Vaporizable formulation

Abstract

To provide use of a cooling agent for extending a shelf life of a vaporizable formulation, where the cooling agent volatilizes at a higher temperature than menthol at an atmospheric pressure.SOLUTION: A vaporizable formulation comprises (i) one or more solvents, and (ii) a cooling agent of less than about 1 wt.% based on weight of the vaporizable formulation, the cooling agent volatilizing at a higher temperature than menthol at an atmospheric pressure. There is also provided a vaporizable formulation comprising a cooling agent, which is a specific compound or a salt and / or solvate thereof, of less than about 12 wt.% based on the weight of the vaporizable formulation.SELECTED DRAWING: None

Description

Field of the Invention

[0001] The present disclosure relates to an electronic vapor supply system such as a vaporizable formulation, a container containing the vaporizable formulation, and an electronic vapor delivery system (e.g., e-cigarette) incorporating the vaporizable formulation. Background of the Invention

[0002] Electronic vapor supply systems such as e-cigarettes generally include a reservoir of a liquid to be vaporized that typically contains nicotine. When a user inhales on the device, a heater activates to vaporize a small amount of the liquid, and thus the vaporized liquid is inhaled by the user. Liquids for e-cigarettes may contain flavor components such as menthol that provide a sensory experience to the user. In certain situations, this liquid may contain flavor components without nicotine.

[0003] However, menthol is highly volatile and readily vaporizes in the presence of heat. This high volatility causes problems in current e-cigarette devices because it can lead to a decrease in flavor quality and customer satisfaction. The volatility of menthol is also detrimental to the shelf life of the e-cigarette device or the liquid used in the e-cigarette device. SUMMARY OF THE INVENTION

[0004] In a first aspect, there is provided a vaporizable formulation comprising (i) one or more solvents and (ii) a coolant of less than about 1 wt% based on the weight of the vaporizable formulation that vaporizes at a temperature higher than menthol at atmospheric pressure.

[0005] In a second aspect, there is provided a vaporizable formulation comprising (i) one or more solvents and (ii) a compound that vaporizes at a temperature higher than menthol at atmospheric pressure and has the formula (I):

Chemical formula

[0006] Unless otherwise specified, the following detailed description applies to both the first and second features of the present invention.

[0007] The present invention further provides a process for generating vapor, comprising: (a) preparing a vaporizable composition as defined herein; and (b) vaporizing the vaporizable composition.

[0008] The present invention further provides a contained vaporizable composition, comprising: (a) a container; and (b) a vaporizable composition as defined herein.

[0009] The present invention further provides an electronic vapor supply system, comprising: (a) a vaporizer configured to vaporize a liquid for inhalation by a user of the electronic vapor supply system; (b) a power source comprising a battery or battery configured to supply power to the vaporizer; and (c) a vaporizable composition as defined herein.

[0010] The present invention further provides the use of a coolant to extend the shelf life of a vaporizable composition, wherein the coolant volatilizes at a temperature higher than menthol at atmospheric pressure. Detailed Description

[0011] As discussed herein, the present invention provides a vaporizable composition comprising (i) one or more solvents and (ii) a coolant of less than about 1 wt% based on the weight of the vaporizable composition that vaporizes at a temperature higher than menthol at atmospheric pressure, or a coolant of less than about 12 wt% based on the weight of the vaporizable composition that vaporizes at a temperature higher than menthol at atmospheric pressure and is a compound of formula (I) or a salt and / or solvate thereof as defined above and herein.

[0012] The use of sensory compounds, particularly coolants, is well documented in the food and pharmaceutical industries. Coolants are typically organic small molecules such as menthol that deliver a cooling sensation to the user when in contact with the oral cavity, nasal cavity, and / or skin. This cooling sensation falls within the category of chemosensory sensations and is caused by organic small molecules activating specific receptors within the skin and / or mucous membranes. Thus, the experience of the cooling sensation relies on the user's chemosensory system. The chemosensory system is typically referred to in the art as the "common chemical sense" or the chemosensation of the trigeminal nerve because it is mediated by the trigeminal nerve and typically refers to the sensations that are elements of the somatosensory system that distinguish it from olfaction and taste.

[0013] Menthol is a widely used coolant. Menthol is used, for example, in mouthwashes and topical analgesic creams to provide a cooling effect. This cooling effect is thought to be due to menthol chemically inducing the user's cold-sensitive TRPM8 receptors within the oral cavity, nasal cavity, and / or skin. Similar effects are seen when menthol is used as a tobacco additive. Menthol provides a smell and flavor like mint when inhaled by the user.

[0014] However, menthol can cause respiratory irritation when used at higher concentrations and is problematic when included in liquids for e-cigarette devices because it is associated with a bitter taste and a burning sensation. Menthol is also an extremely volatile compound. Menthol has a high vapor pressure at room temperature and a low boiling point at atmospheric pressure. At 25 °C, for example, menthol has a vapor pressure of approximately 7.67×10 -3It has a vapor pressure of mm Hg (approximately 1.02 Pa). At atmospheric pressure (760 mmHg or 101325 Pa), menthol has a boiling point of 212 °C. This volatility produces the characteristic minty odor of menthol, but is detrimental to the storage stability of liquids containing menthol. In particular, menthol readily volatilizes under typical storage conditions, such as ambient pressure and temperature, when added to an e-liquid cartridge by the user, so the storage life of the liquid is significantly shortened by the presence of menthol.

[0015] The inventors have found that by incorporating a coolant that is less volatile than menthol at atmospheric pressure and is optionally a compound of formula (I) or a salt and / or solvate thereof, a vaporizable formulation having improved storage stability and thus a longer storage life compared to vaporizable formulations containing menthol can be provided. The coolants described herein have also been shown to deliver a cooling sensation when vapor is generated by the user from the vaporizable formulation, introducing a different sensory benefit compared to menthol. For ease of reference, these and further aspects of the invention are discussed herein under appropriate section headings. However, the teachings of each section are not necessarily limited to each particular section.

[0016] Coolants

[0017] As discussed herein, the vaporizable formulations of the first aspect of the invention contain a coolant in an amount of less than about 1 wt% based on the total weight of the vaporizable formulation. The term "less than" means any amount that is less than 1 wt% but does not include zero. In other words, the vaporizable formulation must contain some amount of coolant.

[0018] In one aspect, the coolant is present in an amount not exceeding about 0.9 wt%.

[0019] In one aspect, the coolant is present in an amount of about 0.001 wt% to about 0.9 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.002 wt% to about 0.9 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.003 wt% to about 0.9 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.004 wt% to about 0.9 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.005 wt% to about 0.9 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.006 wt% to about 0.9 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.007 wt% to about 0.9 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.008 wt% to about 0.9 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.009 wt% to about 0.9 wt% based on the total weight of the vaporizable formulation.

[0020] In one aspect, the coolant is present in an amount of about 0.01 wt% to about 0.9 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.02 wt% to about 0.9 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.03 wt% to about 0.9 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.04 wt% to about 0.9 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.05 wt% to about 0.9 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of 0.06 wt% to about 0.9 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.07 wt% to about 0.9 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.08 wt% to about 0.9 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.09 wt% to about 0.9 wt% based on the total weight of the vaporizable formulation.

[0021] In one aspect, the coolant is present in an amount of about 0.1 wt% to about 0.9 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.2 wt% to about 0.9 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.3 wt% to about 0.9 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.4 wt% to about 0.9 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.5 wt% to about 0.9 wt% based on the total weight of the vaporizable formulation.

[0022] In another aspect, the coolant is present in an amount not exceeding about 0.8 wt%.

[0023] In one aspect, the coolant is present in an amount of from about 0.001 wt% to about 0.8 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.002 wt% to about 0.8 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.003 wt% to about 0.8 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.004 wt% to about 0.8 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.005 wt% to about 0.8 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.006 wt% to about 0.8 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.007 wt% to about 0.8 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.008 wt% to about 0.8 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.009 wt% to about 0.8 wt% based on the total weight of the vaporizable formulation.

[0024] In one aspect, the coolant is present in an amount of about 0.01 wt% to about 0.8 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.02 wt% to about 0.8 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.03 wt% to about 0.8 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.04 wt% to about 0.8 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.05 wt% to about 0.8 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.06 wt% to about 0.8 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.07 wt% to about 0.8 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.08 wt% to about 0.8 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.09 wt% to about 0.8 wt% based on the total weight of the vaporizable formulation.

[0025] In one aspect, the coolant is present in an amount of about 0.1 wt% to about 0.8 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.2 wt% to about 0.8 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.3 wt% to about 0.8 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.4 wt% to about 0.8 wt% based on the total weight of the vaporizable formulation.

[0026] In another aspect, the coolant is present in an amount not exceeding about 0.75 wt%.

[0027] In one aspect, the coolant is present in an amount of about 0.001 wt% to about 0.75 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.002 wt% to about 0.75 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.003 wt% to about 0.75 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.004 wt% to about 0.75 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.005 wt% to about 0.75 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.006 wt% to about 0.75 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.007 wt% to about 0.75 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.008 wt% to about 0.75 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.009 wt% to about 0.75 wt% based on the total weight of the vaporizable formulation.

[0028] In one aspect, the coolant is present in an amount of about 0.01 wt% to about 0.75 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.02 wt% to about 0.75 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.03 wt% to about 0.75 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.04 wt% to about 0.75 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.05 wt% to about 0.75 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.06 wt% to about 0.75 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.07 wt% to about 0.75 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.08 wt% to about 0.75 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.09 wt% to about 0.75 wt% based on the total weight of the vaporizable formulation.

[0029] In one aspect, the coolant is present in an amount of about 0.1 wt% to about 0.75 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.2 wt% to about 0.75 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.3 wt% to about 0.75 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.4 wt% to about 0.75 wt% based on the total weight of the vaporizable formulation.

[0030] In one aspect, the coolant is present in an amount not exceeding about 0.5 wt%.

[0031] In one aspect, the coolant is present in an amount of from about 0.001 wt% to about 0.5 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.002 wt% to about 0.5 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.003 wt% to about 0.5 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.004 wt% to about 0.5 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.005 wt% to about 0.5 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.006 wt% to about 0.5 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.007 wt% to about 0.5 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.008 wt% to about 0.5 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.009 wt% to about 0.5 wt% based on the total weight of the vaporizable formulation.

[0032] In one aspect, the coolant is present in an amount of from about 0.01 wt% to about 0.5 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.02 wt% to about 0.5 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.03 wt% to about 0.5 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.04 wt% to about 0.5 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.05 wt% to about 0.5 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.06 wt% to about 0.5 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.07 wt% to about 0.5 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.08 wt% to about 0.5 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.09 wt% to about 0.5 wt% based on the total weight of the vaporizable formulation.

[0033] In one aspect, the coolant is present in an amount of from about 0.1 wt% to about 0.5 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.2 wt% to about 0.5 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.3 wt% to about 0.5 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.4 wt% to about 0.5 wt% based on the total weight of the vaporizable formulation.

[0034] In another aspect, the coolant is present in an amount not exceeding about 0.3 wt%.

[0035] In one aspect, the coolant is present in an amount of from about 0.001 wt% to about 0.3 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.002 wt% to about 0.3 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.003 wt% to about 0.3 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.004 wt% to about 0.3 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.005 wt% to about 0.3 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.006 wt% to about 0.3 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.007 wt% to about 0.3 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.008 wt% to about 0.3 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.009 wt% to about 0.3 wt% based on the total weight of the vaporizable formulation.

[0036] In one aspect, the coolant is present in an amount of about 0.01 wt% to about 0.3 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.02 wt% to about 0.3 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.03 wt% to about 0.3 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.04 wt% to about 0.3 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.05 wt% to about 0.3 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.06 wt% to about 0.3 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.07 wt% to about 0.3 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.08 wt% to about 0.3 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.09 wt% to about 0.3 wt% based on the total weight of the vaporizable formulation.

[0037] In one aspect, the coolant is present in an amount of about 0.1 wt% to about 0.3 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.2 wt% to about 0.3 wt% based on the total weight of the vaporizable formulation.

[0038] Those skilled in the art will understand that the vaporizable formulations described herein can contain more than one coolant. When the formulation contains more than one coolant, each coolant can be included in the amounts defined above such that each coolant is included in an amount of less than about 1 wt%. For example, the first coolant may be included in an amount of about 0.001 wt% to 0.9 wt% based on the weight of the vaporizable formulation, and the second coolant may be included in an amount of about 0.001 wt% to 0.9 wt% based on the weight of the vaporizable formulation. Alternatively, the second coolant may be included in an amount of about 0.05 wt% to 0.9 wt% based on the weight of the vaporizable formulation. Combinations of these ranges are for purely illustrative purposes, and it is understood that the vaporizable formulation is not limited in this regard.

[0039] In a second feature of the present invention, the coolant is defined as a compound of formula (I) or a salt and / or solvate thereof, and the vaporizable formulation contains the coolant in an amount of less than about 12 wt% based on the total weight of the vaporizable formulation. The term "less than" has the same meaning as in the first feature. The following disclosure relates to the second feature.

[0040] In one aspect, the coolant of the second feature is present in an amount not exceeding about 11 wt%.

[0041] In one aspect, the coolant is present in an amount of about 0.001 wt% to about 11 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.005 wt% to about 11 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.01 wt% to about 11 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.05 wt% to about 11 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.1 wt% to about 11 wt% based on the total weight of the vaporizable formulation.

[0042] In another aspect, the coolant is present in an amount not exceeding about 10 wt%.

[0043] In one aspect, the coolant is present in an amount of from about 0.001 wt% to about 10 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.005 wt% to about 10 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.01 wt% to about 10 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.05 wt% to about 10 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.1 wt% to about 10 wt% based on the total weight of the vaporizable formulation.

[0044] In another aspect, the coolant is present in an amount not exceeding about 8 wt%.

[0045] In one aspect, the coolant is present in an amount of from about 0.001 wt% to about 8 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.005 wt% to about 8 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.01 wt% to about 8 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.05 wt% to about 8 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of from about 0.1 wt% to about 8 wt% based on the total weight of the vaporizable formulation.

[0046] In another aspect, the coolant is present in an amount not exceeding about 5 wt%.

[0047] In one aspect, the coolant is present in an amount of about 0.001 wt% to about 5 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.005 wt% to about 5 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.01 wt% to about 5 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.05 wt% to about 5 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.1 wt% to about 5 wt% based on the total weight of the vaporizable formulation.

[0048] In another aspect, the coolant is present in an amount not exceeding about 3 wt%, for example about 2.5 wt%.

[0049] In one aspect, the coolant is present in an amount of about 0.001 wt% to about 3 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.005 wt% to about 3 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.01 wt% to about 3 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.05 wt% to about 3 wt% based on the total weight of the vaporizable formulation. In one aspect, the coolant is present in an amount of about 0.1 wt% to about 3 wt% based on the total weight of the vaporizable formulation.

[0050] Regarding the first feature, it will be understood by those skilled in the art that the vaporizable formulations described herein with respect to the second feature can include more than one coolant. When the formulation includes more than one coolant, each coolant can be included in the amounts defined above such that each coolant is included in an amount of less than about 12 wt%. Alternatively, one coolant may be included in an amount of less than about 12 wt% according to the second feature of the present invention, and a second coolant may be included in an amount of less than about 1 wt% according to the first feature of the present invention. Combinations of these ranges are for illustrative purposes only, and it is understood that the vaporizable formulation is not limited in this regard.

[0051] In both the first and second features, the coolant is a compound that volatilizes at a temperature higher than menthol at atmospheric pressure. The term "coolant" means a compound that delivers a cooling or refreshing sensation to the user when inhaled as a vapor.

[0052] The term "volatilize" means the physical change of a compound from a liquid state to a gaseous state. The term "volatilize" can be used interchangeably with "vaporize". The vaporization or volatilization of a compound is a phase transition from the liquid phase to vapor, and there are two types: evaporation and boiling. Evaporation is a surface phenomenon, whereas boiling is a bulk phenomenon.

[0053] Boiling is the formation of vapor as vapor bubbles below the surface of the liquid and occurs when the equilibrium vapor pressure of the compound is above the ambient pressure. The temperature at which boiling occurs is the boiling temperature, i.e., the boiling point. Evaporation occurs because the partial pressure of the vapor of the compound is less than the equilibrium vapor pressure and thus occurs at a temperature below the boiling temperature at a given pressure.

[0054] The term "volatilize" in the context of this description refers to evaporation or boiling. Thus, the expression "volatilize at a temperature higher than menthol at atmospheric pressure" means that at atmospheric pressure, the coolant transitions to vapor at a temperature higher than menthol, whether by evaporation or boiling.

[0055] The term "atmospheric pressure" means 101325 Pa, which is equal to 760 mmHg.

[0056] In one aspect, the coolant has a boiling point above 212 °C at atmospheric pressure. In one aspect, the coolant has a boiling point above 220 °C at atmospheric pressure. In one aspect, the coolant has a boiling point above 230 °C at atmospheric pressure. In one aspect, the coolant has a boiling point above 250 °C at atmospheric pressure. In one aspect, the coolant has a boiling point above 300 °C at atmospheric pressure. In one aspect, the coolant has a boiling point above 350 °C at atmospheric pressure. In one aspect, the coolant has a boiling point above 375 °C at atmospheric pressure. In one aspect, the coolant has a boiling point above 400 °C at atmospheric pressure. In one aspect, the coolant has a boiling point above 450 °C at atmospheric pressure. In one aspect, the coolant has a boiling point above 460 °C at atmospheric pressure. In one aspect, the coolant volatilizes at a temperature above 212 °C at atmospheric pressure. In one aspect, the coolant volatilizes at a temperature above 220 °C at atmospheric pressure. In one aspect, the coolant volatilizes at a temperature above 230 °C at atmospheric pressure. In one aspect, the coolant volatilizes at a temperature above 250 °C at atmospheric pressure. In one aspect, the coolant volatilizes at a temperature above 300 °C at atmospheric pressure. In one aspect, the coolant volatilizes at a temperature above 350 °C at atmospheric pressure. In one aspect, the coolant volatilizes at a temperature above 375 °C at atmospheric pressure. In one aspect, the coolant volatilizes at a temperature above 400 °C at atmospheric pressure. In one aspect, the coolant volatilizes at a temperature above 450 °C at atmospheric pressure. In one aspect, the coolant volatilizes at a temperature above 460 °C at atmospheric pressure.

[0057] In one aspect, the coolant has a boiling point in the range of 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 coolant 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.

[0058] In one aspect, the coolant has a boiling point in the range of about 230°C to about 465°C at atmospheric pressure. In one aspect, the coolant has a boiling point in the range of 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.

[0059] In one aspect, the coolant volatilizes at a temperature in the range of about 230°C to about 500°C at atmospheric pressure. In one aspect, the coolant volatilizes at a temperature in the range of about 250°C to about 500°C at atmospheric pressure. In one aspect, the coolant 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.

[0060] In one aspect, the coolant volatilizes at a temperature in the range of about 230°C to about 465°C at atmospheric pressure. In one aspect, the coolant 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.

[0061] The temperature at which a compound changes from a liquid to a vapor can be readily determined by one skilled in the art using techniques known in the art. Well-known methods are distillations such as those described by the JECFA (Joint Expert Committee on Food Additives) at http: / / www.fao.org / docrep / 009 / a0691e / a0691e00.htm. This method relies on the use of a distillation thermometer to determine the initial boiling point. If distillation is not carried out at atmospheric pressure, the observed temperature should be corrected by assuming 0.1° for each 2.7 mm difference.

[0062] In one aspect, the coolant has a lower vapor pressure than menthol at room temperature. In one aspect, the coolant has a vapor pressure lower than that of menthol at 25 °C, for example, a vapor pressure below 7.67×10 -3 mm Hg (1.02 Pa or 102 mPa).

[0063] Vapor pressure, also known as equilibrium vapor pressure, is defined as the pressure exerted by a vapor that is in thermodynamic equilibrium with the condensed phase (solid or liquid) of the vapor in a closed system at a given temperature. Vapor pressure is related to the tendency of particles to escape from a liquid (or solid), and thus is an indicator of the evaporation rate of a liquid. Substances with a high vapor pressure at room temperature, such as menthol, are called volatile.

[0064] As is known in the art, vapor pressure is measured by an isoteniscope. This device consists of an immersed manometer and a container that holds the substance whose vapor pressure is being measured. The liquid in which the manometer is immersed is heated to the required temperature, in this specification 25 °C, and the open end of the manometer is connected to a pressure measuring device. A vacuum pump is used to adjust the pressure of the system and to purify the sample.

[0065] In one aspect, the coolant has a vapor pressure below 50 mPa at 25 °C. In one aspect, the coolant has a vapor pressure below 25 mPa at 25 °C. In one aspect, the coolant has a vapor pressure below 15 mPa at 25 °C. In one aspect, the coolant has a vapor pressure below 10 mPa at 25 °C. In one aspect, the coolant has a vapor pressure below 5 mPa at 25 °C. In one aspect, the coolant has a vapor pressure below 1 mPa at 25 °C. In one aspect, the coolant has a vapor pressure below 0.5 mPa at 25 °C. In one aspect, the coolant has a vapor pressure below 0.1 mPa at 25 °C. In one aspect, the coolant has a vapor pressure below 0.05 mPa at 25 °C. In one aspect, the coolant has a vapor pressure below 0.01 mPa at 25 °C. In one aspect, the coolant has a vapor pressure below 0.005 mPa at 25 °C.

[0066] In one aspect, the coolant has a vapor pressure in the range of 0.001 mPa to 15 mPa at 25°C. In one aspect, the coolant has a vapor pressure in the range of 0.001 mPa to 12 mPa at 25°C. In one aspect, the coolant has a vapor pressure in the range of 0.001 mPa to 10 mPa at 25°C. In one aspect, the coolant has a vapor pressure in the range of 0.001 mPa to 8 mPa at 25°C. In one aspect, the coolant has a vapor pressure in the range of 0.001 mPa to 5 mPa at 25°C. In one aspect, the coolant has a vapor pressure in the range of 0.001 mPa to 3 mPa at 25°C. In one aspect, the coolant has a vapor pressure in the range of 0.001 mPa to 1 mPa at 25°C. In one aspect, the coolant has a vapor pressure in the range of 0.001 mPa to 0.5 mPa at 25°C. In one aspect, the coolant has a vapor pressure in the range of 0.001 mPa to 0.1 mPa at 25°C. In one aspect, the coolant has a vapor pressure in the range of 0.001 mPa to 0.003 mPa at 25°C.

[0067] In one aspect, the coolant has the formula (I):

Chemical formula

[0068] In one embodiment, X is hydrogen.

[0069] In one embodiment, X is OR' (wherein R' is an alkyl group or an alkenyl group that together with R 1 forms a 3- to 5-membered heterocyclyl group, and the heterocyclyl group is optionally substituted with OH, O-alkyl or alkyl-OH). In one embodiment, X is OR' (wherein R' is an alkyl group or an alkenyl group that together with R 1An alkyl group that forms a 4- or 5-membered heterocyclyl group together with, and the heterocyclyl group is optionally substituted with alkyl-OH). In one embodiment, X is OR' (wherein R' is R 1 is an alkyl group that forms a 4- or 5-membered heterocyclyl group together with, and the heterocyclyl group is optionally substituted with alkyl-OH), and R 1 is OR a (wherein R a is an alkyl group), and R 2 is absent or is hydrogen.

[0070] In one embodiment, R 1 is selected from OH, OR a and C(O)NR b R c , and R 2 is absent or is selected from OH and OR a . In one embodiment, R 1 is OH provided that the compound of formula (I) is not menthol. In one embodiment, R 1 is OH, and R 2 is selected from OH and OR a .

[0071] In one embodiment, X is hydrogen, and R 1 is selected from OH, OR a and C(O)NR b R c , provided that when R 1 is OH, the compound of formula (I) is not menthol. R 2 is absent or is selected from OH and OR a . In one embodiment, X is hydrogen, and R 1 is selected from OR a and C(O)NR b R c , and R 2 is absent or is selected from OH and OR a .

[0072] In one embodiment, R 1 is ORa and R a is an alkyl group substituted with one or more OH substituents. R 2 may be hydrogen.

[0073] In one embodiment, 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 (wherein R f is an alkyl group optionally substituted with one or more OH substituents, or R f is OH). R 2 may be hydrogen.

[0074] In one embodiment, R 1 is C(O)NR b R c (wherein 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 embodiment, 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.

[0075] In one embodiment, R 1 is C(O)NR b R c (wherein 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.

[0076] As used herein, the term "alkyl" includes both saturated straight-chain alkyl groups and branched alkyl groups, which may or may not be substituted (mono- or poly-). In one embodiment, the alkyl group is C1-10 is an alkyl group. In one aspect, the alkyl group is C 1-8 is an alkyl group. In one aspect, the alkyl group is C 1-6 is an alkyl group. In one aspect, the alkyl group is C 1-3 is an alkyl group. In one aspect, the alkyl group includes, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, and hexyl. In one aspect, the alkyl group includes methyl, ethyl, propyl, or isopropyl.

[0077] As used herein, the term "alkenyl" includes both unsaturated straight-chain alkenyl groups and unsaturated branched alkenyl groups, which may or may not be substituted (mono- or poly-). In one aspect, the alkenyl group is C 2-10 is an alkenyl group. In one aspect, the alkenyl group is C 2-8 is an alkenyl group. In one aspect, the alkenyl group is C 2-6 is an alkenyl group. In one aspect, the alkenyl group is C 2-3 is an alkenyl group.

[0078] As used herein, the term "aryl" refers to a C 6-12 aromatic group, which may or may not be substituted (mono- or poly-). Typical examples include phenyl and naphthyl. In one aspect, the aryl group is phenyl.

[0079] The term "aralkyl" is used as a combination of the above terms alkyl and aryl. For example, the aryl group is a difunctional alkylene bridge (-CH 2 -) n(wherein n is from 1 to 10) may be attached to the compound of formula (I), and "aryl" is as defined above. Alternatively, the alkyl group may be attached to the compound of formula (I) via a difunctional aryl bridge, such as phenyl, and "alkyl" is as defined above. In one embodiment, the term "aralkyl" refers to a phenyl-alkyl group in which phenyl is attached to the compound of formula (I).

[0080] As used herein, the term "heteroaryl" 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 embodiment, there are 1 to 4 oxygen, nitrogen, and / or sulfur heteroatoms in the ring. In one embodiment, there are 1 to 3 oxygen, nitrogen, and / or sulfur heteroatoms in the ring. In one embodiment, there are 2 oxygen and / or nitrogen heteroatoms in the ring. In one embodiment, there is 1 oxygen or nitrogen heteroatom in the ring. The nitrogen and sulfur heteroatoms may optionally be oxidized. Such heteroaryl groups can have a monocyclic (e.g., pyridyl or furyl) or fused polycyclic ring. However, the point of attachment shall be via a heteroaryl ring atom.

[0081] In one embodiment, 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, benzofuranyl, and benzothiophenyl. The heteroaryl ring may or may not be substituted. In one embodiment, heteroaryl is selected from the group consisting of pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, and pyrrolyl. In one embodiment, heteroaryl is pyridyl.

[0082] As used herein, the term "heterocyclyl" refers to a fully saturated or unsaturated monocyclic group having one or more oxygen, sulfur or nitrogen heteroatoms in the ring. In one embodiment, the heterocyclyl has 1 to 3 heteroatoms in the ring. In one embodiment, the heterocyclyl has 1 to 3 oxygen and / or nitrogen heteroatoms in the ring. In one embodiment, the heterocyclyl has 1 to 3 oxygen heteroatoms in the ring. The nitrogen and sulfur heteroatoms may optionally be oxidized, and the nitrogen heteroatoms may optionally be quaternized. The heterocyclic group may or may not be substituted.

[0083] Exemplary monocyclic heterocyclic groups include, but are not limited to, pyrrolidinyl, pyrrolyl, pyrazolyl, oxiranyl, oxetanyl, pyrazolinyl, imidazolyl, imidazolinyl, imidazolidinyl, oxazolyl, oxazolidinyl, isoxazolinyl, isoxazolyl, thiazolyl, thiadiazolyl, thiazolidinyl, isothiazolyl, isothiazolidinyl, furyl, tetrahydrofuryl, thienyl, oxadiazolyl, piperidinyl, piperazinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolodinyl, 2-oxazepinyl, azepinyl, 4-piperidonyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, tetrahydropyranyl, morpholinyl, thiomorpholinyl, thiomorpholinyl sulfoxide, thiomorpholinyl sulfone, 1,3-dioxolane and tetrahydro-1,1-dioxothienyl, triazolyl, and triazinyl.

[0084] In one embodiment, the heterocyclyl is selected from the group consisting of oxiranyl, oxetanyl, tetrahydrofuryl, tetrahydropyranyl, and 1,3-dioxolane. In one embodiment, the heterocyclyl is 1,3-dioxolane.

[0085] All aspects include, where appropriate, all enantiomers and tautomers of the compounds of formula (I). Those skilled in the art will recognize compounds having optical properties (one or more chiral carbon atoms) or tautomeric characteristics. The corresponding enantiomers and / or tautomers may be isolated / prepared by methods known in the art. Some of the compounds of formula (I) may exist as stereoisomers and / or geometric isomers, for example, may have one or more asymmetric centers and / or geometric centers, and thus may exist in two or more stereoisomeric forms and / or geometric forms. All aspects include, where appropriate, the use of all individual stereoisomers and geometric isomers of those compounds, and mixtures thereof. The terms used in the claims encompass these forms.

[0086] Suitable salts of the compound of formula (I) include its suitable acid addition salts or base salts. Such salts and solvates of the compound of formula (I) will be known in the art. Suitable acid addition salts include carboxylates (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, mandelate, phenylpropionate, phenylbutyrate, benzoate, chlorobenzoate, methylbenzoate, hydroxybenzoate, methoxybenzoate, dinitrobenzoate, o-acetoxybenzoate, salicylate, nicotinate, isonicotinate, cinnamate, oxalate, malonate, succinate, suberate, sebacate, fumarate, malate, maleate, hydroxymaleate, hippurate, phthalate or terephthalate), halide salts (e.g., chloride salt, bromide salt or iodide salt), sulfonate salts (e.g., benzenesulfonate, methyl-, bromo- or chloro-benzenesulfonate, xylenesulfonate, methanesulfonate, ethanesulfonate, propanesulfonate, hydroxyethanesulfonate, 1- or 2-naphthalenesulfonate or 1,5-naphthalenedisulfonate) or sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, phosphate, monohydrogen phosphate, dihydrogen phosphate, metaphosphate, pyrophosphate or nitrate.

[0087] In one embodiment, the coolant is 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)menthylcarboxamide, Menthone-1,2-glycerol ketal, Menthyl lactate, Isopulegol, 3-Methoxypropane-1,2-diol, and Menthyl succinate is selected from the group consisting of.

[0088] In one aspect, the coolant is 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)menthyl carboxamide, Menthone-1,2-glycerol ketal, Menthyl lactate, 3-Methoxypropane-1,2-diol, and Menthyl succinate is selected from the group consisting of.

[0089] In a second feature, the coolant is 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)menthyl carboxamide, Menthone-1,2-glycerol ketal, Menthyl lactate, Isopulegol, 3-Methoxypropane-1,2-diol, and Menthyl succinate from the group consisting of or 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)menthylcarboxamide, Mentone-1,2-glycerol ketal, Menthyl lactate, 3-Menthoxypropane-1,2-diol, and Menthyl succinate may be selected from the group consisting of.

[0090] In one aspect of the first feature, the coolant is

Chemical formula

[0091] In one aspect, the coolant is not WS-23, i.e., N,2,3-trimethyl-2-propan-2-ylbutanamide.

[0092] In one aspect of the first feature, the coolant is WS-23, i.e., N,2-3-trimethyl-2-propan-2-ylbutanamide. WS-23 is not included by the second feature of the present invention.

[0093] In one aspect, the coolant 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)menthylcarboxamide, (-)-menthone 1,2-glycerol ketal, (-)-menthyl lactate, (-)-isopulegol, 3-((-)-menthoxy)propane-1,2-diol, and (-)-menthyl succinate.

[0094] In one aspect, the coolant 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)menthylcarboxamide, (-)-menthone 1,2-glycerol ketal, (-)-menthyl lactate, 3-((-)-menthoxy)propane-1,2-diol, and (-)-menthyl succinate.

[0095] In one aspect, the coolant 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)menthylcarboxamide, (-)-menthone 1,2-glycerol ketal, (-)-menthyl lactate, (-)-isopulegol, and 3-((-)-menthoxy)propane-1,2-diol.

[0096] In one aspect, the coolant 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)menthylcarboxamide, (-)-menthone 1,2-glycerol ketal, (-)-menthyl lactate, (-)-isopulegol, and 3-((-)-menthoxy)propane-1,2-diol.

[0097] In one aspect, the coolant 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)menthylcarboxamide, (-)-menthone 1,2-glycerol ketal, (-)-menthyl lactate, and 3-((-)-menthoxy)propane-1,2-diol.

[0098] In one aspect, the coolant is (1R,2S,5R)-N-(2-(pyridin-2-yl)ethyl)menthylcarboxamide.

[0099] In another aspect, the coolant is (1S,2R,5S)-N-ethyl-5-methyl-2-(propan-2-yl)cyclohexanecarboxamide.

[0100] As described above, all aspects include, where appropriate, all enantiomers and tautomers of the compounds. Those skilled in the art will recognize compounds having optical properties (one or more chiral carbon atoms) or tautomeric characteristics. The corresponding enantiomers and / or tautomers may be isolated / prepared by methods known in the art.

[0101] Vaporizable formulation

[0102] The vaporizable formulation of the present invention may contain one or more additional components. These components may be selected according to the properties of the formulation.

[0103] In one aspect, the formulation further contains a "perfume" or "flavoring agent". The terms "perfume" and "flavoring agent" refer to materials that are added to the formulation when local adjustment permits, in order to create a desired taste or aroma in products for adult consumers. References herein to "perfume" or "flavoring agent" include both single-component perfumes and multi-component perfumes.

[0104] In one aspect, the perfume is selected from the group consisting of extracts such as licorice, hydrangea, Japanese cypress leaves, chamomile, fenugreek, clove, menthol, Japanese mint, aniseed, cinnamon, herbs, wintergreen, cherry, berry, peach, apple, rum, bourbon, scotch, whiskey, spearmint, peppermint, lavender, cardamom, celery, cascarilla, nutmeg, camphor, bergamot, geranium, honey essence, rose oil, vanilla, lemon oil, orange oil, cassia, caraway, cognac, jasmine, ylang-ylang, sage, perilla, bell pepper, ginger, anise, coriander, coffee, flavor enhancers, bitter receptor site blockers, sensory receptor site activators or sensory receptor site stimulants, sugars and / or alternative sugars (such as sucralose, acesulfame potassium, aspartame, saccharin, cyclamate, lactose, sucrose, glucose, fructose, sorbitol, or mannitol), and other additives such as charcoal, chlorophyll, minerals, plant substances, or breath fresheners. These may be imitation raw materials, synthetic raw materials, natural raw materials, or blends thereof. These may be in any suitable form, such as oil, liquid, or powder.

[0105] In one aspect, the formulation further comprises an active agent. The term "active agent" means a drug that has a biological effect on a subject when the vapor is inhaled. The one or more active agents may be selected from nicotine, plant substances, and mixtures thereof. The one or more active agents may be of synthetic or natural origin. The active agent can be an extract from a plant substance such as a plant of the Solanaceae family.

[0106] An example of the active agent is nicotine.

[0107] Thus, in one aspect, the present invention provides (i) one or more solvents, (ii) a coolant of less than about 1 wt% based on the total weight of the vaporizable formulation that volatilizes at a temperature higher than menthol at atmospheric pressure, (iii) an active agent or (i) one or more solvents, (ii) a coolant of less than about 12 wt% based on the total weight of the vaporizable formulation that volatilizes at a temperature higher than menthol at atmospheric pressure and is a compound of formula (I) as defined herein or a salt and / or solvate thereof, (iii) an active agent and provides a vaporizable formulation comprising the same.

[0108] In one aspect, the active agent is nicotine. Thus, in one aspect, the present invention provides (i) one or more solvents, (ii) a coolant of less than about 1 wt% based on the total weight of the vaporizable formulation that volatilizes at a temperature higher than menthol at atmospheric pressure, (iii) nicotine or (i) one or more solvents, (ii) a coolant of less than about 12 wt% based on the total weight of the vaporizable formulation that volatilizes at a temperature higher than menthol at atmospheric pressure and is a compound of formula (I) as defined herein or a salt and / or solvate thereof, (iii) nicotine To provide a vaporizable formulation containing

[0109] Nicotine can be supplied in any suitable amount according to the desired dose when inhaled by the user. In one aspect, nicotine is present in an amount not exceeding about 6 wt% based on the total weight of the vaporizable formulation. In one aspect, nicotine is present in an amount of about 0.4 to about 6 wt% based on the total weight of the vaporizable formulation. In one aspect, nicotine is present in an amount of about 0.8 to about 6 wt% based on the total weight of the vaporizable formulation. In one aspect, nicotine is present in an amount of about 1 to about 6 wt% based on the total weight of the vaporizable formulation. In one aspect, nicotine is present in an amount of about 1.8 to about 6 wt% based on the total weight of the vaporizable formulation.

[0110] In one aspect, nicotine is present in an amount not exceeding about 5 wt% based on the total weight of the vaporizable formulation. In one aspect, nicotine is present in an amount of about 0.4 to about 5 wt% based on the total weight of the vaporizable formulation. In one aspect, nicotine is present in an amount of about 0.8 to about 5 wt% based on the total weight of the vaporizable formulation. In one aspect, nicotine is present in an amount of about 1 to about 5 wt% based on the total weight of the vaporizable formulation. In one aspect, nicotine is present in an amount of about 1.8 to about 5 wt% based on the total weight of the vaporizable formulation.

[0111] In one aspect, nicotine is present in an amount not exceeding about 4 wt% based on the total weight of the vaporizable formulation. In one aspect, nicotine is present in an amount of about 0.4 to about 4 wt% based on the total weight of the vaporizable formulation. In one aspect, nicotine is present in an amount of about 0.8 to about 4 wt% based on the total weight of the vaporizable formulation. In one aspect, nicotine is present in an amount of about 1 to about 4 wt% based on the total weight of the vaporizable formulation. In one aspect, nicotine is present in an amount of about 1.8 to about 4 wt% based on the total weight of the vaporizable formulation.

[0112] In one aspect, nicotine is present in an amount not exceeding about 3 wt% based on the total weight of the vaporizable formulation. In one aspect, nicotine is present in an amount of about 0.4 to about 3 wt% based on the total weight of the vaporizable formulation. In one aspect, nicotine is present in an amount of about 0.8 to about 3 wt% based on the total weight of the vaporizable formulation. In one aspect, nicotine is present in an amount of about 1 to about 3 wt% based on the total weight of the vaporizable formulation. In one aspect, nicotine is present in an amount of about 1.8 to about 3 wt% based on the total weight of the vaporizable formulation.

[0113] In one aspect, nicotine is present in an amount not exceeding about 1.9 wt% based on the total weight of the vaporizable formulation. In one aspect, nicotine is present in an amount not exceeding about 1.8 wt% based on the total weight of the vaporizable formulation. In one aspect, nicotine is present in an amount of about 0.4 to about 1.9 wt% based on the total weight of the vaporizable formulation. In one aspect, nicotine is present in an amount of about 0.4 to about 1.8 wt% based on the total weight of the vaporizable formulation. In one aspect, nicotine is present in an amount of about 0.5 to about 1.9 wt% based on the total weight of the vaporizable formulation. In one aspect, nicotine is present in an amount of about 0.5 to about 1.8 wt% based on the total weight of the vaporizable formulation. In one aspect, nicotine is present in an amount of about 0.8 to about 1.9 wt% based on the total weight of the vaporizable formulation. In one aspect, nicotine is present in an amount of about 0.8 to about 1.8 wt% based on the total weight of the vaporizable formulation. In one aspect, nicotine is present in an amount of about 1 to about 1.9 wt% based on the total weight of the vaporizable formulation. In one aspect, nicotine is present in an amount of about 1 to about 1.8 wt% based on the total weight of the vaporizable formulation.

[0114] In one aspect, nicotine is present in an amount of less than about 1.9 wt% based on the total weight of the vaporizable formulation. In one aspect, nicotine is present in an amount of less than about 1.8 wt% based on the total weight of the vaporizable formulation. In one aspect, nicotine is present in an amount of from about 0.4 to less than about 1.9 wt% based on the total weight of the vaporizable formulation. In one aspect, nicotine is present in an amount of from about 0.4 to less than about 1.8 wt% based on the total weight of the vaporizable formulation. In one aspect, nicotine is present in an amount of from about 0.5 to less than about 1.9 wt% based on the total weight of the vaporizable formulation. In one aspect, nicotine is present in an amount of from about 0.5 to less than about 1.8 wt% based on the total weight of the vaporizable formulation. In one aspect, nicotine is present in an amount of from about 0.8 to less than about 1.9 wt% based on the total weight of the vaporizable formulation. In one aspect, nicotine is present in an amount of from about 0.8 to less than about 1.8 wt% based on the total weight of the vaporizable formulation. In one aspect, nicotine is present in an amount of from about 1 to less than about 1.9 wt% based on the total weight of the vaporizable formulation. In one aspect, nicotine is present in an amount of from about 1 to less than about 1.8 wt% based on the total weight of the vaporizable formulation.

[0115] In one aspect, the vaporizable formulation may include one or more acids. In some embodiments, the vaporizable formulation may include one or more acids in addition to nicotine (as an active agent). In some embodiments, the 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 mixtures thereof. When included in a formulation in combination with nicotine, the one or more acids can produce a formulation in which nicotine is in at least a partially protonated (such as monoprotonated and / or diprotonated) form.

[0116] Solvent

[0117] As discussed herein, the vaporizable formulation includes one or more solvents.

[0118] The one or more solvents may be any suitable solvent. In one embodiment, the one or more solvents are selected from water, glycerol, propylene glycol, 1,3-propanediol, and mixtures thereof. Other suitable solvents will be apparent to those skilled in the art.

[0119] One or more solvents may be present in any suitable amount in the vaporizable formulation. In one aspect, one or more solvents are present in a total amount of at least 5 wt% based on the total weight of the vaporizable formulation. In one aspect, one or more solvents are present in a total amount of at least 10 wt% based on the total weight of the vaporizable formulation. In one aspect, one or more solvents are present in a total amount of at least 15 wt% based on the total weight of the vaporizable formulation. In one aspect, one or more solvents are present in a total amount of at least 20 wt% based on the total weight of the vaporizable formulation. In one aspect, one or more solvents are present in a total amount of at least 25 wt% based on the total weight of the vaporizable formulation. In one aspect, one or more solvents are present in a total amount of at least 30 wt% based on the total weight of the vaporizable formulation. In one aspect, one or more solvents are present in a total amount of at least 35 wt% based on the total weight of the vaporizable formulation. In one aspect, one or more solvents are present in a total amount of at least 40 wt% based on the total weight of the vaporizable formulation. In one aspect, one or more solvents are present in a total amount of at least 45 wt% based on the total weight of the vaporizable formulation. In one aspect, one or more solvents are present in a total amount of at least 50 wt% based on the total weight of the vaporizable formulation. In one aspect, one or more solvents are present in a total amount of at least 55 wt% based on the total weight of the vaporizable formulation. In one aspect, one or more solvents are present in a total amount of at least 60 wt% based on the total weight of the vaporizable formulation. In one aspect, one or more solvents are present in a total amount of at least 65 wt% based on the total weight of the vaporizable formulation. In one aspect, one or more solvents are present in a total amount of at least 70 wt% based on the total weight of the vaporizable formulation. In one aspect, one or more solvents are present in a total amount of at least 75 wt% based on the total weight of the vaporizable formulation. In one aspect, one or more solvents are present in a total amount of at least 80 wt% based on the total weight of the vaporizable formulation. In one aspect, one or more solvents are present in a total amount of at least 85 wt% based on the total weight of the vaporizable formulation.In one aspect, the one or more solvents are present in a total amount of at least 90 wt% based on the total weight of the vaporizable formulation.

[0120] In one aspect, the one or more solvents are present in a total amount of 5 to 99 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 10 to 99 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 15 to 99 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 20 to 99 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 25 to 99 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 30 to 99 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 35 to 99 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 40 to 99 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 45 to 99 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 50 to 99 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 55 to 99 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 60 to 99 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 65 to 99 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 70 to 99 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 75 to 99 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 80 to 99 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 85 to 99 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 90 to 99 wt% based on the vaporizable formulation.

[0121] In one aspect, the one or more solvents are present in a total amount of 5 to 95 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 10 to 95 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 15 to 95 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 20 to 95 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 25 to 95 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 30 to 95 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 35 to 95 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 40 to 95 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 45 to 95 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 50 to 95 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 55 to 95 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 60 to 95 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 65 to 95 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 70 to 95 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 75 to 95 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 80 to 95 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 85 to 95 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 90 to 95 wt% based on the vaporizable formulation.

[0122] In one aspect, the one or more solvents are present in a total amount of 5 to 90 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 10 to 90 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 15 to 90 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 20 to 90 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 25 to 90 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 30 to 90 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 35 to 90 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 40 to 90 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 45 to 90 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 50 to 90 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 55 to 90 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 60 to 90 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 65 to 90 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 70 to 90 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 75 to 90 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 80 to 90 wt% based on the vaporizable formulation. In one aspect, the one or more solvents are present in a total amount of 85 to 90 wt% based on the vaporizable formulation.

[0123] As discussed herein, in one aspect, the solvent is at least glycerol. Glycerol may be present in any suitable amount in the vaporizable formulation. In one aspect, glycerol is present in a total amount of at least 10 wt% based on the vaporizable formulation. In one aspect, glycerol is present in a total amount of at least 20 wt% based on the vaporizable formulation. In one aspect, glycerol is present in a total amount of at least 30 wt% based on the vaporizable formulation. In one aspect, glycerol is present in a total amount of at least 35 wt% based on the vaporizable formulation. In one aspect, glycerol is present in a total amount of at least 40 wt% based on the vaporizable formulation. In one aspect, glycerol is present in a total amount of at least 45 wt% based on the vaporizable formulation. In one aspect, glycerol is present in a total amount of at least 50 wt% based on the vaporizable formulation. In one aspect, glycerol is present in a total amount of at least 55 wt% based on the vaporizable formulation. In one aspect, glycerol is present in a total amount of at least 60 wt% based on the vaporizable formulation.

[0124] In one aspect, glycerol is present in a total amount of 10 - 60 wt% based on the vaporizable formulation. In one aspect, glycerol is present in a total amount of 20 - 60 wt% based on the vaporizable formulation. In one aspect, glycerol is present in a total amount of 25 - 60 wt% based on the vaporizable formulation. In one aspect, glycerol is present in a total amount of 30 - 60 wt% based on the vaporizable formulation. In one aspect, glycerol is present in a total amount of 35 - 60 wt% based on the vaporizable formulation. In one aspect, glycerol is present in a total amount of 40 - 60 wt% based on the vaporizable formulation. In one aspect, glycerol is present in a total amount of 45 - 60 wt% based on the vaporizable formulation.

[0125] As discussed herein, in one aspect, the solvent is at least propylene glycol. Propylene glycol may be present in any suitable amount in the vaporizable formulation. In one aspect, propylene glycol is present in a total amount of at least 10 wt% based on the vaporizable formulation. In one aspect, propylene glycol is present in a total amount of at least 15 wt% based on the vaporizable formulation. In one aspect, propylene glycol is present in a total amount of at least 20 wt% based on the vaporizable formulation. In one aspect, propylene glycol is present in a total amount of at least 25 wt% based on the vaporizable formulation. In one aspect, propylene glycol is present in a total amount of at least 30 wt% based on the vaporizable formulation. In one aspect, propylene glycol is present in a total amount of at least 35 wt% based on the vaporizable formulation. In one aspect, propylene glycol is present in a total amount of at least 40 wt% based on the vaporizable formulation.

[0126] In one aspect, propylene glycol is present in a total amount of 10 - 40 wt% based on the vaporizable formulation. In one aspect, propylene glycol is present in a total amount of 15 - 40 wt% based on the vaporizable formulation. In one aspect, propylene glycol is present in a total amount of 20 - 40 wt% based on the vaporizable formulation. In one aspect, propylene glycol is present in a total amount of 25 - 40 wt% based on the vaporizable formulation. In one aspect, propylene glycol is present in a total amount of 30 - 40 wt% based on the vaporizable formulation. In one aspect, propylene glycol is present in a total amount of 32 - 40 wt% based on the vaporizable formulation. In one aspect, propylene glycol is present in a total amount of 35 - 40 wt% based on the vaporizable formulation.

[0127] As discussed herein, one or more solvents may include water. In one aspect, water is present in a total amount of 0 to 25 wt% based on the vaporizable formulation. This amount may include 0% water based on the vaporizable formulation, and thus, the vaporizable formulation may or may not include water.

[0128] In one aspect, the vaporizable formulation includes water. Water may be present in any suitable amount in the vaporizable formulation. In one aspect, water is present in a total amount of 0 to 24 wt% based on the vaporizable formulation. In one aspect, water is present in a total amount of 0 to 22 wt% based on the vaporizable formulation. In one aspect, water is present in a total amount of 0 to 20 wt% based on the vaporizable formulation. In one aspect, water is present in a total amount of 0 to 19 wt% based on the vaporizable formulation. In one aspect, water is present in a total amount of 0 to 18 wt% based on the vaporizable formulation. In one aspect, water is present in a total amount of 0 to 17 wt% based on the vaporizable formulation. In one aspect, water is present in a total amount of 0 to 16 wt% based on the vaporizable formulation. In one aspect, water is present in a total amount of 0 to 15 wt% based on the vaporizable formulation.

[0129] In an alternative embodiment, the solvent is substantially free of water. It should be noted in this regard that some formulations may be hygroscopic, and thus, it may not be possible to exclude the entry of water into the formulation. Thus, "substantially water-free" means that the amount of water present is less than 0.1 wt% based on the vaporizable formulation.

[0130] Process

[0131] As discussed herein, the present invention provides a process for generating vapor comprising the step of vaporizing a vaporizable formulation comprising (i) one or more solvents and (ii) a coolant of less than about 1 wt% based on the total weight of the vaporizable formulation that vaporizes at a temperature higher than menthol at atmospheric pressure, or a coolant of less than about 12 wt% based on the total weight of the vaporizable formulation that vaporizes at a temperature higher than menthol at atmospheric pressure and is a compound of formula (I) as defined herein or a salt and / or solvate thereof.

[0132] In one aspect, the vapor is generated by heating the vaporizable formulation to a temperature above about 100 °C. In one aspect, the vapor is generated by heating the vaporizable formulation to a temperature above about 110 °C. In one aspect, the vapor is generated by heating the vaporizable formulation to a temperature above about 120 °C.

[0133] In another aspect, the vapor is generated by a process conducted at a temperature below about 100 °C. In one aspect, the vapor is generated by a process conducted at a temperature below about 90 °C. In one aspect, the vapor is generated by a process conducted at a temperature below about 80 °C.

[0134] In one aspect, the vapor is generated by applying ultrasonic energy to the vaporizable formulation.

[0135] Further aspects

[0136] The vaporizable formulation may be contained or delivered by any means. In one aspect, the present invention provides (a) a container, and (b) a vaporizable formulation as defined above herein and provides a contained vaporizable formulation.

[0137] The container may be any suitable container, for example, for enabling storage or delivery of a solution. In one aspect, the container is configured for engagement with an electronic vapor supply system. The container may be a bottle. The container may be configured to be in fluid communication with the electronic vapor supply system so as to be able to deliver the solution to the electronic vapor supply system. As described above, the present disclosure relates to a container that can be used in an electronic vapor supply system such as an e-cigarette. Throughout the following description, the term "e-cigarette" is used, but this term can be used interchangeably with an electronic vapor supply system.

[0138] As discussed herein, the container of the present invention is typically provided for delivery of a vaporizable formulation to or within an e-cigarette. The vaporizable formulation may be held within the e-cigarette or may be sold as a separate container for subsequent use with or within the e-cigarette. As will be understood by those skilled in the art, an e-cigarette may include a unit known as a removable cartridge that typically includes a reservoir for the vaporizable formulation, a wicking material, and a device for vaporizing the vaporizable formulation. In some e-cigarettes, the cartridge is part of an integrally formed device and is not removable. In one aspect, the container is a cartridge or part of a cartridge. In one aspect, the container is not a cartridge or part of a cartridge, but rather a container such as a tank, and the container can be used to deliver a vaporizable formulation to or within an e-cigarette.

[0139] In one aspect, the container is part of an electronic vapor supply system such as an e-cigarette. Thus, in a further aspect, the present invention (a) a vaporizer for vaporizing a formulation for inhalation by a user of the electronic vapor supply system, (b) a power source comprising a battery or batteries for supplying power to the vaporizer comprising (c) the vaporizable formulation described above herein To provide an electronic vapor supply system including the same.

[0140] In addition to systems such as vaporizable formulations of the present invention, containers containing the same, and electronic aerosol supply systems, the present invention provides the use of a coolant that extends the shelf life of the vaporizable formulation, wherein the coolant volatilizes at a temperature higher than menthol at atmospheric pressure.

[0141] Shelf life is typically the length of time that a consumer product can be stored without becoming unsuitable for use, consumption, or sale. The expression "extends the shelf life" means that the coolant enables the vaporizable formulation to be stored for a longer period without its components chemically decomposing, compared to similar formulations containing menthol. Typical storage conditions include ambient temperature and ambient pressure.

[0142] Hereinafter, with reference to the following accompanying drawings, the present invention will be described in more detail by way of example only.

Brief Description of the Drawings

[0143]

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

Figure 10

Figure 11

Figure 12

Example 1

[0144] Here, the present invention will be described with reference to the following non-limiting examples.

[0145] Nine coolants were used in the examples. These compounds are shown in Table 1 below along with their chemical names, trade names, approximate boiling points and approximate vapor pressures. Since the compounds are known, the boiling points and vapor pressures of the compounds were obtained from the literature.

[0146]

Table 1

[0147] Analysis test

[0148] Thermogravimetric analysis Prior to the panel test, the coolants were subjected to thermogravimetric analysis (TGA) to understand the behavior of the coolants when heated. As is known in the art, TGA is an analytical method that can monitor the mass loss of a sample when the sample is heated to a temperature of up to 1000 °C or higher.

[0149] All measurements were performed using a Perkin Elmer STA6000 TGA thermogravimetric analyzer. For solid samples, a spatula was used to transfer 5 - 20 mg of the material into the crucible of the analyzer. The oil was introduced into the apparatus by using a Pasteur pipette to transfer 5 - 20 mg onto a small part of a Cambridge filter pad placed in the crucible. All samples were heated from 30 °C to 600 °C at a constant rate of 5 °C / min. The heating was carried out twice in air and twice in nitrogen for each compound. For a few samples, the test was terminated at 500 - 600 °C if complete mass loss was observed. For comparison, menthol was also analyzed.

[0150] The TGA traces of each compound (Repeat 1 and Repeat 2 in air; and Repeat 1 and Repeat 2 in nitrogen) are shown in FIGS. 1-9 (A-D). The onset temperature of mass loss for each compound was determined by visual inspection of the TGA traces on computer software. The results are summarized in Table 2. Evacool (trademark) 190 showed a mass loss phenomenon more than once, but it was confirmed that the mass loss at approximately 65-75 °C was due to the presence of water in the sample.

[0151]

Table 2

[0152] From these results, it can be seen that good reproducibility of the experiment was achieved and that there was no significant difference between the TGA traces in air and in nitrogen. The latter suggests that the compound is less prone to thermal oxidation at the temperature at which mass loss was observed.

[0153] These results also show that, unlike menthol, the mass loss of all the tested coolants occurred at temperatures above 85 °C. Since this mass loss was generally positively correlated with the molecular weight (see FIG. 10), it is likely due to volatilization / vaporization rather than decomposition. Therefore, it can be said that all the tested compounds are less volatile than menthol and volatilize at a higher temperature than menthol at atmospheric pressure. The low volatility of the coolant is advantageous because it means that the coolant is more stable than menthol under storage.

[0154] Example 1 Observation test Ten volunteers were asked to use each coolant sample in a Vype eTank Pro (electronic cigarette device). All coolants were used at a concentration of 0.18%, except for menthol, which was used at its current commercial concentration of 1.235% in one sample. Each of the menthol samples was tested for comparison.

[0155] Each volunteer was asked to evaluate the cooling intensity objectively (i.e., without considering personal preferences) and subjectively. For the objective evaluation, the volunteers were asked to rate the overall perceived cooling intensity imparted to, for example, the oral cavity or the throat on a scale of 0 - 10, where 0 was no perceptible cooling and 10 was a very strong cooling sensation. For the subjective evaluation, the volunteers were asked to rate the cooling intensity as (1) far too low, (2) slightly too low, (3) just right, (4) slightly too high, or (5) far too high.

[0156] Result The results of the objective and subjective evaluations by the volunteers are shown in Table 3 and Figure 11 below.

[0157]

Table 3

[0158] The results show that some compounds give more cooling sensation at 0.18% than menthol at the same concentration. In particular, 0.18% Evercool (registered trademark) 190 gives a cooling sensation of 7.1 / 10 compared to 8 / 10 for 1.235% menthol.

[0159] Cooling sensation delivery was generally more favorable for non - menthol coolants compared to menthol formulations. Thus, menthol coolants can be included in the vaporizable formulations of the present invention at concentrations much lower than menthol and still be able to deliver a cooling sensation when vaporized by the user. As shown by the above thermogravimetric analysis, the mass loss measured by TGA occurs at much higher temperatures, which also leads to improved storage stability for the coolants compared to menthol formulations. Finally, the results show that the coolants deliver a different cooling sensation than menthol. The area of delivery is mainly in the back of the mouth and throat while there is minimal delivery on the tongue, which avoids the dry - out of the mouth experienced with menthol.

[0160] Example 2 The lowest 4 volunteers were asked to test each of the following e-liquid samples in the eTank Pro (e-cigarette device):

[0161] 2.5 wt% WS-3 in glycerol / propylene glycol; 5 wt% WS-3 in glycerol / propylene glycol; and 10 wt% WS-3 in glycerol / propylene glycol.

[0162] 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.

[0163] Each volunteer was asked to objectively (i.e., without considering personal preferences) and subjectively evaluate the cooling intensity in the same way as in Example 1. For the objective evaluation, the volunteers were asked to rate the overall perceived cooling intensity that gives a cooling sensation, for example, in the mouth, in the throat, etc., on a scale of 0 - 10, where 0 means no perceivable cooling and 10 means a very strong cooling sensation. For the subjective evaluation, the volunteers were asked to rate whether the cooling intensity was (1) far too low, (2) slightly too low, (3) just right, (4) slightly too high, or (5) far too high.

[0164] The results based on the objective and subjective evaluations of the volunteers are shown in Table 4 and Figure 12 below.

[0165]

Table 4

[0166] These results indicate that the cooling intensity of WS-3 increases with increasing concentration and that this compound can be included in an amount of 10 wt% while delivering the cooling sensation experience to the user. From the volunteers' comments, it was also confirmed that the location of the cooling sensation is different from that of menthol even at higher concentrations. The area of delivery was mainly in the back of the throat, with minimal delivery on the tongue. This sensation was also persistent. This sensation would be particularly beneficial in the market that actively seeks "high menthol" or a strong cooling sensation.

[0167] Without departing from the scope and spirit of the present invention, various modifications and variations of the present invention will become apparent to those skilled in the art. Although the present invention has been described in connection with specific preferred embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments. Indeed, various modifications of the described modes for carrying out the invention that are obvious to those skilled in the chemical or related arts are intended to be within the scope of the following claims.

Claims

**Claim 1** A vaporizable formulation for an electronic vapor supply system that provides a cooling sensation to a user upon inhalation, (i) one or more solvents, and (ii) a cooling agent that volatilizes at a temperature higher than the temperature at which menthol volatilizes at atmospheric pressure and lower than 500 °C, and is 0.001 to less than 12 wt% based on the weight of the vaporizable formulation, A vaporizable formulation comprising: The cooling agent is selected from the group consisting of N,2,3-trimethyl-2-propanylbutanamide, or 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)menthylcarboxamide, menthone 1,2-glycerol ketal, menthyl lactate, and 3-(menthoxy)propane-1,2-diol. A vaporizable formulation. **Claim 2** The vaporizable formulation according to claim 1, comprising 0.001 to 0.9 wt% of the cooling agent based on the weight of the vaporizable formulation. **Claim 3** The vaporizable formulation according to claim 2, comprising 0.005 to 0.75 wt% of the cooling agent based on the weight of the vaporizable formulation. **Claim 4** The vaporizable formulation according to claim 3, comprising 0.01 to 0.5 wt% of the cooling agent based on the weight of the vaporizable formulation. **Claim 5** The vaporizable formulation according to claim 4, wherein the cooling agent volatilizes at a temperature in the range of 230 °C to 500 °C at atmospheric pressure. **Claim 6** The vaporizable formulation according to any one of claims 1 to 5, wherein the cooling agent has a vapor pressure lower than the vapor pressure of menthol at 25 °C. **Claim 7** The vaporizable formulation according to claim 6, wherein the cooling agent has a vapor pressure lower than 0.008 mmHg at 25 °C. **Claim 8** The vaporizable formulation according to any one of claims 1 to 7, wherein the cooling agent is N,2,3-trimethyl-2-propanylbutanamide. **Claim 9** The vaporizable formulation according to any one of claims 1 to 8, further comprising an active agent. **Claim 10** The vaporizable formulation according to claim 9, wherein the active agent is nicotine. **Claim 11** The vaporizable formulation according to any one of claims 1 to 10, comprising 0.001 to 11 wt% of the coolant based on the weight of the vaporizable formulation.

12. The vaporizable formulation according to claim 11, comprising 0.005 to 10 wt% of the coolant based on the weight of the vaporizable formulation.

13. The vaporizable formulation according to any one of claims 1 to 7 or 9 to 12, wherein 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-ylcyclohexanecarbonyl]amino]acetate, N-(4-methoxyphenyl)-p-menthanecarboxamide, N-(2-(pyridin-2-yl)ethyl)menthyl carboxamide, menthone 1,2-glycerol ketal, menthyl lactate, and 3-(menthoxy)propane-1,2-diol.

14. The vaporizable formulation according to any one of claims 1 to 13, wherein the one or more solvents are selected from water, glycerol, propylene glycol, and mixtures thereof.

15. The vaporizable formulation according to any one of claims 1 to 13, wherein the one or more solvents are selected from glycerol, propylene glycol, and mixtures thereof.

16. (a) preparing a vaporizable formulation as defined in any one of claims 1 to 15; (b) vaporizing the vaporizable formulation A method of generating vapor, comprising:

17. (a) a container; (b) a vaporizable formulation as defined in any one of claims 1 to 15 A contained vaporizable formulation, comprising:

18. An electronic vapor supply system, comprising: (a) a vaporizer for vaporizing a liquid for inhalation by a user of the electronic vapor supply system; (b) a power source comprising a battery or battery for supplying power to the vaporizer And comprising: (c) a vaporizable formulation as defined in any one of claims 1 to 15 An electronic vapor supply system, comprising:

19. A coolant for use in extending the shelf life of a vaporizable formulation, wherein the coolant has a temperature higher than the temperature at which menthol volatilizes at atmospheric pressure and volatilizes at a temperature lower than 500 °C at atmospheric pressure, and the vaporizable formulation is a vaporizable formulation as defined in any one of claims 1 to 15.

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