阅读说明：本技术 组合物 (Composition comprising a metal oxide and a metal oxide ) 是由 A·S·纳拉西姆汉 R·麦卡格 N·海德 W·杰克逊 于 2019-10-23 设计创作，主要内容包括：本文公开了一种可吸入组合物,其适用于电子烟装置,其包含溶于或分散于溶剂中的至少1g/L的烟碱和二氧化碳。(Disclosed herein is an inhalable composition suitable for use in an electronic smoking device comprising at least 1g/L nicotine and carbon dioxide dissolved or dispersed in a solvent.)

1. An inhalable composition suitable for use in an electronic cigarette device comprising at least 1g/L nicotine and at least 2g/L carbon dioxide dissolved or dispersed in a solvent, wherein the molar ratio of carbon dioxide to nicotine is at least 0.1: 1.

2. The composition according to claim 1, comprising 1-60g/L nicotine, preferably 5-60g/L nicotine.

3. The composition of any one of the preceding claims, comprising 2-40g/L of carbon dioxide.

4. The composition according to any one of the preceding claims, wherein the molar ratio of carbon dioxide to nicotine is from 0.1:1 to 10:1, preferably from 0.25 to 7.5:1, more preferably from 0:4:1 to 5: 1.

5. The composition of any preceding claim, wherein the solvent comprises glycerol or propylene glycol or water or a mixture thereof.

6. The composition of claim 5, wherein propylene glycol, when present, is present in an amount of 0-25% by weight, based on the total weight of the inhalable composition.

7. The composition according to claim 6, wherein propylene glycol, when present, is present in an amount of no greater than 15% by weight, preferably no greater than 10% by weight, more preferably no greater than 5% by weight, based on the total weight of the inhalable composition.

8. The composition of any one of claims 5-7, wherein the solvent comprises glycerol and the glycerol is present in an amount of at least 40 weight percent based on the total weight of the inhalable composition.

9. The composition according to claim 8, wherein the solvent comprises glycerol in an amount of at least 50 wt.%, preferably at least 60 wt.%, more preferably at least 70 wt.%, based on the total weight of the inhalable composition.

10. The composition according to any one of claims 5-9, wherein the solvent comprises water and the water is present in an amount of 1-20 wt.%, preferably 1-15 wt.%, more preferably 1-10 wt.%, based on the total weight of the inhalable composition.

11. The composition according to any one of the preceding claims, wherein the composition comprises less than 10g/L of a flammable solvent, such as ethanol, preferably wherein the composition is free of flammable solvents, such as ethanol.

12. The composition of any one of the preceding claims, further comprising one or more flavor compounds.

13. A cartridge suitable for use in an electronic vaping device, the cartridge comprising an inhalable composition according to any one of claims 1-12.

14. An electronic vaping device comprising the cartridge of claim 10.

15. A method of preparing an inhalable composition according to any one of claims 1-12, comprising the steps of:

adding at least 1g/L of nicotine to a solvent within a sealable container to form a solution or dispersion of nicotine; and

introducing carbon dioxide into the container such that the pressure within the container, measured at 20 ℃, is from 1 to 15 atmospheres, which results in at least 2g/L of carbon dioxide being dissolved or dispersed in the solvent, and such that the molar ratio of carbon dioxide to nicotine is at least 0.1: 1.

16. An inhalable composition suitable for use in an electronic cigarette device comprising at least 1g/L nicotine and at least 0.027g/L carbon dioxide dissolved or dispersed in a solvent, wherein the molar ratio of carbon dioxide to nicotine is at least 0.025:1, wherein the solvent comprises at most 5 volume% water, relative to the total volume of the solvent.

17. A method of preparing an inhalable composition according to claim 16, comprising the steps of:

adding at least 1g/L of nicotine to a solvent within a sealable container to form a solution or dispersion of nicotine; and

introducing carbon dioxide into the container such that the pressure within the container, measured at 20 ℃, is from 1 to 15 atmospheres, which results in at least 0.027g/L of carbon dioxide being dissolved or dispersed in the solvent and the molar ratio of carbon dioxide to nicotine being at least 0.025: 1.

18. A concentrate suitable for forming an inhalable composition for an electronic smoking device comprising carbon dioxide and at least 60g/L nicotine dissolved or dispersed in a solvent, wherein the molar ratio of carbon dioxide to nicotine is at least 0.1: 1.

Technical Field

The invention relates to an inhalable composition for an electronic cigarette device and a preparation method thereof.

Background

Nicotine (3- [ 1-methylpyrrolidin-2-yl ] pyridine) may be obtained from the leaves of the genus Nicotiana (i.e., tobacco plants), or prepared by chemical synthesis. Throughout the tobacco industry, there remains a need for traditional tobacco products (e.g., traditional cigarettes, cigars, or pipe fillers), most likely due to nicotine addiction. However, as people are increasingly concerned about the detrimental effects of traditional tobacco products on consumer health, there is an increasing demand for tobacco replacement products. Tobacco substitute products can be provided as substitutes for traditional tobacco products that can lead to harmful carcinogenic effects, for example, due to the presence of pyridine alkaloids, polycyclic aromatic compounds, phenols, and N-nitrosamines. Such alternative products may be used for pleasure, but may also be used exclusively in the pharmaceutical field for the treatment of nicotine dependence; in the pharmaceutical field, there is also interest in the possible therapeutic applications of nicotine. While many tobacco substitute products exist, there is a particular need for an electronic vaping device. Typically, e-vapor devices contain a nicotine solution or dispersion that evaporates when heated by a heating element and is inhaled by the user.

Consumers appreciate a pleasant user experience for both e-vaping devices and traditional tobacco products. This can be difficult to achieve because nicotine can cause a pleasant and unpleasant sensation in the airways (e.g., in the mouth, throat, and lungs). For example, nicotine can produce a pleasant sensation in the throat, sometimes referred to as a "throat strike," which is believed to be due to the nicotine causing muscle contractions in the throat. There is also a pleasant sensation due to the physiological effects caused by nicotine, which may include a mild dizziness. However, nicotine may also cause an unpleasant sensation in the airways. In particular, some users have an unpleasant rough or astringent sensation in the throat. In order to provide a pleasant experience for the user, nicotine should be formulated to maintain its pleasant effects, but to minimize its unpleasant effects.

In the field of electronic cigarettes, korean patent KR10-1208473 provides a composition containing nicotine up to 20mg/25ml (corresponding to a maximum of 0.8 g/l or 0.08% weight/volume). Such compositions, which have particularly low nicotine levels, attempt to promote smoking cessation. KR10-1208473 reports the presence of carbon dioxide dissolved in a reduced nicotine composition to assist in the atomisation of the solution. However, in this document, the solubility of carbon dioxide in the composition is low, and thus KR10-1208473 reports the necessity of a "food grade alcohol" (particularly ethanol) and a certain amount of water as a means of increasing the solubility of carbon dioxide. The production of nicotine-containing preparations in KR10-1208473 involves the production of a solution of carbon dioxide dissolved/dispersed in the relevant solvent, and only subsequently adding nicotine to this solution, i.e. after charging it with carbon dioxide.

Conventional tobacco products are also disclosed in the art, in US 3,878,580 and US 4,830,028, which attempt to avoid the harsh, irritating or "choking" sensation caused by nicotine. In the field of electronic cigarettes, WO 2014/182736 relates to electronic cigarette formulations which attempt to provide user satisfaction with nicotine salt formulations.

However, challenges still exist for providing a pleasant user experience for electronic cigarettes. In addition to the challenge of providing a pleasant user experience, electronic cigarettes face challenges in nicotine formulation beyond those faced by conventional tobacco products. For example, in addition to ensuring a pleasant user experience, liquid nicotine formulations also have other desirable qualities, such as a pleasant appearance to the consumer, a good shelf life, low adverse health effects, and good compatibility with the electronic smoking device itself.

Disclosure of Invention

The present invention relates to an inhalable composition having sufficient nicotine to provide a sufficiently satisfactory user experience, i.e. having at least 1g/L nicotine. The unpleasant rough or astringent taste on the airway caused by nicotine when vapor is inhaled from an e-cigarette may be due to its alkalinity. The present invention is based in part on the following recognition: upon inhalation, the components present in the inhalable composition dissolve in the water present on and in the airway tissue, thereby reversibly forming carbonic acid from the carbon dioxide. This neutralizes the alkalinity of nicotine, thereby reducing astringency.

In the prior art (e.g. korean patent KR10-1208473) it is disclosed that the presence of certain solvents, namely water and ethanol, is required for carbon dioxide to achieve sufficient solubility in inhalable compositions. Even in the presence of these solvents, the solubility of the disclosed carbon dioxide is at most 18.1mg/25 ml; i.e. 0.724g/L (about 0.07 wt%), which is not optimal for e-cigarettes with higher nicotine content.

The present invention provides new inhalable compositions that are unexpectedly a new means of achieving a pleasant user experience by finding a more efficient way of introducing carbon dioxide into an inhalable composition.

In a first aspect of the invention, there is provided an inhalable composition suitable for use in an electronic smoking device comprising at least 1g/L nicotine and at least 2g/L carbon dioxide dissolved or dispersed in a solvent, wherein the molar ratio of carbon dioxide to nicotine is at least 0.1: 1.

A first aspect of the present invention provides an inhalable composition having an increased carbon dioxide content compared to the prior art, thereby improving the neutralization of nicotine. The following findings enable an unexpected increase in carbon dioxide concentration: the solubility of carbon dioxide is improved when carbon dioxide is added to a composition already comprising nicotine and a solvent. This results in an increase in the solubility of carbon dioxide compared to compositions provided by the prior art (e.g. KR10-1208473) where carbon dioxide is added to the solvent prior to the addition of nicotine. It is believed that the presence of nicotine in the composition affects solubility when carbon dioxide is dissolved. The increased solubility of carbon dioxide in a solvent already containing nicotine is particularly unexpected in view of the low solubility of carbon dioxide in nicotine alone. This increased solubility of carbon dioxide is provided without having to rely on solvent systems that might otherwise impart undesirable qualities to the composition, particularly those containing ethanol, which is a flammable solvent and therefore has a potential explosion hazard when evaporated.

The compositions disclosed herein are compatible with a variety of different solvent systems and may, for example, include different levels of water. However, although the compositions are compatible with different water contents, they do not require high water contents to dissolve the carbon dioxide. Accordingly, in a second aspect of the invention, there is provided an inhalable composition suitable for use in an electronic smoking device comprising at least 1g/L nicotine and at least 0.027g/L carbon dioxide dissolved or dispersed in a solvent, wherein the molar ratio of carbon dioxide to nicotine is at least 0.025:1, wherein the solvent comprises at most 5% by volume water, relative to the total volume of the solvent.

A second aspect of the invention provides an inhalable composition comprising carbon dioxide, and specifically excludes the following: wherein the solvent comprises more than 5 vol.% of water relative to the total volume of the solvent. This is in surprising contrast to compositions such as those in KR10-1208473 which are achieved by the prior art which teaches that significantly higher amounts of water are required to dissolve the carbon dioxide. The following findings make possible a surprisingly effective dissolution of carbon dioxide in such low (or zero) water content: as described in the first aspect, when carbon dioxide is added to a composition already containing nicotine and a solvent, the solubility of carbon dioxide in the composition is improved. The second aspect provides a further improvement in that, due to its lower water content, the composition exhibits reduced discoloration upon storage, thereby giving the composition a more pleasing appearance to the consumer. This coloration is an indication of decomposition, indicating that the compositions disclosed herein have improved stability and longer shelf life. Thus, the inhalable compositions disclosed herein have the additional advantage of not relying on methods of masking the coloration, such as by using packaging.

The inhalable compositions according to the first and second aspects have good smoothness due to the inclusion of carbon dioxide, which reduces astringency while maintaining a pleasant "throat-hit" sensation. Improved user experience is achieved without the use of undesirable solvents (e.g., ethanol) or excessive flavoring agents to mask the unpleasant astringent taste. It is beneficial not to rely on excess flavoring, as excess flavoring increases the risk of detrimental long term health effects for the user. The inhalable compositions also exhibit good compatibility with electronic smoking devices, which is believed to be due to the properties of carbon dioxide. The properties of carbon dioxide are believed to be such that the inhalable composition has improved compatibility with the electronic smoking device compared to an inhalable solution containing optional additives to overcome astringency. For example, carbon dioxide does not leave any undesirable residue in the e-vapor device that may otherwise build up over time and potentially cause device failure. Furthermore, the use of carbon dioxide greatly reduces the risk of undesired interactions between other ingredients (e.g. solvents) present in the inhalable composition, which might otherwise lead to uncharacterized compounds of unknown characteristics, compared to alternative methods which mask unpleasant astringency and thus provide a more pleasant user experience. Hence, the inhalable compositions according to the first and second aspects are considered to be safer in terms of impact on user health.

In a third aspect, there is provided a cartridge (cartridge) suitable for use in an electronic vaping device, the cartridge comprising an inhalable composition according to the first or second aspect.

In a fourth aspect, there is provided an electronic vaping device incorporating the cartridge of the third aspect.

In a fifth aspect, there is provided use of an inhalable composition according to the first or second aspect in an electronic vaping device.

In a sixth aspect, there is provided a method of preparing an inhalable composition according to the first or second aspect.

In a seventh aspect, there is provided a concentrate suitable for forming an inhalable composition for use in an electronic smoking device comprising at least 60g/L nicotine and carbon dioxide dissolved or dispersed in a solvent, wherein the molar ratio of carbon dioxide to nicotine is at least 0.1: 1. The concentrate may be used for storage and transportation purposes, may provide a raw material to produce e-cigarette solutions of various concentrations or different tastes for market use, or may provide a concentrated solution for a strong user experience.

Detailed description of the preferred embodiments

As used herein, the term "inhalable composition" refers to a composition that is suitable for inhalation by a user. The inhalable compositions disclosed herein are suitable for use in e-vapor devices, meaning that they can be vaporized by the heating element of such devices, allowing the user to inhale. The term "inhalable composition" refers to the inhalable compositions of the first and second aspects of the invention, unless otherwise specified.

As used herein, the term "nicotine" refers to nicotine obtained from a tobacco plant or from chemical synthesis, and may refer to (R) -nicotine, (S) -nicotine, or a combination thereof. Although the improvement in user experience applies to all forms of nicotine, the nicotine is preferably predominantly (S) -nicotine, i.e. with an enantiomeric excess of 50% of (S) -nicotine. More preferably, nicotine is (S) -nicotine with an enantiomeric excess of at least 60%, at least 70%, at least 80%, at least 90% or at least 95%. It is well known that (S) -nicotine (i.e., [ (S) -3- (1-methylpyrrolidin-2-yl) pyridine ]) is significantly more active than (R) -nicotine.

It has been found that the improvement in user experience is even more pronounced when nicotine extracted from tobacco is used rather than nicotine prepared by chemical synthesis. This is believed to be due to the fact that carbon dioxide is particularly effective in neutralizing not only nicotine itself but also nicotine impurities present in tobacco, thereby avoiding other unpleasant sensations that these impurities may cause. The content of such impurities in tobacco is not consistent as their content varies according to geographical origin, harvesting time of the tobacco, etc. Thus, the inclusion of carbon dioxide to neutralize the effects of such impurities may provide a more consistent product in terms of user experience. However, for nicotine made by chemical synthesis, the consistency of the user experience is also improved. The synthetic nicotine may also be contaminated with small amounts of process related impurities, the content of which may vary, thereby altering the user experience, and thus the inclusion of carbon dioxide provides additional advantages: which avoids the possibility of a change in user experience due to the presence of such impurities.

The inhalable compositions disclosed herein may more effectively help a user get rid of traditional smoking through their improved user experience. In the transition from smoking to e-cigarette, the user is pleasurable for all the sensations that the e-cigarette produces — they associate the e-cigarette with the smoking experience they are accustomed to. Tobacco smoke contains a significant amount of carbon dioxide which is generated by the combustion of the cigarette material and which plays an important role in the sensation obtained by the user from smoking. Without wishing to be bound by theory, it is believed that by incorporating carbon dioxide into a liquid formulation for an electronic device, the carbon dioxide will, in part, create a familiar sensation that is believed to contribute to a pleasant experience. Thus, by better simulating the composition of tobacco smoke, the present invention can help them to quit smoking more effectively.

The inhalable composition comprises at least 1g/L nicotine, preferably at least 3g/L nicotine, more preferably at least 5g/L nicotine. The inhalable composition may comprise up to 60g/L nicotine, preferably up to 50g/L or up to 40g/L nicotine. Such amount of nicotine refers to the amount of nicotine added to the inhalable composition.

According to a first aspect of the invention, the inhalable composition comprises at least 2g/L carbon dioxide. According to a second aspect of the invention, the inhalable composition comprises at least 0.027g/L carbon dioxide, preferably at least 1g/L, more preferably at least 2 g/L.

More preferably, according to any aspect of the present invention, the inhalable composition comprises at least 3g/L, more preferably at least 5g/L carbon dioxide. The inhalable compositions may comprise at most 40g/L of carbon dioxide, preferably at most 34g/L of carbon dioxide, more preferably at most 20g/L or at most 10g/L of carbon dioxide. Such an amount of carbon dioxide refers to the amount of carbon dioxide initially introduced into the inhalable composition.

In such amounts disclosed herein, carbon dioxide does not itself cause any toxic or irritating effects in the airways. After the initial introduction of carbon dioxide into the inhalable composition, depending on the solvent conditions, a proportion of the carbon dioxide may form carbonic acid derivatives and salts thereof in the composition prior to inhalation. In this case, the skilled person will be able to readily calculate the amount of carbon dioxide initially introduced into the inhalable composition.

In the inhalable composition according to the first aspect, the molar ratio of carbon dioxide to nicotine is at least 0.1: 1. In the inhalable composition according to the second aspect, the molar ratio of carbon dioxide to nicotine is at least 0.025:1, preferably at least 0.1: 1. The ratio is calculated based on the nicotine and carbon dioxide added to the composition. The skilled person will be able to deduce the molar ratio between the two components by taking into account the mass in g of carbon dioxide and nicotine that has been added to the composition, and the relative molecular weights of carbon dioxide and nicotine.

More preferably, according to any aspect of the present invention, the molar ratio of carbon dioxide to nicotine in the inhalable composition is at least 0.25:1, more preferably at least 0.4:1, more preferably at least 0.5: 1. The molar ratio of carbon dioxide to nicotine may be at least 0.75:1, at least 1:1, or at least 7.5: 1. The molar ratio of carbon dioxide to nicotine may be at most 10:1, at most 7.5:1, at most 5:1, or at most 2.5: 1.

Within the scope of nicotine disclosed herein, there is a particularly preferred corresponding amount of carbon dioxide, depending on whether the composition comprises a relatively higher or lower amount of nicotine. Thus, their proportions can be adjusted accordingly depending on whether the composition requires a higher or lower nicotine content. For example, when the inhalable composition comprises 1-30g/L or 1-25g/L nicotine, the molar ratio of carbon dioxide to nicotine is preferably 0.75:1 to 10:1, more preferably 2:1 to 9: 1. Meanwhile, when the inhalable composition comprises 30-60g/L or 30-50g/L nicotine, the molar ratio of carbon dioxide to nicotine is preferably 0.1:1 to 2:1, more preferably 1.5:1 to 2:1.

The inhalable compositions comprise a solvent, preferably an organic solvent. Preferably, the solvent comprises or is selected from glycerol (propane-1, 2, 3-triol), propylene glycol (propane-1, 2-diol), water or mixtures thereof. As can be seen by the examples, a variety of different solvent systems may be used in the inhalable compositions while still achieving the desired dissolution of the carbon dioxide. Thus, the exact nature of the solvent system can be adjusted accordingly to the formulation preferences.

The solvent may comprise propylene glycol. For example, propylene glycol may be present in the inhalable composition in an amount of 0-25% by weight, based on the total weight of the inhalable composition. The presence of propylene glycol provides some formulation advantages, primarily by helping to form a plume of vapor from the device at the time of use by the user. However, for the inhalable compositions disclosed herein, little or no propylene glycol is preferred due to the potential impact on user health. For example, some users report that the presence of propylene glycol in inhalable compositions causes headache. It is also believed that the presence of propylene glycol in the inhalable composition may lead to various irritants. Furthermore, the risk of long-term inhalation of formulations containing propylene glycol is not clear. Thus, propylene glycol is preferably present in an amount of no more than 15 wt.%, preferably no more than 10 wt.%, more preferably no more than 5 wt.%, based on the total weight of the inhalable composition. In some embodiments, the inhalable composition is free of propylene glycol.

Preferably, the solvent comprises glycerol. Glycerol is considered to have less long-term health risks compared to propylene glycol, making the composition considered safer due to the lower risk of negative impact on the health of the user. It was previously believed that carbon dioxide has a lower solubility in glycerol than propylene glycol. Unexpectedly, however, the inhalable compositions disclosed herein achieve unexpectedly high solubility of carbon dioxide, regardless of the solvent system, as a result of the discovery that the addition of carbon dioxide to a composition already containing nicotine and a solvent improves the solubility of carbon dioxide. Typically, glycerin may be present in the inhalable composition in an amount of 40-95% by weight, based on the total weight of the inhalable composition. The glycerol may be present in an amount of at least 50 weight percent, preferably at least 60 weight percent, more preferably at least 70 weight percent, based on the total weight of the inhalable composition.

When the solvent comprises glycerol and propylene glycol, the ratio of glycerol to propylene glycol present in the solvent may be 95:5 to 5:95, preferably 80:20 to 20:80 or 70:30 to 30:70 on a volume basis. As mentioned above, since it is preferred that the ratio of glycerol to propylene glycol is increased, the ratio of glycerol to propylene glycol present in the solvent is preferably at least 70:30, more preferably at least 80:20, even more preferably at least 90:10 on a volume basis.

The solvent may comprise water. Inhalable compositions are compatible with various concentrations of water. This has the added benefit that the water content can be adjusted for a given composition to adjust the viscosity to a desired level. Although inhalable compositions are compatible with water at various concentrations, they do not require the presence of water in order to obtain sufficient solubility of carbon dioxide. In fact, the second aspect of the invention particularly excludes the presence of water in excess of a certain amount, which is in unexpected contrast to the prior art. In particular, according to the second aspect of the invention, when water is present, it is present in an amount of up to 5% by volume relative to the total volume of the solvent. More generally, however, according to the first aspect of the present invention, water may be present in an amount of no greater than 20% by weight, preferably no greater than 15% by weight, more preferably no greater than 10% by weight, based on the total weight of the inhalable composition. The first aspect of the present invention is also compatible with not more than 5% by weight of water, based on the total weight of the inhalable composition. Sufficient carbon dioxide dissolution can still be achieved at such reduced water content, which in turn provides the additional advantage of minimising leakage when the inhalable composition is contained in a container for delivery to a user.

Although sufficient dissolution of carbon dioxide does not require the presence of water, a small amount of water may be beneficial because it is believed that the vaporized water, upon inhalation, further wets the tissue surfaces of the user's airways, thereby resulting in a larger medium in which the carbon dioxide may dissolve, thereby increasing the amount of carbonic acid available to counteract the nicotine alkalinity and thus counteracting the unpleasant astringent taste. Furthermore, the presence of small amounts of water will generally bring the average volatility of the solvent system closer to that of nicotine, which allows a more constant level of nicotine to be delivered during a single inhalation. Thus, in the first or second aspect of the invention, water is preferably present in an amount of at least 1 wt%, based on the total weight of the inhalable composition. It is to be understood that when the solvent comprises water in the amounts disclosed herein, the solvent may further comprise one or more of glycerol and propylene glycol, preferably in the proportions disclosed herein.

Preferably, the inhalable composition comprises less than 10g/L of flammable solvent, such as ethanol. More preferably, the inhalable composition is free of flammable solvents such as ethanol. The presence of volatile flammable solvents (particularly ethanol) is undesirable because it can reach high concentrations in the initial vapor in the device and pose a potential explosion hazard.

The composition may comprise one or more optional ingredients, such as one or more flavouring compounds or one or more additives.

The improved user experience associated with the compositions disclosed herein is such that there is no need to include excessive flavoring agents to mask the unpleasant astringent effect. However, the compositions disclosed herein may have one or more flavoring compounds added, which may comprise up to 15 volume% or up to 10 volume%, based on the total volume of the composition.

The inhalable composition may be included in a cartridge adapted for insertion into an electronic vaping device. Typically, the cartridge is provided in the form of a sealed cartridge containing the inhalable composition prior to insertion into the e-vaping device.

As will be appreciated by those skilled in the art, the volume of inhalable solution will vary depending on the size of the particular electronic cigarette device and associated cartridge in question. Typically, the volume of inhalable solution may be 0.2ml to 10ml, or 0.25ml to 7 ml.

The method of preparing the inhalable compositions disclosed herein comprises the steps of:

forming a dispersion or solution of nicotine in a solvent within a sealable container; and

the carbon dioxide is introduced into the container such that the pressure within the container, measured at 20 ℃, is from 1 to 15 atmospheres, preferably from 2 to 10 atmospheres, more preferably from 2 to 5 atmospheres, most preferably from 4 to 5 atmospheres, which allows the carbon dioxide to be dissolved or dispersed into the dispersion or solution of nicotine.

Also disclosed herein is a concentrate suitable for forming an inhalable composition useful in an electronic smoking device, the concentrate comprising carbon dioxide and at least 60g/L nicotine dissolved or dispersed in a solvent, wherein the molar ratio of carbon dioxide to nicotine is at least 0.1: 1. The concentrate may comprise at least 80g/L or at least 100 g/L. Preferably, the concentrate comprises at most 500g/L nicotine, more preferably at most 300g/L nicotine. The dissolution of carbon dioxide in such concentrates can be achieved by charging the container with carbon dioxide at high pressure to compensate for the particularly concentrated nature of the composition. As previously mentioned, the most preferred molar ratio of carbon dioxide to nicotine can be adjusted according to the nicotine content. For particularly high nicotine levels in the concentrate, the molar ratio of carbon dioxide to nicotine is preferably from 0.1:1 to 2:1, more preferably from 0.1:1 to 1: 1.

The following non-limiting examples serve to illustrate the invention.

Example 1 (Using synthetic nicotine)

A solution of synthetic nicotine was prepared in an 80:20 mixture of glycerol and propylene glycol at a concentration of 2.5% w/w (i.e. 2.5g/100 g). The solution was divided in half and 1.0% water (w/w) was added to one half. A portion (20ml) of each solution was introduced into a screw-cap plastic bottle with a capacity of 520ml, and 4-5g of solid carbon dioxide (dry ice) sufficient to achieve a pressure of 4-5 bar was added to each container. The capped bottle was equilibrated to build up pressure therein. Control mixtures were also prepared as described above, except that no carbon dioxide was added. This resulted in four samples:

sample 1: 2.5% (w/w) synthetic nicotine

Sample 2: 2.5% (w/w) synthetic nicotine and carbon dioxide

Sample 3: 2.5% (w/w) synthetic nicotine and 1% (w/w) water

Sample 4: 2.5% (w/w) synthetic nicotine with carbon dioxide and 1% (w/w) water

As previously described, the amount of nicotine in each sample was 2.5% (w/w) such that the density of the solvent system was about 3.0g/100ml or 3.0% w/v for each sample.

The pH of each sample was measured by taking a portion of each sample, diluting the portion with an equal volume of water and measuring the pH. Control solution (no CO)₂) The pH of (3) was 9.3. The pH of the solution made from the mixture with the introduced carbon dioxide is 6.9-7.0.

Samples 1-4 were tested for inhalation experience in a vaporizer. The gasification unit used in the tests had a Reconstitutable Drip Atomizer (RDA), in particular a Tsumani 24RDA of the "geek vape" type, consisting of two drip atomizers fitted with 8 turns of a coil of 0.4mm Kanthal wire with a resistance of about 1.1 ohm. Gasification was achieved using 24 watts of power. Each RDA used the same Nakamichi (Japan) Cotton as the core (wick). The core was replaced and the atomizer cleaned between each test of e-liquid (eLiquid). Module (mod), which provides power to the nebulizer, is a Vaporshark rDNA unit or an Aspire NX75 unit. Both of these modules are close enough in design and performance to make the comparison meaningful. These modules all have temperature and power control. These modules are used in an energized mode, each set to provide 24 watts of power to the atomizer. At this power level and with the use of the coil, the temperature of the coil used may be about 200 ℃, well below the boiling point of glycerol (the main component of e-liquid). For the initial test, only two vapershark modules are available, so the initial test is performed using a pair-wise comparison. For subsequent tests, five liquids may be compared in one test run. A more extensive test may use a constant "standard" as described below, and other results may be benchmarked as desired. The use of standard liquid allows the standard liquid and two pairs of e-liquid to be tested in 5 tests per batch. The results of the initial test using 2 modules were confirmed using the extended 5 module set.

The user experienced that the mixture without CO2 presented a harsh astringent taste in the mouth and throat upon inhalation. The blend with CO2 produced a smoother sensation in the mouth and throat. The user tabulates the results in table 1:

TABLE 1

Example 2 (use of Nicotine tobacco)

Solutions were prepared as described in example 1, except that nicotine that had been extracted from tobacco was used and the concentrations of the solutions were 1.0% w/w (i.e., 1g/100g) and 2.5% nicotine w/w (i.e., 2.5g/100g), respectively. The details of the gasification unit are as described in example 1. The results are shown in Table 2.

As previously mentioned, the nicotine content in each sample was 2.5% (w/w) such that the density of the solvent system of each sample was about 3.0g/100ml or 3.0% w/v; or 1% (w/w), which gives a density of the solvent system of about 1.2% w/v for each sample.

TABLE 2

Example 3: solubility of carbon dioxide in nicotine solutions

To a weighed 500ml plastic bottle containing about 50g nicotine solution in glycerol/propylene glycol according to table 3 was added 4-5g solid carbon dioxide (dry ice) sufficient to reach a pressure of 4-5 bar. The mixture was kept under pressure for 3 days before releasing the pressure, then the mixture was allowed to stand at ambient temperature for 48 hours, and then the new weight of the solution was measured. The change in weight before and after addition of CO2 allows for the derivation of the amount of CO2 introduced into the solution and the molar ratio of CO2 to nicotine. The results are shown in Table 3.

In a comparative experiment, a bottle containing 20g of pure nicotine was similarly filled with carbon dioxide.

This caused no weight gain at all, indicating that no CO2 was introduced into the solution.

Example 4: comparative examples

Experiments were performed according to the method steps for forming an inhalable composition in KR 10-1208473. The following experiments were performed on twice the scale shown in KR10-1208473 for more accurate weighing. The room temperature used in the following experiments was about 16 ℃, which is considered to be lower than the laboratory temperature in KR 10-1208473. It is therefore believed that the levels of CO2 achieved in the following experiments were higher than the levels actually achieved in KR 10-1208473.

A liquid composition was prepared using 65 vol% propylene glycol, 23 vol% vegetable glycerin, 2 vol% ethanol, 7 vol% water and menthol. Menthol (a solid material) was added in an amount of 3g to 97ml of a propylene glycol/vegetable glycerol/ethanol/water mixture to make up a total volume of 100ml, leaving menthol present in an amount of 3g/100 ml. The liquid composition was saturated with carbon dioxide at room temperature and atmospheric pressure by adding 100ml of the liquid composition and 2g of dry ice in a 500ml bottle. The bottle was then sealed and then shaken for a few minutes to dissolve the carbon dioxide in the liquid composition. After about 1 hour, the bottle was depressurized. The bottle was then unsealed and shaken again for about 1 minute. It was left at room temperature and atmospheric pressure for about 30 minutes to saturate the liquid composition with carbon dioxide.

By measuring the weight of the composition before and after saturation with CO2, the following results were obtained.

Sample 1:106.772g of the mixture had 1.5mg/g (40mg/25ml) of CO 2.

Sample 2 106.465g of the mixture had 1.62mg/g (43mg/25ml) of CO 2.

80mg of nicotine was then added. After 48 hours, the following amounts of CO2 were added:

sample 1 0.9mg/g, i.e. 0.96mg/ml, of CO2

Sample 2 1.06mg/g, i.e. 1.13mg/ml, of CO2

Thus, the method of KR10-1208473 gives a lower carbon dioxide introduction amount than the method used in example 3.

Example 5: solubility of carbon dioxide in nicotine solutions with low propylene glycol

Using the same method as in example 3, a solution of nicotine dissolved in glycerin, nicotine, water and propylene glycol (if present) was prepared as shown in table 4. In table 4, propylene glycol is referred to as "PG". Propylene glycol (when present) is derived fromAddition of a tobacco flavoring composition. The tobacco flavor composition (consisting of tobacco flavor dissolved/dispersed in propylene glycol) referred to as "TF" in table 4 included 65 wt.% propylene glycol. Thus, as detailed in the table below, the addition of 8% of the flavour composition results in the addition of 5.2% by weight of propylene glycol to the total inhalable composition. For each experiment, 0.2g of 50.0g of solution was used. As in example 3, the solution was weighed before and after the addition of CO2, with the addition of CO₂The change in weight before and after can be deduced as the CO introduced into the solution₂The amount of (c). The recorded amount of carbon dioxide introduced into the solution is the average result of two experiments.

TABLE 4