RU2772501C2 - Vaporised composition - Google Patents

Abstract

FIELD: smoking devices.

SUBSTANCE: vaporised composition for electronic vapour supply systems comprises one or multiple solvents, less than 1 wt.% of a cooling agent as calculated for the mass of the vaporised composition, wherein the cooling agent volatilises at a higher temperature than menthol at atmospheric pressure. The cooling agent constitutes N,2,3-trimethyl-2-propane-2-ylbutanamide, or a compound of the structural formula (I) or a salt and/or solvate thereof.

EFFECT: stability is improved, sensory advantages are provided with a change in the cooling sensation.

20 cl, 12 dwg, 4 tbl

Description

The field of technology to which the invention belongs

The present invention relates to a vaporizable composition, to containers in which the vaporizable composition is contained, and to electronic vapor delivery systems such as electronic vapor delivery systems (eg, electronic cigarettes) comprising said composition.

State of the art invention

Electronic vapor delivery systems, such as electronic cigarettes, typically contain a reservoir of liquid to be vaporized, typically containing nicotine. When the user puffs on the device, the heater is turned on to vaporize a small amount of liquid, which is therefore inhaled by the user. Electronic cigarette liquid may also contain a flavor component such as menthol to provide a sensory experience to the user. In some cases, the e-liquid may contain a nicotine-free flavor.

However, menthol is extremely volatile and easily evaporates in the presence of heat. This high volatility is problematic for current e-cigarette devices as it can lead to degraded flavor quality and consumer satisfaction. The volatility of menthol also adversely affects the shelf life of the liquid in or for an electronic cigarette device.

The essence of the invention

In a first characteristic, a vaporizable formulation is provided comprising (i) one or more solvents; and (ii) less than about 1% by weight of coolant, based on the weight of the vaporized composition, wherein the coolant volatilizes at a higher temperature than menthol at atmospheric pressure.

In a second characteristic, a vaporizable formulation is provided comprising (i) one or more solvents; and (ii) less than about 12% by weight of a cooling agent, preferably equal to or less than about 10% by weight based on the weight of the vaporized composition, wherein the cooling agent volatilizes at a higher temperature than menthol at atmospheric pressure, and is a compound of formula (I) or a salt and/or solvate thereof:

where X is hydrogen or OR', where R' is an alkyl group or an alkenyl group, which can be taken together with R ₁ to form a three to five membered heterocyclyl group, where the heterocyclyl group is optionally substituted with one or more selected substituents from OH, O -alkyl, alkyl-OH, alkyl-O-alkyl, NH ₂ , NH-alkyl, N- (alkyl) ₂ , NO ₂ and CN; and where each of R ₁ and R ₂ is independently selected from hydrogen, OH, OR _a , C(O)NR _b R _c and C(O)OR _b R _c ; with the proviso that when R ₁ is OH, the compound of formula (I) is not menthol; and when a double bond is present, R ₂ is absent;

where R _a is an alkyl group, an alkenyl group, a C(O)R _f group, or a C(O)-alkyl-C(O)R _f group, where the alkyl groups and alkenyl groups are optionally substituted with one or more substituents selected from OH , O-alkyl, NH ₂ , NH-alkyl, N-(alkyl) ₂ , NO ₂ and CN; and where R _f is an alkyl group, an alkenyl group, OH, O-alkyl, NH ₂ , NH-alkyl, or N-(alkyl) ₂ , where the alkyl groups and alkenyl groups are optionally substituted with one or more substituents selected from OH, O -alkyl, NH ₂ , NH-alkyl, N-(alkyl) ₂ , NO ₂ and CN;

where R _b and R _c are each independently hydrogen, an alkyl group, an alkenyl group, an aryl group, an aralkyl group, a heteroaryl group, or a heteroaralkyl group, wherein the alkyl groups, alkenyl groups, aryl groups, and heteroaryl groups are optionally substituted with one or more substituents selected from from OH, O-alkyl, NH ₂ , NH-alkyl, N-(alkyl) ₂ , NO ₂ , CN and C(O)R _f .

Unless otherwise indicated, the detailed description below applies to both the first and second features of the invention.

The present invention further provides a process for generating steam, comprising (a) providing a vaporizable composition as defined herein, and (b) vaporizing the composition.

The present invention further provides (a) a container containing a vaporizable composition, and (b) a vaporizable composition as defined herein.

The present invention also provides an electronic vapor supply system, comprising (a) a vaporizer for vaporizing liquid for inhalation by a user of the electronic vapor supply system, (b) a power supply containing a cell or battery for supplying energy to the vaporizer, and (c) a vaporizable composition, as defined here.

The present invention further provides for the use of a coolant to extend the shelf life of a vaporizable formulation, where the coolant volatilizes at a higher temperature than menthol at atmospheric pressure.

Detailed description

As discussed in the present description, the present invention provides a vaporizable composition containing (i) one or more solvents, and either (ii) less than about 1 wt. higher temperature than menthol at atmospheric pressure, or less than about 12 wt.% coolant, based on the weight of the evaporated composition, where the coolant volatilizes at a higher temperature than menthol at atmospheric pressure, and is a compound of formula (I ) or its salt and/or solvent as defined above and herein.

The use of sensitive substances and especially cooling agents is well known in the food and pharmaceutical industries. Cooling agents are typically small organic molecules, such as menthol, that provide the user with a sensation of coldness upon contact with the mouth, nasal cavity, and/or skin. This sensation of cooling belongs to the category of hemestetic (chemically perceptible) sensations and is due to the fact that a small organic molecule activates certain receptors on the skin and/or mucous membranes. Thus, the sensation of cooling depends on the user's chemesthesis. Chemestesis is also referred to in the art as "general chemical sense" or trigeminal chemosensitivity because it usually refers to sensations that are mediated by the trigeminal nerve and are elements of the somatosensory system that distinguish them from smell and taste.

Menthol is a widely used cooling agent. It is, for example, used in mouthwashes and topical anesthetic creams to provide a cooling effect. This cooling effect is believed to result from the user's cold-sensitive TRPM8 receptors in the mouth, nasal cavity and/or skin being chemically activated by menthol. A similar effect is observed when using menthol as a tobacco additive. Menthol provides a minty smell and taste when inhaled by the user.

Menthol, however, is problematic when added to liquid in an e-cigarette device because it can cause respiratory irritation and is associated with a bitter taste and burning sensation when used at higher concentrations. Menthol is also an extremely volatile compound. It has a high vapor pressure at room temperature and a low boiling point at atmospheric pressure. For example, at 25°C, the vapor pressure of menthol is approximately 7.67 x 10 ^-3 mmHg. (approximately 1.02 Pa). At atmospheric pressure (760 mmHg or 101325 Pa), menthol has a boiling point of 212°C. This volatility causes the minty smell of menthol, but adversely affects the storage stability of the liquid containing menthol. In particular, the shelf life of the liquid is greatly reduced due to the presence of menthol, as it readily volatilizes under typical storage conditions, such as the pressure and ambient temperature applied by the user to an electronic cigarette liquid cartridge.

The inventors have found that by including a cooling agent which is less volatile at atmospheric pressure than menthol and optionally a compound of formula (I) or a salt and/or solvate thereof, a volatilization composition can be obtained which has improved storage stability and, hence longer shelf life compared to a vaporized formulation containing menthol. The cooling agents described herein also produce a sensation of coldness when the user generates vapor from the vaporized composition and have been shown to have various sensory benefits over menthol.

For ease of reference, these and other aspects of the present invention are now discussed under their respective section headings. However, the principles of each section are not necessarily limited to each specific section.

coolant

As discussed herein, the evaporative composition of the first characteristic of the present invention contains a cooling agent in an amount of less than about 1 wt.% based on the total weight of the evaporable composition. The term "less than" means any amount lower than 1 wt.%, but not including zero. In other words, the evaporating composition must include some amount of refrigerant.

In one aspect, the cooling agent is present in an amount of not more than about 0.9 wt.%.

In one aspect, the cooling agent is present in an amount of from about 0.001 wt.% to about 0.9 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.002 wt.% to about 0.9 wt.%, based on the total weight of the vaporized composition. In one aspect, the cooling agent is present in an amount of from about 0.003 wt.% to about 0.9 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.004 wt.% to about 0.9 wt.%, based on the total weight of the vaporized composition. In one aspect, the cooling agent is present in an amount of from about 0.005 wt.% to about 0.9 wt.%, based on the total weight of the vaporized composition. In one aspect, the cooling agent is present in an amount of from about 0.006 wt.% to about 0.9 wt.%, based on the total weight of the vaporized composition. In one aspect, the cooling agent is present in an amount of from about 0.007 wt.% to about 0.9 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.008 wt.% to about 0.9 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.009 wt.% to about 0.9 wt.%, based on the total weight of the evaporated composition.

In one aspect, the cooling agent is present in an amount of from about 0.01 wt.% to about 0.9 wt.%, based on the total weight of the vaporized composition. In one aspect, the cooling agent is present in an amount of from about 0.02 wt.% to about 0.9 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.03 wt.% to about 0.9 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.04 wt.% to about 0.9 wt.%, based on the total weight of the vaporized composition. In one aspect, the cooling agent is present in an amount of from about 0.05 wt.% to about 0.9 wt.%, based on the total weight of the vaporized composition. In one aspect, the cooling agent is present in an amount of from 0.06 wt.% to about 0.9 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.07 wt.% to about 0.9 wt.%, based on the total weight of the vaporized composition. In one aspect, the cooling agent is present in an amount of from about 0.08 wt.% to about 0.9 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.09 wt.% to about 0.9 wt.%, based on the total weight of the evaporated composition.

In one aspect, the cooling agent is present in an amount of from about 0.1 wt.% to about 0.9 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.2 wt.% to about 0.9 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.3 wt.% to about 0.9 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.4 wt.% to about 0.9 wt.%, based on the total weight of the evaporating composition. In one aspect, the cooling agent is present in an amount of from about 0.5 wt.% to about 0.9 wt.%, based on the total weight of the evaporated composition.

In another aspect, the cooling agent is present in an amount of not more than about 0.8 wt.%.

In one aspect, the cooling agent is present in an amount of from about 0.001 wt.% to about 0.8 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.002 wt.% to about 0.8 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.003 wt.% to about 0.8 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.004 wt.% to about 0.8 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.005 wt.% to about 0.8 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.006 wt.% to about 0.8 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.007 wt.% to about 0.8 wt.%, based on the total weight of the vaporized composition. In one aspect, the cooling agent is present in an amount of from about 0.008 wt.% to about 0.8 wt.%, based on the total weight of the vaporized composition. In one aspect, the cooling agent is present in an amount of from about 0.009 wt.% to about 0.8 wt.%, based on the total weight of the vaporized composition.

In one aspect, the cooling agent is present in an amount of from about 0.01 wt.% to about 0.8 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.02 wt.% to about 0.8 wt.%, based on the total weight of the vaporized composition. In one aspect, the cooling agent is present in an amount of from about 0.03 wt.% to about 0.8 wt.%, based on the total weight of the vaporized composition. In one aspect, the cooling agent is present in an amount of from about 0.04 wt.% to about 0.8 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.05 wt.% to about 0.8 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.06 wt.% to about 0.8 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.07 wt.% to about 0.8 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.08 wt.% to about 0.8 wt.%, based on the total weight of the vaporized composition. In one aspect, the cooling agent is present in an amount of from about 0.09 wt.% to about 0.8 wt.%, based on the total weight of the evaporated composition.

In one aspect, the cooling agent is present in an amount of from about 0.1 wt.% to about 0.8 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.2 wt.% to about 0.8 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.3 wt.% to about 0.8 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.4 wt.% to about 0.8 wt.%, based on the total weight of the evaporated composition.

In another aspect, the cooling agent is present in an amount of no more than about 0.75% by weight.

In one aspect, the cooling agent is present in an amount of from about 0.001 wt.% to about 0.75 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.002 wt.% to about 0.75 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.003 wt.% to about 0.75 wt.%, based on the total weight of the vaporized composition. In one aspect, the cooling agent is present in an amount of from about 0.004 wt.% to about 0.75 wt.%, based on the total weight of the vaporized composition. In one aspect, the cooling agent is present in an amount of from about 0.005 wt.% to about 0.75 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.006 wt.% to about 0.75 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.007 wt.% to about 0.75 wt.%, based on the total weight of the vaporized composition. In one aspect, the cooling agent is present in an amount of from about 0.008 wt.% to about 0.75 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.009 wt.% to about 0.75 wt.%, based on the total weight of the evaporated composition.

In one aspect, the cooling agent is present in an amount of from about 0.01 wt.% to about 0.75 wt.%, based on the total weight of the vaporized composition. In one aspect, the cooling agent is present in an amount of from about 0.02 wt.% to about 0.75 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.03 wt.% to about 0.75 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.04 wt.% to about 0.75 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.05 wt.% to about 0.75 wt.%, based on the total weight of the vaporized composition. In one aspect, the cooling agent is present in an amount of from about 0.06 wt.% to about 0.75 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.07 wt.% to about 0.75 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.08 wt.% to about 0.75 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.09 wt.% to about 0.75 wt.%, based on the total weight of the evaporated composition.

In one aspect, the cooling agent is present in an amount of from about 0.1 wt.% to about 0.75 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.2 wt.% to about 0.75 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.3 wt.% to about 0.75 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.4% to about 0.75% by weight, based on the total weight of the evaporating composition.

In one aspect, the cooling agent is present in an amount of no more than about 0.5 wt%.

In one aspect, the cooling agent is present in an amount of from about 0.001 wt.% to about 0.5 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.002 wt.% to about 0.5 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.003 wt.% to about 0.5 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.004 wt.% to about 0.5 wt.%, based on the total weight of the vaporized composition. In one aspect, the cooling agent is present in an amount of from about 0.005 wt.% to about 0.5 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.006 wt.% to about 0.5 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.007 wt.% to about 0.5 wt.%, based on the total weight of the vaporized composition. In one aspect, the cooling agent is present in an amount of from about 0.008 wt.% to about 0.5 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.009 wt.% to about 0.5 wt.%, based on the total weight of the evaporated composition.

In one aspect, the cooling agent is present in an amount of from about 0.01 wt.% to about 0.5 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.02 wt.% to about 0.5 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.03 wt.% to about 0.5 wt.%, based on the total weight of the vaporized composition. In one aspect, the cooling agent is present in an amount of from about 0.04 wt.% to about 0.5 wt.%, based on the total weight of the vaporized composition. In one aspect, the cooling agent is present in an amount of from about 0.05 wt.% to about 0.5 wt.%, based on the total weight of the vaporized composition. In one aspect, the cooling agent is present in an amount of from about 0.06 wt.% to about 0.5 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.07% to about 0.5% by weight, based on the total weight of the evaporating composition. In one aspect, the cooling agent is present in an amount of from about 0.08 wt.% to about 0.5 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.09 wt.% to about 0.5 wt.%, based on the total weight of the evaporated composition.

In one aspect, the cooling agent is present in an amount of from about 0.1 wt.% to about 0.5 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.2 wt.% to about 0.5 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.3 wt.% to about 0.5 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.4 wt.% to about 0.5 wt.%, based on the total weight of the evaporated composition.

In another aspect, the cooling agent is present in an amount of no more than about 0.3 wt%.

In one aspect, the cooling agent is present in an amount of from about 0.001 wt.% to about 0.3 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.002 wt.% to about 0.3 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.003 wt.% to about 0.3 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.004 wt.% to about 0.3 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.005 wt.% to about 0.3 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.006 wt.% to about 0.3 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.007 wt.% to about 0.3 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.008 wt.% to about 0.3 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.009 wt.% to about 0.3 wt.%, based on the total weight of the evaporated composition.

In one aspect, the cooling agent is present in an amount of from about 0.01 wt.% to about 0.3 wt.%, based on the total weight of the vaporized composition. In one aspect, the cooling agent is present in an amount of from about 0.02 wt.% to about 0.3 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.03 wt.% to about 0.3 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.04 wt.% to about 0.3 wt.%, based on the total weight of the vaporized composition. In one aspect, the cooling agent is present in an amount of from about 0.05 wt.% to about 0.3 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.06 wt.% to about 0.3 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.07 wt.% to about 0.3 wt.%, based on the total weight of the vaporized composition. In one aspect, the cooling agent is present in an amount of from about 0.08 wt.% to about 0.3 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.09 wt.% to about 0.3 wt.%, based on the total weight of the evaporated composition.

In one aspect, the cooling agent is present in an amount of from about 0.1 wt.% to about 0.3 wt.%, based on the total weight of the evaporated composition. In one aspect, the cooling agent is present in an amount of from about 0.2 wt.% to about 0.3 wt.%, based on the total weight of the evaporated composition.

The specialist will understand that the evaporative composition described here may include more than one cooling agent. When the composition includes more than one cooling agent, each cooling agent may be included in the above amounts, so that each cooling agent is included in an amount of less than about 1 wt.%. For example, the first cooling agent may be included in an amount of from about 0.001 wt.% to 0.9 wt.% of the mass of the vaporized composition, and the second cooling agent may be included in an amount of from about 0.001 wt.% to 0.9 wt.% . based on the mass of the evaporated composition. Alternatively, the second cooling agent may be included in an amount of from about 0.05 to 0.9 wt.% based on the weight of the vaporized composition. It is understood that this combination of ranges is for the purposes of the example only, the volatilized composition is not limited in this regard.

In a second characteristic of the present invention, a cooling agent is defined as a compound of formula (I) or a salt and/or solvate thereof, and the evaporating composition comprises said cooling agent in an amount of less than about 12% by weight, based on the total weight of the evaporating composition. The term "less than" has the same meaning as in the first characteristic. The following disclosure relates to the second characteristic.

In one aspect, said second feature coolant is present in an amount of no more than about 11% by weight.

In one aspect, said cooling agent is present in an amount of from about 0.001 wt.% to about 11 wt.%, based on the total weight of the vaporized composition. In one aspect, said cooling agent is present in an amount of from about 0.005% to about 11% by weight, based on the total weight of the evaporating composition. In one aspect, said cooling agent is present in an amount of from about 0.01 wt.% to about 11 wt.%, based on the total weight of the vaporized composition. In one aspect, said cooling agent is present in an amount of from about 0.05 wt.% to about 11 wt.%, based on the total weight of the vaporized composition. In one aspect, said cooling agent is present in an amount of from about 0.1 wt.% to about 11 wt.%, based on the total weight of the vaporized composition.

In another aspect, said cooling agent is present in an amount of no more than about 10% by weight.

In one aspect, said cooling agent is present in an amount of from about 0.001 wt.% to about 10 wt.%, based on the total weight of the vaporized composition. In one aspect, said cooling agent is present in an amount of from about 0.005 wt.% to about 10 wt.%, based on the total weight of the vaporized composition. In one aspect, said cooling agent is present in an amount of from about 0.01 wt.% to about 10 wt.%, based on the total weight of the vaporized composition. In one aspect, said cooling agent is present in an amount of from about 0.05 wt.% to about 10 wt.%, based on the total weight of the vaporized composition. In one aspect, said cooling agent is present in an amount of from about 0.1 wt.% to about 10 wt.%, based on the total weight of the vaporized composition.

In another aspect, said cooling agent is present in an amount of no more than about 8% by weight.

In one aspect, said cooling agent is present in an amount of from about 0.001 wt.% to about 8 wt.%, based on the total weight of the vaporized composition. In one aspect, said cooling agent is present in an amount of from about 0.005 wt.% to about 8 wt.%, based on the total weight of the vaporized composition. In one aspect, said cooling agent is present in an amount of from about 0.01 wt.% to about 8 wt.%, based on the total weight of the vaporized composition. In one aspect, said cooling agent is present in an amount of from about 0.05 wt.% to about 8 wt.%, based on the total weight of the vaporized composition. In one aspect, said cooling agent is present in an amount of from about 0.1 wt.% to about 8 wt.%, based on the total weight of the vaporized composition.

In another aspect, said cooling agent is present in an amount of no more than about 5% by weight.

In one aspect, said cooling agent is present in an amount of from about 0.001 wt.% to about 5 wt.%, based on the total weight of the vaporized composition. In one aspect, said cooling agent is present in an amount of from about 0.005 wt.% to about 5 wt.%, based on the total weight of the vaporized composition. In one aspect, said cooling agent is present in an amount of from about 0.01 wt.% to about 5 wt.%, based on the total weight of the vaporized composition. In one aspect, said cooling agent is present in an amount of from about 0.05 wt.% to about 5 wt.%, based on the total weight of the vaporized composition. In one aspect, said cooling agent is present in an amount of from about 0.1 wt.% to about 5 wt.%, based on the total weight of the vaporized composition.

In another aspect, the specified cooling agent is present in an amount of not more than about 3 wt.%, for example, about 2.5% of the mass.

In one aspect, said cooling agent is present in an amount of from about 0.001 wt.% to about 3 wt.%, based on the total weight of the vaporized composition. In one aspect, said cooling agent is present in an amount of from about 0.005 wt.% to about 3 wt.%, based on the total weight of the vaporized composition. In one aspect, said cooling agent is present in an amount of from about 0.01 wt.% to about 3 wt.%, based on the total weight of the vaporized composition. In one aspect, said cooling agent is present in an amount of from about 0.05 wt.% to about 3 wt.%, based on the total weight of the vaporized composition. In one aspect, said cooling agent is present in an amount of from about 0.1 wt.% to about 3 wt.%, based on the total weight of the vaporized composition.

With regard to the first characteristic feature, the specialist will understand that the evaporative composition described here for the second characteristic feature may include more than one cooling agent. When the composition includes more than one coolant, each coolant may be included in the above amounts, so that each coolant is included in an amount of less than about 12 wt.%. Alternatively, one refrigerant may be included in an amount of less than about 12 wt.% In accordance with the second characteristic feature of the invention, and the second refrigerant may be included in an amount of less than about 1 wt.% In accordance with the first characteristic feature of the invention. It should be understood that this combination of ranges is for exemplary purposes only, and the volatilized composition is not limited in this regard.

In both the first and second characteristics, the cooling agent is a compound that volatilizes at a higher temperature than menthol at atmospheric pressure. By "cooling agent" is meant a compound which, when inhaled as a vapor, causes the wearer to feel cool or refreshed.

The term "volatilizes" refers to the physical change of a compound from a liquid state to a gaseous state. The term "volatilizes" can be used interchangeably with "evaporates". Evaporation or volatilization of a compound is a phase transition from a liquid phase to vapor and is of two types: evaporation and boiling. Evaporation is a surface phenomenon while boiling is a volumetric phenomenon.

Boiling is the formation of vapor in the form of vapor bubbles below the surface of a liquid, and which occurs when the equilibrium vapor pressure of a compound is greater than or equal to the ambient pressure. The temperature at which boiling occurs is the boiling point or boiling point. Evaporation occurs at temperatures below the boiling point at a given pressure because it occurs when the partial vapor pressure of the compound is less than the equilibrium vapor pressure.

The term "volatilizes" in the context of the present description refers to evaporation or boiling. Thus, the expression "volatilizes at a higher temperature than menthol at atmospheric pressure" means that at atmospheric pressure the refrigerant vaporizes by evaporating or boiling at a higher temperature than menthol.

The term "atmospheric pressure" means 101325 Pa, which is equivalent to 760 mmHg.

In one aspect, the cooling agent has a boiling point above 212° C. at atmospheric pressure.

In one aspect, the cooling agent has a boiling point above 220° C. at atmospheric pressure.

In one aspect, the cooling agent has a boiling point above 230° C. at atmospheric pressure.

In one aspect, the cooling agent has a boiling point above 250° C. at atmospheric pressure.

In one aspect, the cooling agent has a boiling point above 300° C. at atmospheric pressure.

In one aspect, the cooling agent has a boiling point above 350° C. at atmospheric pressure.

In one aspect, the cooling agent has a boiling point above 375° C. at atmospheric pressure.

In one aspect, the cooling agent has a boiling point above 400° C. at atmospheric pressure.

In one aspect, the cooling agent has a boiling point above 450° C. at atmospheric pressure.

In one aspect, the cooling agent has a boiling point above 460° C. at atmospheric pressure.

In one aspect, the cooling agent volatilizes at a temperature above 212° C. at atmospheric pressure. In one aspect, the cooling agent volatilizes at a temperature above 220° C. at atmospheric pressure. In one aspect, the cooling agent volatilizes at a temperature above 230° C. at atmospheric pressure. In one aspect, the cooling agent volatilizes at a temperature above 250° C. at atmospheric pressure. In one aspect, the cooling agent volatilizes at temperatures above 300° C. at atmospheric pressure. In one aspect, the cooling agent volatilizes at a temperature above 350° C. at atmospheric pressure. In one aspect, the cooling agent volatilizes at a temperature above 375° C. at atmospheric pressure. In one aspect, the cooling agent volatilizes at temperatures above 400° C. at atmospheric pressure. In one aspect, the cooling agent volatilizes at a temperature above 450° C. at atmospheric pressure. In one aspect, the cooling agent volatilizes at a temperature above 460° C. at atmospheric pressure.

In one aspect, the cooling agent has a boiling point in the range from about 230°C to about 500°C at atmospheric pressure. In one aspect, the coolant has a boiling point in the range of about 250°C to about 500°C at atmospheric pressure. In one aspect, the cooling agent has a boiling point in the range of about 300° C. to about 500° C. at atmospheric pressure. In one aspect, the coolant has a boiling point in the range of about 340° C. to about 500° C. at atmospheric pressure.

In one aspect, the cooling agent has a boiling point in the range from about 230°C to about 465°C at atmospheric pressure. In one aspect, the cooling agent has a boiling point in the range from about 250°C to about 465°C at atmospheric pressure. In one aspect, the coolant has a boiling point in the range of about 300° C. to about 465° C. at atmospheric pressure. In one aspect, the coolant has a boiling point in the range of about 340°C to about 465°C at atmospheric pressure.

In one aspect, the cooling agent volatilizes at a temperature in the range of about 230° C. to about 500° C. at atmospheric pressure. In one aspect, the cooling agent volatilizes at a temperature in the range of about 250° C. to about 500° C. at atmospheric pressure. In one aspect, the cooling agent volatilizes at a temperature in the range of about 300° C. to about 500° C. at atmospheric pressure. In one aspect, the coolant volatilizes at a temperature in the range of about 340° C. to about 500° C. at atmospheric pressure.

In one aspect, the cooling agent volatilizes at a temperature in the range of about 230° C. to about 465° C. at atmospheric pressure. In one aspect, the cooling agent volatilizes at a temperature in the range of about 250° C. to about 465° C. at atmospheric pressure. In one aspect, the coolant volatilizes at a temperature in the range of about 300° C. to about 465° C. at atmospheric pressure. In one aspect, the coolant volatilizes at a temperature in the range of about 340° C. to about 465° C. at atmospheric pressure.

The temperature at which the compound changes from liquid to vapor can be easily determined by one of skill in the art using techniques known in the art. A well-known method is distillation, such as described by JECFA (Joint Expert Committee on Food Additives) at http://www.fao.org/docrep/009/a0691e/a0691e00.htm. This method is based on the use of a distillation thermometer to determine the initial boiling point. If the distillation is not carried out at atmospheric pressure, then the observed temperature should be corrected, allowing 0.1° for every 2.7 mm deviation.

In one aspect, the cooling agent has a vapor pressure lower than menthol at room temperature. In one aspect, the cooling agent has a vapor pressure lower than that of menthol at 25°C, for example, a vapor pressure of less than 7.67x10 ^-3 mmHg. (1.02 Pa or 102 MPa).

Vapor pressure is also known as equilibrium vapor pressure and is defined as the pressure exerted by steam in thermodynamic equilibrium with its condensed phases (solid or liquid) at a given temperature in a closed system. Vapor pressure is a measure of the rate of evaporation of a liquid because it is related to the propensity of particles to escape from the liquid (or solid). A substance with a high vapor pressure at normal temperatures, such as menthol, is said to be volatile.

As is known in the art, vapor pressure is measured with an isoteniscope. This device consists of a submersible pressure gauge and a container containing the substance whose vapor pressure is being measured. The liquid in which the manometer is immersed is heated to the required temperature, here 25° C., and the open end of the manometer is connected to a pressure measuring device. The vacuum pump is used to regulate the pressure in the system and clean the sample.

In one aspect, the cooling agent has a vapor pressure at 25°C below 50 MPa. In one aspect, the cooling agent has a vapor pressure at 25°C below 25 MPa. In one aspect, the coolant has a vapor pressure at 25°C below 15 MPa. In one aspect, the cooling agent has a vapor pressure at 25°C below 10 MPa. In one aspect, the coolant has a vapor pressure at 25°C below 5 MPa. In one aspect, the coolant has a vapor pressure at 25°C below 1 MPa. In one aspect, the coolant has a vapor pressure at 25°C below 0.5 MPa. In one aspect, the coolant has a vapor pressure at 25°C below 0.1 MPa. In one aspect, the coolant has a vapor pressure at 25°C below 0.05 MPa. In one aspect, the coolant has a vapor pressure at 25°C below 0.01 MPa. In one aspect, the coolant has a vapor pressure at 25°C below 0.005 MPa.

In one aspect, the coolant has a vapor pressure at 25° C. in the range of 0.001 MPa to 15 MPa. In one aspect, the coolant has a vapor pressure at 25° C. in the range of 0.001 MPa to 12 MPa. In one aspect, the coolant has a vapor pressure at 25° C. in the range of 0.001 MPa to 10 MPa. In one aspect, the coolant has a vapor pressure at 25° C. in the range of 0.001 MPa to 8 MPa. In one aspect, the coolant has a vapor pressure at 25° C. in the range of 0.001 MPa to 5 MPa. In one aspect, the coolant has a vapor pressure at 25° C. in the range of 0.001 MPa to 3 MPa. In one aspect, the coolant has a vapor pressure at 25° C. in the range of 0.001 MPa to 1 MPa. In one aspect, the coolant has a vapor pressure at 25° C. in the range of 0.001 MPa to 0.5 MPa. In one aspect, the coolant has a vapor pressure at 25° C. in the range of 0.001 MPa to 0.1 MPa. In one aspect, the coolant has a vapor pressure at 25° C. in the range of 0.001 MPa to 0.003 MPa.

In one aspect, the cooling agent is a compound of formula (I) or a salt and/or solvate thereof:

where X is hydrogen or OR', where R' is an alkyl group or an alkenyl group, which can be taken together with R ₁ to form a three to five membered heterocyclyl group, where the heterocyclyl group is optionally substituted with one or more substituents selected from OH, O-alkyl, alkyl-OH, alkyl-O-alkyl, NH ₂ , NH-alkyl, N-(alkyl) ₂ , NO ₂ and CN; and where each of R ₁ and R ₂ is independently selected from hydrogen, OH, OR _a , C(O) NR _b R _c and C(O)OR _b R _c ; with the proviso that when R ₁ is OH, the compound of formula (I) is not menthol; and when a double bond is present, R ₂ is absent;

where R _a represents an alkyl group, an alkenyl group, a C(O)R _f group, or a C(O)-alkyl-C(O)Rf group, where the alkyl groups and alkenyl groups are optionally substituted with one or more substituents selected from OH, O-alkyl, NH ₂ , NH-alkyl, N-(alkyl) ₂ , NO ₂ and CN; and where R _f is an alkyl group, an alkenyl group, OH, O-alkyl, NH ₂ , NH-alkyl, or N-(alkyl) ₂ , where the alkyl groups and alkenyl groups are optionally substituted with one or more substituents selected from OH, O -alkyl, NH ₂ , NH-alkyl, N-(alkyl) ₂ , NO ₂ and CN;

where R _b and R _c are each independently hydrogen, an alkyl group, an alkenyl group, an aryl group, an aralkyl group, a heteroaryl group, or a heteroaralkyl group, wherein the alkyl groups, alkenyl groups, aryl groups, and heteroaryl groups are optionally substituted with one or more substituents selected from from OH, O-alkyl, NH ₂ , NH-alkyl, N-(alkyl) ₂ , NO ₂ , CN and C(O)R _f .

In one aspect, X is hydrogen.

In one aspect, X is OR', where R' is an alkyl group or an alkenyl group taken together with R ₁ to form a three- or five-membered heterocyclyl group, where the heterocyclyl group is optionally substituted with OH, O-alkyl, or alkyl-OH. In one aspect, X is OR', where R' is an alkyl group which together with R ₁ forms a four- or five-membered heterocyclyl group, wherein the heterocyclyl group is optionally substituted with alkyl-OH. In one aspect, X is OR', where R' is an alkyl group which, taken together with R ₁ , forms a four- or five-membered heterocyclyl group, where the heterocyclyl group is optionally substituted with alkyl-OH, and where R ₁ is OR _a where R _a is an alkyl group and R ₂ is absent or is hydrogen.

In one aspect, R ₁ is selected from OH, OR _a and C(O)NR _b R _c , and R ₂ is either absent or selected from OH and OR _a . In one aspect, R ₁ is OH, with the proviso that the compound of formula (I) is not menthol. In one aspect, R ₁ is OH and R ₂ is selected from OH and OR _a .

In one aspect, X is hydrogen and R ₁ is selected from OH, OR _a and C(O)NR _b R _c , with the proviso that when R ₁ is OH, the compound of formula (I) is not menthol. R ₂ is either absent or selected from OH and OR _a . In one aspect, X is hydrogen, R ₁ is selected from OR _a and C(O)NR _b R _c , and R ₂ is either absent or selected from OH and OR _a .

In one aspect, R ₁ is OR _a , and R _a is an alkyl group substituted with one or more OH substituents. R ₂ may be hydrogen.

In one aspect, R ₁ is OR _a and R _a is a C(O)R _f group or a C(O)-alkyl-C(O)R _f group, where R _f is an alkyl group optionally substituted with one or several OH substituents, or R _f is OH. R ₂ may be hydrogen.

In one aspect, R ₁ is C(O)NR _b R _c , where R _b and R _c are each independently hydrogen, an alkyl group, an aryl group, an aralkyl group, a heteroaryl group, or a heteroaralkyl group. In one aspect, R ₁ is C(O)NR _b R _c , and at least one of R _b and R _c is hydrogen. R ₂ may be hydrogen.

In one aspect, R ₁ is C(O)NR _b R _c , where R _b is hydrogen and R _c is selected from the group consisting of an alkyl group, an aryl group, an aralkyl group, and a heteroaralkyl group. R ₂ may be hydrogen.

As used herein, the term "alkyl" includes both saturated linear and branched alkyl groups, which may be substituted (mono- or poly-) or unsubstituted. In one aspect, the alkyl group is a C _1-10 alkyl group. In one aspect, the alkyl group is a C _1-8 alkyl group. In one aspect, the alkyl group is a C _1-6 alkyl group. In one aspect, the alkyl group is a C _1-3 alkyl group. In one aspect, alkyl groups include, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, and hexyl. In one aspect, alkyl groups include methyl, ethyl, propyl, or isopropyl.

As used herein, the term "alkenyl" includes both straight chain and branched unsaturated alkenyl groups, which may be substituted (mono- or poly-) or unsubstituted. In one aspect, the alkenyl group is a C _2-10 alkenyl group. In one aspect, the alkenyl group is a C _2-8 alkenyl group. In one aspect, the alkenyl group is a C _2-6 alkenyl group. In one aspect, the alkenyl group is a C _2-3 alkenyl group.

The term "aryl" as used herein refers to a C _6-12 aromatic group which may be substituted (mono or poly) or unsubstituted. Typical examples include phenyl and naphthyl, etc. In one aspect, the aryl group is phenyl.

The term "aralkyl" is used as an amalgamation of the terms alkyl and aryl as defined above. For example, an aryl group may be linked to a compound of formula (I) via a diradical alkylene bridge (-CH ₂ -) _n , where n is 1-10 and where "aryl" has the meanings given above. Alternatively, an alkyl group may be linked to a compound of formula (I) via an aryl diradical bridge, eg phenyl, where "alkyl" is defined above. In one aspect, the term "aralkyl" refers to a phenylalkyl group wherein the phenyl is linked to a compound of formula (I).

The term "heteroaryl" as used herein refers to a monovalent aromatic group of 1 to 12 carbon atoms having one or more oxygen, nitrogen and sulfur heteroatoms in the ring. In one aspect, the ring contains from 1 to 4 oxygen, nitrogen and/or sulfur heteroatoms. In one aspect, the ring contains from 1 to 3 oxygen, nitrogen and/or sulfur heteroatoms. In one aspect, there are 2 oxygen and/or nitrogen heteroatoms within the ring. In one aspect, there is 1 oxygen or nitrogen heteroatom within the ring. The nitrogen and sulfur heteroatoms may optionally be oxidized. Such heteroaryl groups may have a single ring (eg, pyridyl or furyl) or multiple fused rings, provided that the point of attachment passes through an atom of the heteroaryl ring.

In one aspect, heteroaryl is selected from the group consisting of pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, pyrrolyl, indolyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, furanyl, thiophenyl, furyl, pyrrolyl, imidazolyl, oxazolyl, isoxazolyl, isothiazolyl, pyrazolyl, benzofuranil and benzothiophenyl. Heteroaryl rings may be unsubstituted or substituted. In one aspect, heteroaryl is selected from the group consisting of pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, and pyrrolyl. In one aspect, heteroaryl is pyridyl.

The term "heterocyclyl" as used herein refers to fully saturated or unsaturated monocyclic groups that contain one or more oxygen, sulfur or nitrogen heteroatoms in the ring. In one aspect, a heterocyclyl has 1 to 3 ring heteroatoms. In one aspect, the heterocyclyl has 1 to 3 oxygen and/or nitrogen heteroatoms in the ring. In one aspect, a heterocyclyl has 1 to 3 ring oxygen heteroatoms. The nitrogen and sulfur heteroatoms may optionally be oxidized, and the nitrogen heteroatoms may optionally be quaternized. The heterocyclic group may be unsubstituted or substituted.

Examples of monocyclic heterocyclic groups include, but are not limited to, pyrrolidinyl, pyrrolyl, pyrazolyl, oxiranyl, oxetanyl, pyrazolinyl, imidazolyl, imidazolinyl, imidazolidinyl, oxazolyl, oxazolidinyl, isoxazolinyl, isoxazolyl, thiazolyl, thiadiazolyl, hydro-thiazolidinyl, isothiazolyl, isothiazolyl, tetradinyl , thienyl, oxadiazolyl, piperidinyl, piperazinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolodinyl, 2-oxoazepinyl, azepinyl, 4-piperidonyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, tetrahydropyranyl, morpholine, thiamorpholinyl, thiomorphylinyl oxide, thiomorpholinyl , 1,3-dioxolane and tetrahydro-1,1-dioxothienyl, triazolyl and triazinyl.

In one aspect, the heterocyclyl is selected from the group consisting of oxiranil, oxetanyl, tetrahydrofuryl, tetrahydropyranyl, and 1,3-dioxolane. In one aspect, the heterocyclyl is 1,3-dioxolane.

All aspects include, where appropriate, all enantiomers and tautomers of the compounds of formula (I). One skilled in the art will recognize compounds that have optical properties (one or more chiral carbon atoms) or tautomeric characteristics. The corresponding enantiomers and/or tautomers can be isolated/obtained by methods known in the art. Some of the compounds of formula (I) may exist as stereoisomers and/or geometric isomers - for example, they may have one or more asymmetric and/or geometric centers and therefore may exist in two or more stereoisomeric and/or geometric forms. All aspects include, where appropriate, the use of all individual stereoisomers and geometric isomers of these compounds and mixtures thereof. The terms used in the claims cover these forms.

Suitable salts of the compounds of formula (I) include their suitable acid addition or base salts. Such and their salt solvates are known in the art. Suitable acid addition salts include carboxylate salts (e.g., formate, acetate, trifluoroacetate, propionate, isobutyrate, heptanoate, decanoate, caprate, caprylate, stearate, acrylate, caproate, propiolate, ascorbate, citrate, glucuronate, glutamate, glycolate, α-hydroxybutyrate , lactate, tartrate, phenylacetate, mandelic acid salt, phenylpropionate, phenylbutyrate, benzoate, chlorobenzoate, methylbenzoate, hydroxybenzoate, methoxybenzoate, dinitrobenzoate, o-acetoxybenzoate, salicylate, nicotinate, isonicotinate, sinnamate, oxalate, malonate, subcaterate, succinate, succinate , malate, maleate, hydroxymaleate, hippurate, phthalate or terephthalate salts), halide salts (for example, chloride, bromide or iodide salts), sulfonate salts (for example, benzenesulfonate, methyl, bromo or chlorobenzenesulfonate, xylenesulfonate, methanesulfonate, ethanesulfonate, pro pansulfonate, hydroxyethanesulfonate, 1- or 2-naphthalenesulfonate or 1,5-naphthalenesulfonate salts) or sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, phosphate, monohydrogen phosphate, dihydrogen phosphate, metaphosphate, pyrophosphate or nitrate salts.

In one aspect, the cooling agent is selected from the group consisting of:

N-ethyl-5-methyl-2- (propan-2-yl) cyclohexanecarboxamide,

ethyl 2-(5-methyl-2-propan-2-ylcyclohexanecarbonylamino) acetate,

N-(4-methoxyphenyl)-p-menthanecarboxamide,

N-2,3-trimethyl-2-propan-2-ylbutanamide,

N- (2-pyridin-2-yl) ethyl) mentylcarboxamide,

menthone-1,2-glycerinketal,

mentyl lactate,

isopulegol,

3-mentoxypropane-1,2-diol and

menthylsuccinate.

In one aspect, the coolant is selected from the group consisting of:

N-ethyl-5-methyl-2- (propan-2-yl) cyclohexanecarboxamide,

ethyl 2-(5-methyl-2-propan-2-yl cyclohexanecarbonylamino) acetate,

N-(4-methoxyphenyl)-p-menthanecarboxamide,

N-2,3-trimethyl-2-propan-2-ylbutanamide,

N-(2-pyridin-2-yl)ethyl)mentylcarboxamide,

menthone-1,2-glycerinketal,

mentyl lactate,

3-mentoxypropane-1,2-diol and

menthylsuccinate.

In the second characteristic, the coolant may be selected from the group consisting of:

N-ethyl-5-methyl-2-(propan-2-yl)cyclohexanecarboxamide,

ethyl 2-(5-methyl-2-propan-2-ylcyclohexanecarbonylamino)acetate,

N-(4-methoxyphenyl)-p-menthanecarboxamide,

N-(2-pyridin-2-yl)ethyl)mentylcarboxamide,

menthone-1,2-glycerinketal,

mentyl lactate,

isopulegol,

3-mentoxypropane-1,2-diol and

menthyl succinate,

or

from the group consisting of:

N-ethyl-5-methyl-2-(propan-2-yl)cyclohexanecarboxamide,

ethyl 2-(5-methyl-2-propan-2-ylcyclohexanecarbonylamino)acetate,

N-(4-methoxyphenyl)-p-menthanecarboxamide,

N-(2-pyridin-2-yl)ethyl)mentylcarboxamide,

menthone-1,2-glycerinketal,

mentyl lactate,

3-mentoxypropane-1,2-diol and

menthylsuccinate.

In one aspect of the first characteristic, the cooling agent is selected from the group consisting of:

In one aspect, the cooling agent is not WS-23, ie N,2,3-trimethyl-2-propan-2-ylbutanamide.

In one aspect of the first characteristic, the cooling agent is WS-23, i.e., N,2-3-trimethyl-2-propan-2-ylbutanamide. WS-23 is not covered by the second characteristic of the invention.

In one aspect, the cooling agent is selected from the group consisting of (1S,2R,5S)-N-ethyl-5-methyl-2-(propan-2-yl)cyclohexanecarboxamide, ethyl-2-[[(1R,2S,5R )-5-methyl-2-propan-2-ylcyclohexanecarbonyl]amino]acetate, (1R,2S,5R)-N-(4-methoxyphenyl-p-menthanecarboxamide, (1R,2S,5R)-N-(2- (pyridin-2-yl)ethyl)mentylcarboxamide, (-)-mentone 1,2-glycerol ketal, (-)-mentyl lactate, (-)-isopulegol, 3-((-)-mentoxy) propane-1,2-diol and (-)-menthylsuccinate.

In one aspect, the cooling agent is selected from the group consisting of (1S,2R,5S)-N-ethyl-5-methyl-2-(propan-2-yl)cyclohexanecarboxamide, ethyl-2-[[(1R,2S,5R )-5-methyl-2-propan-2-ylcyclohexanecarbonyl]amino]acetate, (1R,2S,5R)-N-(4-methoxyphenyl-p-menthanecarboxamide, (1R,2S,5R)-N-(2- (pyridin-2-yl)ethyl)mentylcarboxamide, (-)-menthone-1,2-glycerol ketal, (-)-mentyl lactate, 3-((-)-mentoxy)propane-1,2-diol, and (-) - menthylsuccinate.

In one aspect, the cooling agent is selected from the group consisting of (1S,2R,5S)-N-ethyl-5-methyl-2-(propan-2-yl)cyclohexanecarboxamide, ethyl-2-[[(1R,2S,5R )-5-methyl-2-propan-2-ylcyclohexanecarbonyl]amino]acetate, (1R,2S,5R)-N-(4-methoxyphenyl-p-menthanecarboxamide, (1R,2S,5R)-N-(2- (pyridin-2-yl)ethyl)mentylcarboxamide, (-)-menthone-1,2-glycerol ketal, (-)-mentyl lactate, (-)-isopulegol and 3-((-)-mentoxy) propane-1,2- diol.

In one aspect, the cooling agent is selected from the group consisting of (1S,2R,5S)-N-ethyl-5-methyl-2-(propan-2-yl)cyclohexanecarboxamide, ethyl-2-[[(1R,2S,5R )-5-methyl-2-propan-2-ylcyclohexanecarbonyl]amino]acetate, ((1R,2S,5R)-N-(2-(pyridin-2-yl)ethyl)mentylcarboxamide, (-)-menthone 1, 2-glycerol ketal, (-)-mentyl lactate, (-)-isopulegol and 3-((-)-mentoxy) propane-1,2-diol.

In one aspect, the cooling agent is selected from the group consisting of (1S,2R,5S)-N-ethyl-5-methyl-2-(propan-2-yl)cyclohexanecarboxamide, ethyl-2-[[(1R,2S,5R )-5-methyl-2-propan-2-ylcyclohexanecarbonyl]amino]acetate, ((1R,2S,5R)-N-(2-(pyridin-2-yl)ethyl)mentylcarboxamide, (-)-menthone 1, 2-glycerol ketal, (-)-mentyl lactate and 3-((-)-mentoxy) propane-1,2-diol.

In one aspect, the cooling agent is (1R,2S,5R)-N-(2-(pyridin-2-yl)ethyl)mentylcarboxamide.

In another aspect, the cooling agent is (1S,2R,5S)-N-ethyl-5-methyl-2-(propan-2-yl)cyclohexanecarboxamide.

As noted above, all aspects include, where appropriate, all enantiomers and tautomers of the compounds. One skilled in the art will recognize compounds that have optical properties (one or more chiral carbon atoms) or tautomeric characteristics. The corresponding enantiomers and/or tautomers can be isolated/obtained by methods known in the art.

Evaporated composition

Vaporized compositions of the present invention may contain one or more additional components. These components may be selected depending on the nature of the composition.

In one aspect, the composition further comprises a "flavour" or "flavour". The terms "flavor" and "flavoring" refer to materials that, if permitted by local regulations, are added to a formulation to create a desired taste or aroma in a product for adult consumers. Reference here to "flavouring" or "flavoring substance" includes both single and multi-component flavors.

In one aspect, the flavoring agent is selected from the group consisting of extracts of e.g. , Drambuie, Bourbon, Scotch, Whiskey, Spearmint, Peppermint, Lavender, Cardamom, Celery, Cascarilla, Nutmeg, Sandalwood, Bergamot, Geranium, Honey Essence, Rose Oil, Vanilla, Lemon Oil, Orange Oil, Cassia Oil, Cumin , konjac, jasmine, ylang ylang, sage, fennel, (piment) pepper, ginger, anise, coriander, coffee, flavor enhancers, bitterness receptor blockers, sensory receptor activators or stimulants, sugar and/or sugar substitutes (e.g. sucralose, acesulfame potassium, aspartame, saccharin, cyclamates, lactose, sucrose, glucose, fructose, sorbitol or mannitol) and other additives such as charcoal, chlorophyll, minerals, botanicals or breath freshening agents. They may be imitations, synthetic or natural ingredients, or mixtures thereof. They may be in any suitable form, such as an oil, liquid or powder.

In one aspect, the composition further comprises an active agent. By "active agent" is meant an agent that exerts a biological effect on a subject when the vapor is inhaled. One or more active agents may be selected from nicotine, botanicals, and mixtures thereof. One or more active agents may be of synthetic or natural origin. The active substance may be an extract of a plant, such as a plant from the tobacco family.

An example of an active substance is nicotine.

Thus, in one aspect, the present invention provides a vaporizable formulation comprising:

(i) one or more solvents,

(ii) less than about 1 wt.% coolant, based on the total weight of the vaporized composition, wherein the coolant volatilizes at a higher temperature than menthol at atmospheric pressure, and

(iii) active agent

or

(i) one or more solvents,

(ii) less than about 12% by weight of a coolant, based on the total weight of the composition to be vaporized, wherein the coolant volatilizes at a higher temperature than menthol at atmospheric pressure and is a compound of formula (I) or a salt thereof and/or solvate as defined herein, and

(iii) an active agent.

In one aspect, the active agent is nicotine.

Thus, in one aspect, the present invention provides a vaporizable formulation comprising:

(i) one or more solvents,

(ii) less than about 1 wt.% coolant, based on the total weight of the vaporized composition, wherein the coolant volatilizes at a higher temperature than menthol at atmospheric pressure, and

(iii) nicotine

or

(i) one or more solvents,

(ii) less than about 12% by weight of a coolant, based on the total weight of the composition to be vaporized, wherein the coolant volatilizes at a higher temperature than menthol at atmospheric pressure and is a compound of formula (I) or a salt thereof and/or solvate as defined herein, and

(iii) nicotine.

The nicotine may be provided in any suitable amount depending on the desired inhalation dosage by the user. In one aspect, nicotine is present in an amount of no more than about 6% by weight, based on the total weight of the vaporized composition. In one aspect, nicotine is present in an amount of from about 0.4% to about 6% by weight, based on the total weight of the vaporized formulation. In one aspect, nicotine is present in an amount of from about 0.8% to about 6% by weight, based on the total weight of the vaporized composition. In one aspect, nicotine is present in an amount of from about 1% to about 6% by weight, based on the total weight of the vaporized composition. In one aspect, nicotine is present in an amount of from about 1.8% to about 6% by weight, based on the total weight of the vaporized formulation.

In one aspect, nicotine is present in an amount of no more than about 5% by weight, based on the total weight of the vaporized composition. In one aspect, nicotine is present in an amount of from about 0.4% to about 5% by weight, based on the total weight of the vaporized formulation. In one aspect, nicotine is present in an amount of from about 0.8% to about 5% by weight, based on the total weight of the vaporized formulation. In one aspect, nicotine is present in an amount of from about 1% to about 5% by weight, based on the total weight of the vaporized formulation. In one aspect, nicotine is present in an amount of from about 1.8% to about 5% by weight, based on the total weight of the vaporized formulation.

In one aspect, nicotine is present in an amount of no more than about 4% by weight, based on the total weight of the vaporized composition. In one aspect, nicotine is present in an amount of from about 0.4% to about 4% by weight, based on the total weight of the vaporized formulation. In one aspect, nicotine is present in an amount of from about 0.8% to about 4% by weight, based on the total weight of the vaporized formulation. In one aspect, nicotine is present in an amount of from about 1% to about 4% by weight, based on the total weight of the vaporized formulation. In one aspect, nicotine is present in an amount of from about 1.8% to about 4% by weight, based on the total weight of the vaporized composition.

In one aspect, nicotine is present in an amount of no more than about 3% by weight, based on the total weight of the vaporized composition. In one aspect, nicotine is present in an amount of from about 0.4% to about 3% by weight, based on the total weight of the vaporized composition. In one aspect, nicotine is present in an amount of from about 0.8% to about 3% by weight, based on the total weight of the vaporized formulation. In one aspect, nicotine is present in an amount of from about 1% to about 3% by weight, based on the total weight of the vaporized composition. In one aspect, nicotine is present in an amount of from about 1.8% to about 3% by weight, based on the total weight of the vaporized composition.

In one aspect, nicotine is present in an amount of no more than about 1.9% by weight, based on the total weight of the vaporized composition. In one aspect, nicotine is present in an amount of no more than about 1.8% by weight, based on the total weight of the vaporized composition. In one aspect, nicotine is present in an amount of from about 0.4% to about 1.9% by weight, based on the total weight of the vaporized formulation. In one aspect, nicotine is present in an amount of from about 0.4% to about 1.8% by weight, based on the total weight of the vaporized composition. In one aspect, nicotine is present in an amount of from about 0.5 to about 1.9 wt.%, based on the total weight of the vaporized composition. In one aspect, nicotine is present in an amount of from about 0.5% to about 1.8% by weight, based on the total weight of the vaporized formulation. In one aspect, nicotine is present in an amount of from about 0.8 to about 1.9 wt.%, based on the total weight of the vaporized composition. In one aspect, nicotine is present in an amount of from about 0.8 to about 1.8 wt.%, based on the total weight of the vaporized composition. In one aspect, nicotine is present in an amount of from about 1 to about 1.9% by weight, based on the total weight of the vaporized formulation. In one aspect, nicotine is present in an amount of from about 1 to about 1.8% by weight, based on the total weight of the vaporized composition.

In one aspect, nicotine is present in an amount of less than about 1.9% by weight, based on the total weight of the vaporized composition. In one aspect, nicotine is present in an amount of less than about 1.8% by weight, based on the total weight of the vaporized composition. In one aspect, nicotine is present in an amount of from about 0.4% to less than about 1.9% by weight, based on the total weight of the vaporized formulation. In one aspect, nicotine is present in an amount of from about 0.4% to less than about 1.8% by weight, based on the total weight of the vaporized formulation. In one aspect, nicotine is present in an amount of from about 0.5% to less than about 1.9% by weight, based on the total weight of the vaporized formulation. In one aspect, nicotine is present in an amount of from about 0.5% to less than about 1.8% by weight, based on the total weight of the vaporized composition. In one aspect, nicotine is present in an amount of from about 0.8% to less than about 1.9% by weight, based on the total weight of the vaporized formulation. In one aspect, nicotine is present in an amount of from about 0.8% to less than about 1.8% by weight, based on the total weight of the vaporized formulation. In one aspect, nicotine is present in an amount of from about 1% to less than about 1.9% by weight, based on the total weight of the vaporized formulation. In one aspect, nicotine is present in an amount of from about 1% to less than about 1.8% by weight, based on the total weight of the vaporized formulation.

In one aspect, the vaporizable composition may contain one or more acids. In some embodiments of the invention, the vaporized composition may contain one or more acids in addition to nicotine (as an active agent). In some embodiments of the invention, one or more acids may be one or more organic acids. In some embodiments, the one or more acids may be one or more organic acids selected from the group consisting of benzoic acid, levulinic acid, malic acid, maleic acid, fumaric acid, citric acid, lactic acid, acetic acid, succinic acid, and their mixtures. When included in a formulation in combination with nicotine, one or more acids can provide a formulation in which the nicotine is at least partially in a protonated (eg, monoprotonated and/or diprotonated) form.

Solvent

As discussed here, the vaporized composition includes one or more solvents.

One or more solvents may be any suitable solvents. In one aspect, one or more solvents are selected from water, glycerin, propylene glycol, 1,3-propanediol, and mixtures thereof. Other suitable solvents will be apparent to those skilled in the art.

One or more solvents may be present in any suitable amount in the volatilized composition. In one aspect, one or more solvents are present in a total amount of at least 5% by weight, based on the total weight of the composition to be vaporized. In one aspect, one or more solvents are present in a total amount of at least 10% by weight, based on the total weight of the composition to be vaporized. In one aspect, one or more solvents are present in a total amount of at least 15% by weight, based on the total weight of the composition to be vaporized. In one aspect, one or more solvents are present in a total amount of at least 20% by weight, based on the total weight of the composition to be vaporized. In one aspect, one or more solvents are present in a total amount of at least 25% by weight, based on the total weight of the composition to be vaporized. In one aspect, one or more solvents are present in a total amount of at least 30% by weight, based on the total weight of the composition to be vaporized. In one aspect, one or more solvents are present in a total amount of at least 35% by weight, based on the total weight of the composition to be vaporized. In one aspect, one or more solvents are present in a total amount of at least 40% by weight, based on the total weight of the composition to be vaporized. In one aspect, one or more solvents are present in a total amount of at least 45% by weight, based on the total weight of the volatilized composition. In one aspect, one or more solvents are present in a total amount of at least 50% by weight, based on the total weight of the composition to be vaporized. In one aspect, one or more solvents are present in a total amount of at least 55% by weight, based on the total weight of the composition to be vaporized. In one aspect, one or more solvents are present in a total amount of at least 60% by weight, based on the total weight of the composition to be vaporized. In one aspect, one or more solvents are present in a total amount of at least 65% by weight, based on the total weight of the composition to be vaporized. In one aspect, one or more solvents are present in a total amount of at least 70% by weight, based on the total weight of the composition to be vaporized. In one aspect, one or more solvents are present in a total amount of at least 75% by weight, based on the total weight of the composition to be vaporized. In one aspect, one or more solvents are present in a total amount of at least 80% by weight, based on the total weight of the composition to be vaporized. In one aspect, one or more solvents are present in a total amount of at least 85% by weight, based on the total weight of the composition to be vaporized. In one aspect, one or more solvents are present in a total amount of at least 90% by weight, based on the total weight of the composition to be vaporized.

In one aspect, one or more solvents are present in a total amount of from 5 to 99% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 10 to 99% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 15 to 99% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 20 to 99% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 25 to 99% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 30 to 99% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 35 to 99% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 40 to 99% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 45 to 99% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 50 to 99% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 55 to 99% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 60 to 99% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 65 to 99% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 70 to 99% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 75 to 99% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 80 to 99% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 85 to 99% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 90 to 99% by weight, based on the volatilized composition.

In one aspect, one or more solvents are present in a total amount of 5 to 95% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 10 to 95% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 15 to 95% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 20 to 95% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 25 to 95% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 30 to 95% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 35 to 95% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 40 to 95% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 45 to 95% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 50 to 95% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 55 to 95% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 60 to 95% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 65 to 95% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 70 to 95% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 75 to 95% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 80 to 95% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 85 to 95% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 90 to 95% by weight, based on the volatilized composition.

In one aspect, one or more solvents are present in a total amount of 5 to 90% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 10 to 90% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 15 to 90% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 20 to 90% by weight, based on the volatilized composition. In one aspect, the one or more solvents are present in a total amount of 25 to 90% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 30 to 90% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 35 to 90% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 40 to 90% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 45 to 90% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 50 to 90% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 55 to 90% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 60 to 90% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 65 to 90% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 70 to 90% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 75 to 90% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 80 to 90% by weight, based on the volatilized composition. In one aspect, one or more solvents are present in a total amount of 85 to 90% by weight, based on the volatilized composition.

As discussed herein, in one aspect, the solvent is at least glycerol. Glycerin may be present in the volatilized composition in any suitable amount. In one aspect, glycerol is present in a total amount of at least 10% by weight, based on the volatilized composition. In one aspect, the glycerol is present in a total amount of at least 20% by weight, based on the volatilized composition. In one aspect, glycerol is present in a total amount of at least 30% by weight, based on the volatilized composition. In one aspect, glycerol is present in a total amount of at least 35% by weight, based on the volatilized composition. In one aspect, glycerol is present in a total amount of at least 40% by weight, based on the volatilized composition. In one aspect, glycerol is present in a total amount of at least 45% by weight, based on the volatilized composition. In one aspect, glycerol is present in a total amount of at least 50% by weight, based on the volatilized composition. In one aspect, the glycerol is present in a total amount of at least 55% by weight, based on the volatilized composition. In one aspect, the glycerol is present in a total amount of at least 60% by weight, based on the volatilized composition.

In one aspect, the glycerol is present in a total amount of 10 to 60% by weight, based on the volatilized composition. In one aspect, the glycerol is present in a total amount of 20 to 60% by weight, based on the volatilized composition. In one aspect, the glycerol is present in a total amount of 25 to 60% by weight, based on the volatilized composition. In one aspect, the glycerol is present in a total amount of 30 to 60% by weight, based on the volatilized composition. In one aspect, the glycerol is present in a total amount of 35 to 60% by weight, based on the volatilized composition. In one aspect, glycerol is present in a total amount of 40 to 60% by weight, based on the volatilized composition. In one aspect, glycerol is present in a total amount of 45 to 60% by weight, based on the volatilized composition.

As discussed herein, in one aspect, the solvent is at least propylene glycol. Propylene glycol may be present in any suitable amount in the volatilized composition. In one aspect, the propylene glycol is present in a total amount of at least 10% by weight, based on the volatilized composition. In one aspect, the propylene glycol is present in a total amount of at least 15% by weight, based on the volatilized composition. In one aspect, the propylene glycol is present in a total amount of at least 20% by weight, based on the volatilized composition. In one aspect, the propylene glycol is present in a total amount of at least 25% by weight, based on the volatilized composition. In one aspect, the propylene glycol is present in a total amount of at least 30% by weight, based on the volatilized composition. In one aspect, the propylene glycol is present in a total amount of at least 35% by weight, based on the volatilized composition. In one aspect, the propylene glycol is present in a total amount of at least 40% by weight, based on the volatilized composition.

In one aspect, the propylene glycol is present in a total amount of 10 to 40% by weight, based on the volatilized composition. In one aspect, the propylene glycol is present in a total amount of 15 to 40% by weight, based on the volatilized composition. In one aspect, the propylene glycol is present in a total amount of 20 to 40% by weight, based on the volatilized composition. In one aspect, the propylene glycol is present in a total amount of 25 to 40% by weight, based on the volatilized composition. In one aspect, the propylene glycol is present in a total amount of 30 to 40% by weight, based on the volatilized composition. In one aspect, the propylene glycol is present in a total amount of 32 to 40% by weight, based on the volatilized composition. In one aspect, the propylene glycol is present in a total amount of 35 to 40% by weight, based on the volatilized composition.

As discussed here, one or more solvents may include water. In one aspect, water is present in a total amount of 0 to 25% by weight, based on the volatilized composition. This amount includes 0% water based on the evaporating composition, and therefore the evaporating composition may or may not contain water.

In one aspect, the vaporizable composition contains water. Water may be present in the vaporizing composition in any suitable amount. In one aspect, water is present in a total amount of 0 to 24% by weight, based on the volatilized composition. In one aspect, water is present in a total amount of 0 to 22% by weight, based on the volatilized composition. In one aspect, water is present in a total amount of 0 to 20% by weight, based on the volatilized composition. In one aspect, water is present in a total amount of 0 to 19% by weight, based on the volatilized composition. In one aspect, water is present in a total amount of 0 to 18% by weight, based on the volatilized composition. In one aspect, water is present in a total amount of 0 to 17% by weight, based on the volatilized composition. In one aspect, water is present in a total amount of 0 to 16% by weight, based on the volatilized composition. In one aspect, water is present in a total amount of 0 to 15% by weight, based on the volatilized composition.

In an alternative embodiment, the solvent is substantially free of water. In this regard, it should be noted that some compositions may be hygroscopic, and therefore the ingress of water into the composition cannot be excluded. Accordingly, by "substantially free of water" is meant that the amount of water present is less than 0.1% by weight, based on the volatilized composition.

Way

As discussed herein, the present invention provides a process for generating steam, the process comprising evaporating a vaporizable composition containing (i) one or more solvents and (ii) less than about 1 wt.% coolant, based on the total weight of the vaporizable composition, in which agent volatilizes at a higher temperature than menthol at atmospheric pressure, or less than about 12 wt. a compound of formula (I), or a salt and/or solvate thereof, as defined herein.

In one aspect, steam is generated by heating the vaporizable composition to a temperature above about 100°C. In one aspect, steam is generated by heating the evaporating composition to a temperature above about 110°C. In one aspect, steam is generated by heating the evaporating composition to a temperature above about 120°C.

In another aspect, steam is generated by a process performed at a temperature below about 100°C. In one aspect, steam is generated by a process performed at a temperature below about 90°C. In one aspect, steam is generated in a process performed at a temperature below about 80°C.

In one aspect, vapor is generated by applying ultrasonic energy to a vaporizing composition.

Additional aspects

The vaporizable composition may be contained or delivered by any means. In one aspect, the present invention provides a vaporizable formulation comprising:

(a) a container; as well as

(b) vaporizable composition as defined above.

The container may be any suitable container, such as for storing or delivering a solution. In one aspect, the container is configured to interact with an electronic steam supply system. The container may be a bottle. The container may be configured to be in fluid communication with the electronic vapor delivery system so that the solution can be delivered to the electronic vapor delivery system. As described above, the present invention relates to a container that can be used in an electronic vaporization system such as an electronic cigarette. In the following description, the term "electronic cigarette" is used; however, the term may be used as a synonym for an electronic vaporization system.

As discussed herein, the container of the present invention is generally designed to deliver a vaporized formulation to or within an electronic cigarette. The vaporizable formulation may be stored within the electronic cigarette or may be sold as a separate container for later use with or in the electronic cigarette. As one of skill in the art will appreciate, electronic cigarettes may comprise a unit known as a plug-in cartomizer, which typically includes a reservoir of vaporized composition, wick material, and a device for vaporizing the vaporized composition. In some electronic cigarettes, the cartomizer is part of a single device and is not removable. In one aspect, the container is a cartomizer or part of a cartomizer. In one aspect, the container is not a cartomizer or part of a cartomizer, but is a container, such as a reservoir, that can be used to deliver a volatile composition to or within an electronic cigarette.

In one aspect, the container is part of an electronic vaporization system such as an electronic cigarette. Therefore, in a further aspect, the present invention provides an electronic vaporization system comprising:

(a) a vaporizer for vaporizing the inhalation composition by a user of the electronic vapor delivery system;

(b) a power supply containing a cell or battery to power the vaporizer; as well as

(c) vaporizable composition as described above.

In addition to the vaporizable formulations of the present invention and systems such as containers and electronic aerosol delivery systems containing them, the present invention provides for the use of a refrigerant to extend the shelf life of a vaporizable formulation in which the refrigerant volatilizes at a higher temperature than menthol at atmospheric pressure.

Shelf life is generally the length of time a consumer product can be stored without becoming unfit for use, consumption, or sale. The expression "extended shelf life" means that the cooling agent allows the vaporized composition to be stored for a longer period of time without chemical decomposition of its components compared to a similar composition including menthol. Typical storage conditions include ambient temperature and pressure.

Brief description of the drawings

Hereinafter, the present invention will be described in more detail, by way of example only, with reference to the accompanying drawings, in which:

In FIG. 1A-1D are thermogravimetric traces of (1S,2R,5S)-N-ethyl-5-methyl-2-(propan-2-yl)cyclohexanecarboxamide (WS-3) in air (A and B) and nitrogen (C and D).

In FIG. 2A-2D are thermogravimetric traces of ethyl-2-[[(1R,2S,5R)-5-methyl-2-propan-2-ylcyclohexanecarbonyl]amino]acetate (WS-5) in air (A and B) and nitrogen (C and D).

In FIG. 3A-3D are thermogravimetric traces of (1R, 2S, 5R)-N-(4-methoxyphenyl-p-menthanecarboxamide (WS-12) in air (A and B) and nitrogen (C and D).

In FIG. 4A-4D are thermogravimetric traces of N,2,3-trimethyl-2-propan-2-ylbutanamide (WS-23) in air (A and B) and nitrogen (C and D).

In FIG. 5A-5D are thermogravimetric traces of (1R,2S,5R)-N-(2-(pyridin-2-yl)ethyl)mentylcarboxamide (Evercool® 190) in air (A and B) and nitrogen (C and D) .

In FIG. 6A-6D are thermogravimetric traces for (−)-menthone 1,2-glycerin ketal (Frescolat® MGA) in air (A and B) and in nitrogen (C and D).

In FIG. 7A-7D are thermogravimetric traces for (-)-mentillacate (Frescolat® ML) in air (A and B) and in nitrogen (C and D).

In FIG. 8A-8D are thermogravimetric traces of 3-((-)-mentoxy) propane-1,2-diol (Coolact® 10) in air (A and B) and nitrogen (C and D).

In FIG. 9A-9D are thermogravimetric traces for (-)-menthylsuccinate (monomenthylsuccinate) in air (A and B) and in nitrogen (C and D).

Fig. 10 is a scatterplot of peak mass loss T (°C) versus molecular weight (g·mol ⁻¹ ) for the compounds shown in Table 1 below and menthol.

In FIG. 11 shows the results of subjective cooling rate testing carried out as described in Example 1 below.

In FIG. 12 shows the results of the cooling rate test carried out as described in Example 2 below.

Examples

The invention will now be described with reference to the following non-limiting examples.

Nine refrigerants were used in the examples. These compounds are shown in Table 1 below along with chemical name, trade name, approximate boiling point and approximate vapor pressure. Given that the compounds are known, their boiling points and vapor pressures have been obtained from the literature.

Table 1

chemical name Trade name Chemical structure Boiling point (°C) @ 760 mmHg unless otherwise specified Vapor pressure (mmHg) @ 25°C (1S,2R,5S)-N-ethyl-5-methyl-2-(propan-2-yl)cyclohexanecarboxamide WS-3

340.55 8.50E-5 ethyl 2-[[(1R,2S,5R)-5-methyl-2-propan-2-ylcyclohexanecarbonyl]amino]acetate WS-5

151.00
(@ 2.00 mmHg) unknown (1R,2S,5R)-N-(4-methoxyphenyl-p-menthanecarboxamide WS-12

447.8 ± 28.0 3.25E-8 N,2,3-trimethyl-2-propan-2-ylbutanamide WS-23

233.00-234.00 5.73E2 (1R,2S,5R)-N-(2-(pyridin-2-yl)ethyl)mentylcarboxamide Evercool® 190

461.6 ± 24.0 1.06E-8 (-)-menthone 1,2-glycerine ketal Frescolat® MGA

138-142 2.15E-5 (-)-menthyl lactate Frescolat® ML

304.0±15.0 8.58E-5 3-((-)-mentoxy) propane-1,2-diol Coolact® 10

362.8 ± 22.0 9.88E-7 (-)-menthyl succinate Monomentyl succinate

374.35 1.23E-6

Analytical testing

Thermogravimetric analysis

Before panel (set) tests, the coolants were subjected to thermogravimetric analysis (TGA) to understand their behavior when heated. As is known in the art, TGA is an analytical method by which the weight loss of a sample can be monitored when it is heated to temperatures up to 1000°C and above.

All measurements were carried out on a Perkin Elmer STA6000 TGA thermogravimetric analyzer. For solid samples, 5–20 mg of material was transferred with a spatula into the analyzer crucible. Oils were introduced into the apparatus by transferring 5-20 mg with a Pasteur pipette to a small portion of a Cambridge filter pad which was placed in the crucible. All samples were heated from 30°C to 600°C at a constant rate of 5°C/min. This was done for each compound twice in air and twice in nitrogen. For a small number of samples, the experiment was stopped at 500-600°C when a complete weight loss was observed. For comparative purposes, menthol was also analyzed.

TGA curves for each compound (repeat 1 and repeat 2 in air; and repeat 1 and repeat 2 in nitrogen) are shown in Figures 1 to 9 (AD). The weight loss onset temperature for each compound was determined by visual inspection of the TGA traces in the computer software, and the results are summarized in Table 2. Evercool ^TM 190 showed more than one weight loss, but weight loss at about 65-75°C was confirmed to be due to the presence of water. in the sample.

table 2

Compound T _max weight loss (°C) Air (rep 1) Air (rep 2) Nitrogen (rep 1) Nitrogen (rep 2) WS-3 127 132 132 128 WS-5 149 151 154 158 WS-12 202 203 199 197 WS-23 88 88 90 86 ^EvercoolTM 190 161 164 169 174 Frescolat® MGA 93 85 102 94 Frescolat® ML 86 88 86 91 Coolact® 10 119 112 115 119 Monomentyl succinate 144 148 151 151 Menthol 53 55 52 55

From these results, it can be seen that good repeatability of the experiments was achieved and little difference was observed between the TGA traces in air and in nitrogen. The latter suggests that the compounds are not subject to thermal oxidation at temperatures at which mass loss was observed.

These results also show that, in contrast to menthol, weight loss for all coolants tested occurred above 85°C. Because this weight loss was generally positively correlated with molecular weight (see FIG. 10), it can be attributed to volatilization/evaporation rather than degradation. Therefore, all compounds tested are less volatile than menthol and can be said to volatilize at a temperature higher than menthol at atmospheric pressure. Reducing the volatility of cooling agents is an advantage because it means they are more storage stable than menthol.

Example 1

observational testing

10 volunteers were asked to use each sample of coolant in a Vype eTank Pro (electronic cigarette device). All refrigerants were used at 0.18% except for menthol, which was used at the current commercial concentration of 1.235% in one sample. Each of the menthol samples was tested for comparison.

Each volunteer was asked to rate the cooling intensity on an objective basis (i.e. without regard to personal preference) and on a subjective basis. The objective assessment required the volunteer to rate the overall perceived intensity of cooling from 0 to 10, where 0 meant no perceived cooling and 10 was a very strong sensation of cooling, and placed the sensation of cooling, e.g., in the mouth, throat, etc. Subjective evaluation required that the cooling rate be rated as (1) too low, (2) slightly too low, (3) just right, (4) slightly too high, or (5) too high.

Results

The results of the objective and subjective evaluation of the volunteers are shown in Table 3 below and in FIG. eleven.

Table 3

coolant Average intensity
cooling (0-10) WS-3 3.045 WS-5 2.5454 WS-23 2.1818 Evercool® 190 7.1 Frescolat MGA one Frescolat ML 2 Coolact 10 0.75 Menthol (control) 2.1 Menthol (1.235%) eight

The results show that some compounds provide a greater cooling sensation at 0.18% than menthol at the same concentration. In particular, Evercool® 190 at 0.18% provides a cooling sensation of 7.1/10 compared to menthol at 1.235% of 8/10.

Because the delivery of non-menthol coolants has generally been more favorable than a menthol formulation, the coolants can be included in the vaporizable formulation of the present invention at much lower concentrations than menthol and still provide a cooling sensation when vaporized by the user. As shown by the thermogravimetric analysis above, coolants also lead to improved storage stability compared to menthol formulations, since the weight loss measured by TGA occurs at much higher temperatures. Finally, the results show that cooling agents produce a different cooling sensation compared to menthol. The area of delivery is mainly the mouth and posterior pharyngeal wall, while delivery on the tongue is minimal. This avoids drying out in the mouth, as is the case with menthol.

Example 2

At least 4 volunteers were asked to test each of the following e-liquid samples in the eTank Pro (e-cigarette device):

- WS-3 in the amount of 2.5 wt.% in glycerol/propylene glycol;

- WS-3 in the amount of 5 wt.% in glycerol/propylene glycol; as well as

- WS-3 at a concentration of 10 wt.% in glycerol/propylene glycol.

WS-3 is a compound of formula (I) and is known by the chemical name (1S,2R,5S)-N-ethyl-5-methyl-2-(propan-2-yl)cyclohexanecarboxamide.

Each volunteer was asked to rate the intensity of cooling on an objective basis (i.e. without regard to personal preferences) and on a subjective basis in the same manner as in example 1. The objective assessment required the volunteer to rate the overall perceived cooling intensity from 0 to 10, where 0 meant the absence of perceptible cooling, and 10 meant a very strong feeling of cooling, and to place a feeling of cooling, for example in the mouth, throat, etc. Subjective evaluation required that the cooling rate be rated as (1) too low, (2) slightly too low, (3) just right, (4) slightly too high, or (5) too high.

The results of the objective and subjective evaluation of the volunteers are shown in Table 4 below and in FIG. 12.

Table 4

WS-3 concentration Average intensity
cooling (0-10) 2.5 wt% 6 5 wt% 8.5 10 wt% 9.8

These results show that the intensity of cooling of WS-3 increases as the concentration increases and that this compound can be included in an amount of 10 wt.%, while providing a feeling of cooling to the user. From the comments of the volunteers, it was also confirmed that the cooling sensation is different from menthol even at higher concentrations. The delivery area was primarily in the posterior pharynx with minimal delivery to the tongue. This sensation was long lasting and would be especially useful in markets that are actively looking for a "high menthol content" or strong cooling sensation.

Various modifications and variations of the present invention will be apparent to those skilled in the art without departing from the scope and spirit of the invention. Although the invention has been described in connection with specific preferred embodiments, it should be understood that the claimed invention should not be unduly limited to such specific embodiments. Indeed, various modifications of the described modes of carrying out the invention, which are obvious to those skilled in chemistry or related fields, are intended to be within the scope of the following claims.

Claims (45)

1. Evaporative composition for electronic steam supply systems, containing (i) one or more solvents; and (ii) less than 1 wt.% cooling agent, based on the weight of the evaporated composition; where the cooling agent volatilizes at a higher temperature than menthol at atmospheric pressure; where the cooling agent is N,2,3-trimethyl-2-propan-2-ylbutanamide, or a compound of formula (I) or a salt and/or solvate thereof:

(I) where X is hydrogen or OR', where R' is an alkyl group or an alkenyl group, which can be taken together with R ₁ to form a three to five membered heterocyclyl group, where the heterocyclyl group is optionally substituted with one or more selected substituents from OH, O -alkyl, alkyl-OH, alkyl-O-alkyl, NH ₂ , NH-alkyl, N-(alkyl) ₂ , NO ₂ and CN; and where each of R ₁ and R ₂ is independently selected from hydrogen, OH, OR _a , C(O)NR _b R _c and C(O)OR _b R _c ; with the proviso that when R ₁ is OH, the compound of formula (I) is not menthol; and when a double bond is present, R ₂ is absent; where R _a represents an alkyl group, an alkenyl group, a C(O)R _f group, where the alkyl groups and alkenyl groups are optionally substituted with one or more substituents selected from OH, O-alkyl, NH ₂ , NH-alkyl, N-( alkyl) ₂ , NO ₂ and CN; and where R _f is an alkyl group, an alkenyl group, OH, O-alkyl, NH ₂ , NH-alkyl, or N-(alkyl) ₂ , where the alkyl groups and alkenyl groups are optionally substituted with one or more substituents selected from OH, O -alkyl, NH ₂ , NH-alkyl, N-(alkyl) ₂ , NO ₂ and CN; where R _b and R _c are each independently hydrogen, an alkyl group, an alkenyl group, an aryl group, an aralkyl group, a heteroaryl group, or a heteroaralkyl group, wherein the alkyl groups, alkenyl groups, aryl groups, and heteroaryl groups are optionally substituted with one or more substituents selected from from OH, O-alkyl, NH ₂ , NH-alkyl, N-(alkyl) ₂ , NO ₂ , CN and C(O)R _f . 2. Evaporated composition according to claim 1, characterized in that the composition contains from 0.001 to 0.9 wt.% of the cooling agent, based on the weight of the evaporated composition. 3. Evaporated composition according to claim 2, characterized in that the composition contains from 0.005 to 0.75 wt.% of the cooling agent, based on the weight of the evaporated composition. 4. Evaporable composition according to claim 3, characterized in that the composition contains from 0.01 to 0.5 wt.% of the cooling agent, based on the weight of the evaporated composition. 5. Evaporated composition according to any one of paragraphs. 1-4, characterized in that the cooling agent evaporates at a temperature above 212°C at atmospheric pressure. 6. Evaporative composition according to claim 5, characterized in that the cooling agent volatilizes at a temperature in the range from 230°C to 500°C at atmospheric pressure. 7. Evaporated composition according to any one of paragraphs. 1-6, characterized in that the cooling agent has a vapor pressure lower than the vapor pressure of menthol at 25°C. 8. The evaporative composition according to claim 7, characterized in that the refrigerant has a vapor pressure below 0.008 mm Hg. at 25°C. 9. Evaporative composition for electronic steam supply systems, containing (i) one or more solvents; and (ii) less than 12 wt.% coolant based on the weight of the evaporated composition; where the cooling agent volatilizes at a higher temperature than menthol at atmospheric pressure and is a compound of formula (I) or a salt and/or solvate thereof:

(I) where X is hydrogen or OR', where R' is an alkyl group or an alkenyl group, which can be taken together with R ₁ to form a three to five membered heterocyclyl group, where the heterocyclyl group is optionally substituted with one or more selected substituents from OH, O -alkyl, alkyl-OH, alkyl-O-alkyl, NH ₂ , NH-alkyl, N-(alkyl) ₂ , NO ₂ and CN; and where each of R ₁ and R ₂ is independently selected from hydrogen, OH, OR _a , C(O)NR _b R _c and C(O)OR _b R _c ; with the proviso that when R ₁ is OH, the compound of formula (I) is not menthol; and when a double bond is present, R ₂ is absent; where R _a represents an alkyl group, an alkenyl group, a C(O)R _f group, where the alkyl groups and alkenyl groups are optionally substituted with one or more substituents selected from OH, O-alkyl, NH ₂ , NH-alkyl, N-( alkyl) ₂ , NO ₂ and CN; and where R _f is an alkyl group, an alkenyl group, OH, O-alkyl, NH ₂ , NH-alkyl, or N-(alkyl) ₂ , where the alkyl groups and alkenyl groups are optionally substituted with one or more substituents selected from OH, O -alkyl, NH ₂ , NH-alkyl, N-(alkyl) ₂ , NO ₂ and CN; where R _b and R _c are each independently hydrogen, an alkyl group, an alkenyl group, an aryl group, an aralkyl group, a heteroaryl group, or a heteroaralkyl group, wherein the alkyl groups, alkenyl groups, aryl groups, and heteroaryl groups are optionally substituted with one or more substituents selected from from OH, O-alkyl, NH ₂ , NH-alkyl, N-(alkyl) ₂ , NO ₂ , CN and C(O)R _f . 10. Evaporated composition according to claim 9, characterized in that the composition contains from 0.001 to 11 wt.% of the cooling agent, based on the weight of the evaporated composition. 11. Evaporated composition according to claim 10, characterized in that the composition contains from 0.005 to 10 wt.% of the cooling agent, based on the weight of the evaporated composition. 12. Evaporative composition, for electronic steam supply systems, containing (i) one or more solvents; and (ii) less than 12 wt.% coolant based on the weight of the evaporated composition; where the cooling agent volatilizes at a higher temperature than menthol at atmospheric pressure; where the cooling agent is selected from the group consisting of N-ethyl-5-methyl-2-(propan-2-yl)cyclohexanecarboxamide, ethyl 2-[[[5-methyl-2-propan-2-ylcyclohexanecarbonyl]amino]acetate , N-(4-methoxyphenyl-p-menthanecarboxamide, N-(2-(pyridin-2-yl)ethyl)mentylcarboxamide, menthone 1,2-glycerol ketal, menthyl lactate, and 3-(mentoxy)propan-1,2-diol . 13. Evaporated composition according to any one of paragraphs. 1-12, characterized in that one or more solvents are selected from water, glycerin, propylene glycol and mixtures thereof. 14. Evaporated composition according to any one of paragraphs. 1-12, characterized in that one or more solvents are selected from glycerol, propylene glycol and mixtures thereof. 15. Evaporated composition according to any one of paragraphs. 1-14, characterized in that the composition additionally contains an active agent. 16. A vaporizable composition according to claim 15, characterized in that the active agent is nicotine. 17. A method for generating steam, including: (a) providing a vaporizable composition as defined in any of paragraphs. 1-16; and (b) evaporation of the composition. 18. The volatile composition contained in the container, containing: (a) a container; and (b) vaporizable composition according to any one of paragraphs. 1-16. 19. An electronic vaporization system, comprising: (a) a vaporizer for vaporizing the inhalation liquid by the user of the electronic vapor delivery system; (b) a power supply containing a cell or battery to power the vaporizer; and (c) vaporizable composition according to any one of paragraphs. 1-16. 20. The use of a refrigerant to extend the shelf life of an evaporative composition for electronic vapor systems, where the refrigerant volatilizes at a higher temperature than menthol at atmospheric pressure, and where the vaporized composition is a vaporized composition, as defined in any of paragraphs. 1-16.

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