CROSS REFERENCE TO RELATED APPLICATIONS

This application is a National Stage of International Application No. PCT/JP2018/038425 filed on Oct. 16, 2018, claiming priority from Japanese Application No. 2017-200504 filed Oct. 16, 2017, the disclosures of which are incorporated herein in their entirety by reference.

TECHNICAL FIELD

The present invention relates to a cooling agent composition containing a novel 2,2,6-trimethylcyclohexanecarboxylic acid derivative. Further, the present invention relates to a sensory stimulant composition containing the cooling agent composition, a flavor or fragrance composition containing the sensory stimulant composition, a product containing the sensory stimulant composition or the flavor or fragrance composition, a method for manufacturing the product, and a novel 2,2,6-trimethylcyclohexanecarboxylic acid derivative.

BACKGROUND ART

Up to now, cooling agents which exert a refreshing sense (refresh-feeling) or cool sense (cool-feeling), namely cooling effect, on human skin, oral cavity, nose and throat are used in dentifrices, sweets (e.g., chewing gum, candy, and the like), tobacco, poultice, cosmetics, and the like. As a flavor or fragrance substance that provides such a refresh-feeling or cool-feeling, 1-menthol is now broadly used. However, the cooling effect of 1-menthol has a weak point that the cooling effect thereof lacks persistence, and the cooling effect is enhanced when the using amount thereof is increased but different stimuli such as bitterness sometimes accompanies. Furthermore, there is a problem that 1-menthol has a unique strong minty odor and high volatility.

In view of the above-described weak points of 1-menthol, synthesis of 1-menthol derivatives has been actively conducted as studies of compounds having a cooling effect in recent years. As a result, a large number of substitutes for 1-menthol have been proposed and used. Examples thereof include 3-substituted-p-menthane (e.g., see PTL 1), N-substituted-p-menthan-3-carboxamides (e.g., see PTL 2 to PTL 5), 1-menthyl glucoside (e.g., see PTL 6), 3-(1-menthoxy)propane-1,2-diol (e.g., see PTL 7), 1-menthyl-3-hydroxybutyrate (e.g., see PTL 8), 1-alkoxy-3-(1-menthoxy) propan-2-ol (e.g., see PTL 9), esters of 3-hydroxymethyl-p-menthane (e.g., see PTL 10), N-acetylglycinementhane methyl ester (e.g., see PTL 11), 1-isopulegol (e.g., see PTL 12), (2S)-3-{(1R,2S,5R)-[5-methyl-2-(1-methylethyl)cyclohexyl]oxy}-1,2-propanediol (e.g., see PTL 13), 2-hydroxymethyl menthol (e.g., see PTL 14), menthoxyalkane-1-ol (e.g., see PTL 15), (1-menthyloxyalkoxy)alkanol (e.g., see PTL 16), N-α-(menthanecarbonyl)amino acid amide (e.g., see PTL 17), menthyl ketone derivatives (e.g., see PTL 18), isopulegol derivatives (e.g., see PTL 19), menthol derivatives having a structure similar to 8,4′-oxyneolignan (e.g., see PTL 20), and the like.

Currently, many of the compounds commercialized as cooling agents are derivatives of 1-menthol.

On the other hand, compounds which are structurally different from 1-menthol and have a cooling effect have been developed. Examples thereof include N-monosubstituted acyclic carboxamides represented by N,2,3-trimethyl-2-isopropylbutanamide (e.g., see PTL 21), icilin analogs (e.g., see PTL 22), N-phenyl-N-pyridinylbenzamide and benzenesulfonamide (e.g., see PTL 23), arylcarboxamides (e.g., see PTL 24 and PTL 25), aromatic ring-containing compound groups (e.g., see PTL 26), α-keto enamine derivatives (e.g., see PTL 27), and the like. In addition, N,2,2,6-tetramethylcyclohexanecarboxamide (e.g., see PTL 28 and Non-patent literature 4) is exemplified as the compound having a cooling effect.

CITATION LIST

Patent Literature

PTL 1: JP S47-16647 A

PTL 2: JP S47-16648 A

PTL 3: JP 2007-530689 A

PTL 4: JP 2007-511546 A

PTL 5: JP 2011-530608 A

PTL 6: JP S48-33069 A

PTL 7: JP S58-88334 A

PTL 8: JP S61-194049 A

PTL 9: JP H02-290827 A

PTL 10: JP H05-255186 A

PTL 11: JP H05-255217 A

PTL 12: JP H06-65023 A

PTL 13: JP H07-82200 A

PTL 14: JP H07-118119 A

PTL 15: JP 2001-294546 A

PTL 16: JP 2005-343915 A

PTL 17: JP 2008-115181 A

PTL 18: JP 2010-527943 A

PTL 19: WO 2013/033501 A1

PTL 20: JP 2014-227390 A

PTL 21: U.S. Pat. No. 4,230,688

PTL 22: JP 2006-512294 A

PTL 23: WO 2007/048265 A1

PTL 24: JP 2008-530806 A

PTL 25: JP 2014-503486 A

PTL 26: JP 2013-511270 A

PTL 27: U.S. Pat. No. 6,592,884

PTL 28: U.S. Pat. No. 7,482,378

PTL 29: JP H05-112494 A

PTL 30: JP 2001-348353 A

PTL 31: JP 2002-53520 A

Non Patent Literature

Non-Patent Literature 1: Shuchi Kanyo Gijutsu Shu (Koryo) Daiichibu (Known/Common Technical Book (Flavor or Fragrances) Part I)” (Jan. 29, 1999, published by the Japanese Patent Office)

Non-Patent Literature 2: Adv. Synth. Catal. (2008), Vol. 350, Issue 5,652-656

Non-patent Literature 3: J. Neurobiol. (2004), Vol. 61, 3-12

Non-patent Literature 4: J. Agric. Food Chem. (2017), DOI: 10.1021/acs.jafc.6b04838

Non-patent Literature 5: Angew. Chem. Int. Ed. (1978), Vol. 17,522-524

SUMMARY OF INVENTION

Technical Problem

However, the above-mentioned common compounds having a cooling effect have a certain level of cooling effect, but are not yet sufficiently satisfactory in terms of persistence of the cooling effect or the like. In addition, a sensory stimulation effect is required to be further improved. Further, since major commercial cooling agents including N-substituted-p-menthane-carboxamides commercially known as “WS series” (e.g., see PTL 2) are derivatives of 1-menthol, the synthesis process is multi-step and complicated. Therefore, it is expensive to manufacture derivatives of 1-menthol on an industrial scale, and thus many of these compounds become relatively expensive components.

Therefore, an object of the present invention is to provide a cooling agent composition containing a novel 2,2,6-trimethylcyclohexanecarboxylic acid derivative which is a novel compound that can be used as a cooling agent or a sensory stimulant with less undesirable stimulus feeling and excellent persistence of a refresh-feeling or a cool-feeling, and has a carbon skeleton structurally different from 1-menthol as a main structure, and which may be synthesized very simply and at low cost from inexpensive raw materials.

In addition, another object of the present invention is to provide a sensory stimulant composition containing the cooling agent composition.

Further, still another object of the present invention is to provide a flavor or fragrance composition containing the sensory stimulant composition, a product containing the sensory stimulant composition or the flavor or fragrance composition, a method for manufacturing the product, and a novel 2,2,6-trimethylcyclohexanecarboxylic acid derivative.

Solution to Problem

With the aim of achieving the objects described above, the present inventors have conducted intensive studies and found that the objects can be achieved by using a novel 2,2,6-trimethylcyclohexanecarboxylic acid derivative represented by the following general formula (1), and have accomplished the present invention.

That is, the present invention relates to the following [1] to [22].

[1] A cooling agent composition comprising a 2,2,6-trimethylcyclohexanecarboxylic acid derivative represented by the following general formula (1):



wherein the symbol * represents an asymmetric carbon atom,

X represents NH, N(ZAr2), O or S, Z represents a single bond or an alkylene group having 1 to 3 carbon atoms which may have a substituent, Ar2represents an aryl group having 6 to 20 carbon atoms which may have a substituent or an aromatic heterocyclic group having 2 to 15 carbon atoms which may have a substituent,

Y each independently represents a methylene group which may have a substituent,

n represents an integer of 0 to 3, and

Ar1represents an aryl group having 6 to 20 carbon atoms which may have a substituent or an aromatic heterocyclic group having 2 to 15 carbon atoms which may have a substituent.

[2] The cooling agent composition according to [1], wherein X represents NH or N(ZAr2) in the 2,2,6-trimethylcyclohexanecarboxylic acid derivative.

[3] The cooling agent composition according to [1], wherein X represents NH or N(ZAr2) in the 2,2,6-trimethylcyclohexanecarboxylic acid derivative, and the 2,2,6-trimethylcyclohexanecarboxylic acid derivative is a (1R, 6S)-form.

[4] The cooling agent composition according to [1], wherein X represents NH or N(ZAr2), n represents 0 or 2, and Z represents a single bond or an ethylene group which may have a substituent in the 2,2,6-trimethylcyclohexanecarboxylic acid derivative.

[5] The cooling agent composition according to [1], wherein X represents NH or N(ZAr2), n represents 0 or 2, and Z represents a single bond or an ethylene group which may have a substituent in the 2,2,6-trimethylcyclohexanecarboxylic acid derivative, and the 2,2,6-trimethylcyclohexanecarboxylic acid derivative is a (1R, 6S)-form.

[6] The cooling agent composition according to [1], wherein X represents NH or N(ZAr2), n represents 2, and Z represents an ethylene group which may have a substituent, in the 2,2,6-trimethylcyclohexanecarboxylic acid derivative.

[7] The cooling agent composition according to [1], wherein X represents NH or N(ZAr2), n represents 2, and Z represents an ethylene group which may have a substituent in the 2,2,6-trimethylcyclohexanecarboxylic acid derivative, and the 2,2,6-trimethylcyclohexanecarboxylic acid derivative is a (1R, 6S)-form.

[8] The cooling agent composition according to any one of [1] to [7], further comprising at least one kind of cooling substance other than the 2,2,6-trimethylcyclohexanecarboxylic acid derivative.

[9] The cooling agent composition according to [8], wherein the cooling substance is at least one cooling substance selected from the group consisting of:

one or more kinds of compounds selected from menthol, menthone, camphor, pulegol, isopulegol, cineole, cubenol, menthyl acetate, pulegyl acetate, isopulegyl acetate, menthyl salicylate, pulegyl salicylate, isopulegyl salicylate, 3-(1-menthoxy)propane-1,2-diol, 2-methyl-3-(1-menthoxy)propane-1,2-diol, 2-(1-menthoxy)ethane-1-ol, 3-(1-menthoxy)propane-1-ol, 4-(1-menthoxy)butan-1-ol, menthyl 3-hydroxybutanoate, menthyl glyoxylate, p-menthane-3,8-diol, 1-(2-hydroxy-4-methylcyclohexyl)ethanone, menthyl lactate, menthone glycerin ketal, menthyl-2-pyrrolidone-5-carboxylate, monomenthyl succinate, alkali metal salts of monomenthyl succinate, alkaline earth metal salts of monomenthyl succinate, monomenthyl glutarate, alkali metal salts of monomenthyl glutarate, alkaline earth metal salts of monomenthyl glutarate, N-[[5-methyl-2-(1-methylethyl)cyclohexyl]carbonyl]glycine, p-menthane-3-carboxylic acid glycerol ester, menthol propylene glycol carbonate, menthol ethylene glycol carbonate, p-menthane-2,3-diol, 2-isopropyl-N,2,3-trimethylbutanamide, N-ethyl-p-menthane-3-carboxamide, 3-(p-menthane-3-carboxamide) ethyl acetate, N-(4-methoxyphenyl)-p-menthane carboxamide, N-ethyl-2,2-diisopropylbutanamide, N-cyclopropyl-p-menthane carboxamide, N-(4-cyanomethylphenyl)-p-menthanecarboxamide, N-(2-pyridin-2-yl)-3-p-menthane carboxamide, N-(2-hydroxyethyl)-2-isopropyl-2,3-dimethylbutanamide, N-(1,1-dimethyl-2-hydroxyethyl)-2,2-diethylbutanamide, cyclopropanecarboxylic acid (2-isopropyl-5-methylcyclohexyl)amide, N-ethyl-2,2-diisopropylbutanamide, N-[4-(2-amino-2-oxoethyl)phenyl]-p-menthanecarboxamide, 2-[(2-p-menthoxy)ethoxy]ethanol, 2,6-diethyl-5-isopropyl-2-methyltetrahydropyran, and trans-4-tert-butylcyclohexanol;

one or more kinds of sugar alcohols selected from xylitol, erythritol, dextrose, and sorbitol; and

one or more kinds of natural products selected from Japanese mint oil, peppermint oil, spearmint oil, and eucalyptus oil.

[10] A sensory stimulant composition comprising the cooling agent composition according to any one of [1] to [9].

[11] The sensory stimulant composition according to [10], further comprising at least one kind of warming substance.

[12] The sensory stimulant composition according to [11], wherein the warming substance is at least one warming substance selected from the group consisting of:

one or more kinds of compounds selected from vanillyl methyl ether, vanillyl ethyl ether, vanillyl propyl ether, vanillyl isopropyl ether, vanillyl butyl ether, vanillyl amyl ether, vanillyl isoamyl ether, vanillyl hexyl ether, isovanillyl methyl ether, isovanillyl ethyl ether, isovanillyl propyl ether, isovanillyl isopropyl ether, isovanillyl butyl ether, isovanillyl amyl ether, isovanillyl isoamyl ether, isovanillyl hexyl ether, ethyl vanillyl methyl ether, ethyl vanillyl ethyl ether, ethyl vanillyl propyl ether, ethyl vanillyl isopropyl ether, ethyl vanillyl butyl ether, ethyl vanillyl amyl ether, ethyl vanillyl isoamyl ether, ethyl vanillyl hexyl ether, vanillin propylene glycol acetal, isovanillin propylene glycol acetal, ethyl vanillin propylene glycol acetal, vanillyl butyl ether acetate, isovanillyl butyl ether acetate, ethyl vanillyl butyl ether acetate, 4-(1-menthoxymethyl)-2-(3′-methoxy-4′-hydroxyphenyl)-1,3-dioxolane, 4-(1-menthoxymethyl)-2-(3′-hydroxy-4′-methoxyphenyl)-1,3-dioxolane, 4-(1-menthoxymethyl)-2-(3′-ethoxy-4′-hydroxyphenyl)-1,3-dioxolane, capsaicin, dihydrocapsaicin, nordihydrocapsaicin, homodihydrocapsaicin, homocapsaicin, bis-capsaicin, trishomocapsaicin, nomorcapsaicin, norcapsaicin, capsaicinol, vanillyl caprylamide (octylic acid vanillylamide), vanillyl pelargonamide (nonylic acid vanillylamide), vanillyl caproamide (decylic acid vanillylamide), vanillyl undecanamide (undecylic acid vanillylamide), N-trans-feruloyltyramine, N-5-(4-hydroxy-3-methoxyphenyl)-2E,4E-pentadienoylpiperidine, N-trans-feruloylpiperidine, N-5-(4-hydroxy-3-methoxyphenyl)-2E-pentenoylpiperidine, N-5-(4-hydroxyphenyl)-2E,4E-pentadienoylpiperidine, piperine, isopiperine, chavicine, isochavicine, piperamine, piperettine, piperolein B, retrofractamide A, pipercide, guineenside, piperiline, piperamide C5:1 (2E), piperamide C7:1 (6E), piperamide C7:2 (2E,6E), piperamide C9:1 (8E), piperamide C9:2 (2E,8E), piperamide C9:3 (2E,4E,8E), fagaramide, sanshool-I, sanshool-II, hydroxysanshool, sanshoamide, gingerol, shogaol, zingerone, methylgingerol, paradol, spilanthol, chavicine, polygodial (tadeonal), isopolygodial, dihydropolygodial, and tadeon; and

one or more kinds of natural products selected from capsicum pepper oil, capsicum pepper oleoresin, ginger oleoresin, jambu oleoresin (extract fromSpilanthes acmellaL. var.oleraccaClarke), Japanese pepper extract, sanshoamide, black pepper extract, white pepper extract, and Polygonum extract.

[13] A flavor or fragrance composition comprising the sensory stimulant composition according to any one of [10] to [12].

[14] The flavor or fragrance composition according to [13], wherein a content of the sensory stimulant composition is from 0.00001 mass % to 90 mass %.

[15] A product comprising the sensory stimulant composition according to any one of [10] to [12], the product being any one of products selected from the group consisting of drinks, foods, fragrances or cosmetics, toiletry products, air care products, daily necessities and household goods, oral compositions, hair care products, skin care products, body care products, detergents for clothes, soft finishing agents for clothes, quasi-drugs and pharmaceuticals.

[16] The product according to [15], wherein a content of the sensory stimulant composition is from 0.00001 mass % to 50 mass %.

[17] A product comprising the flavor or fragrance composition according to [13] or [14], the product being any one of products selected from the group consisting of drinks, foods, fragrances or cosmetics, toiletry products, air care products, daily necessities and household goods, oral compositions, hair care products, skin care products, body care products, detergents for clothes, soft finishing agents for clothes, quasi-drugs and pharmaceuticals.

[18] The product according to [17], wherein a content of the flavor or fragrance composition is from 0.00001 mass % to 50 mass %.

[19] A method for manufacturing a product, comprising blending a product with the sensory stimulant composition according to any one of [10] to [12], wherein the product is any one of products selected from the group consisting of drinks, foods, fragrances or cosmetics, toiletry products, air care products, daily necessities and household goods, oral compositions, hair care products, skin care products, body care products, detergents for clothes, soft finishing agents for clothes, quasi-drugs and pharmaceuticals.

[20] A method for manufacturing a product, comprising blending a product with the flavor or fragrance composition according to [13] or [14], wherein the product is any one of products selected from the group consisting of drinks, foods, fragrances or cosmetics, toiletry products, air care products, daily necessities and household goods, oral compositions, hair care products, skin care products, body care products, detergents for clothes, soft finishing agents for clothes, quasi-drugs and pharmaceuticals.

[21] A 2,2,6-trimethylcyclohexanecarboxylic acid derivative represented by the following general formula (1-1):



wherein the symbol * represents an asymmetric carbon atom, and R, R′ and R″ each independently represent a hydrogen atom, a hydroxy group, or a methoxy group.

[22] A 2,2,6-trimethylcyclohexanecarboxylic acid derivative represented by the following structural formula (10-1):



wherein the symbol * represents an asymmetric carbon atom.

Advantageous Effects of Invention

The present invention can provide a cooling agent composition containing a novel 2,2,6-trimethylcyclohexanecarboxylic acid derivative which can be used as a cooling agent or a sensory stimulant with less undesirable stimulus feeling and excellent persistence of a refresh-feeling or a cool-feeling, and has a carbon skeleton structurally different from 1-menthol as a main structure. The cooling agent composition of the present invention is blended with various products, so that a refresh-feeling or a cool-feeling excellent in the persistence can be imparted to these products.

Currently, most of the commercially available compounds having a cooling effect are derivatives of 1-menthol, and the derivatives of 1-menthol are relatively expensive components due to the complexity of the synthesis process thereof. However, the 2,2,6-trimethylcyclohexanecarboxylic acid derivative is a novel compound having a carbon skeleton structurally different from 1-menthol as a main structure, and can be synthesized very simply and at low cost by using citronellal as an inexpensive raw material.

In the flavor or fragrance composition including the sensory stimulant composition containing the cooling agent composition of the present invention, odorous diffusivity and lingering scent of the flavor or fragrance composition is enhanced, and a high odor quality improvement effect is also imparted to a product perfumed with the flavor or fragrance composition.

Further, the 2,2,6-trimethylcyclohexanecarboxylic acid derivative exhibits excellent characteristics that an undesirable stimulus feeling for skin is hardly given to a human body.

