JP2016023284A - Ws-12 fine particle and cool-feeling agent composition containing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a WS-12 ((1R,2S,5R)-N-(4-methoxyphenyl)-2-isopropyl-5-methylcyclohexane carboxamide), which is though known as a cool-feeling agent, fine particle that solves the problem that WS-12 does not provide cool-feeling even when the usually available powder having an average particle size of 100 μm is directly taken up into mouth cavity, and that it has a high melting point and is difficult to be dissolved into water, oil or other many solvents, and it was difficult to achieve the cool-feeling effect.SOLUTION: An aggregate of powder is obtained by comminuting WS-12 by use of a grinder such that the average particle size (median size) as measured by a laser diffraction and scattering particle size distribution measuring apparatus is 0.01 μm to 50 μm; the aggregate provides, when taken up into mouth cavity, an extremely strong cool-feeling and the cool-feeling continues for a long period of time.SELECTED DRAWING: None

Description

  The present invention relates to a powder comprising an aggregate of fine particles of WS-12 ((1R, 2S, 5R) -N- (4-methoxyphenyl) -2-isopropyl-5-methylcyclohexanecarboxamide), which is a cooling sensation substance, and It is related with the composition to contain. More specifically, fine powder which is easily dissolved in a solvent such as water, oil, organic solvent, etc., and finely pulverizes WS-12 that is less likely to exhibit the action as a cooling sensation agent. The present invention relates to a cooling sensation agent composition containing the same.

  A cooling sensation gives the human skin, especially the mouth, nose, and throat a cool and refreshing feeling, so it has a cool and cool sensation in foods such as chewing gum, candy, confectionery, and beverages, as well as in toothpaste, cosmetics, and pharmaceuticals. It is widely used for the purpose of imparting.

  Menthol is most widely used as a cooling sensation agent, and in order to produce a strong cooling sensation using menthol, increasing the amount of menthol is the simplest and most effective, but a large amount of menthol is used. However, it is difficult to use in large quantities alone, because the cold feeling is enhanced, but the drawbacks such as strong irritation, volatility, strong mint smell, and bitter taste are conspicuous. is there.

  Therefore, various cooling sensates with relatively few defects inherent in menthol have been found in nature, or have been developed by synthetic methods and are actually used. Among the compounds having the action as a cooling sensation agent, for example, menthone acetate, isopulegol, 1,8-cineole, etc., menthyl acetate, menthyl lactate, menthyl salicylate, monomenthyl succinate, glutaric acid Menthol esters such as monomenthyl and monomenthyl adipate; N-ethyl-p-menthane-3-carboxamide (WS-3), ethyl 3- (p-menthane-3-carboxamide) acetate (WS-5), N Cyclic carboxamides such as tert-butyl paramentane carboxamide (WS-14); Acyclic carboxamides such as N, 2,3-trimethyl-2-isopropylbutanamide (WS-23); Menton ketal, Menton Substituted p-menthane such as glycerol ketal And the like.

  WS-12 ((1R, 2S, 5R) -N- (4-methoxyphenyl) -2-isopropyl-5-methylcyclohexanecarboxamide: CAS-RN 68489-09-8, FEMA number 4681) is a 3-substituted-para -It is a cooling sensation agent developed as one of the menthane compounds, and the cooling sensation threshold is considered to be a very low concentration (patent document 1). WS-12 has an extremely strong cooling effect and duration, has a small aroma, and is moderately stimulated. It is also known to be a specific TRPM8 agonist selected from TRPM8 agonist antibodies (Non-patent Document 1).

  WS-12 is known to have various uses as a cooling sensation agent. For example, it is used for treating skin (Patent Document 2), chewing gum (Patent Document 3), and a pharmaceutical composition for treating dry eye (Patent Document 3). Patent Document 4), razor blade applications (Patent Document 5), skin irritation mitigation applications (Patent Document 6), and the like have been proposed.

Cell Calcium 41 (3) (2007), p.285-294

U.S. Pat. No. 4,136,163 US Patent Application Publication No. 2005/087211 International Publication No. 2011/159935 Special table 2013-537887 gazette International Publication No. 2014/052390 US Patent Application Publication No. 2014-0134113

  WS-12 has a very low cooling sensation threshold, has a very strong cooling sensation and duration, has low aroma, is moderately irritating, and is known for a variety of uses. In fact, it is actually not so widely used in the market. Accordingly, an object of the present invention is to promote utilization of WS-12, which is a very useful compound as a cooling sensation substance, as a cooling sensation agent. Another object is to provide WS-12 in a form that can be easily used as a cooling sensation agent.

  As a reason why WS-12 is difficult to use, the present inventors have found that WS-12 has a higher melting point (163 to 177 ° C.) and lower solubility than other general cooling agents such as menthol. (Insoluble in water, fats and oils, approximately 2% in ethanol, approximately 2% in dimethylformamide), handling is inconvenient, that is, as a cooling sensation agent even when blended directly into various foods and drinks It was thought that the big factor was that the effect was not sufficiently exhibited.

  The present inventors contacted commercially available WS-12 powder (average particle diameter (median diameter) of about 100 μm when measured using a laser diffraction / scattering particle size distribution analyzer) directly to the oral mucosa and skin. As a result, it was confirmed that the feeling of coldness was hardly felt contrary to expectations. Moreover, even when commercially available WS-12 powder is dispersed in water together with an emulsifier, emulsified particles are prepared, dried to obtain an emulsified powder, and this is directly brought into contact with the oral mucosa and skin, a cold feeling is still felt. Confirmed that there is no. For example, in the case of menthol (melting point: 40 ° C.), fine particles of an emulsion (about 0.2 to 10 μm) can be prepared by emulsifying with an emulsifier after heating and melting. Since menthol is in a finely dispersed state when coming into contact with the skin, it tends to exert a cooling effect. On the other hand, since WS-12 has a high melting point, it was practically impossible to emulsify after melting like menthol. Considering the solubility of WS-12 in ethanol (about 2%), a method of diluting in water after dissolving in ethanol is conceivable, but actual dissolution requires a longer time than expected from the solubility. did. In addition, when ethanol is used as a solvent, ethanol itself hinders emulsification, and it is difficult to produce WS-12 emulsified capsules. Furthermore, since it is very expensive to remove ethanol used as a solvent on an industrial scale, it can be said that it is practically difficult to blend it into a dry food such as chewing gum after dissolving the ethanol.

  The present inventors have intensively studied to solve the above-mentioned problems. As a result, surprisingly, when commercially available WS-12 powder (about 100 μm) was pulverized into particles of about 1 μm by a pulverizer and the pulverized product was directly brought into contact with the oral mucosa and skin, extremely cold The present inventors have found that a feeling can be felt, a stimulus is moderate, and a feeling of cooling lasts for a very long time, and the present invention has been completed.

Thus, the present invention provides the following.
(1) WS-12 ((1R, 2S, 5R) -N- having an average particle diameter (median diameter) of 0.01 μm to 50 μm when measured using a laser diffraction / scattering particle size distribution analyzer. (4-methoxyphenyl) -2-isopropyl-5-methylcyclohexanecarboxamide) fine powder.
(2) The powder of (1) obtained by pulverizing WS-12 with a dry pulverizer.
(3) A paste-like composition in which the powder of (1) is dispersed, obtained by pulverizing a mixture of WS-12 and a liquid medium with a wet pulverizer.
(4) An emulsified composition obtained by emulsifying the powder or paste composition according to any one of (1) to (3).
(5) A powder composition obtained by drying the paste-like composition or emulsion composition of (3) or (4).
(6) A cooling sensation agent composition containing the powder, paste-form composition, emulsion composition or powder composition according to any one of (1) to (5) as an active ingredient.
(7) Food / beverage products, cosmetics or pharmaceuticals containing the cooling sensation agent composition of (6).

  According to the present invention, WS-12, which has not been able to exert a function as a cooling sensation agent even when directly blended with foods, beverages, cosmetics or pharmaceuticals, is directly used as a cooling sensation agent composition in an easily handled state. It can be added to foods, drinks, cosmetics or pharmaceuticals. In addition, when the product of the present invention is blended with a food, drink, cosmetic or pharmaceutical product, it is excellent in that a strong cooling effect can be imparted to the food product, cosmetic product or pharmaceutical product over a long period of time with moderate irritation and low odor. It has the effect. In addition, the product of the present invention can exert its cooling effect advantageously when blended with chewing gum.

  Embodiments of the present invention will be described below.

  WS-12 used in the present invention is (1R, 2S, 5R) -N- (4-methoxyphenyl) -2-isopropyl-5-methylcyclohexanecarboxamide, CAS-RN 68489-09-8, FEMA number. 4681 is a compound provided. WS-12 can be prepared, for example, by the synthesis method described in German Patent Application Publication No. 102012202885, or can be purchased as a commercial product. Such commercial products can be obtained from Renessenz, Santa Cruz, Torcris Bioscience, and the like.

  WS-12 obtained as a synthesis method or as a commercial product is crystalline or powdery, but the average particle size varies depending on the crystallization method and product, and it cannot be generally stated, but laser diffraction / scattering type particle size distribution The average particle diameter (median diameter) when measured using a measuring apparatus is about 100 μm to 500 μm.

  In the present invention, these WS-12s are pulverized from an aggregate of fine particles having an average particle diameter (median diameter) of 0.01 μm to 50 μm as measured using a laser diffraction / scattering particle size distribution analyzer. It is characterized in that it becomes a powder.

  Since WS-12 is extremely insoluble in water (generally insoluble in water), a commercially available WS-12 powder (an aggregate of particles of about 100 μm to 500 μm) is brought into contact with human skin and mucous membranes. However, it is considered that only a very small part of the surface of the particle is dissolved. In the case of an aggregate of particles having a constant mass, the surface area is relatively small when the average particle size is large, and the surface area is relatively large when the average particle size is fine. Therefore, in the aggregate of particles of a substance having low solubility such as WS-12, when the average particle size is large, a phenomenon in which only a very small part of the surface of the particle is dissolved is considered to be more remarkable. In this case, the particles in the center after only a very small part of the surface is dissolved are poured from the oral cavity into the esophagus and stomach by swallowing, and do not exert a cooling effect on the oral cavity. In contrast, as the average particle size decreases, the surface area per mass is relatively large, and even if it has only very low solubility, a greater amount is believed to dissolve. As a result, the concentration of WS-12 in the oral cavity increases, exerts a cooling effect in the oral cavity, and less undissolved particle portions are swallowed from the oral cavity to the esophagus and stomach by swallowing.

  The preferred average particle size (average particle size as measured using a laser diffraction / scattering particle size distribution measuring device) of the powder comprising the aggregate of fine particles in the present invention is 0.01 μm to 50 μm, preferably 0.05 μm. -30 μm, more preferably 0.1 μm-20 μm, still more preferably 0.2 μm-10 μm. When the average particle diameter exceeds 50 μm, the effect as a cooling sensation agent is not obtained so much. In general, the smaller the average particle diameter (median diameter), the greater the effect as a cooling sensation agent, but it is extremely difficult to make it less than 0.01 μm. In the case of dry pulverization, the powder itself This is not preferable because the jet property of the powder is increased and it may become difficult to handle the powder. Further, the 90% cumulative particle diameter of the powder composed of the aggregate of fine particles is preferably about 0.1 μm to 50 μm.

  There are many ways to determine the average particle size, and the simplest average method is to divide the total diameter of all particles by the solid number of the particles (solid number average). In this case, there are many small particles. Sometimes it has a very small diameter. Therefore, in many cases, an accumulated average particle diameter (median diameter or median diameter or D50 or the like) which means a diameter giving a height of 50% in the cumulative distribution chart is used. Furthermore, when obtaining from a cumulative distribution chart, volume basis and mass basis can be considered, but the average particle size in the present invention is the average particle size when measured on a volume basis using a laser diffraction / scattering type particle size distribution measuring device ( Median diameter). Furthermore, there are a wet method (a method in which powder is dispersed in an insoluble solvent) and a dry method (a method in which powder is directly measured) as measurement methods, but the average particle size of the present invention is water. It is the value measured using the wet method by a flow type used as a solvent.

  As a method for preparing a powder comprising an aggregate of fine particles of WS-12 in the present invention, the above-mentioned synthetic product or commercially available WS-12 is made into fine particles by a physical method using a pulverizer. Can be illustrated. Examples of the pulverization method include dry pulverization in which WS-12 is pulverized as it is, or wet pulverization in which WS-12 is dispersed in a fluid medium and then pulverized. When wet pulverization is performed, the pulverized product comprising the aggregate of fine particles of the present invention can be obtained as a paste-like composition in which a powder comprising an aggregate of WS-12 fine particles is dispersed in a fluid medium. .

  Examples of the dry pulverization include a method of using a device that can pulverize a solid material to an average particle size (median diameter) of 50 μm or less to obtain a powder composed of an aggregate of fine particles. Any apparatus can be used as long as the apparatus can pulverize the particle diameter (median diameter) to 0.01 μm to 50 μm. Examples of these commercially available pulverizers include fluidized bed jet mill JEDI (Earth Technica), continuous dry bead mill Dry Star SDA (registered trademark: manufactured by Ashizawa Finetech), Micro ACM Pulverizer AC- 30H (registered trademark: manufactured by Hosokawa Micron Corporation), Micron Jet MJ-3 type (registered trademark: manufactured by Hosokawa Micron Corporation), Micros (MIC) (registered trademark: manufactured by Nara Machinery Co., Ltd.), New Cosmizer (COS) (registered trademark) : Nara Machinery Co., Ltd.), Single Track Jet Mill, Jet Oh Mill (above, Seisin Enterprise Co., Ltd.), Super Jet Mill / SJ Series (Nisshin Engineering Co., Ltd.), Nano Jet Mizer (Aisin Nano Technologies Co., Ltd.), etc. It can be illustrated.

  As a fluid medium in wet pulverization, WS-12 is not particularly limited because it is insoluble in many solvents, and can be used as long as it is fluid at room temperature. Water, glycerin, propylene glycol, sorbitol Edible media such as aqueous solutions and edible oils and fats are preferred, and these may be used in combination. When water is used as a medium, WS-12 is difficult to disperse with water alone, so it is preferable to dissolve a water-soluble emulsifier such as gum arabic or modified starch in advance. 1 to 20 parts by mass of these fluid media is added to 1 part by mass of WS-12, dispersed, and poured into a wet pulverizer while flowing, so that WS-12 is a laser diffraction / scattering type particle size distribution measuring device. By using a device that can be pulverized to an average particle diameter (median diameter) of 0.01 μm to 50 μm or less when measured using a powder, the powder composed of the aggregate of WS-12 particles is dispersed. A pasty composition can be obtained.

  Examples of the apparatus that can be used for wet grinding include a container drive medium mill and a medium agitation mill. Examples of the container drive medium mill include a rolling ball mill, a vibrating ball mill, a planetary ball mill, a centrifugal fluidizing mill, and the like, and examples of the medium agitating mill include a tower pulverizer, a stirring tank mill, a flow tank mill (horizontal type). , Vertical type), annular mill, and the like. In any of these apparatuses, miniaturization by wet pulverization is possible. Specific examples of such a pulverizer include a bead mill (manufactured by Imex), a dyno mill (DYNO (registered trademark) -MILL) manufactured by WAB (Shinmaru Enterprises), and a sand mill.

  The paste-like composition containing the powder of the aggregate of WS-12 or the powder of the aggregate of the fine particles obtained in this way can be incorporated into foods, beverages, cosmetics or pharmaceuticals as it is, The effect can be exerted. However, since WS-12 itself has a low polarity and is insoluble in water, by emulsifying these to obtain an emulsified composition, it is possible to exhibit a cooling effect more effectively.

  In order to obtain an emulsified composition, an emulsifier is added to the paste-like composition containing the powder or aggregate of fine particles of WS-12 according to the present invention, if necessary, and emulsified. Can be obtained. The emulsifier is not particularly limited, and various emulsifiers conventionally used in foods and drinks, for example, fatty acid monoglyceride, fatty acid diglyceride, fatty acid triglyceride, propylene glycol fatty acid ester, sucrose fatty acid ester, polyglycerin fatty acid ester , Lecithin, modified starch, sorbitan fatty acid ester, polysorbate, quilaya extract, gum arabic, tragacanth gum, guar gum, caraya gum, xanthan gum, pectin, alginic acid and its salts, carrageenan, gelatin, casein and the like. Moreover, examples of the apparatus used for the emulsification treatment include a homomixer, a colloid mill, a rotating disk type homogenizer, a high-pressure homogenizer, and the like. By emulsifying using these, an emulsion having excellent stability can be obtained. The amount of emulsifier used is not strictly limited and can be varied over a wide range depending on the type of emulsifier used, etc., but is usually WS-12 of the present invention (in the case of a paste-like composition, WS-12) is contained in an amount of 0.01 to 100 parts by weight, preferably 0.1 to 50 parts by weight per 1 part by weight. In order to stabilize the emulsification, the water-soluble solution is one of polyhydric alcohols such as glycerin, propylene glycol, sorbitol, maltitol, sucrose, glucose, trehalose, sugar solution, and reduced starch syrup, in addition to water. A seed or a mixture of two or more can be blended.

  Moreover, the emulsion thus obtained can be made into a powder composition by drying by a drying method such as spray mist drying (spray drying), vacuum drying, freeze drying or the like, if desired. In obtaining the powder composition, saccharides such as trehalose, dextrin, sugar, lactose, glucose, starch syrup, and reduced starch syrup can be appropriately added to the emulsion composition as necessary. The amount of these used can be suitably selected according to the properties desired for the powder composition.

  Further, the powder of the WS-12 fine particle aggregate of the present invention, the paste composition, the emulsion composition or the powder composition in which the powder of the fine particle aggregate is dispersed, particularly the emulsion composition or the powder composition. Menthol esters such as menthol, menthone, isopulegol, 1,8-cineole and the like, as well as menthyl acetate, menthyl lactate, menthyl salicylate, monomenthyl succinate, monomenthyl glutarate and monomenthyl adipate; N-ethyl-p- Cyclic carboxyamides such as menthane-3-carboxamide (WS-3), ethyl 3- (p-menthane-3-carboxamide) acetate (WS-5), N-tert-butylparamentanecarboxamide (WS-14) N, 2,3-trimethyl-2-isopropylbutanamide (WS- Acyclic carboxamides such as 3); menthone ketals, can contain various substitutions p- menthane such WS-12 other than the cooling agent, such as menthone glycerol ketal.

  Among these cooling sensates, a combination with menthol is particularly preferable. The sensation-specific cooling sensation characteristic is that the cooling sensation action is immediate, strong, and decays in a short time, while WS-12's cooling sensation action characteristic is somewhat delayed and irritate. Somewhat calm and lasts for a very long time. When these different properties act synergistically, for example, when blended in chewing gum, a cooling effect can be felt quickly from the beginning of chewing, and an excellent effect that the cooling effect lasts for a long time can be obtained. The blending ratio of WS-12 and the other cooling sensation agent is usually 0.001 to 1000 parts by mass, preferably 0.005 to 200 parts by mass, more preferably, based on mass, with respect to 1 part by mass of WS-12. About 0.02-50 mass parts can be illustrated.

  Further, the powder composed of the aggregate of fine particles of WS-12 of the present invention, the paste-like composition in which the powder composed of the aggregate of fine particles is dispersed, the emulsified composition, or the powder composition further includes a sweetener, a fragrance, and a colorant. In addition, acidulants, antioxidants, seasonings, preservatives, thickeners, stabilizers, gelling agents, pastes, nutrient fortifiers and the like can be added and used as food additive preparations.

  Sweeteners include, for example, acesulfame K, sucralose, aspartame, neotame, disodium glycyrrhizinate, thaumatin, saccharin and its salts, Luohan fruit extract, licorice extract, rebaudioside A, stevia extract, enzyme-treated stevia extract Sweeteners such as foods, neohesperidin dihydrochalcone; sugar alcohols such as xylitol, erythritol, sorbitol, maltitol, palatinit, reduced syrup; sugar, glucose, fructose, maltose, lactose, galactose, maltose, trehalose, etc. Examples of such sugars.

  Examples of the fragrances include fragrances having various fragrance characteristics such as citrus, fruit, mint, spice, nut, meat, milk, marine products, vegetable, tea / coffee, and vanilla. Examples of the fragrance ingredients used in these are “Patent Office, Well-known and conventional technology collection (fragrance) Part II Food fragrance, page 8-87, issued on January 14, 2000” and “Japan Patent Office, Well-known and conventional technology collection ( Fragrances) Synthetic fragrances, natural essential oils, natural fragrances, animal and plant extracts described in Part III Cosmetic fragrances, pages 49-103, issued on June 15, 2001.

  Examples of the colorant include α-carotene, β-carotene, lycopene, paprika pigment, anato pigment, chlorophyll, gardenia pigment, safflower pigment, monascus pigment, beet pigment, elderberry pigment, marigold pigment, and cochineal pigment. .

  Examples of acidulants include citric acid, monopotassium citrate, tripotassium citrate, trisodium citrate, fumaric acid, monosodium fumarate, DL-malic acid, DL-sodium malate, DL-tartaric acid, L- Examples thereof include tartaric acid, DL-sodium tartrate, L-sodium tartrate, acetic acid, sodium acetate, succinic acid, sodium succinate and the like.

  The amount of the aggregate of the fine particles of WS-12 of the present invention in the food additive preparation is, for example, 1 ppm to 20%, preferably 10 ppm to 5% as WS-12 based on the mass in the food additive preparation. More preferably, the range of 100 ppm to 1% can be exemplified.

  The WS-12 fine particle aggregate of the present invention, a powder comprising the fine particle aggregate, a paste-like composition containing the fine particle aggregate, an emulsified composition, or a food or drink that can be given a cooling effect by the powder composition As specific examples, for example, chewing gum, candy, caramel, tablet confectionery, crackers, biscuits, cookies, pie, chocolate, snacks and other mixes such as cake mixes for producing them; cola drinks, with fruit juice Carbonated beverages such as carbonated beverages, carbonated beverages containing milk; soft drinks such as fruit juice beverages, vegetable beverages, sports drinks, honey beverages, soy milk, vitamin supplemented beverages, mineral supplemented beverages, nutritional drinks, nourishing drinks, lactic acid bacteria beverages, and milk beverages Beverages: green tea, black tea, oolong tea, herbal tea, milk tea, coffee drink Alcoholic beverages such as Chuhai, cocktail drinks, sparkling liquor, fruit liquor, condiment liquor; dairy products such as butter, cheese, milk, yogurt; ice cream, lacto ice, ice confectionery, yogurt, pudding, jelly, daily Desserts such as desserts and mixes for producing them; general foods such as bread, soup and various instant foods;

  Specific examples of cosmetics include, for example, fragrance products, basic cosmetics, finished cosmetics, hair cosmetics, tanned cosmetics, medicated cosmetics, hair care products, soap, body detergents, bath preparations, detergents, softeners, bleaching agents, There may be mentioned aerosols, deodorants / fragrances, repellents, and the like.

  In addition, specific examples of pharmaceuticals include, for example, a haptic agent, an external preparation for skin, a composition for oral cavity, an internal preparation and the like.

  The blending amount of the powder comprising the aggregate of fine particles of WS-12 of the present invention, the paste-like composition in which the aggregate of fine particles is dispersed, the emulsified composition or the powder composition into the cosmetics or pharmaceuticals is as follows. It is usually 0.01 to 1000 ppm, preferably 0.1 to 500 ppm, more preferably about 0.5 to 100 ppm as WS-12 with respect to 1 part by mass of cosmetics or pharmaceuticals.

    Hereinafter, the present invention will be described more specifically with reference to examples.

(Example 1) Preparation of dry pulverized product (1) of WS-12 1000 g of commercially available WS-12 powder (obtained from Renessenz: referred to as reference product 1) using Nanojet Mizer (manufactured by Aisin Nano Technologies), Fine grinding was performed to obtain 980 g of WS-12 fine particle powder of the product 1 of the present invention.
Grinding conditions;
Classification rotor rotation speed: 2000rpm
Total air volume: 4.5m ³ / min
Nozzle flow rate: 3.2 m ³ / min
Nozzle pressure: 0.64 MPa
Grinding time: 60 minutes, throughput: 1.0 kg / hr.

(Example 2) Preparation of WS-12 dry pulverized product (2) Reference product 1 (1000 g) was pulverized with a power mill (Dalton) screen 0.5 mm, and WS-12 fine particle powder 980 g of the product 2 of the present invention. Got.

(Example 3) Preparation of wet pulverized product of WS-12 Reference product 1 (100 g) was added to a mixture of 600 g of 20% by weight aqueous gum arabic solution and 300 g of 30% by weight sorbitol aqueous solution, and mixed well. A suspension was prepared. This was put into a batch type wet pulverizer “Bead Mill (manufactured by Imex Co., Ltd.)” to obtain 980 g of a paste-like composition containing WS-12 fine particles (present product 3: containing 10% WS-12).

(Measurement of average particle diameter of WS-12)
The particle size before and after pulverization was measured with the following apparatus and conditions.
Measuring device: HORIBA LA-920 (manufactured by Horiba Ltd.)
Measurement conditions: Table 1 shows the measurement results of the volume-based average particle diameter using a wet method based on a flow method using water as a solvent using a laser diffraction / scattering particle size distribution measuring apparatus.

(Example 4) Preparation of emulsified powder of WS-12 dry pulverized product (1) 845 g of gum arabic was dissolved in 2000 g of water, and 350 g of a 30% by mass sorbitol aqueous solution was further added. The product 1 (50 g) of the present invention was mixed and dispersed therein, and stirred at 6000 rpm for 10 minutes using a TK-homomixer (manufactured by PRIMIX Corporation) to obtain an emulsion composition. Subsequently, this emulsified composition was spray-dried at a hot air inlet temperature of 160 ° C., an exhaust air temperature of 90 ° C., and an atomizer rotation speed of 20000 rpm using a spray dryer L-8 type (Okawara Kako), and a powder composition of 800 g (Containing WS-12 of 5.0%) was obtained (Product 4 of the present invention).

(Example 5) Preparation of emulsified powder of dry pulverized product (2) of WS-12 The present invention product 2 (50 g) was treated in the same manner as in Example 4, and 800 g of powder composition (5.0 of WS-12 was 5.0). % Content) was obtained (Invention product 5).

(Example 6) Preparation of emulsified powder of wet pulverized product of WS-12 In an aqueous solution obtained by dissolving 845 g of gum arabic in 1800 g of water, 500 g of the paste-like composition of the present invention product 3 (containing WS-12 at 10% by mass) After mixing and dispersing, the mixture was stirred at 6000 rpm for 10 minutes using a TK-homomixer (manufactured by PRIMIX Corporation) to obtain an emulsified composition. Subsequently, this emulsified composition was spray-dried at a hot air inlet temperature of 160 ° C., an exhaust air temperature of 90 ° C., and an atomizer rotation speed of 20000 rpm using a spray dryer L-8 type (Okawara Kako), and a powder composition of 800 g (Containing WS-12 of 5.0%) was obtained (Invention product 6).

(Comparative example 1) Preparation of emulsified powder of unmilled product of WS-12 845 g of gum arabic was dissolved in 2000 g of water, and 350 g of a 30% by mass sorbitol aqueous solution was further added. Reference product 1 (50 g) was mixed and dispersed therein, and stirred at 6000 rpm for 10 minutes using a TK-homomixer (manufactured by PRIMIX Corporation) to obtain an emulsified composition. Subsequently, this emulsified composition was spray-dried at a hot air inlet temperature of 160 ° C., an exhaust air temperature of 90 ° C., and an atomizer rotation speed of 20000 rpm using a spray dryer L-8 type (Okawara Kako), and a powder composition of 800 g (Containing WS-12 of 5.0%) was obtained (Comparative product 1).

(Sensory evaluation 1) Evaluate the product of the present invention as it is The product of the present invention 1 (0.001 g), the product of the present invention 2 (0.001 g), the product of the present invention 3 (0.01 g), the product of the present invention 4 (0.02 g) ), Invention product 5 (0.02 g), Invention product 6 (0.02 g), Reference product 1 (0.001 g), or Comparative product 1 (0.02 g) (both as WS-12, 0. 001 g) was put into the oral cavity as it was by 5 panelists using a spatula, and sensory evaluation was performed. The sensory evaluation method is a process in which the sample is naturally dissolved or swallowed and disappears, and the intensity of the cold feeling and how it feels after the disappearance while actively tasting the input sample. Compared. The evaluation of one sample was followed for sensation in the oral cavity and pharynx up to 10 minutes after entering the oral cavity. Regarding the evaluation of the second and subsequent samples, after the previous sample was put into the oral cavity, 10 minutes later, after rinsing the oral cavity and pharynx by rinsing with water, the oral cavity and pharynx were further cooled. I went after a while until I felt no longer.

  The criteria for sensory evaluation are a 6-level evaluation of the sensation of cooling sensation, the strength of cooling sensation, and the persistence of cooling sensation, and the evaluation criteria are 5: very strong, 4: strong, 3: normal, 2: slightly Table 2 shows the average score of 5 people and the average comment of 5 panelists as weak, 1: very weak, 0: not felt at all.

  As shown in Table 2, the unsintered product of WS-12 on the market had an average particle size of about 100 μm. Only the touch with no inorganic powder was felt. On the other hand, the product 1 of the present invention, which was dry pulverized by a fluidized bed jet mill, had an average particle size of less than 10 μm (7.15 μm), but a slightly irritating feeling of cooling was felt quite strongly, and the feeling of cooling was It lasted for a long time and had a completely different sensation from the unmilled product.

  The product 2 of the present invention 2 which was pulverized slightly coarsely by dry pulverization had an average particle size of about 40 μm (37.82 μm). It was much better than 1 (commercially unground).

  In addition, the product 3 of the present invention subjected to wet pulverization had an average particle size of less than 1 μm (0.69 μm), and the sensory evaluation was superior to the product 1 of the present invention in terms of cooling strength and sustainability. It was not a big difference.

  WS-12 unground and pulverized products (reference product 1, products 1 to 3 of the present invention) were prepared as emulsion powders, and sensory evaluation was performed. The unmilled emulsified powder product (Comparative product 1) had a slight feeling of cooling. The strength was much weaker than the coarsely pulverized product 2 of the present invention. On the other hand, the emulsified powder product of the pulverized product (the products of the present invention 4 to 6) each had a good result with slightly increased strength and duration of cooling feeling compared to the original pulverized product.

  From the above results, when WS-12 has a particle size of about 100 μm as an average particle size, almost no cooling sensation is felt even if it is put into the oral cavity, but when it is less than 10 μm, a strong cooling sensation is felt, It was found to last. Further, when the thickness is less than 1 μm, the feeling of cooling is further enhanced, but it is not so large as compared with that of less than 10 μm, but the feeling of cooling is felt at about 40 μm. Expected. Moreover, it was found that the emulsification treatment slightly enhanced the cool feeling.

(Sensory evaluation 2) Evaluation by adding the product of the present invention to chewing gum Chewing gum base (100 parts by weight of chewing gum base, 250 parts by weight of sugar, 40 parts by weight of glucose, 60 parts by weight of corn syrup (Bx85), 3 parts by weight of glycerin Invention product 1 (0.02 g), Invention product 2 (0.02 g), Invention product 4 (0.4 g), Invention product 5 (0.4 g), Invention product 6 (0. 4 g), Reference product 1 (0.02 g), or Comparative product 1 (0.4 g) (both containing 0.02 g as WS-12), and using a high shear mixer, about The mixture was mixed at 50 ° C., and after cooling, it was subjected to pressure molding by rolling, to prepare 3 g of chewing gum.

  This chewing gum was sensory-evaluated by 10 expert panelists. Table 3 shows the average comments of the 10 panelists.

  As shown in Table 3, in the sensory evaluation-1, the evaluation result was almost the same as the case where the sample was directly evaluated.

(Example 7) WS-12 wet pulverized product and menthol combined emulsified powder After dissolving 500 g of chemical starch and 180 g of dextrin in 1800 g of soft water, 274 g of menthol and 150 g of product 3 of the present invention were added and emulsified with a homomixer. To obtain an emulsified composition. The melting point of menthol was 40 ° C., but the one melted at 50 ° C. was used. The resulting emulsified composition was spray-dried at a hot air inlet temperature of 160 ° C., an exhaust air temperature of 80 ° C. and an atomizer speed of 20000 rpm using a spray dryer L-8 type (Okawara Kako), and menthol was 27. 800 g of a powder fragrance containing 4% by mass and 1.5% by mass of WS-12 was obtained (Product 7 of the present invention).

(Example 8) Combined emulsified powder of wet pulverized product of WS-12, menthol and WS-5 After dissolving 500 g of modified starch, 180 g of dextrin and 18 g of gum arabic in 1800 g of soft water, an additional 45 g of 30% by mass sorbitol aqueous solution was added, To this was added a mixture of 274 g of menthol and WS-5 (15 g), and finally the product 1 (15 g) of the present invention was added and emulsified with a homomixer to obtain an emulsion composition. In addition, although WS-5 was dissolved in menthol melted at 50 ° C. by visual observation, the product 1 of the present invention was not dissolved in the melted menthol. The resulting emulsified composition was spray-dried at a hot air inlet temperature of 160 ° C., an exhaust air temperature of 90 ° C., and an atomizer speed of 20000 rpm using a spray dryer L-8 type (Okawara Kako) to prepare menthol at 27. 800 g of a powder fragrance containing 4% by mass, 1.5% by mass of WS-12 and 1.5% by mass of WS-5 was obtained (Product 8 of the present invention).

(Comparative Example 2) Combined emulsified powder of unmilled WS-12 and menthol After dissolving 500 g of modified starch, 180 g of dextrin and 18 g of gum arabic in 1800 g of soft water, gram of menthol 274 g and A mixture of Reference Product 1 (15 g) was added and emulsified with a homomixer to obtain an emulsified composition. In addition, the reference product 1 was not dissolved in menthol melted at 50 ° C. in the naked eye observation. The resulting emulsified composition was spray-dried at a hot air inlet temperature of 160 ° C., an exhaust air temperature of 90 ° C., and an atomizer speed of 20000 rpm using a spray dryer L-8 type (Okawara Kako) to prepare menthol at 27. 800 g of a powder fragrance containing 4% by mass and 1.5% by mass of WS-12 was obtained (Comparative product 2).

(Comparative product 3) emulsified powder only of menthol After dissolving 500 g of modified starch, 195 g of dextrin and 18 g of gum arabic in 1800 g of soft water, gram of menthol (melted at 50 ° C.) was added to this after adding 45 g of a 30% by weight sorbitol solution. Was added and emulsified with a homomixer to obtain an emulsified composition. This emulsified composition was spray-dried at a hot air inlet temperature of 160 ° C., an exhaust air temperature of 90 ° C. and an atomizer speed of 20000 rpm using a spray dryer L-8 type (Okawara Kako), and 27.4 mass of menthol. % Powdered fragrance was obtained (Comparative product 3).

(Sensory Evaluation 3) Evaluation by adding the product of the present invention to chewing gum Chewing gum base (100 parts by weight of chewing gum base, 250 parts by weight of sugar, 40 parts by weight of glucose, 60 parts by weight of corn syrup (Bx85), 3 parts by weight of glycerin The inventive product 7 (0.4 g), the inventive product 8 (0.4 g), the comparative product 2 (0.4 g) or the comparative product 3 (0.4 g) are added to the mixture), respectively, and a high shear type The mixture was mixed at about 50 ° C. by a conventional method using a mixer, and after cooling, it was subjected to pressure forming by rolling onto a roll to prepare 3 g of chewing gum.

  This chewing gum was sensory-evaluated by 10 expert panelists. Table 3 shows the average comments of the 10 panelists.

  As shown in Table 4, the chewing gum containing the menthol-only emulsified powder (Comparative Product 3) showed a strong cooling sensation as soon as it started to chew, but after a few minutes no sensation was felt. Moreover, the chewing gum which mix | blended the powder (comparative product 2) which emulsified the unmilled thing of WS-12 with the menthol was not different at all from the chewing gum which mix | blended the emulsified powder only of menthol, and was the same evaluation.

  On the other hand, the chewing gum containing the present invention product 7 containing emulsified powder containing WS-12 finely pulverized with menthol has a sharp cooling sensation and a cooling sensation that lasts for more than 10 minutes. The result was that a strong sensation of coldness was felt even after minutes had passed, and a sharp sensation of sensation spread throughout the mouth. Therefore, it was recognized that the use of finely ground WS-12 in combination with menthol significantly extended the duration of the cooling effect compared to menthol alone. In addition, chewing gum blended with menthol, which was finely ground WS-12 and WS-5 and blended with the product 8 of the present invention as an emulsified powder, has a cooling sensation duration almost equal to that of the product 7 of the present invention. The feeling was clear and smooth, and its usefulness was recognized as bringing about a cool feeling of different sensations.

Claims (7)

WS-12 ((1R, 2S, 5R) -N- (4-) having an average particle diameter (median diameter) of 0.01 μm to 50 μm when measured using a laser diffraction / scattering particle size distribution analyzer. (Methoxyphenyl) -2-isopropyl-5-methylcyclohexanecarboxamide) fine particles. The powder according to claim 1, obtained by pulverizing WS-12 with a dry pulverizer. The paste-like composition in which the powder according to claim 1 is obtained, which is obtained by pulverizing a mixture of WS-12 and a liquid medium with a wet pulverizer. The emulsified composition obtained by emulsifying the powder or paste-like composition of any one of Claims 1-3. The powder composition obtained by drying the paste-like composition or emulsion composition of Claim 3 or 4. The cooling sensation agent composition which contains the powder of any one of Claims 1-5, a paste-form composition, an emulsion composition, or a powder composition as an active ingredient. A food / beverage product, a cosmetic product or a pharmaceutical product comprising the cooling sensation agent composition according to claim 6.