JP3245748B2 - P-menthane derivative and cooling sensate containing the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel menthane derivative having a cooling effect, a cooling sensation agent and a cooling sensation composition containing the same.

[0002]

2. Description of the Related Art Menthol, which is a main component of peppermint oil, has been known as a compound having a so-called cooling effect, which gives a physiologically cold feeling to the skin and the mucous membrane of the mouth. It is widely used in foods, beverages, toothpaste, tobacco, etc., and as a cooling agent in various cosmetics, paints and the like.

[0003] The cooling effect of menthol is not due to latent heat during vaporization, but rather to the physiological effect of menthol acting directly on sensory nerve peripheral parts of the human body, that is, menthol feels the cold of peripheral nerves. It is thought that stimulation is directly applied to the sensory receptors, which in turn stimulates the central nervous system.

As mentioned above, menthol has a well-established use as a physiological cooling sensation agent, but its cooling action is transient and non-persistent, has sublimability, and has a unique When blended in cosmetics or the like because of its strong mint odor, the elegant fragrance of the cosmetics is often impaired, and there has been a problem that the range of use is limited.

[0005] Under such circumstances, researches on substances which have a physiological cooling effect on the skin have been actively conducted in recent years, and menthol is a compound which gives a cooling sensation and has a weak aroma instead of menthol. Odorless compounds obtained by chemical modification of JP-A-47-16647 and JP-A-47-647.
No. 16649, JP-B-51-12690, JP-A-51-15098, JP-A-58-88334, JP-A-61-194049, and JP-A-2-29082.
No. 7), tricyclic alcohols (JP-A-58-934).
No. 54, No. 58-95194), tricyclic amides (JP-A-60-136544), N-substituted ureas (JP-A-50-142737), and the like.

[0006] However, even these substances are not sufficiently satisfactory in terms of the strength, persistence and fragrance of the cooling action, and when mixed with cosmetics and the like, there are some substances which cause a hot flash.

[0007]

Means for Solving the Problems The present inventors have conducted sincere studies to overcome the above-mentioned problems, and as a result, have found that a compound 3-substituted-p derived from 3-hydroxymethyl-p-menthane has been obtained.
-It has been found that the menthane derivative has a sufficiently satisfactory action and the fragrance is extremely weak, and the present invention has been completed.
That is, the present invention provides the following general formula (I) (Wherein, R ¹ and R ² represent a hydrogen atom or a linear or branched alkyl group having 1 to 5 carbon atoms, and R ³ represents a 1 to 5 carbon atom.
Represents a linear or branched alkyl group. ), A cooling sensation agent and a cooling sensation agent composition containing the same.

The 3-substituted-p-menthane derivative of the present invention is represented by the above general formula (I), wherein R ¹ , R ² , and R ³ represent a straight-chain having 1 to 4 carbon atoms. Examples of the linear or branched alkyl group include a methyl group, an ethyl group, an n-propyl group, an iso-propyl group, and a t-butyl group.

The 3-substituted-p-menthane derivative of the present invention can be produced, for example, by the following method. That is, 3-hydroxymethyl-p-menthane (I
By reacting I) with the glycine derivative (III) in the presence of an acid such as sulfuric acid, paratoluenesulfonic acid, boron fluoride etherate at 20 to 200 ° C, preferably 50 to 150 ° C for several hours to several tens of hours, The 3-substituted-p-menthane derivative (I) of the present invention can be obtained. In this reaction, the glycine derivative (III) is used in an equivalent amount or an excess amount with respect to 3-hydroxymethyl-p-menthane (II), and water produced using benzene or toluene as a solvent is separated from the reaction system by azeotropic distillation. And the acid is preferably from 0.05 to glycine derivative (III).
It is preferable to use 5 times equivalent. After completion of the reaction, the organic phase is separated by diluting with water, washing and drying, and the solvent is distilled off under reduced pressure. Finally, recrystallization with hexane or the like or distillation under reduced pressure gives purified 3-substituted-p. -A menthan derivative (I) is obtained.

The cooling sensation agent of the present invention comprises 3-substituted-p-
Menthane derivative alone, or as a solution of alcohol, propylene glycol, benzyl benzoate, etc., or as an emulsion mixed with an emulsifier, or as a powder adsorbed on starch, talc, etc., or a low-boiling hydrocarbon or a low-boiling halogen hydrocarbon It is manufactured as an aerosol propellant. The cooling sensation agent may further contain other components such as a preservative, an antioxidant, a fragrance, a coloring agent, a surfactant and the like as long as the cooling action of the menthane derivative is not impaired.

Although the cooling sensation agent of the present invention can be used as it is, it is generally used as a pharmaceutical such as an ointment, a patch, an internal medicine, and the like: cosmetics such as creams, lotions, powders, hair tonics, shampoos, and lipsticks: Toothpaste, mouthwash: It is preferable to use it as a cool sensation composition which is added to foods such as chewing gum, candy, frozen desserts and soft drinks to give a cooling effect. The amount of the present cooling sensation agent is not particularly limited, but is preferably used in the range of 0.01 to 10% by weight at the time of use.

[0012]

The 3-substituted-p-menthane derivative of the present invention has the same cooling effect as menthol. Further, it is a compound which is not sublimable and is very stable like menthol, and also has a weak scent which is not stimulating.

[0013]

EXAMPLES The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples. Example 1 Synthesis of N-acetylglycine menthan methyl ester N-acetylglycine (8.3 g, 70.5 mmol)
l), 3-hydroxymethyl-p-menthane (10.0
g, 58.7 mmol) and 170 ml of benzene in a mixture of paratoluenesulfonic acid (0.3 g, 1.7 mmol).
1) and refluxed for 6.5 hours. After allowing to cool, dilute with water and separate the organic layer. After washing with an aqueous sodium hydrogen carbonate solution and drying over anhydrous magnesium sulfate, the solvent was distilled off to obtain a colorless oil. This is 15mm at 4mmHg
By subjecting the mixture to a vacuum treatment at 0 ° C. or more, the target N-acetylglycinementhane methyl ester which was pure in terms of analysis was obtained as a colorless oil. (10.8 g, 69% yield) MS (M / e): 269 (M + 1) NMR (CDCl 3, ppm): 0.78 (3H, d) 0.90~0.91 (6H, m) 0 .80 to 1.10 (5H, m) 1.35 (1H, m) 1.65 to 1.87 (4H, m) 2.05 (3H, s) 3.99 to 4.23 (4H, m) ) 5.98 (1H, s)

Example 3 Patch Each of the above components was heated and mixed to form a paste, which was then spread on a base fabric to prepare a poultice. It had a cool sensation and sustained a cool sensation.

Example 4 Hair Tonic The above composition was mixed and made uniform to prepare a hair tonic. When this hair tonic was applied to the scalp, an exhilarating cooling sensation was maintained even after the cooling effect by the evaporation of ethanol was over.

Example 5 Cooling agent A cooling sensation agent having the above composition was prepared. This gave a persistent cooling sensation when applied to the skin.

Example 6 Skin lotion The above components were mixed to prepare a skin lotion. When this was used on the skin, it was not irritating and gave a refreshing cooling effect to the skin, and the cooling sensation was maintained even after ethanol evaporated.

Example 7 Toothpaste The above components were mixed to prepare a toothpaste. When this was used, a refreshing refreshing sensation without bitterness spread in the mouth and lasted for a long time.

Example 8 Shampoo The above components were stirred and dispersed to prepare a shampoo. When this shampoo was used, a refreshing cool feeling was maintained on the scalp even after use.

[0020]

The novel 3-substituted-p-menthane derivative obtained according to the present invention has the same cooling effect as menthol. Further, it is a very stable compound without sublimation like menthol. In addition, the compounds of the present invention are used as a cooling sensation agent or a cooling sensation composition in applications such as pharmaceuticals, quasi-drugs, cosmetics, foods, etc., because they exhibit a weak aroma instead of an irritating one.

──────────────────────────────────────────────────の Continuing on the front page (51) Int.Cl. ⁷ Identification code FI C09K 3/00 C09K 3/00 B (72) Inventor Akira Nakagawa 408 Tashiro Daikancho, Tosu City, Saga Prefecture Hisamitsu Pharmaceutical Co., Ltd. Examination Takeshi Kanmi (56) References JP-A-61-194049 (JP, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) CA (STN) CAOLD (STN) REGISTRY (STN)

Claims (3)

(57) [Claims] 1. Formula (I) (Wherein, R ¹ and R ² represent a hydrogen atom or a linear or branched alkyl group having 1 to 5 carbon atoms, and R ³ represents a 1 to 5 carbon atom.
Represents a linear or branched alkyl group. A) 3-substituted-p-menthane derivative; 2. A cooling sensate comprising the 3-substituted-p-menthane derivative according to claim 1. 3. A cooling composition comprising the 3-substituted-p-menthane derivative according to claim 1.