 0.9 ml of the above-mentioned 1-menthol 1% solution
0.1 ml of a 1% solution of methyl-3- (l-menthoxy) propane-1,2-diol was added dropwise with stirring to 100 g of a hand cream prepared according to the following formulation, mixed uniformly, and mixed with 90 ppm of l-menthol. And 2-methyl-3-
(L-menthoxy) propane-1,2-diol 10ppm
Was prepared. Similarly, l
1 ml of a 1% menthol solution was taken and mixed with 100 g of the following hand cream to prepare a hand cream containing 100 ppm of 1-menthol.

[0042]

About 0.2 g of the obtained hand cream was weighed, applied to a gauze, stuck on the back of one hand of a paneler, and a blank was stuck on the back of the other hand as a control, and the irritation degree was 4 It was evaluated on a scale.
Table 1 shows the results.

[0044]

[Table 1]

[Embodiment 3]

According to the above formula, each component was mixed in a blender to prepare a toothpaste. When used as toothpaste,
Excellent cooling effect (lasting effect) was obtained.

Embodiment 4

Each ingredient was kneaded with a kneader according to the above-mentioned formula to prepare a chewing gum. Compared to those without l-menthol and 2-methyl-3- (l-menthoxy) propane-1,2-diol, the chewing gum obtained showed a foaming sensation similar to the irritation of drinking cider on a cola flavor. Was added, leaving a refreshing feeling in the mouth for a long time.

Embodiment 5

The component A of the above formulation was blended, heated to 150 ° C. under normal pressure at normal pressure, cooled, and added with the component B before solidifying to prepare a hard candy. l-menthol and 2-methyl-3- (l-menthoxy) propane-1,2-
When compared with those containing no diol, the hard candy of the present invention had a mild spinyness of cider flavor, a noticeable foaming sensation similar to the stimulus when drinking cider, and a refreshing sensation was maintained. .

Embodiment 6

Solution A and Solution B were uniformly dissolved at room temperature to prepare Solution A and Solution B. Solution A was gradually added while stirring, solubilized, and filtered. Make up lotion. When used as a lotion, an excellent cooling effect (persistence and less irritating effect) was obtained.

[0053]

The refreshing agent of the present invention, 2-methyl-3
-(L-menthoxy) propane-1,2-diol is
For human skin, mucous membranes, give a refreshing and cool cooling sensation or refreshing sensation, enhance the persistence of conventional cooling sensation agents, and oral compositions containing this with a cooling sensation agent,
Foods and beverages and cosmetics maintain a refreshing sensation, reduce irritation, and have an increased commercial value.

[Brief description of the drawings]

FIG. 1 shows the results of a five-level evaluation of a sensory test of Example 1 and Comparative Example 1.

────────────────────────────────────────────────── ─── of the front page continued (51) Int.Cl ⁷ identification mark FI // C07C 43/196 C07C 43/196 (58 ) investigated the field (Int.Cl. ^7, DB name) C11B 9/00 -. 9 / 02 A61K 7/00-7/46 CA (STN) REGISTRY (STN)

Claims (3)

(57) [Claims] 1. A refreshing sensation improver comprising 2-methyl-3- (1-menthyloxy) propane-1,2-diol. 2. An oral composition, a food or drink or a cosmetic containing 0.01 to 10% by weight of 2-methyl-3- (1-menthyloxy) propane-1,2-diol. 3. A method for improving the refreshing sensation of an oral composition, a food or drink or a cosmetic containing 0.01 to 10% by weight of 2-methyl-3- (1-menthyloxy) propane-1,2-diol.