Liquid nicotine preparations

Abstract

To provide liquid nicotine formulation and a cartridge for use in an aerosol-generating system, and the aerosol-generating system.SOLUTION: There is provided a liquid nicotine formulation comprising: one or more water-miscible solvents; one or more water-immiscible solvents having a water solubility at 20°C of about 100 mg / mL or less; and one or more water-soluble organic acids, wherein the liquid nicotine formulation has a water-immiscible solvent content of about 2 weight percent or more. There is provided a liquid nicotine formulation comprising: one or more water-miscible solvents; one or more water-immiscible solvents having a partition coefficient (log P) at 20°C of about 0.05 or more; and one or more water-soluble organic acids, wherein the liquid nicotine formulation has a water-immiscible solvent content of about 2 weight percent or more. There is provided a cartridge that accommodates the liquid nicotine formulation. There is provided an aerosol-generating system comprising the liquid nicotine formulation and an atomiser configured to generate an aerosol from the liquid nicotine formulation.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a liquid nicotine formulation for use in an aerosol generating system. The present invention also relates to a cartridge for an aerosol generating system containing a liquid nicotine formulation, and an aerosol generating system comprising a liquid nicotine formulation and an atomizer configured to generate an aerosol from the liquid nicotine formulation.

Background Art

[0002] Aerosol generating systems for delivering nicotine to a user and comprising an atomizer configured to generate an inhalable aerosol from a liquid nicotine formulation are known. Some known aerosol generating systems comprise a thermal atomizer, such as an electric heater, configured to heat and vaporize the liquid nicotine formulation to generate an aerosol. Other known aerosol generating systems comprise a non-thermal atomizer configured to generate an aerosol from the liquid nicotine formulation using, for example, impinging jets, ultrasonic, or vibrating mesh technology.

[0003] In such aerosol generating systems, efficient pulmonary delivery of the inhalable aerosol generated from the liquid nicotine formulation is considered an important criterion for user preference and satisfaction. Typical liquid nicotine formulations for use in aerosol generating systems contain glycerin, propylene glycol, and water as solvents.

Summary of the Invention

Problems to be Solved by the Invention

[0004] It would be desirable to provide a liquid nicotine formulation for use in an aerosol generating system that enables aerosol generation, which provides users with improved nicotine satisfaction compared to typical liquid nicotine formulations. Specifically, it would be desirable to provide a liquid nicotine formulation for use in an aerosol generating system that enables aerosol generation, which provides users with nicotine satisfaction similar to that of tobacco smoke produced by the combustion of conventional cigarettes. [Means for solving the problem]

[0005] According to a first aspect of the present invention, a liquid nicotine preparation for use in an aerosol generating system is provided, comprising one or more water-miscible solvents, one or more water-immiscible solvents having a water solubility of about 100 mg / mL or less at 20°C, and one or more water-soluble organic acids.

[0006] According to a first aspect of the present invention, a cartridge for use in an aerosol generating system is also provided, which contains a liquid nicotine preparation comprising one or more water-miscible solvents, one or more water-immiscible solvents having a water solubility of about 100 mg / mL or less at 20°C, and one or more water-soluble organic acids.

[0007] According to a first aspect of the present invention, an aerosol generating system is further provided, comprising a liquid nicotine preparation containing one or more water-miscible solvents, one or more water-immiscible solvents having a water solubility of about 100 mg / mL or less at 20°C, and one or more water-soluble organic acids, and an atomizer configured to generate an aerosol from the liquid nicotine preparation.

[0008] According to a second aspect of the present invention, a liquid nicotine formulation for use in an aerosol generating system is provided, comprising one or more water-miscible solvents, one or more water-immiscible solvents having a partition coefficient (log P) of about 0.05 or more at 20°C, and one or more water-soluble organic acids.

[0009] A second aspect of the present invention also provides a cartridge for use in an aerosol generating system, which contains a liquid nicotine preparation comprising one or more water-miscible solvents, one or more water-immiscible solvents having a partition coefficient (log P) of about 0.05 or more at 20°C, and one or more water-soluble organic acids.

[0010] A second aspect of the present invention further provides an aerosol generating system comprising a liquid nicotine preparation containing one or more water-miscible solvents, one or more water-immiscible solvents having a partition coefficient (log P) of about 0.05 or more at 20°C, and one or more water-soluble organic acids, and an atomizer configured to generate an aerosol from the liquid nicotine preparation.

[0011] When used herein in connection with the present invention, the term "liquid nicotine preparation" refers to a liquid preparation containing nicotine.

[0012] As used herein in connection with the present invention, the term "nicotine" refers to nicotine, a nicotine base, or a nicotine salt. In embodiments in which a liquid nicotine preparation comprises a nicotine base or a nicotine salt, the amounts of nicotine listed herein are, respectively, amounts of free base nicotine or amounts of protonated nicotine.

[0013] As used herein in connection with the present invention, the term "water-miscible solvent" refers to a compound other than water or an organic acid that is liquid at 20°C and mixes with water in all proportions to form a homogeneous solution.

[0014] As used herein in connection with the present invention, the term "water-soluble organic acid" refers to an organic acid having a water solubility of about 500 mg / mL or more at 20°C.

[0015] Unless otherwise stated, the water solubility values ​​listed herein are water solubility measured based on the preliminary test in OECD (1995), Test No. 105: Water Solubility, OECD Guidelines for the Testing of Chemicals, Section 1, OECD Publishing, Paris, https: / / doi.org / 10.1787 / 9789264069589-en. In the stepwise procedure, increasing volume of distilled water is added to 0.1 g of the sample (solid material must be crushed) in a 10 mL graduated cylinder with a glass stopper at 20°C. However, if the substance is an acid, the sample is added to the distilled water in the first step. After each addition of a certain amount of water, the mixture is shaken for 10 minutes and visually checked for any undissolved portions of the sample. If, after adding 10 mL of water, the sample or a portion of the sample remains undissolved, the experiment is continued in a 100 mL graduated cylinder. The approximate solubility is provided in Table 1 below, in units less than the volume of water at which the sample is completely dissolved.

[0016] If the solubility is low, it may take a long time to dissolve the substance, and it should be assumed that it will take at least 24 hours. If the substance is still not dissolved after 24 hours, the graduated cylinder should be placed in an ultrasonic bath at 40°C for 15 minutes, and it should be assumed that it will take another 24 hours (up to 96 hours). If the substance is still not dissolved, it is assumed that the solubility is below the limit or that it will not dissolve. [Table 1] Table 1

[0017] As used herein in relation to a first aspect of the present invention, the term "water-immiscible solvent" refers to a compound that is liquid at 20°C and has a water solubility of about 100 mg / mL or less at 20°C.

[0018] As used herein in relation to a second aspect of the present invention, the term "water-immiscible solvent" refers to a compound that is liquid at 20°C and has a partition coefficient (log P) of about 0.05 or greater at 20°C.

[0019] Unless otherwise stated, the partition coefficient (log P) values ​​listed herein refer to the octanol / water partition coefficient (log P OW ) and this is according to OECD (1995), test number 107: partition coefficient (n-octanol / water): shaking flask method, OECD Guidelines for the Testing of Chemicals, Section 1, OECD Publishing, Paris, https: / / doi.org / 10.1787 / 9789264069626-en (log P in the range of -2 to 4) OW (For values), OECD (2004), Test No. 117: Partition coefficient (n-octanol / water), HPLC method, OECD Guidelines for the Testing of Chemicals, Section 1, OECD Publishing, Paris, https: / / doi.org / 10.1787 / 9789264069824-en (log P in the range of 0-6) OW (For values), and OECD (2006), Test No. 123: Partition coefficient (1-octanol / water): Slow stirring method, OECD Guidelines for the Testing of Chemicals, Section 1, OECD Publishing, Paris, https: / / doi.org / 10.1787 / 9789264015845-en (log P in the range up to 8.2) OW It is measured according to the value.

[0020] In the liquid nicotine formulation according to the present invention, the inclusion of a combination of one or more water-miscible solvents, one or more water-immiscible solvents, and one or more water-soluble organic acids advantageously enables the generation of an inhalable aerosol that provides improved nicotine satisfaction to the user compared to typical liquid nicotine formulations. Specifically, as further discussed below, the inclusion of a combination of one or more water-miscible solvents, one or more water-immiscible solvents, and one or more water-soluble organic acids in the liquid nicotine formulation according to the present invention advantageously enables the generation of an inhalable aerosol having improved nicotine retention characteristics compared to typical liquid nicotine formulations.

[0021] The tobacco smoke generated by the combustion of conventional cigarettes contains thousands of different smoke components. Surprisingly, it has been found that the inclusion of a combination of one or more water-miscible solvents, one or more water-immiscible solvents, and one or more water-soluble organic acids in the liquid nicotine formulation according to the present invention advantageously enables the generation of an inhalable aerosol having nicotine retention characteristics similar to those of the tobacco smoke generated by the combustion of conventional cigarettes.

[0022] Unless otherwise stated, the weight percentages of the components of the liquid nicotine formulation recited herein are based on the total weight of the liquid nicotine formulation.

[0023] The liquid nicotine formulation may contain natural nicotine or synthetic nicotine.

[0024] The liquid nicotine formulation may have a nicotine content of about 0.5 weight percent or more.

[0025] Preferably, the liquid nicotine formulation has a nicotine content of about 1 weight percent or more. More preferably, the liquid nicotine formulation has a nicotine content of about 1.5 weight percent or more.

[0026] Liquid nicotine preparations may have a nicotine content of approximately 10% by weight or less. Liquid nicotine preparations may have a nicotine content of approximately 8% by weight or less.

[0027] It is preferable that the liquid nicotine preparation has a nicotine content of approximately 5% by weight or less. It is more preferable that the liquid nicotine preparation has a nicotine content of approximately 3% by weight or less.

[0028] Liquid nicotine preparations may have a nicotine content of approximately 0.5% to approximately 10% by weight. For example, liquid nicotine preparations may have a nicotine content of approximately 0.5% to approximately 8% by weight, approximately 0.5% to approximately 5% by weight, or approximately 0.5% to approximately 3% by weight.

[0029] It is preferable that the liquid nicotine preparation has a nicotine content of about 1% to about 10% by weight. For example, the liquid nicotine preparation may have a nicotine content of about 1% to about 8% by weight, about 1% to about 5% by weight, or about 1% to about 3% by weight.

[0030] It is more preferable that the liquid nicotine preparation has a nicotine content of about 1.5% to about 10% by weight. For example, the liquid nicotine preparation may have a nicotine content of about 1.5% to about 8% by weight, about 1.5% to about 5% by weight, or about 1.5% to about 3% by weight.

[0031] Liquid nicotine formulations contain one or more water-miscible solvents. These water-miscible solvents can, advantageously, help dissolve and stabilize the polar and ionic components of the liquid nicotine formulation.

[0032] It is preferable that the liquid nicotine preparation has a water-miscible solvent content of about 5% by weight or more. It is more preferable that the liquid nicotine preparation has a water-miscible solvent content of about 10% by weight or more. For example, the liquid nicotine preparation may have a water-miscible solvent content of about 15% by weight or more, about 20% by weight or more, or about 25% by weight or more.

[0033] Liquid nicotine preparations may have a water-miscible solvent content of approximately 80% by weight or less, or approximately 75% by weight or less.

[0034] It is preferable that the liquid nicotine preparation has a water-miscible solvent content of about 70% by weight or less. It is more preferable that the liquid nicotine preparation has a water-miscible solvent content of about 60% by weight or less. For example, the liquid nicotine preparation may have a water-miscible solvent content of about 50% by weight or less or about 40% by weight or less.

[0035] It is preferable that the liquid nicotine preparation has a water-miscible solvent content of about 5% to about 70% by weight. For example, the liquid nicotine preparation may have a water-miscible solvent content of about 5% to about 60% by weight, about 5% to about 50% by weight, or about 5% to about 40% by weight.

[0036] It is more preferable that the liquid nicotine formulation has a water-miscible solvent content of about 10% to about 70% by weight. For example, the liquid nicotine formulation may have a water-miscible solvent content of about 10% to about 60% by weight, about 10% to about 50% by weight, or about 10% to about 40% by weight.

[0037] Liquid nicotine preparations may have a water-miscible solvent content of approximately 15% to 70% by weight, approximately 15% to 60% by weight, approximately 15% to 50% by weight, or approximately 15% to 40% by weight.

[0038] The liquid nicotine preparation may have a water-miscible solvent content of approximately 20% to 70% by weight, approximately 20% to 60% by weight, approximately 20% to 50% by weight, or approximately 20% to 40% by weight.

[0039] Liquid nicotine preparations may have a water-miscible solvent content of approximately 25% to 70% by weight, approximately 25% to 60% by weight, approximately 25% to 50% by weight, or approximately 25% to 40% by weight.

[0040] Preferably, one or more water-miscible solvents are one or more water-miscible polyhydric alcohols.

[0041] As used herein in connection with the present invention, the term "water-miscible polyhydric alcohol" refers to a polyhydric alcohol that is liquid at 20°C and mixes with water in all proportions to form a homogeneous solution.

[0042] According to a preferred embodiment of the first aspect of the present invention, a liquid nicotine preparation for use in an aerosol generating system is provided, comprising one or more water-miscible polyhydric alcohols, one or more water-immiscible solvents having a water solubility of about 100 mg / mL or less at 20°C, and one or more water-soluble organic acids.

[0043] A preferred embodiment of the first aspect of the present invention also provides a cartridge for use in an aerosol generating system, which contains a liquid nicotine preparation comprising one or more water-miscible polyhydric alcohols, one or more water-immiscible solvents having a water solubility of about 100 mg / mL or less at 20°C, and one or more water-soluble organic acids.

[0044] According to a preferred embodiment of the first aspect of the present invention, an aerosol generating system is further provided, comprising a liquid nicotine preparation containing one or more water-miscible polyhydric alcohols, one or more water-immiscible solvents having a water solubility of about 100 mg / mL or less at 20°C, and one or more water-soluble organic acids, and an atomizer configured to generate an aerosol from the liquid nicotine preparation.

[0045] A preferred embodiment of a second aspect of the present invention provides a liquid nicotine formulation for use in an aerosol generating system, comprising one or more water-miscible polyhydric alcohols, one or more water-immiscible solvents having a partition coefficient (log P) of about 0.05 or more at 20°C, and one or more water-soluble organic acids.

[0046] A preferred embodiment of a second aspect of the present invention also provides a cartridge for use in an aerosol generating system, which contains a liquid nicotine preparation comprising one or more water-miscible polyhydric alcohols, one or more water-immiscible solvents having a partition coefficient (log P) of about 0.05 or more at 20°C, and one or more water-soluble organic acids.

[0047] A preferred embodiment of a second aspect of the present invention further provides an aerosol generating system comprising a liquid nicotine formulation containing one or more water-miscible polyhydric alcohols, one or more water-immiscible solvents having a partition coefficient (log P) of about 0.05 or more at 20°C, and one or more water-soluble organic acids, and an atomizer configured to generate an aerosol from the liquid nicotine formulation.

[0048] It is preferable that the liquid nicotine preparation has a water-miscible polyhydric alcohol content of about 5% by weight or more. It is more preferable that the liquid nicotine preparation has a water-miscible polyhydric alcohol content of about 10% by weight or more. For example, the liquid nicotine preparation may have a water-miscible polyhydric alcohol content of about 15% by weight or more, about 20% by weight or more, or about 25% by weight or more.

[0049] Liquid nicotine preparations may have a water-miscible polyhydric alcohol content of approximately 80% by weight or less, or approximately 75% by weight or less.

[0050] It is preferable that the liquid nicotine preparation has a water-miscible polyhydric alcohol content of about 70% by weight or less. It is more preferable that the liquid nicotine preparation has a water-miscible polyhydric alcohol content of about 60% by weight or less. For example, the liquid nicotine preparation may have a water-miscible polyhydric alcohol content of about 50% by weight or less or about 40% by weight or less.

[0051] It is preferable that the liquid nicotine preparation has a water-miscible polyhydric alcohol content of about 5% to about 70% by weight. For example, the liquid nicotine preparation may have a water-miscible polyhydric alcohol content of about 5% to about 60% by weight, about 5% to about 50% by weight, or about 5% to about 40% by weight.

[0052] It is more preferable that the liquid nicotine preparation has a water-miscible polyhydric alcohol content of about 10% to about 70% by weight. For example, the liquid nicotine preparation may have a water-miscible polyhydric alcohol content of about 10% to about 60% by weight, about 10% to about 50% by weight, or about 10% to about 40% by weight.

[0053] Liquid nicotine preparations may have a water-miscible polyhydric alcohol content of approximately 15% to 70% by weight, approximately 15% to 60% by weight, approximately 15% to 50% by weight, or approximately 15% to 40% by weight.

[0054] Liquid nicotine preparations may have a water-miscible polyhydric alcohol content of approximately 20% to 70% by weight, approximately 20% to 60% by weight, approximately 20% to 50% by weight, or approximately 20% to 40% by weight.

[0055] Liquid nicotine preparations may have a water-miscible polyhydric alcohol content of approximately 25% to 70% by weight, approximately 25% to 60% by weight, approximately 25% to 50% by weight, or approximately 25% to 40% by weight.

[0056] Preferably, one or more water-miscible polyhydric alcohols are selected from the group consisting of 1,3-butanediol, glycerin, propylene glycol, and triethylene glycol.

[0057] It is more preferable that one or more water-miscible polyhydric alcohols are selected from the group consisting of glycerin and propylene glycol.

[0058] It is most preferable that one or more water-miscible polyhydric alcohols are selected from the group consisting of vegetable glycerin and propylene glycol.

[0059] According to a preferred embodiment of the first aspect of the present invention, a liquid nicotine formulation for use in an aerosol generating system is provided, comprising one or more water-miscible polyhydric alcohols selected from the group consisting of glycerin and propylene glycol, one or more water-immiscible solvents having a water solubility of about 100 mg / mL or less at 20°C, and one or more water-soluble organic acids.

[0060] A preferred embodiment of the first aspect of the present invention also provides a cartridge for use in an aerosol generating system, which contains a liquid nicotine preparation comprising one or more water-miscible polyhydric alcohols selected from the group consisting of glycerin and propylene glycol, one or more water-immiscible solvents having a water solubility of about 100 mg / mL or less at 20°C, and one or more water-soluble organic acids.

[0061] According to a preferred embodiment of the first aspect of the present invention, an aerosol generating system is further provided, comprising a liquid nicotine formulation comprising one or more water-miscible polyhydric alcohols selected from the group consisting of glycerin and propylene glycol, one or more water-immiscible solvents having a water solubility of about 100 mg / mL or less at 20°C, and one or more water-soluble organic acids, and an atomizer configured to generate an aerosol from the liquid nicotine formulation.

[0062] A preferred embodiment of a second aspect of the present invention provides a liquid nicotine formulation for use in an aerosol generating system, comprising one or more water-miscible polyhydric alcohols selected from the group consisting of glycerin and propylene glycol, one or more water-immiscible solvents having a partition coefficient (log P) of about 0.05 or more at 20°C, and one or more water-soluble organic acids.

[0063] A preferred embodiment of a second aspect of the present invention also provides a cartridge for use in an aerosol generating system, which contains a liquid nicotine preparation comprising one or more water-miscible polyhydric alcohols selected from the group consisting of glycerin and propylene glycol, one or more water-immiscible solvents having a partition coefficient (log P) of about 0.05 or more at 20°C, and one or more water-soluble organic acids.

[0064] A preferred embodiment of a second aspect of the present invention further provides an aerosol generating system comprising: a liquid nicotine formulation comprising one or more water-miscible polyhydric alcohols selected from the group consisting of glycerin and propylene glycol; one or more water-immiscible solvents having a partition coefficient (log P) of about 0.05 or more at 20°C; and one or more water-soluble organic acids; and an atomizer configured to generate an aerosol from the liquid nicotine formulation.

[0065] It is preferable that the liquid nicotine preparation has a combined content of glycerin and propylene glycol of about 5% by weight or more. It is more preferable that the liquid nicotine preparation has a combined content of glycerin and propylene glycol of about 10% by weight or more. For example, the liquid nicotine preparation may have a combined content of glycerin and propylene glycol of about 15% by weight or more, about 20% by weight or more, or about 25% by weight or more.

[0066] Liquid nicotine preparations may contain a combination of glycerin and propylene glycol of approximately 80% by weight or less, or approximately 75% by weight or less.

[0067] It is preferable that the liquid nicotine preparation has a combined content of glycerin and propylene glycol of about 70% by weight or less. It is more preferable that the liquid nicotine preparation has a combined content of glycerin and propylene glycol of about 60% by weight or less. For example, the liquid nicotine preparation may have a combined content of glycerin and propylene glycol of about 50% by weight or less, or about 40% by weight or less.

[0068] It is preferable that the liquid nicotine preparation has a combined content of glycerin and propylene glycol in an amount of about 5% to about 70% by weight. For example, the liquid nicotine preparation may have a combined content of glycerin and propylene glycol in an amount of about 5% to about 60% by weight, about 5% to about 50% by weight, or about 5% to about 40% by weight.

[0069] It is more preferable that the liquid nicotine preparation has a combined content of glycerin and propylene glycol of about 10% to about 70% by weight. For example, the liquid nicotine preparation may have a combined content of glycerin and propylene glycol of about 10% to about 60% by weight, about 10% to about 50% by weight, or about 10% to about 40% by weight.

[0070] Liquid nicotine preparations may have a combined content of glycerin and propylene glycol of approximately 15% to 70% by weight, approximately 15% to 60% by weight, approximately 15% to 50% by weight, or approximately 15% to 40% by weight.

[0071] Liquid nicotine preparations may have a combined content of glycerin and propylene glycol of approximately 20% to 70% by weight, approximately 20% to 60% by weight, approximately 20% to 50% by weight, or approximately 20% to 40% by weight.

[0072] Liquid nicotine preparations may have a combined content of glycerin and propylene glycol of approximately 25% to 70% by weight, approximately 25% to 60% by weight, approximately 25% to 50% by weight, or approximately 25% to 40% by weight.

[0073] It is preferable that the liquid nicotine preparation has a glycerin content of approximately 5% by weight or more.

[0074] It is more preferable that the liquid nicotine preparation has a glycerin content of about 6% by weight or more. For example, the liquid nicotine preparation may have a glycerin content of about 7% by weight or more, or about 8% by weight or more.

[0075] Liquid nicotine preparations may have a glycerin content of approximately 80% by weight or less, or approximately 75% by weight or less.

[0076] It is preferable that the liquid nicotine preparation has a glycerin content of about 70% by weight or less. It is more preferable that the liquid nicotine preparation has a glycerin content of about 60% by weight or less. For example, the liquid nicotine preparation may have a glycerin content of about 50% by weight or less or about 40% by weight or less.

[0077] It is preferable that the liquid nicotine preparation has a glycerin content of about 5% to about 70% by weight. For example, the liquid nicotine preparation may have a glycerin content of about 5% to about 60% by weight, about 5% to about 50% by weight, or about 5% to about 40% by weight.

[0078] It is more preferable that the liquid nicotine preparation has a glycerin content of about 6% to about 70% by weight. For example, the liquid nicotine preparation may have a glycerin content of about 6% to about 60% by weight, about 6% to about 50% by weight, or about 6% to about 40% by weight.

[0079] Liquid nicotine preparations may have a glycerin content of approximately 7% to 70% by weight, approximately 7% to 60% by weight, approximately 7% to 50% by weight, or approximately 7% to 40% by weight.

[0080] Liquid nicotine preparations may have a glycerin content of approximately 8% to 70% by weight, approximately 8% to 60% by weight, approximately 8% to 50% by weight, or approximately 8% to 40% by weight.

[0081] It is preferable that the liquid nicotine preparation contains water and one or more water-miscible solvents.

[0082] According to a preferred embodiment of the first aspect of the present invention, a liquid nicotine formulation for use in an aerosol generating system is provided, comprising water, one or more water-miscible solvents, one or more water-immiscible solvents having a water solubility of about 100 mg / mL or less at 20°C, and one or more water-soluble organic acids.

[0083] A preferred embodiment of the first aspect of the present invention also provides a cartridge for use in an aerosol generating system, which contains a liquid nicotine preparation comprising water, one or more water-miscible solvents, one or more water-immiscible solvents having a water solubility of about 100 mg / mL or less at 20°C, and one or more water-soluble organic acids.

[0084] According to a preferred embodiment of the first aspect of the present invention, an aerosol generating system is further provided, comprising a liquid nicotine formulation containing water, one or more water-miscible solvents, one or more water-immiscible solvents having a water solubility of about 100 mg / mL or less at 20°C, and one or more water-soluble organic acids, and an atomizer configured to generate an aerosol from the liquid nicotine formulation.

[0085] A preferred embodiment of a second aspect of the present invention provides a liquid nicotine formulation for use in an aerosol generating system, comprising water, one or more water-miscible solvents, one or more water-immiscible solvents having a partition coefficient (log P) of about 0.05 or more at 20°C, and one or more water-soluble organic acids.

[0086] A preferred embodiment of a second aspect of the present invention also provides a cartridge for use in an aerosol generating system, which contains a liquid nicotine preparation comprising water, one or more water-miscible solvents, one or more water-immiscible solvents having a partition coefficient (log P) of about 0.05 or more at 20°C, and one or more water-soluble organic acids.

[0087] A preferred embodiment of a second aspect of the present invention further provides an aerosol generating system comprising: a liquid nicotine formulation containing water, one or more water-miscible solvents, one or more water-immiscible solvents having a partition coefficient (log P) of about 0.05 or more at 20°C, and one or more water-soluble organic acids; and an atomizer configured to generate an aerosol from the liquid nicotine formulation.

[0088] In combination, water and one or more water-miscible solvents can, advantageously, help dissolve and stabilize the polar and ionic components of liquid nicotine formulations.

[0089] Liquid nicotine preparations may contain approximately 5% by weight or more of water.

[0090] It is preferable that the liquid nicotine preparation has a water content of about 10% by weight or more. It is more preferable that the liquid nicotine preparation has a water content of about 15% by weight or more. It is most preferable that the liquid nicotine preparation has a water content of about 20% by weight or more. For example, the liquid nicotine preparation may have a water content of about 25% by weight or more, about 30% by weight or more, or about 35% by weight or more.

[0091] It is preferable that the liquid nicotine preparation has a water content of about 90% by weight or less. It is more preferable that the liquid nicotine preparation has a water content of about 85% by weight or less. For example, the liquid nicotine preparation may have a water content of about 80% by weight or less, about 75% by weight or less, about 70% by weight or less, or about 65% by weight or less.

[0092] Liquid nicotine preparations may have a water content of approximately 5% to 90% by weight. For example, liquid nicotine preparations may have a water content of approximately 5% to 85% by weight, approximately 5% to 80% by weight, approximately 5% to 75% by weight, approximately 5% to 70% by weight, or approximately 5% to 65% by weight.

[0093] It is preferable that the liquid nicotine preparation has a water content of about 10% to about 90% by weight. For example, the liquid nicotine preparation may have a water content of about 10% to about 85% by weight, about 10% to about 80% by weight, about 10% to about 75% by weight, about 10% to about 70% by weight, or about 10% to about 65% by weight.

[0094] It is more preferable that the liquid nicotine preparation has a water content of about 15% to about 90% by weight. For example, the liquid nicotine preparation may have a water content of about 15% to about 85% by weight, about 15% to about 80% by weight, about 15% to about 75% by weight, about 15% to about 70% by weight, or about 15% to about 65% by weight.

[0095] It is most preferable that the liquid nicotine preparation has a water content of about 20% to about 90% by weight. For example, the liquid nicotine preparation may have a water content of about 20% to about 85% by weight, about 20% to about 80% by weight, about 20% to about 75% by weight, about 20% to about 70% by weight, or about 20% to about 65% by weight.

[0096] Liquid nicotine preparations may have a water content of approximately 25% to 90% by weight. For example, liquid nicotine preparations may have a water content of approximately 25% to 85% by weight, approximately 25% to 80% by weight, approximately 25% to 75% by weight, approximately 25% to 70% by weight, or approximately 25% to 65% by weight.

[0097] Liquid nicotine preparations may have a water content of approximately 30% to 90% by weight. For example, liquid nicotine preparations may have a water content of approximately 30% to 85% by weight, approximately 30% to 80% by weight, approximately 30% to 75% by weight, approximately 30% to 70% by weight, or approximately 30% to 65% by weight.

[0098] Liquid nicotine preparations may have a water content of approximately 35% to 90% by weight. For example, liquid nicotine preparations may have a water content of approximately 35% to 85% by weight, approximately 35% to 80% by weight, approximately 35% to 75% by weight, approximately 35% to 70% by weight, or approximately 35% to 65% by weight.

[0099] Liquid nicotine preparations may contain a combination of water and a water-miscible solvent in a quantity of approximately 50% by weight or more, approximately 55% by weight or more, approximately 60% by weight or more, approximately 65% ​​by weight or more, or approximately 70% by weight or more.

[0100] It is preferable that the liquid nicotine preparation has a combined content of water and a water-miscible solvent of about 75% by weight or more. It is more preferable that the liquid nicotine preparation has a combined content of water and a water-miscible solvent of 80% by weight or more. For example, the liquid nicotine preparation may have a combined content of water and a water-miscible solvent of about 85% by weight or more.

[0101] It is more preferable that the liquid nicotine preparation contains water and one or more water-miscible polyhydric alcohols.

[0102] According to a more preferred embodiment of the first aspect of the present invention, a liquid nicotine formulation for use in an aerosol generating system is provided, comprising water, one or more water-miscible polyhydric alcohols, one or more water-immiscible solvents having a water solubility of about 100 mg / mL or less at 20°C, and one or more water-soluble organic acids.

[0103] A more preferred embodiment of the first aspect of the present invention is also provided, which is a cartridge for use in an aerosol generating system, and contains a liquid nicotine preparation comprising water, one or more water-miscible polyhydric alcohols, one or more water-immiscible solvents having a water solubility of about 100 mg / mL or less at 20°C, and one or more water-soluble organic acids.

[0104] A more preferred embodiment of the first aspect of the present invention further provides an aerosol generating system comprising: a liquid nicotine preparation containing water, one or more water-miscible polyhydric alcohols, one or more water-immiscible solvents having a water solubility of about 100 mg / mL or less at 20°C, and one or more water-soluble organic acids; and an atomizer configured to generate an aerosol from the liquid nicotine preparation.

[0105] A more preferred embodiment of a second aspect of the present invention provides a liquid nicotine formulation for use in an aerosol generating system, comprising water, one or more water-miscible polyhydric alcohols, one or more water-immiscible solvents having a partition coefficient (log P) of about 0.05 or more at 20°C, and one or more water-soluble organic acids.

[0106] A more preferred embodiment of a second aspect of the present invention is also provided, which is a cartridge for use in an aerosol generating system, and contains a liquid nicotine preparation comprising water, one or more water-miscible polyhydric alcohols, one or more water-immiscible solvents having a partition coefficient (log P) of about 0.05 or more at 20°C, and one or more water-soluble organic acids.

[0107] A more preferred embodiment of a second aspect of the present invention further provides an aerosol generating system comprising: a liquid nicotine formulation containing water, one or more water-miscible polyhydric alcohols, one or more water-immiscible solvents having a partition coefficient (log P) of about 0.05 or more at 20°C, and one or more water-soluble organic acids; and an atomizer configured to generate an aerosol from the liquid nicotine formulation.

[0108] In embodiments in which the liquid nicotine preparation comprises water and one or more water-miscible polyhydric alcohols, the liquid nicotine preparation may have a combined content of water and water-miscible polyhydric alcohols of about 50% by weight or more, about 55% by weight or more, about 60% by weight or more, about 65% by weight or more, or about 70% by weight or more.

[0109] In embodiments in which the liquid nicotine preparation contains water and one or more water-miscible polyhydric alcohols, it is preferable that the liquid nicotine preparation has a combined content of water and water-miscible polyhydric alcohols of about 75% by weight or more. It is more preferable that the liquid nicotine preparation has a combined content of water and water-miscible polyhydric alcohols of 80% by weight or more. For example, the liquid nicotine preparation may have a combined content of water and water-miscible polyhydric alcohols of about 85% by weight or more.

[0110] It is most preferable that the liquid nicotine preparation contains water and one or more water-miscible polyhydric alcohols selected from the group consisting of glycerin and propylene glycol.

[0111] A more preferred embodiment of the first aspect of the present invention provides a liquid nicotine formulation for use in an aerosol generating system, comprising water, one or more water-miscible polyhydric alcohols selected from the group consisting of glycerin and propylene glycol, one or more water-immiscible solvents having a water solubility of about 100 mg / mL or less at 20°C, and one or more water-soluble organic acids.

[0112] A more preferred embodiment of the first aspect of the present invention is also provided, which is a cartridge for use in an aerosol generating system, containing a liquid nicotine preparation comprising water, one or more water-miscible polyhydric alcohols selected from the group consisting of glycerin and propylene glycol, one or more water-immiscible solvents having a water solubility of about 100 mg / mL or less at 20°C, and one or more water-soluble organic acids.

[0113] According to a more preferred embodiment of the first aspect of the present invention, an aerosol generating system is further provided, comprising: a liquid nicotine formulation comprising water; one or more water-miscible polyhydric alcohols selected from the group consisting of glycerin and propylene glycol; one or more water-immiscible solvents having a water solubility of about 100 mg / mL or less at 20°C; and one or more water-soluble organic acids; and an atomizer configured to generate an aerosol from the liquid nicotine formulation.

[0114] A more preferred embodiment of a second aspect of the present invention provides a liquid nicotine formulation for use in an aerosol generating system, comprising water, one or more water-miscible polyhydric alcohols selected from the group consisting of glycerin and propylene glycol, one or more water-immiscible solvents having a partition coefficient (log P) of about 0.05 or more at 20°C, and one or more water-soluble organic acids.

[0115] A more preferred embodiment of a second aspect of the present invention is also provided, which is a cartridge for use in an aerosol generating system, and contains a liquid nicotine formulation comprising water, one or more water-miscible polyhydric alcohols selected from the group consisting of glycerin and propylene glycol, one or more water-immiscible solvents having a partition coefficient (log P) of about 0.05 or more at 20°C, and one or more water-soluble organic acids.

[0116] A more preferred embodiment of a second aspect of the present invention further provides an aerosol generating system comprising: a liquid nicotine formulation comprising water, one or more water-miscible polyhydric alcohols selected from the group consisting of glycerin and propylene glycol, one or more water-immiscible solvents having a partition coefficient (log P) of about 0.05 or more at 20°C, and one or more water-soluble organic acids; and an atomizer configured to generate an aerosol from the liquid nicotine formulation.

[0117] In embodiments in which the liquid nicotine preparation comprises water and one or more water-miscible polyhydric alcohols selected from the group consisting of glycerin and propylene glycol, the liquid nicotine preparation may have a combined content of water, glycerin and propylene glycol of about 50% by weight or more, about 55% by weight or more, about 60% by weight or more, about 65% by weight or more, or about 70% by weight or more.

[0118] In embodiments in which the liquid nicotine preparation comprises water and one or more water-miscible polyhydric alcohols selected from the group consisting of glycerin and propylene glycol, it is preferable that the liquid nicotine preparation has a combined content of water, glycerin and propylene glycol of about 75% by weight or more. It is more preferable that the liquid nicotine preparation has a combined content of water, glycerin and propylene glycol of 80% by weight or more. For example, the liquid nicotine preparation may have a combined content of water, glycerin and propylene glycol of about 85% by weight or more.

[0119] Liquid nicotine formulations contain one or more water-immiscible solvents. These water-immiscible solvents can, advantageously, help dissolve and stabilize the non-polar components of the liquid nicotine formulation.

[0120] When used in an aerosol generating system, one or more water-immiscible solvents can reduce the hygroscopicity of aerosols generated from liquid nicotine formulations. This is advantageous because it can reduce or prevent an increase in the particle or droplet size of the aerosol when inhaled by the user as a result of water adsorption in the respiratory tract.

[0121] When used in aerosol generating systems, liquid nicotine formulations generate aerosols containing two-phase particles or droplets comprising a water-miscible phase and a water-immiscible phase. This can advantageously reduce nicotine adsorption in the upper respiratory tract and enhance pulmonary nicotine delivery and retention. While we do not wish to be bound by theory, the improved delivery and retention of pulmonary nicotine is thought to be due to the coating or encapsulation of the water-miscible phase by the water-immiscible phase. This is thought to reduce nicotine evaporation and adsorption in the upper respiratory tract.

[0122] It is preferable that the liquid nicotine preparation has a water-immiscible solvent content of about 1% by weight or more. It is more preferable that the liquid nicotine preparation has a water-immiscible solvent content of about 2% by weight or more. For example, the liquid nicotine preparation may have a water-immiscible solvent content of about 4% by weight or more, about 6% by weight or more, or about 8% by weight or more.

[0123] Liquid nicotine preparations may contain a water-immiscible solvent content of approximately 40% by weight or less.

[0124] It is preferable that the liquid nicotine preparation has a water-immiscible solvent content of about 35% by weight or less. It is more preferable that the liquid nicotine preparation has a water-immiscible solvent content of about 30% by weight or less. For example, the liquid nicotine preparation may have a water-immiscible solvent content of about 25% by weight or less, about 20% by weight or less, or about 15% by weight or less.

[0125] The liquid nicotine preparation may have a water-immiscible solvent content of about 1% to about 40% by weight. Preferably, the liquid nicotine preparation has a water-immiscible solvent content of about 1% to about 35% by weight. For example, the liquid nicotine preparation may have a water-immiscible solvent content of about 1% to about 30% by weight, about 1% to about 25% by weight, about 1% to about 20% by weight, or about 1% to about 15% by weight.

[0126] The liquid nicotine formulation may have a water-immiscible solvent content of about 2% to about 40% by weight. It is more preferable that the liquid nicotine formulation has a water-immiscible solvent content of about 2% to about 35% by weight. For example, the liquid nicotine formulation may have a water-immiscible solvent content of about 2% to about 30% by weight, about 2% to about 25% by weight, about 2% to about 20% by weight, or about 2% to about 15% by weight.

[0127] Liquid nicotine preparations may have a water-immiscible solvent content of approximately 4% to approximately 40% by weight or approximately 4% to approximately 35% by weight. For example, liquid nicotine preparations may have a water-immiscible solvent content of approximately 4% to approximately 30% by weight, approximately 4% to approximately 25% by weight, approximately 4% to approximately 20% by weight, or approximately 4% to approximately 15% by weight.

[0128] Liquid nicotine formulations may have a water-immiscible solvent content of about 6 to about 40 by weight or about 6 to about 35 by weight. For example, liquid nicotine formulations may have a water-immiscible solvent content of about 6 to about 30 by weight, about 6 to about 25 by weight, about 6 to about 20 by weight, or about 6 to about 15 by weight.

[0129] Liquid nicotine formulations may have a water-immiscible solvent content of about 8 to 40 weight percent or about 8 to 35 weight percent. For example, liquid nicotine formulations may have a water-immiscible solvent content of about 8 to 30 weight percent, about 8 to 25 weight percent, about 8 to 20 weight percent, or about 8 to 15 weight percent.

[0130] It is preferable that one or more water-immiscible solvents include one or more partially water-soluble solvents.

[0131] As used herein in relation to a first aspect of the present invention, the term “partially water-soluble solvent” refers to a compound that is liquid at 20°C and has a water solubility of about 20 mg / mL to about 100 mg / mL at 20°C.

[0132] As used herein in relation to a second aspect of the present invention, the term “partially water-soluble solvent” refers to a compound that is liquid at 20°C and has a partition coefficient (log P) of about 0.05 to about 0.5 at 20°C.

[0133] One or more partially water-soluble solvents may have a maximum carbon chain length of 12 or less. For example, one or more partially water-soluble solvents may have a maximum carbon chain length of 10 or less.

[0134] Suitable partially water-soluble solvents include, but are not limited to, polysorbate 80, triethyl citrate, and triacetin.

[0135] It is preferable that the liquid nicotine preparation has a partially water-soluble solvent content of about 0.5% by weight or more. It is more preferable that the liquid nicotine preparation has a partially water-soluble solvent content of about 1% by weight or more. For example, the liquid nicotine preparation may have a partially water-soluble solvent content of about 2% by weight or more, about 4% by weight or more, about 6% by weight or more, about 7% by weight or more, or about 8% by weight or more.

[0136] It is preferable that the liquid nicotine preparation has a partially water-soluble solvent content of about 30% by weight or less. For example, the liquid nicotine preparation may have a partially water-soluble, water-immiscible solvent content of about 25% by weight or less, about 20% by weight or less, or about 15% by weight or less.

[0137] It is preferable that the liquid nicotine preparation has a partially water-soluble, water-immiscible solvent content of about 0.5% to about 30% by weight. For example, the liquid nicotine preparation may have a partially water-soluble solvent content of about 0.5% to about 25% by weight, about 0.5% to about 20% by weight, or about 0.5% to about 15% by weight.

[0138] It is more preferable that the liquid nicotine formulation has a partially water-soluble solvent content of about 1% to about 30% by weight. For example, the liquid nicotine formulation may have a partially water-soluble solvent content of about 1% to about 25% by weight, about 1% to about 20% by weight, or about 1% to about 15% by weight.

[0139] Liquid nicotine preparations may have a partially water-soluble solvent content of about 2% to about 30% by weight. For example, liquid nicotine preparations may have a partially water-soluble solvent content of about 2% to about 25% by weight, about 2% to about 20% by weight, or about 2% to about 15% by weight.

[0140] Liquid nicotine preparations may have a partially water-soluble solvent content of about 4% to about 30% by weight. For example, liquid nicotine preparations may have a partially water-soluble solvent content of about 4% to about 25% by weight, about 4% to about 20% by weight, or about 4% to about 15% by weight.

[0141] Liquid nicotine formulations may have a partially water-soluble solvent content of about 6% to about 30% by weight. For example, liquid nicotine formulations may have a partially water-soluble solvent content of about 6% to about 25% by weight, about 6% to about 20% by weight, or about 6% to about 15% by weight.

[0142] Liquid nicotine formulations may have a partially water-soluble solvent content of about 7% to about 30% by weight. For example, liquid nicotine formulations may have a partially water-soluble solvent content of about 7% to about 25% by weight, about 7% to about 20% by weight, or about 7% to about 15% by weight.

[0143] Liquid nicotine formulations may have a partially water-soluble solvent content of about 8% to about 30% by weight. For example, liquid nicotine formulations may have a partially water-soluble solvent content of about 8% to about 25% by weight, about 8% to about 20% by weight, or about 8% to about 15% by weight.

[0144] The ratio of the weight percentage of the partially water-soluble solvent content in a liquid nicotine preparation to the weight percentage of the nicotine content may be approximately 0.75 or higher.

[0145] In other words, the weight percentage of the partially water-soluble solvent content in the liquid nicotine preparation may be at least about 0.75 times the weight percentage of the nicotine content in the liquid nicotine preparation.

[0146] It is preferable that the ratio of the weight percentage of the partially water-soluble solvent content of the liquid nicotine preparation to the weight percentage of the nicotine content is about 1 or more. For example, the ratio of the weight percentage of the partially water-soluble solvent content of the liquid nicotine preparation to the weight percentage of the nicotine content may be about 1.25 or more, about 1.5 or more, or about 1.75 or more.

[0147] The ratio of the weight percentage of the partially water-soluble solvent content in a liquid nicotine preparation to the weight percentage of the nicotine content may be approximately 20 or less.

[0148] In other words, the weight percentage of the partially water-soluble solvent content in the liquid nicotine preparation may be approximately 20 times or less the weight percentage of the nicotine content in the liquid nicotine preparation.

[0149] It is preferable that the ratio of the weight percentage of the partially water-soluble solvent content of the liquid nicotine preparation to the weight percentage of the nicotine content is about 18 or less. For example, the ratio of the weight percentage of the partially water-soluble solvent content of the liquid nicotine preparation to the weight percentage of the nicotine content may be about 16 or less, about 14 or less, or about 12 or less.

[0150] The ratio of the weight percentage of the partially water-soluble solvent content of a liquid nicotine preparation to the weight percentage of the nicotine content may be approximately 0.75 to approximately 20, approximately 0.75 to approximately 18, approximately 0.75 to approximately 16, approximately 0.75 to approximately 14, or approximately 0.75 to approximately 12.

[0151] The ratio of the weight percentage of the partially water-soluble solvent content of the liquid nicotine preparation to the weight percentage of the nicotine content is preferably about 1 to about 20, about 1 to about 18, about 1 to about 16, about 1 to about 14, or about 1 to about 12.

[0152] The ratio of the weight percentage of the partially water-soluble solvent content of a liquid nicotine preparation to the weight percentage of the nicotine content may be approximately 1.25 to approximately 20, approximately 1.25 to approximately 18, approximately 1.25 to approximately 16, approximately 1.25 to approximately 14, or approximately 1.25 to approximately 12.

[0153] The ratio of the weight percentage of the partially water-soluble solvent content of a liquid nicotine preparation to the weight percentage of the nicotine content may be approximately 1.5 to approximately 20, approximately 1.5 to approximately 18, approximately 1.5 to approximately 16, approximately 1.5 to approximately 14, or approximately 1.5 to approximately 12.

[0154] The ratio of the weight percentage of the partially water-soluble solvent content of a liquid nicotine preparation to the weight percentage of the nicotine content may be approximately 1.75 to approximately 20, approximately 1.75 to approximately 18, approximately 1.75 to approximately 16, approximately 1.75 to approximately 14, or approximately 1.75 to approximately 12.

[0155] The ratio of the weight percentage of the partially water-soluble solvent content in a liquid nicotine preparation to the weight percentage of the water-miscible solvent content may be approximately 0.06 or higher.

[0156] In other words, the weight percentage of the partially water-soluble solvent content of the liquid nicotine preparation may be at least about 0.06 times the weight percentage of the water-miscible solvent content of the liquid nicotine preparation.

[0157] It is preferable that the ratio of the weight percentage of water-miscible solvent content to the weight percentage of partially water-soluble solvent content in the liquid nicotine preparation is about 0.08 or higher. For example, the ratio of the weight percentage of partially water-soluble solvent content in the liquid nicotine preparation to the weight percentage of water-miscible solvent content may be about 0.1 or higher, about 0.12 or higher, or about 0.14 or higher.

[0158] The ratio of the weight percentage of the partially water-soluble solvent content in a liquid nicotine preparation to the weight percentage of the water-miscible solvent content may be approximately 1.2 or less.

[0159] In other words, the weight percentage of the partially water-soluble solvent content in the liquid nicotine preparation may be approximately 1.2 times or less the weight percentage of the water-miscible solvent content in the liquid nicotine preparation.

[0160] It is preferable that the ratio of the weight percentage of water-miscible solvent content to the weight percentage of partially water-soluble solvent content in the liquid nicotine preparation is about 1 or less. For example, the ratio of the weight percentage of partially water-soluble solvent content in the liquid nicotine preparation to the weight percentage of water-miscible solvent content may be about 0.8 or less, about 0.6 or less, or about 0.4 or less.

[0161] The ratio of the weight percentage of the partially water-soluble solvent content of a liquid nicotine preparation to the weight percentage of the water-miscible solvent content may be approximately 0.06 to 1.2, approximately 0.06 to 1, approximately 0.06 to 0.8, approximately 0.06 to 0.6, or approximately 0.06 to 0.4.

[0162] The ratio of the weight percentage of the partially water-soluble solvent content of the liquid nicotine preparation to the weight percentage of the water-miscible solvent content is preferably about 0.08 to about 1.2, about 0.08 to about 1, about 0.08 to about 0.8, about 0.08 to about 0.6, or about 0.08 to about 0.4.

[0163] The ratio of the weight percentage of the partially water-soluble solvent content of a liquid nicotine preparation to the weight percentage of the water-miscible solvent content may be approximately 0.1 to 1.2, approximately 0.1 to 1, approximately 0.1 to 0.8, approximately 0.1 to 0.6, or approximately 0.1 to 0.4.

[0164] The ratio of the weight percentage of the partially water-soluble solvent content of a liquid nicotine preparation to the weight percentage of the water-miscible solvent content may be approximately 0.12 to 1.2, approximately 0.12 to 1, approximately 0.12 to 0.8, approximately 0.1 to 0.6, or approximately 0.12 to 0.4.

[0165] The ratio of the weight percentage of the partially water-soluble solvent content of a liquid nicotine preparation to the weight percentage of the water-miscible solvent content may be approximately 0.14 to 1.2, approximately 0.14 to 1, approximately 0.14 to 0.8, approximately 0.14 to 0.6, or approximately 0.14 to 0.4.

[0166] The ratio of the weight percentage of the partially water-soluble solvent content in the liquid nicotine preparation to the weight percentage of the water content may be approximately 0.025 or higher.

[0167] In other words, the weight percentage of the partially water-soluble solvent content in the liquid nicotine preparation may be at least about 0.02 times the weight percentage of the water content in the liquid nicotine preparation.

[0168] It is preferable that the ratio of the weight percentage of the partially water-soluble solvent content of the liquid nicotine preparation to the weight percentage of the water content is about 0.03 or higher. For example, the ratio of the weight percentage of the partially water-soluble solvent content of the liquid nicotine preparation to the weight percentage of the water content may be about 0.05 or higher, about 0.075 or higher, or about 0.1 or higher.

[0169] The ratio of the weight percentage of the partially water-soluble solvent content of a liquid nicotine preparation to the weight percentage of the water content may be approximately 5 or less.

[0170] In other words, the weight percentage of the partially water-soluble solvent content in the liquid nicotine preparation may be about five times or less the weight percentage of the water content in the liquid nicotine preparation.

[0171] It is preferable that the ratio of the weight percentage of the partially water-soluble solvent content of the liquid nicotine preparation to the weight percentage of the water content is about 1 or less. For example, the ratio of the weight percentage of the partially water-soluble solvent content of the liquid nicotine preparation to the weight percentage of the water content may be about 0.8 or less, about 0.6 or less, or about 0.4 or less.

[0172] The ratio of the weight percentage of the partially water-soluble solvent content of the liquid nicotine preparation to the weight percentage of the water content may be approximately 0.02 to approximately 1.2, approximately 0.02 to approximately 1, approximately 0.02 to approximately 0.8, approximately 0.02 to approximately 0.6, or approximately 0.02 to approximately 0.4.

[0173] The ratio of the weight percentage of the partially water-soluble solvent content of the liquid nicotine preparation to the weight percentage of the water content is preferably about 0.03 to about 1.2, about 0.03 to about 1, about 0.03 to about 0.8, about 0.03 to about 0.6, or about 0.03 to about 0.4.

[0174] The ratio of the weight percentage of the partially water-soluble solvent content of a liquid nicotine preparation to the weight percentage of the water content may be approximately 0.05 to approximately 1.2, approximately 0.05 to approximately 1, approximately 0.05 to approximately 0.8, approximately 0.05 to approximately 0.6, or approximately 0.05 to approximately 0.4.

[0175] The ratio of the weight percentage of the partially water-soluble solvent content of a liquid nicotine preparation to the weight percentage of the water content may be approximately 0.75 to approximately 1.2, approximately 0.75 to approximately 1, approximately 0.75 to approximately 0.8, approximately 0.75 to approximately 0.6, or approximately 0.75 to approximately 0.4.

[0176] The ratio of the weight percentage of the partially water-soluble solvent content of the liquid nicotine preparation to the weight percentage of the water content may be approximately 0.1 to approximately 1.2, approximately 0.1 to approximately 1, approximately 0.1 to approximately 0.8, approximately 0.1 to approximately 0.6, or approximately 0.1 to approximately 0.4.

[0177] It is preferable that one or more water-immiscible solvents contain one or more water-insoluble solvents.

[0178] As used herein in relation to a first aspect of the present invention, the term "water-insoluble solvent" refers to a compound that is liquid at 20°C and has a water solubility of about 5 mg / mL or less at 20°C.

[0179] As used herein in relation to a second aspect of the present invention, the term "water-insoluble solvent" refers to a compound that is liquid at 20°C and has a partition coefficient (log P) greater than about 5 at 20°C.

[0180] One or more water-insoluble solvents may have a maximum carbon chain length of 30 or less. For example, one or more water-insoluble solvents may have a maximum carbon chain length of 20 or less, 18 or less, 16 or less, 14 or less, or 12 or less.

[0181] Suitable water-insoluble solvents include, but are not limited to, oleic acid and MIGLYOL® (a mixture of decanoyl glyceride and octanoyl glyceride).

[0182] It is preferable that the liquid nicotine preparation has a water-insoluble solvent content of about 0.5% by weight or more. It is more preferable that the liquid nicotine preparation has a water-insoluble solvent content of about 1% by weight or more. For example, the liquid nicotine preparation may have a water-insoluble solvent content of about 2% by weight or more, about 3% by weight or more, about 4% by weight or more, or about 6% by weight or more.

[0183] Liquid nicotine preparations may contain a water-insoluble solvent content of approximately 30% by weight or less.

[0184] It is preferable that the liquid nicotine preparation has a water-insoluble solvent content of about 25% by weight or less. For example, the liquid nicotine preparation may have a water-insoluble solvent content of about 20% by weight or less, about 15% by weight or less, or about 10% by weight or less.

[0185] It is preferable that the liquid nicotine preparation has a water-insoluble solvent content of about 0.5% to about 25% by weight. For example, the liquid nicotine preparation may have a water-insoluble solvent content of about 0.5% to about 20% by weight, about 0.5% to about 15% by weight, or about 0.5% to about 10% by weight.

[0186] It is more preferable that the liquid nicotine preparation has a water-insoluble solvent content of about 1% to about 25% by weight. For example, the liquid nicotine preparation may have a water-insoluble solvent content of about 1% to about 20% by weight, about 1% to about 15% by weight, or about 1% to about 10% by weight.

[0187] Liquid nicotine preparations may have a water-insoluble solvent content of approximately 2% to 25% by weight. For example, liquid nicotine preparations may have a water-insoluble solvent content of approximately 2% to 20% by weight, approximately 2% to 15% by weight, or approximately 2% to 10% by weight.

[0188] Liquid nicotine preparations may have a water-insoluble solvent content of approximately 3% to 25% by weight. For example, liquid nicotine preparations may have a water-insoluble solvent content of approximately 3% to 20% by weight, approximately 3% to 15% by weight, or approximately 3% to 10% by weight.

[0189] Liquid nicotine preparations may have a water-insoluble solvent content of approximately 4% to 25% by weight. For example, liquid nicotine preparations may have a water-insoluble solvent content of approximately 4% to 20% by weight, approximately 4% to 15% by weight, or approximately 4% to 10% by weight.

[0190] It is more preferable that one or more water-immiscible solvents include one or more partially water-soluble solvents and one or more water-insoluble solvents.

[0191] The ratio of the weight percentage of the partially water-soluble solvent content in a liquid nicotine preparation to the weight percentage of the water-insoluble solvent content may be approximately 0.2 or higher.

[0192] In other words, the weight percentage of the partially water-soluble solvent content of the liquid nicotine preparation may be at least about 0.2 times the weight percentage of the water-insoluble solvent content of the liquid nicotine preparation.

[0193] It is preferable that the ratio of the weight percentage of the partially water-soluble solvent content of the liquid nicotine preparation to the weight percentage of the water-insoluble solvent content is about 0.4 or higher. For example, the ratio of the weight percentage of the partially water-soluble solvent content of the liquid nicotine preparation to the weight percentage of the water-insoluble solvent content may be about 0.6 or higher, about 0.8 or higher, or about 1 or higher.

[0194] The ratio of the weight percentage of the partially water-soluble solvent content of a liquid nicotine preparation to the weight percentage of the water-insoluble solvent content may be approximately 35 or less.

[0195] In other words, the weight percentage of the partially water-soluble solvent content in the liquid nicotine preparation may be 35 times or less the weight percentage of the water-insoluble solvent content in the liquid nicotine preparation.

[0196] It is preferable that the ratio of the weight percentage of the partially water-soluble solvent content of the liquid nicotine preparation to the weight percentage of the water-insoluble solvent content is about 30 or less. For example, the ratio of the weight percentage of the partially water-soluble solvent content of the liquid nicotine preparation to the weight percentage of the water-insoluble solvent content may be about 25 or less, about 20 or less, or about 15 or less.

[0197] The ratio of the weight percentage of the partially water-soluble solvent content of a liquid nicotine preparation to the weight percentage of the water-insoluble solvent content may be approximately 0.2 to approximately 35, approximately 0.2 to approximately 30, approximately 0.2 to approximately 25, approximately 0.2 to approximately 20, or approximately 0.2 to approximately 15.

[0198] The ratio of the weight percentage of the partially water-soluble solvent content of the liquid nicotine preparation to the weight percentage of the water-insoluble solvent content is preferably about 0.4 to about 35, about 0.4 to about 30, about 0.4 to about 25, about 0.4 to about 20, or about 0.4 to about 15.

[0199] The ratio of the weight percentage of the partially water-soluble solvent content of a liquid nicotine preparation to the weight percentage of the water-insoluble solvent content may be approximately 0.6 to approximately 35, approximately 0.6 to approximately 30, approximately 0.6 to approximately 25, approximately 0.6 to approximately 20, or approximately 0.6 to approximately 15.

[0200] The ratio of the weight percentage of the partially water-soluble solvent content of a liquid nicotine preparation to the weight percentage of the water-insoluble solvent content may be approximately 0.8 to approximately 35, approximately 0.8 to approximately 30, approximately 0.8 to approximately 25, approximately 0.8 to approximately 20, or approximately 0.8 to approximately 15.

[0201] The liquid nicotine preparation contains one or more water-soluble organic acids. Advantageously, the one or more water-soluble organic acids can bind to nicotine in the liquid nicotine preparation by forming one or more nicotine salts.

[0202] One or more nicotine salts can be advantageously stabilized by dissolving them in one or more water-miscible solvents. This can advantageously reduce nicotine adsorption in the upper respiratory tract and enhance pulmonary nicotine delivery and retention.

[0203] In embodiments in which the liquid nicotine formulation comprises water and one or more water-miscible solvents, one or more nicotine salts can be advantageously dissolved and stabilized in water and one or more water-miscible solvents.

[0204] It is preferable that the liquid nicotine preparation contains one or more water-soluble carboxylic acids.

[0205] Suitable water-soluble carboxylic acids include, but are not limited to, acetic acid, citric acid, lactic acid, levulinic acid, malic acid, malonic acid, and pyruvic acid.

[0206] It is more preferable for the liquid nicotine preparation to contain lactic acid.

[0207] It is preferable that the liquid nicotine preparation contains approximately 2% by weight or more of water-soluble organic acids. It is more preferable that the liquid nicotine preparation contains approximately 3% by weight or more of water-soluble acids.

[0208] It is preferable that the liquid nicotine preparation has a water-soluble organic acid content of about 8% by weight or less. It is more preferable that the liquid nicotine preparation has a water-soluble organic acid content of about 6% by weight or less.

[0209] It is preferable that the liquid nicotine preparation contains about 2% to 8% by weight of water-soluble organic acids. For example, the liquid nicotine preparation may contain about 2% to 6% by weight of water-soluble organic acids.

[0210] It is more preferable that the liquid nicotine preparation contains about 3% to 8% by weight of water-soluble organic acids. For example, the liquid nicotine preparation may contain about 2% to 6% by weight of water-soluble organic acids.

[0211] The liquid nicotine preparation may be a liquid nicotine preparation from which caffeine has been substantially removed.

[0212] As used herein in connection with the present invention, the term “substantially caffeine-free liquid nicotine preparation” refers to a liquid nicotine preparation having a caffeine content of less than 0.5 weight percent. For example, a liquid nicotine preparation may have a caffeine content of less than about 0.4 weight percent, less than about 0.3 weight percent, or less than about 0.2 weight percent.

[0213] The liquid nicotine preparation may be a liquid nicotine preparation that is substantially free of caffeine.

[0214] As used herein in connection with the present invention, the term "substantially caffeine-free liquid nicotine preparation" refers to a liquid nicotine preparation having a caffeine content of less than about 0.1 weight percent.

[0215] The liquid nicotine preparation may be a caffeine-free liquid nicotine preparation.

[0216] As used herein in connection with the present invention, the term "caffeine-free liquid nicotine preparation" refers to a liquid nicotine preparation having a caffeine content of 0 weight percent.

[0217] When used herein in connection with the present invention, the term "caffeine" refers to caffeine or a caffeine salt. When referring to a caffeine salt, the amounts of caffeine listed herein refer to the amounts of caffeine cations.

[0218] Liquid nicotine preparations may contain one or more solid emulsifiers.

[0219] As used herein in connection with the present invention, the term "solid emulsifier" refers to an emulsifier that is solid at 20°C. Suitable solid emulsifiers include, but are not limited to, 1-stearoyl-rac-glycerol, Kolliphor® P 188, sodium caseinate, sodium dodecanoate, and sodium docusate.

[0220] It is preferable that the liquid nicotine preparation contains a solid emulsifier content of approximately 8% by weight or less. It is more preferable that the liquid nicotine preparation contains a solid emulsifier content of approximately 5% by weight or less.

[0221] Liquid nicotine preparations may contain one or more flavoring agents. Suitable flavoring agents include, but are not limited to, menthol.

[0222] It is preferable that the liquid nicotine preparation contains a flavoring agent content of approximately 4% by weight or less. It is more preferable that the liquid nicotine preparation contains a flavoring agent content of approximately 3% by weight or less.

[0223] According to the present invention, a cartridge for use in an aerosol generating system is provided, which contains a liquid nicotine preparation according to the present invention.

[0224] The cartridge may include an atomizer configured to generate an aerosol from a liquid nicotine preparation.

[0225] A cartridge containing a liquid nicotine preparation and an atomizer configured to generate an aerosol from the liquid nicotine preparation may be referred to as a "cartridge."

[0226] The atomizer may also be a thermal atomizer.

[0227] As used herein in connection with the present invention, the term "thermal atomizer" refers to an atomizer configured to heat a liquid nicotine preparation to generate an aerosol.

[0228] The cartridge may be equipped with any suitable type of thermal atomizer.

[0229] The thermal atomizer may comprise a heater and a liquid transport element configured to transport a liquid nicotine formulation to the heater.

[0230] The liquid transport element may include a capillary core. The heater may include a heater coil.

[0231] A thermal atomizer may be equipped with an electric heater. For example, a thermal atomizer may be equipped with an electric heater that includes a resistance heating element or an induction heating element.

[0232] The atomizer may be a non-thermal atomizer.

[0233] As used herein in connection with the present invention, the term "non-thermal atomizer" refers to an atomizer configured to generate an aerosol from a liquid nicotine formulation by means other than heating.

[0234] The cartridge may be equipped with any suitable type of non-thermal atomizer.

[0235] For example, a non-thermal atomizer may be a collider atomizer, an ultrasonic atomizer, or a vibrating mesh atomizer.

[0236] According to the present invention, an aerosol generation system is further provided, comprising a liquid nicotine formulation according to the present invention and an atomizer configured to generate an aerosol from the liquid nicotine formulation.

[0237] The atomizer may also be a thermal atomizer.

[0238] The aerosol generation system may be equipped with any suitable type of thermal atomizer.

[0239] The thermal atomizer may comprise a heater and a liquid transport element configured to transport a liquid nicotine formulation to the heater.

[0240] The liquid transport element may include a capillary core. The heater may include a heater coil.

[0241] A thermal atomizer may be equipped with an electric heater. For example, a thermal atomizer may be equipped with an electric heater that includes a resistance heating element or an induction heating element.

[0242] The atomizer may be a non-thermal atomizer.

[0243] The aerosol generation system may include any suitable type of non-thermal atomizer.

[0244] For example, a non-thermal atomizer may be a collider atomizer, an ultrasonic atomizer, or a vibrating mesh atomizer.

[0245] The aerosol generating system may include a cartridge according to the present invention that contains a liquid nicotine formulation, and an aerosol generating device having a housing that defines a device recess configured to receive at least a portion of the cartridge.

[0246] The aerosol generating system may comprise a disposable cartridge according to the present invention containing a liquid nicotine formulation, and a reusable aerosol generating device having a housing that defines a device recess configured to receive at least a portion of the cartridge.

[0247] The aerosol generator may include a battery and a control electronic circuit.

[0248] The aerosol generating system may comprise an aerosol generating device comprising a cartridge according to the present invention that houses a liquid nicotine formulation and an atomizer, and a housing that defines a device recess configured to receive at least a portion of the cartridge.

[0249] The aerosol generating system may include a cartridge according to the present invention for containing a liquid nicotine formulation, and an aerosol generating device having a housing that defines a device recess configured to receive at least a portion of the cartridge and atomizer.

[0250] To avoid any doubt, the above-described features relating to one aspect of the present invention may also apply to other aspects of the present invention. Specifically, the above-described features relating to the liquid nicotine formulation according to the present invention may also relate to the cartridge and the aerosol generating system according to the present invention, where appropriate. Specifically, the above-described features relating to the cartridge according to the present invention may also relate to the aerosol generating system according to the present invention, and vice versa.

[0251] Here, embodiments of the present invention will be described with reference to the following examples, which are just a few examples.

[0252] Examples 1-3 Three liquid nicotine formulations according to the present invention (Examples 1, 2, and 3) were prepared to have the compositions shown in Tables 2, 3, and 4. [Table 2] Table 2 [Table 3] Table 3 [Table 4] Table 4

[0253] Examples A-F Six liquid nicotine formulations according to the present invention (Examples A, B, C, D, E, and F) were prepared to have the compositions shown in Table 5. For comparison, two liquid nicotine formulations not according to the present invention (Examples G and H) were also prepared to have the compositions shown in Table 5.

[0254] The liquid nicotine preparations of Examples A to H were each loaded into a Solaris e-cigarette cartridge. The nicotine retention rate of the aerosol generated when using the cartridge in the Solaris e-cigarette was measured in Seeman, JI; Lipowicz, PJ; Piade, J.-J.; Poget, L.; Sanders, EB; Snyder, JP; Trowbridge, CG, On the Deposition of Volatiles and Semivolatiles from Cigarette Smoke Aerosols: Relative Rates of Transfer of Nicotine and Ammonia from Particles to the Gas Phase. Chemical Research in Toxicology. The Denuda tube technique, essentially described in 2004, 17, 1020-1037, was measured using the following modifications: the aerosol was pulled instead of pushed; a 55 mL puff was used instead of a 35 mL puff; the Denuda used was a 30 mL Tygon® tube; and the difference in nicotine yield was measured by comparing the amount collected on the Cambridge pad from the product with and without the Tygon® tube, rather than measuring the amount collected by the Denuda and the amount collected by the Cambridge pad positioned after the Denuda. For comparison, the nicotine retention rate of the smoke produced when a conventional cigarette (Example I) was burned was also measured. The results are shown in Table 5.

[0255] As shown in Table 5, the aerosols generated from the liquid nicotine formulations according to the present invention (Examples A-F) provide a nicotine retention rate of over 40%. In contrast, the aerosols generated from liquid formulations not according to the present invention (Examples G and H) provide a lower nicotine retention rate of less than 30%.

[0256] The nicotine retention characteristics of the aerosol generated from the liquid nicotine formulations according to the present invention (Examples A to F) are at least 13.5 times higher than those of a liquid formulation not according to the present invention (Example G), which does not contain either a water-immiscible solvent having a water solubility of approximately 100 mg / mL or less at 20°C, nor a water-soluble organic acid.

[0257] The nicotine retention characteristics of the aerosol generated from the liquid nicotine formulations according to the present invention (Examples A to F) are at least about 1.5 times higher than those of a liquid formulation not according to the present invention (Example H) that does not contain a water-immiscible solvent having a water solubility of about 100 mg / mL or less at 20°C.

[0258] The nicotine retention characteristics of aerosols generated from the liquid nicotine preparations according to the present invention (Examples A-F), which contain both a water-immiscible solvent having a water solubility of approximately 100 mg / mL or less at 20°C and a water-soluble organic acid, are similar to those of smoke generated from conventional cigarettes (Example I). [Table 5]

Claims

1. A liquid nicotine preparation for use in an aerosol generating system, One or more water-miscible polyhydric alcohols selected from the group consisting of glycerin and propylene glycol, Water and, A water-immiscible solvent, selected from the group consisting of triacetin and triethyl citrate, having a water solubility of approximately 100 mg / mL or less at 20°C, comprising one or more water-soluble carboxylic acids, The liquid nicotine preparation has a nicotine content of 0.5% to 5% by weight, a combined content of glycerin and propylene glycol of about 10% or more by weight, a water-immiscible solvent content of about 2% to about 15% by weight, and a water-soluble carboxylic acid content of about 2% to about 8% by weight.

2. The liquid nicotine preparation according to claim 1, wherein the one or more water-immiscible solvents include one or more partially water-soluble solvents having a water solubility of about 20 mg / mL to about 100 mg / mL at 20°C.

3. The liquid nicotine preparation according to claim 1 or 2, wherein the one or more water-immiscible solvents include one or more water-insoluble solvents having a water solubility of about 5 mg / mL or less at 20°C.

4. A liquid nicotine preparation for use in an aerosol generating system, One or more water-miscible polyhydric alcohols selected from the group consisting of glycerin and propylene glycol, Water and, A water-immiscible solvent, selected from the group consisting of triacetin and triethyl citrate, having a partition coefficient (log P) of approximately 0.05 or higher at 20°C, comprising one or more water-soluble carboxylic acids, The liquid nicotine preparation has a nicotine content of 0.5% to 5% by weight, a combined content of glycerin and propylene glycol of about 10% or more by weight, a water-immiscible solvent content of about 2% to about 15% by weight, and a water-soluble carboxylic acid content of about 2% to about 8% by weight.

5. The liquid nicotine preparation according to claim 4, wherein the one or more water-immiscible solvents comprises one or more partially water-soluble solvents having a partition coefficient (log P) of about 0.05 to about 0.5 at 20°C.

6. The liquid nicotine preparation according to claim 4 or 5, wherein the one or more water-immiscible solvents include one or more water-insoluble solvents having a partition coefficient (log P) greater than about 5 at 20°C.

7. The liquid nicotine preparation according to any one of claims 1 to 6, wherein the one or more water-soluble carboxylic acids are selected from the group consisting of acetic acid, lactic acid, levulinic acid, and pyruvic acid.

8. A cartridge for use in an aerosol generating system, comprising a cartridge containing a liquid nicotine preparation according to any one of claims 1 to 7.

9. The cartridge according to claim 8, comprising an atomizer configured to generate an aerosol from the liquid nicotine preparation.

10. an aerosol generation system, A liquid nicotine preparation according to any one of claims 1 to 7, an aerosol generating system comprising an atomizer configured to generate an aerosol from the liquid nicotine preparation.

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