JPS5936674B2 - Method for imparting physiological cooling activity - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to compositions and compounds that have a physiological cooling effect on the skin and mucous membranes of the human body, in particular the mucous membranes of the mouth, nose, throat, and gastrointestinal tract.

It is well known that menthol has a physiological cooling effect on the skin and the mucous membranes of the mouth, and it is also used as a fragrance (menthol is the main component of peppermint oil) in foods, beverages, toothpaste, It is widely used in mouth cleansers, and as a compound in various cosmetics, plasters, and cleaning agents for the purpose of topical application. Menthol is also a well-known tobacco additive to produce a "cool" sensation in the mouth when smoking. It is controversial that the "cooling" effect of menthol is a physiological effect due to menthol acting directly on the nerve endings in the human body that are responsible for the sensation of heat and cold, and is not due to the heat generated during vaporization. This is thought to be due to the fact that menthol directly stings the sensory receptors that sense the coldness of the nerve endings, which in turn stings the central nervous system.

Although menthol's use as a physiological cooling agent is well established, certain compositions
It is limited by its strong, fleeting odor and relative volatility. Several other compounds have been reported in the technical literature as having odors or odors similar to menthol, and are often reported as pleasant-tasting odorants in various topical and furuncture compositions. .

For example, Japanese Patent Publication No. 39-19627 shows that 3-hydroxymethyl p-tantane (menthyl carbinol) has a flavor similar to 1-menthol and is used as a flavoring agent for confectionery, chewing gum, and tobacco. has been done. Swiss Patent No. 484,032 proposes certain saccharide esters of menthol as tobacco additives. First French patent
In the specification of No. 572332, N-N-dimethyl-2
- Ethylbutanamide has been reported to have a fragrance and cooling effect, and N - N -
Diethyl-2.2-dimethylpropanamide is also said to have a similar effect. It is reported in Berichte, Vol. 39, No. 1223, that N-N-diethyl-2-ethylbutanamide has a similar effect.
(1906).

2,4,6-trimethylheptan-4-ol and 2
・The fact that 4,6-trimethylhept-2-en-4-ol has a strong fragrance is said to be the reason why 4,6-trimethylhept-2-en-4-ol has a strong fragrance.
SavOns) May 956, pp. 17-20.

The cooling effects of menthol and other related terpene alcohols and their derivatives have been studied and reported in Perfume 95, (1970), pages 39-43. 2,3-p-tantanediol has been reported to have a significantly cool taste.
ilsteinHandbuchderOrganis
chenChemie) 4th edition (1923) Volume 6 No. 7
See page 44.

The physiological cooling effect of other derivatives of p-tantanes is also reported in German Patent Application Publication P22O25.
35, P22O3947, P22O3273 and P2
2O5255. Although this other known compound has an odor and odor similar to menthol, menthol [despite the disadvantages mentioned above, i.e., a very strong odor and relatively volatile It is still widely used in commercial and other compositions.

It is an object of the present invention to provide other compounds which have a pronounced physiological cooling effect, are often more persistent than menthol, are not associated with a strong and fleeting odor, and have a selective odor. That's true.

Another objective is to provide compounds that have a pronounced physiological cooling effect and are of relatively low volatility. Another object of the present invention is to use a furunculum that is capable of stimulating cold receptors in the nervous system of the human body, thereby providing a desirable cooling sensation.
The present invention provides topical and other compositions, as well as methods of making them. Still another object of the present invention is to provide a method of stimulating the cold receptors of the nervous system of the human body to provide a cooling sensation. Still other objects will be apparent from the detailed description of the invention that follows. The present invention is based on the discovery that certain cycloaliphatic amides have significant physiological cooling activity, but do not have the strong, pungent odor characteristic of menthol.

These compounds are alicyclic amides represented by the following general formula (I). (wherein n is o or an integer from 2 to 6; in the alkyl group, at least one R group is in the 1, 2 or 3 position relative to the amide group, and all R groups The total number of carbon atoms contained in the carbocycle to which they are bonded is 8 to 14; R'', when independently, is a hydrogen atom or a C1-ClO alkyl group; R'1 is, independently When hydrogen atoms, C1 to Cl
O is an alkyl group or hydroxyalkyl group, or an alkoxycarbonylalkyl group having up to 8 carbon atoms; however, when R'' is H, R7' is a cycloalkyl group having up to 8 carbon atoms, a phenyl group, or It may be a substituted phenyl group containing an alkyl, hydroxy or methoxy substituent of up to 10 carbon atoms; or when R'' and R''''5 taken together, an alkylene group of up to 8 carbon atoms. and an oxygen atom may be present in this carbon atom chain.

) Therefore, according to the present invention, an effective amount of one or more alicyclic amide of the above general formula is incorporated into a consumer product base material so as to pierce the cold receptors of the nervous system of the human body. A consumable product that is applied to or consumed by the human body is provided.

Consumer products referred to in the present invention (Consumer products)
T) refers to products used or consumed by humans for facial cleansing, cosmetics, hygiene, nutrition, treatment, prevention, or other purposes, and refers to products that contain the above-mentioned alicyclic amide on the skin, mucous membranes, and other areas inside and outside the human body. It consists of a vehicle for contacting tissue surfaces such as those of the nose, throat, mouth and gastrointestinal tract, and the consumable products include essentially formless liquid and solid phase products such as solutions, emulsions, pastes, Ointments, powders, and other semi-permanently shaped solid products such as shaped facial cleansing products, cosmetic products, shaped edible products, etc. - These shaped products are only for temporary use. Products that lose their shape - and permanently shaped products, i.e. products that are essentially thrown away after use, such as cleaning tissues, toothpicks, etc.

Representative consumer products containing a cycloaliphatic amide in accordance with the present invention and supported by a vehicle for administering the compound to humans are as follows. 1. Edible or drinkable compositions such as alcoholic and non-alcoholic beverages, confectionery, chewing gum, lozenges, ice creams, jellies, etc.

2. After one. Cheve. Lotion, shaving soap, cream and foam (FOame), facial cleansing water,
Deodorants and antiperspirants, “solid cologne”, toilet soaps,
Bath oil and bath salt, Jump, hair oil, talcum powder, face cream, hand cream, sunscreen lotion, tissue paper, toothpaste, toothpicks, water toothpaste, hair tonic, eye cream.

3. Medications, including antiseptics, hemorrhoid ointments, liniments, lotions, decongestants, anti-stinging agents, cough suppressants, throat tablets, antacids, and ingestibles, analgesics.

4. Water-soluble adhesive compositions for envelopes, postal stamps, adhesive labels, and other various compositions.

5. Tobacco products, such as cigarettes, pipe tobacco, chewing tobacco, snuff, and cigars (hereinafter, products other than smoking tobacco may be referred to as tobacco-containing products).

According to the present invention, the alicyclic amide used as a cold receptor stimulant has high cooling activity,
The odor is minimal or absent.

Preferred amides used in the present invention are represented by the following general formula ().

(where n is O or an integer of 2 to 6; x is 1, 2 or 3; R is a C1 to C5 alkyl group, at least one of the R groups
one is in the 1, 2 or 3-position relative to the amide group,
The total number of carbon atoms provided by the R group and the carbocycle is 8
-14, preferably 8-12; R'' and R'1 are as described above) Particularly preferred amides useful in the present invention are those represented by the following formula (). .

(wherein, n is 0, 2 or 3; at least one of R1 and R2 is a C1-C5 alkynole group; the others are H or C1-C5 alkyl group; R is, when independent, H or C1-C5 alkyl group; C5 alkyl group; RV, when independent, is a H..Cl to C5 alkyl group or hydroxyalkyl group, or an alkylcarboxylalkyl group having up to 6 carbon atoms; when R is H, a C5 to C6 cyclo Alkyl group, phenyl group or hydroxy group, methyl group
or a methoxy monosubstituted phenyl group; R and RV are
Particularly preferred are compounds represented by the formula (), where R1 and R2 are A branched alkyl group, preferably a group with a branch in the α-position relative to the ring, especially an isopropyl group or a Sec-butyl group.

Amides used in the present invention are prepared from appropriate starting materials by methods well known in the art.

For example, amides are prepared by conventional methods from their corresponding acids, such as by converting the acids to acid chlorides and then reacting with ammonia or amines. The starting acid is prepared as follows. (
1) Alkylation of nitriles: Examples, TilfOrd et al., J. et al. A. C. S. (1947)
, 71, 1705 (9) Alkylation of ketonic bases: Examples, StOrk et al., J. et al. A. C. S. (1963), Tei, 2178B0tt0nC0mpt. Rendu. (1
963), 256, (1:1) Alkylation of Ketoesters: Can be used to determine the relative activity of when applied to other parts of the human body, such as the face or forearm, which may be useful for specific external topical applications. Useful in selecting compounds for use in products.

It should be noted that such testing methods were also done on a statistical basis.

This is important because the activity of these O compounds varies not only from compound to compound and from place to place in the human body, but also from person to person. This type of test is commonly used for sensory tests such as taste, smell, etc. of organic or inorganic compounds. [Encyclopedia of Chemical Technology, 2nd edition, by Kirk-Othmer, Ency
clOpediaOfChemicalTechnOl
Ogy2ndEd. ) (1967) VOl. l4336
See pages 344 to 344]. Test Method The test method described below is used to determine the minimum amount of a compound required to produce a sensation of coolness to an average person.

The test is conducted by a selected 6-person test panel with moderate sensitivity to 11 menthol. Panel Selection The following method is used to select an average-sensing test panel.

A known amount of 1-menthol in petroleum ether (boiling point 40-60) solution is placed on 51 td (test piece) of a filter vaporizer and the solvent is evaporated. The observer's name is written down, and the person is asked to place one of the soaked pieces on their tongue and report whether or not it has a cooling effect. The amount of 1-menthol in each of the impregnated specimens is gradually reduced from substantially more than 0.25 μf/Md to less than 0.25 μy/ml. The exact range is not important. The test starts with a test piece containing 1-menthol in an amount of 2.0 μm per square millimeter, and then the amount is halved, and then the amount is halved, and so on.

That is, the second test piece was . Contains 1.0μt, 3
The test pieces for the second time are gradually reduced in weight so that they contain 0.5 μv.
Each amount is tested on the tongue at least 10 times. In this method, the onset of stinging of cold receptors by 1-menthol is determined by each individual on the panel, and each individual's onset of stinging is determined by the amount of 1-menthol in a series of 10 or more tests.
The amount of menthol.

The cooling effect is reported in 50% of the tests. The starting doses of the six panel members for 1-menthol were chosen in the range 0.1 .mu.v to 10 .mu.v, with an average value of about 0.25 .mu.v.

This selected panel is considered an average sensitivity test panel. Testing of Compounds To test the activity of compounds according to this invention,
The method described above was repeated with a select panel of only 6 people with average sensitivity to 1-menthol.

Individual sting onset doses for each compound in a select panel of six people were determined and averaged.

Compounds with an average starting dose of 100 μv or less according to the Select Panel were recognized as having cooling activity in this invention.

Test Results The following table shows the results of testing the relative cooling activity of compounds of the general formula described above using the method described above.

The activity results shown in the table above indicate that highly active compounds have an isopropyl or Sec-butyl substituent at the 11- or 21-position of the ring.

Therefore, compounds that have a very high activity and are preferred for most applications (in some cases, compounds that have a rather low activity for other reasons, such as odor or to increase skin penetration) are preferred. (although it may be preferable to use isopropyl or Sec. It is an amide with a butyl group. This cold receptor stinging agent varies widely in its efficacy as a consumable product, depending on how it is consumed or applied to the human body. These products are generally divided into ingestible and topical products, with both terms used in the broadest sense possible. Therefore, the term "ingestion" includes not only foods and beverages that are eaten or drunk, but also other products that are ingested orally for reasons other than nutritional value, such as digestive tablets, antacids, and laxatives. . Ingestible also includes compositions that are taken orally, but are not swallowed, such as chewing gum. Topical products include perfumes, white powders and other cosmetics, lotions, liniments, oils and ointments, as well as compositions applied to the external surfaces of the human body for medical or other reasons, as well as the nose, mouth, etc. It is a composition that is applied or, in its usual usage, brought into contact with the internal mucosa of the human body, such as any internal mucosa, by directly or indirectly applying or inhaling it. Therefore, nose and throat sprays, toothpaste,
Also included are mouth cleansers and gargle compositions. In this context, topical products also include cosmetic products such as wipes and toothpicks. In manufacturing the products of this invention, the cold receptor stimulant is mixed into a vehicle for application to the human body.

The vehicle may be entirely inert or other active ingredients, and usually contains other active ingredients. Various types of vehicles are suitable depending on the particular product involved, but such vehicles include solids, liquids, emulsions, foams and gels.

Typical vehicles for cold receptor stimulants include water or alcohol solutions, oils and fats such as hydrocarbon oils, fatty acid esters, long chain alcohols and silicone oils; particles such as starch or talc. fine solids; cellulosic materials such as paper; low-boiling hydrocarbons and halogens used as aerosol propellants7
carbonized hydrocarbons; including rubber and natural or synthetic resins. Generally, these vehicles will include one or more of the excipients commonly used in topical and ingestible compositions, such as flavoring agents, colorants, fragrances, surfactants, preservatives, and the like.

A more detailed description of the special products according to the invention is given below.

Cosmetics The main field of application of the cold receptor stimulant of this invention is in the field of cosmetics, which are broadly classified as appearance protection products.

These are defined as products applied to humans for grooming or hygiene or cosmetic purposes, including cosmetics and fragrances, but excluding prescription and proprietary pharmaceutical products.
Special appearance protection products are described in the Examples and special examples are shown below. 1 of the appearance protection products containing the compound of the present invention
Examples include topical lotions, such as aftershave lotions, toners, etc., in which the compound is used as an alcoholic or hydroalcoholic solution, which usually contains fragrance and/or moderate preservatives. including. The amount of compound added to the composition is usually within the range of 0.1 to 5% by weight, based on the total composition. Another type of appearance protection products are soaps and soap-based compositions, in which the compounds are used together with oils, fats or natural or synthetic surfactants, such as fatty acid salts or lauryl sulfates. It will be done. The composition usually also includes essential oils or fragrances.

In soap compositions, which include all types of soaps, such as cosmetic soaps, shaving soaps, shaving foams, especially aerosol shaving foams, this compound is usually present in an amount of 0.5 to 5% by weight. is added to the composition in amounts ranging from . Other classes of appearance protection products in which cold receptor stinging agents are included are cosmetic creams, emollients and lotions; such cream emollients and lotions usually contain O/W emulsions as a base. and optional ingredients such as wax, preservatives, fragrances, antifouling agents, astringents, pigments, and others.

This class includes lipstick compositions, which usually consist of an oil and a wax space to which a cooling agent has been added together with other ingredients such as pigments. on the other hand,
The incorporation of cold receptor stinging agents in such products is as described above, but the amount usually ranges from 0.01 to 5% by weight. Mouth hygiene agents into which the cold receptor stinging agent of the present invention is mixed include mouthwashes, mouthwashes, and water toothpaste compositions.

The first two are usually recognized as the same thing and are usually an aqueous, alcoholic, or water-alcoholic solution of the detergent, often colored;
Flavoring agents are also added to make it more delicious, and 0.01 to 1% by weight of a cold receptor stimulant is added. Toothbrushing compositions may be of solid block, powder, paste or liquid type and usually contain finely divided polishing substances such as precipitate, silica, magnesium silicate, aluminum hydroxide, or the like. It consists of similar materials known in the art and cleaning or foaming agents. It may contain optional ingredients such as perfumes, colorants, anti-fouling agents, lubricants, thickeners, emulsifiers or plasticizers. The amount of cold receptor stinging agent added to these compositions is generally 0.1% of the total composition.
~1% by weight. Edible and Edible Composition The cold receptor stinging agent according to the present invention is an edible composition comprising an edible base and generally one or more flavoring or coloring agents. widely mixed.

The characteristic effect of this cold receptor stinging agent is that it produces a cooling effect in the mouth and in some cases even in the stomach, so it can be used in sugar-based chocolates, sweets, mint candied ice creams, jellies, etc. and confectionery such as chewing gum. This type of confectionery production is based on traditional techniques and manufacturing methods and does not fall within the scope of the present invention. The cold receptor stinging agent is appropriately added in an amount sufficient to provide the desired cooling effect in the product. As already mentioned, the amount will vary depending on the compounds in the product, the degree of cooling effect desired, and the intensity of other fragrances. However, as a general guideline, 0.01~
The amount ranges from 5.0% by weight. Similar ideas apply to the production of beverages.

Generally, the compounds are most useful in soft drinks, such as fruit squash, lemonade, colas, etc., but can also be used in alcoholic beverages. The amount of compound used is usually 0.00% based on the total composition.
It is between 1 and 2.5% by weight. Due to their cooling effect on the skin and the mucous membranes of the mouth, throat, nose, and gastrointestinal tract, cold receptor stinging agents are needed in various oral medications, nasal and throat sprays, and especially in topical compositions of anti-stinging agents. It can be used as

Generally, these pharmaceutical agents, whether topical, ingestible, proprietary, or by certified standard, contain a pharmaceutically acceptable liquid or solid carrier, a pharmaceutically active ingredient, and Cold receptor stimulating agents are mixed into the drugs that are mixed into the skin, other body surfaces, or the mouth.
It has a pleasant cooling effect on the gastrointestinal system, depending on its formulation and method of external application or internal administration.

Special properties of the compounds of the invention include antacids, especially those based on sodium bicarbonate, magnesium oxide, calcium or magnesium carbonate, aluminum or magnesium hydroxide or magnesium trisilicate;
Useful in digestive preparation. In such compositions, the compound is generally added in an amount of 0.01 to 1.0% by weight. Cold receptor stinging agents are included in oral pain relievers.
It is added and mixed together with acetylsalicylic acid or its salt, and together with ephedrin-containing substances in nasal anti-inflammatories.

A consumable product according to the invention is shown in the examples below, with all percentages given by weight.

Next, examples of consumer products according to the present invention will be given.

In each example, all % indicates weight %. Example 1 Paste toothpaste The following ingredients are mixed in a kneading machine to make a paste toothpaste. Immediately before the above ingredients are kneaded, 0.5% by weight of N-ethyl 1-isopropyl cycloheptanecarboxamide is added to the kneader.
added.

When this was used as toothpaste, a strong cooling sensation was observed in the mouth. Example 2 Aerosol Shaping Soap The formulation is as follows.

Add water to make the total volume 100%.

This composition is obtained by dissolving the acid in water, adding triethanolamine, and adding the other ingredients while cooling.

Next, N-(1,1-dimethyl-2-hydroxyethyl) corresponding to 0.5% of the total amount of the composition is added to this mixture.
1-Ethylcycloheptanecarboxamide was added.

When this composition, packaged as an aerosol dispersed in the presence of a butane propellant, was used for shaving, the face felt distinctly fresh and cool. Example 3 Toothpick The tip of a wooden toothpick was impregnated with an alcohol solution of N-N-dimethyl-1-ethylcyclooctanecarboxamide so that the toothpick contained 0.05η of the alcohol, and then dried.

When I put this on my tongue, I immediately felt a sharp cooling sensation. Example 4 Eye Lotion An eye lotion was prepared by blending the following ingredients.

Add water to make the total volume 100%.

Next, add 0.003% N.1 to the total composition to this formulation.
- Added diethylcycloundecane carboxamide.

When I washed my eyes with this eye lotion, I felt a fresh, cool sensation on my eyeballs and eyelids. Example 5 A lotion was made using the following recipe.

Add water to make the total volume 100%.

To this formulation, 0.5% of the total amount of N-methyl-1-isopropyl-2-methylcycloheptanecarboxamide was added.

When this product was used, the skin remained cool even after the cooling sensation caused by the evaporation of the alcohol disappeared, similar to the case with after-shave lotion.

Example 6 Soft Sweet 1A/1f4rek1min9,1n2A85peyu,J1kah
I made 1-10 strikes.

Next, 0.05% of N-2'-hydroxyethyl-N-methyl-1-isopropyl-2-methylcycloheptanecarboxamide was added to this with stirring and allowed to solidify. The product obtained in this way had a soft sweetness in the mouth with a unique cooling effect, although it had no fragrance or fragrance. Example 7 Digestive Tablet The following ingredients were milled.

While grinding this mixture, 0.05% N.1-diethyl-
2-Methylcycloheptanecarboxamide was added.

After mixing, the mixture was compressed into 0.5y tablets.
When these tablets were taken orally, they immediately produced a distinct cooling effect in the stomach. Example 8 Hydrophilic Ointment A hydrophilic ointment was prepared according to the following formulation.

Add water to make the total volume 100%.

Sodium lauryl sulfate was added to water and heated to 60°C.

Next, paraffin heated to 60° C. and melted was added to this mixture while stirring, and then propylene glycol and 1-octadecanol were added to the mixture. To the mixture thus obtained was added 2% N-(1-isopropylcyclopentanecarbonyl)piveridine.

When this ointment was applied to the skin, a noticeable cooling effect appeared. Example 9 A deodorant composition suitable for making and formulating an aerosol in the presence of a deodorant propellant has the following formulation.

To this formulation was added 1.3% by weight N-ethyl-1-isopropyl 2-methylcyclopentanecarboxamide. When I used this product on my skin, I felt a cooling sensation. Example 10 Lipstick 0.06% by weight of N-1-butyl-2-isopropylcycloheptanecarboxyamide was mixed into a molten proprietary lipstick and the mixture was again made into a solid lipstick.

When I applied this to my mouth, I could clearly feel the lasting cooling effect. Example 11 Solid Colon A solid colon was prepared according to the following recipe.

Add water to make the total volume 100%.

Sodium stearate was dissolved in a warm mixture of ethanol, propylene glycol and water with stirring.

To this solution was added perfume and 3.0% N-methyl-2-ethylcycloheptanecarboxamide, and the mixture was then solidified into a wax cake. When I used this on my forehead, it had a cooling effect. Example 12 Hair Tonic A hair tonic was prepared.

Dissolve star oil, resorcinol and fragrance in ethanol component, and add 2% N-2-hydroxyethyl-
N-Methyl-1-isopropyl-2-methylcycloheptanecarboxamide was added.

When I applied this to my scalp, I felt a cooling sensation. Example 13 A concentrated mouthwash composition was prepared according to the following formulation.

Add water to make the total volume 100%. In this composition 0.1
% of N.1-diisopropyl-2-methylcyclobentanecarboxamide was added.

When this was diluted with about 10 times the volume of water and used to rinse the mouth, it gave a cooling effect to the mouth. Example 14 Talcum Powder Talcum powder was prepared by grinding with the following ingredients.

During milling, 3% N-ethyl-1-Sec. Butylcyclohebutanecarboxamide was added.

A fresh cooling effect was obtained from this talcum powder. The above examples are provided to illustrate the scope of the compounds and compositions included in the present invention, and are not intended to limit the scope of the present invention.

A number of other compounds of the above general formula are likewise suitable for use in the compositions of Examples 1-14, and the physiological cooling effect obtained by the compounds of the invention is In addition to the above, it can also be suitably used in various other compositions where the cooling effect is respected. The aforementioned alicyclic amides described as cold receptor stinging agents in exfoliative and topical compositions are also useful as cold receptor stinging agents in tobacco products.

As already mentioned, menthol is widely used despite its strong, nutty aroma and relative volatility.

Other similar compounds have also been proposed as replacements for menthol in tobacco (see e.g. the above publication).
. Other compounds have also been proposed as flavoring agents in tobacco rather than as cooling agents, among them 2-isopropyl-5-methylhexanol (or 2,6-dimethylhept-3-ylmethanol) and the related Certain compounds are disclosed in US Pat. No. 3,704,714. Despite these various disclosures, there remains a need for menthol as a substitute for menthol, which is added to cigarettes to provide a cooling effect when smoking. Another object of the present invention is to contain ingredients that give a cooling sensation when the ingredients come into contact with the mucous membranes of the nose and mouth, or when smoking a cigarette, and furthermore, when the cigarette comes into direct contact with the mucous membranes of the nose and mouth. The objective is to provide tobacco and tobacco-containing products, which do not suffer from the disadvantages of strong musty odor and storage instability.

Another object of the invention is an improved method of imparting physiological cooling activity to tobacco and tobacco-containing products.

According to the invention, tobacco or tobacco-containing products contain an effective amount to sting cold receptors in the nervous system of the mucous membranes of the nose or mouth when a person smokes, chews or sips the tobacco or tobacco-containing product. Tobacco and tobacco-containing products containing cold receptor sting additives are provided.

The additive referred to herein has the above general formula (1) that can sting the sense of cold.
).

For the purposes of this invention, tobacco and tobacco-containing products are defined as any composition prepared for human use, whether for smoking or non-smoking, such as cigarettes, cigars or pipes or chewing tobacco, snuff, i.e. manufactured tobacco. This includes all forms of combustion, inhalation of tobacco smoke, chewing or direct inhalation of tobacco.

Tobacco and tobacco-containing products of the active compounds of the invention include:
For example, it is usually added during the manufacturing process by impregnating the tobacco with an appropriate alcoholic solution of the active ingredient.

However, in another preferred preparation, the active ingredient is added to tobacco smoking filters used in pipes, cigar tobacco filters, and cigar tobacco filter tips. More specifically regarding the latter, a particularly advantageous form of use of the invention is that the active compound is simply added to the filler of filter tip-forming material. These include, for example, the familiar cigarette filters of cellulose acetate, cotton, alpha-cellulose or asbestos fibres. Typically, filter tips are impregnated with an alcoholic solution of the active compound and this is dried to deposit the active compound onto them. The amounts of active compounds impregnated into tobacco or tobacco-containing products according to the invention are those necessary to contact the skin and feel the cooling effect, and they also vary depending on the application, such as the tobacco itself, the filter tip, Or it may change depending on many other accessories. However, as a guideline, for more active compounds, it is effective to apply a small amount of about 1 C0.01 m' to the filter tip of a cigarette with a tip. Next, tobacco and tobacco-containing products according to the present invention will be mentioned.

Example 15 Cigarettes A proprietary product of cigarettes was sprayed with an ethanolic solution of N.1-diisopropyl 2-methylcyclopentanecarboxamide so that each cigarette contained approximately 0.0% of the active compound.
This was wrapped in paper so that it contained 1 m'.

When I smoked this impregnated cigarette, it gave me the cooling effect in my mouth that is characteristic of menthol-treated cigarettes, and I did not notice any strange odor other than the aroma that is typical of ordinary cigarettes.
Example 16 Cigarettes with Filters A company's cigarette filter chips contain an amount of N-ethyl 1-Sec. sufficient to deposit 0.1 w of active compound on the filter chips. It was impregnated with an ethanol solution of butylcycloheptanecarboxamide.

Cigarettes with this impregnated chip had a clear cooling effect on the mouth when sipped. Example 17 Pipe Tobacco A proprietary product of pipe tobacco was sprayed with an ethanolic solution of Nt-butyl-2-isopropylcycloheptanecarboxamide 27 to 5 w of active compound and filled into a pipe.

When smoking this impregnated cigarette, a cooling effect characteristic of menthol-treated cigarettes was obtained in the mouth. Example 1
8 Cigar Tobacco A proprietary product of cigar tobacco was impregnated with an ethanolic solution of N-ethyl-1-isopropylcycloheptanecarboxamide so that 2η of active substance was added.

When I smoked this cigar, I felt a cooling effect in my mouth. Example 19 Snuff Snuff Proprietary 17 was impregnated with an ethanolic solution of N.1-diethylcycloheptanecarboxamide so that 5η of active substance was added.

Claims (1)

[Claims] 1 General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, n is 0 or an integer from 2 to 6; x is 1
, 2 or 3; R is a C_1-C_5 alkyl group, and at least one R group has a value of 1 to amide group;
, 2 or 3, and the total number of carbon atoms contained in all R groups and the carbon rings to which they are bonded is from 8 to 14; R'', when independently, is a hydrogen atom or C_1 ~C_1_0 is an alkyl group; R″′ is
When independent, it is a hydrogen atom, an alkyl group or hydroxyalkyl group of C_1 to C_1_0, or an alkoxycarbonylalkyl group having up to 8 carbon atoms; however, when R″ is H, R″′ is a carbon Number of atoms: 8
may be a cycloalkyl group, a phenyl group, or a substituted phenyl group containing an alkyl, hydroxy or methoxy substituent having up to 10 carbon atoms; or when R″ and R″′ taken together, , represents an alkylene group having up to 8 carbon atoms, and an oxygen atom may be present in the carbon atom chain. ) A method for imparting physiological cooling activity to toiletries, cosmetics, foods, beverages, pharmaceuticals, and tobacco, the method comprising incorporating a cyclic carboxyamide having the following properties into an article.