Compositions containing nicotine and / or nicotine salts, and ultrasonic aerosolization methods for compositions containing nicotine and / or nicotine salts.

Abstract

To provide a method that can prevent the denaturation of nicotine molecules and salts during aerosolization and deliver nicotine at a higher rate than heated coil ENDS. [Solution] The present invention relates to a composition comprising nicotine and / or a salt of nicotine, and more particularly to a composition comprising nicotine and / or a salt of nicotine for ultrasonic aerosolization.

Description

Technical Field

[0001] The present invention relates to a composition containing nicotine and / or a nicotine salt. The present invention also relates to the ultrasonic aerosolization of a composition containing nicotine and / or a nicotine salt.

Background Art

[0002] Electronic nicotine delivery systems ("ENDS") provide an alternative to combustible tobacco smoking. Their increasing popularity is due in part to their ability to provide nicotine and the associated satisfaction to users.

[0003] Some users prefer a relatively high level of nicotine in the composition inhaled from the device to achieve their desired level of satisfaction. A high level of nicotine in the composition is preferably 40 - 60 mg / ml, optionally 50 mg / ml. A high level of nicotine in the inhaled vapor generated by ENDS can cause a sensory irritation that users find unpleasant, generally known as a "throat hit". In recent years, the development of "nicotine salts" has made it possible to increase the concentration of nicotine contained in ENDS to more than twice the highest concentration initially available on the market.

[0004] The popularity of nicotine salts is due to the fact that nicotine salts have two important functions: reducing the irritation felt by users in the throat and enhancing the pharmacological effect of nicotine by promoting the uptake of nicotine into the bloodstream.

[0005] Traditionally, commercially available ENDS have used a heating coil to vaporize a nicotine-containing liquid. Recently, a new class of ENDS has been developed that generates an inhalable aerosol using ultrasonic vibrations, and this trend continues. One such device utilizing ultrasonic vibrations was developed by Shaheen Innovations Holding Limited and is described in PCT application number PCT / IB2019 / 060810 (its disclosure is incorporated herein in its entirety by reference).

[0006] One advantage of these new devices that utilize ultrasonic vibrations is that they can generate a vaporized aerosol without heating the nicotine-containing liquid. Because there is no heat, the denaturation of nicotine molecules and salts during aerosolization can be prevented, and these devices that utilize ultrasonic vibrations have been found to be able to deliver nicotine at even higher rates than heated coil ENDS. [Overview of the Initiative] [Means for solving the problem]

[0007] In some non-limiting aspects, the present invention relates to the aerosolization of compositions comprising nicotine and / or salts of nicotine, wherein the aerosolization utilizes ultrasonic vibrations.

[0008] The present invention is as described in the claims. Typical features are described in the following sections, which may be used individually or in any combination with one or more features disclosed in the text and / or drawings of this document:

[0009] 1. An electroliquid composition for use in an ultrasonic device, comprising the following: Nicotine salts.

[0010] 2. The electron liquid composition of item 1, further comprising one, two, three, or four of the following: Propylene glycol Vegetable glycerin water fragrance

[0011] 3. The electron liquid composition of item 2, wherein the relative amount of vegetable glycerin in the composition is 55 to 80% (w / w), or 60 to 80% (w / w), or 65 to 75% (w / w), or 70% (w / w):

[0012] 4. The electronic liquid composition according to item 2 or 3, wherein the relative amount of propylene glycol in the composition is 5-30% (w / w), or 10-30% (w / w), or 15-25% (w / w), or 20% (w / w).

[0013] 5. An electronic liquid composition according to any of items 2 to 4, wherein the relative amount of water in the composition is 5-15% (w / w), or 7-12% (w / w), or 10% (w / w).

[0014] 6. Any of the electronic liquid compositions according to items 2 to 4, wherein the amount of nicotine and / or nicotine salt in the composition is 0.1 to 80 mg / ml, or 0.1 to 50 mg / ml, or 1 to 25 mg / ml, or 10 to 20 mg / ml, or 17 mg / ml.

[0015] 7. An electronic liquid composition (in %(w / w)) of any of the following, comprising or containing the following: Propylene glycol 10%~20% Vegetable glycerin 65%~75% Water 5%~15% Nicotine 1%~5% Organic acid 0.1%~5.0% Fragrance balance Here, the organic acids consist of or comprise benzoic acid, levulinic acid, malic acid, tartaric acid, salicylic acid, citric acid, lactic acid, or any combination of 2, 3, 4, 5, 6, or 7 of these organic acids.

[0016] 8. The electronic liquid composition according to any one of claims 2 to 7, further comprising the following (% (w / w)): Organic acid: 0.1 to 5.0, or 1.0 to 4.0, or 0.1 to 2.0.

[0017] 9. The electronic liquid composition according to any one of claims 2 to 8, wherein the composition is composed of the following or contains the following (% (w / w)): Propylene glycol: 11% to 16% Vegetable glycerin: 69% to 71% Water: 9% to 11% Nicotine: 1% to 3% Levulinic acid: 0.1% to 4.0% Flavor: balance

[0018] 10. The electronic liquid composition of claim 9, further comprising the following (% (w / w)): Propylene glycol: 14% to 16%.

[0019] 11. The electronic liquid composition according to any one of claims 1 to 10, further comprising the following (% (w / w)): Organic acid: 0.1 to 4.0, or 0.1 to 1.0, or 0.1 to 0.5.

[0020] 12. The electronic liquid composition according to any one of claims 2 to 11, further comprising the following (% (w / w)): · Propylene glycol: 15.1 Vegetable glycerin: 70 Water: 10 Nicotine: 1.7 Levulinic acid: 0.2 Flavor: 3 or · Propylene glycol: 12.87 Vegetable glycerin: 70 Water: 10 Nicotine: 1.7 Levulinic acid: 2.43 Flavor: 3 or • Propylene glycol 14.08 Vegetable glycerin 70 water 10 Nicotine 1.7 Levulinic acid 1.22 Fragrance 3 or • Propylene glycol 11.64 Vegetable glycerin 70 water 10 Nicotine 1.7 Levulinic acid 3.66 fragrance 3

[0021] 13. An electronic liquid composition according to any of items 1 to 12, wherein the nicotine salt is selected from the following group: Nicotine benzoate, nicotine lactate, nicotine maleate, nicotine distartrate, nicotine salicylate, nicotine citrate, and nicotine levulinate, or any combination of 2, 3, 4, 5, 6, or 7 of these nicotine salts.

[0022] 14. An electronic liquid composition according to any of items 1 to 13, wherein the nicotine salt is nicotine levulinate.

[0023] 15. Electrolyte liquid compositions of item 13 or 14 having a molar ratio of nicotine to organic acid salt (nicotine:organic acid salt) of 1:1 or greater, or 1:2 or greater, or 1:1 to 1:4, or 1:1 to 1:3.

[0024] 16. Use of any of the electronic liquid compositions described in paragraphs 1 to 15 when providing nicotine to a user, including: A step of providing an electron liquid composition according to any of the items 1 to 15. Placing an electron liquid composition into an ultrasonic device. Aerosolizing an electron liquid composition within an ultrasonic device.

[0025] 17. For the uses described in paragraph 16, the following are provided: Inhaling an aerosolized composition.

[0026] 18. The use described in paragraph 16 or 17, wherein the ultrasonic device is an ultrasonic mist inhaler comprising: - Adapted to accept liquids to be atomized Liquid reservoir structure including liquid chamber - Ultrasonic irradiation chamber in fluid communication with a liquid chamber - Capillary element placed between the liquid chamber and the ultrasonic treatment chamber

[0027] 19. Use as described in paragraph 18, wherein the capillary element is at least partially made of bamboo fiber material.

[0028] 20. The use according to paragraph 19, wherein the capillary element material is 100% bamboo fiber, or the capillary element material is at least 75% bamboo fiber and preferably 25% cotton.

[0029] 21. In the use described in paragraph 19 or 20, the capillary element is preferably between 0.27 mm and 0.32 mm in thickness and between 38 g / m² and 48 g / m² in density.

[0030] 22. The method described in any one of paragraphs 19 to 21, wherein the capillary element is flat.

[0031] 23. Use of any of items 19 to 22, wherein the capillary element consists of a central part and a peripheral part.

[0032] 24. Use of any of the items 19 to 23, wherein the peripheral portion has an L-shaped cross-section extending to the liquid chamber.

[0033] 25. Use of any of the devices described in items 19 to 24, having a U-shaped cross-section with the central portion extending to the ultrasonic irradiation chamber.

[0034] 26. A method for delivering nicotine salts to a user, comprising the following: A step of providing an electron liquid composition according to any of the items 1 to 15. Placing an electron liquid composition into an ultrasonic device. Aerosolizing an electron liquid composition within an ultrasonic device.

[0035] 27. The method described in paragraph 26, comprising: Inhaling an aerosolized composition. [Modes for carrying out the invention]

[0036] Embodiments of this disclosure are described in full below. However, embodiments of the claims can be embodied in many different forms and should not be construed as being limited to embodiments described herein. The examples described herein are non-limiting examples and are merely examples of other possible examples.

[0037] definition Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art. All patents, applications, published applications, and other publications referenced herein are incorporated by reference in their entirety unless otherwise noted. If there are multiple definitions of a term herein, the definition in this section shall prevail unless otherwise noted.

[0038] An "aerosol" refers to a suspension of solid particles or liquid droplets in air or other gases. The aerosols produced by ENDS contain droplets of nicotine and other components in the air, which are inhaled by the user during use.

[0039] "Bioactivity" refers to compounds that act on living organisms.

[0040] "Electronic liquid" refers to the flavored or unflavored liquid used in e-cigarettes, ENDS, or similar devices.

[0041] "ENDS" refers to an electronic nicotine delivery system. ENDS offer an alternative to smoking combustible cigarettes. Typical ENDS on the market utilize a heating coil system to vaporize a nicotine-containing liquid. Newer types of ENDS use ultrasonic vibrations to generate an inhalable aerosol.

[0042] "Free basic nicotine" refers to nicotine molecules that have not been protonated.

[0043] "Nicotine salts" refer to salts of nicotine, such as nicotine benzoate, nicotine lactate, nicotine malate, nicotine ditartarate, nicotine salicylate, nicotine citrate, and nicotine levulinate, but are not limited to these.

[0044] "Off-gasification" refers to the release of volatile compounds into the atmosphere.

[0045] A weak acid (for example, a weak organic acid) is an acid that only partially dissociates into ions in an aqueous solution, in contrast to a "strong acid" that completely dissociates into ions.

[0046] "%(w / w)" refers to the amount of a component present in "weight ratio," that is, the proportion of a specific substance in a composition or mixture measured by weight.

[0047] Nicotine delivery Nicotine salts are preferable for use in ultrasound devices due to their effectiveness in nicotine delivery and the increased sensory stimulation that occurs at nicotine levels above 6 mg / ml.

[0048] Nicotine salts are formed by combining nicotine, a basic free radical, with a weak organic acid (such as benzoic acid, levulinic acid, malic acid, tartaric acid, salicylic acid, citric acid, or lactic acid).

[0049] When nicotine is combined with a weak organic acid in an aqueous solution, the pH decreases, and the free radical (or aprotonated) nicotine molecule changes into two protonated forms: monoprotonation and diprotonation (reaction scheme 1).

[0050] [ka]

[0051] In reaction scheme 1, Z - This is a counteranion produced by the deprotonation of the corresponding weak organic acid.

[0052] In monoprotonation, one of the two nitrogen atoms in the nicotine molecule acquires a proton from the acid and becomes ionized. In diprotonation, both nitrogen atoms in the nicotine molecule are protonated. This decrease in pH and the protonation of nicotine are thought to contribute to the reduction of irritation when inhaling nicotine salts.

[0053] Nicotine salts include nicotine benzoate, nicotine lactate, nicotine malate, nicotine ditartarate, nicotine salicylate, nicotine citrate, and nicotine levulinate. All of these salts are formulated to exist in a monoprotonated form in an electron liquid. Their effectiveness in both reducing throat hit and nicotine uptake into the body has been studied, and they are being converted from salt to salt in heating coil systems. The inventors have found that similar variations in effect occur in ultrasonic devices, although the degree of variation is surprisingly different.

[0054] e-liquid A typical electronic liquid consists of nicotine (optionally in the form of a nicotine salt), flavorings, propylene glycol, and vegetable glycerin.

[0055] A typical electron liquid consists of 57–69% (w / w) vegetable glycerin and 30–42% (w / w) propylene glycol. The remainder is formed by water, nicotine and / or nicotine salts, and any flavorings. Optionally, the amount of nicotine (optionally in the form of a nicotine salt) in the electron liquid is 0.1–80 mg / ml, or 0.1–50 mg / ml.

[0056] In this invention, the electronic liquid consists of vegetable glycerin, propylene glycol, and water. The balance is formed with nicotine and / or a nicotine salt and an optional flavoring.

[0057] The relative amount of vegetable glycerin in the composition is 55 to 80% (w / w), or 60 to 80% (w / w), or 65 to 75% (w / w), or at least 70% (w / w).

[0058] The relative amount of propylene glycol in the composition is 5–30% (w / w), or 10–30% (w / w), or 15–25% (w / w), or at least 20% (w / w). Optionally, nicotine and / or nicotine salts, and any flavorings are included as part of the total % (w / w) relative amount of propylene glycol.

[0059] The relative amount of water in the composition is 5-15% (w / w), or 7-12% (w / w), or at least 10% (w / w).

[0060] Optionally, the relative amount of nicotine in the electronic liquid is 0.1–80 mg / ml, 0.1–50 mg / ml, or 1–25 mg / ml, or 10–20 mg / ml, or at least 17 mg / ml.

[0061] In a typical electron liquid composition, as the percentage (w / w) of vegetable glycerin decreases, the percentage (w / w) of propylene glycol increases proportionally. In one non-limiting example, when vegetable glycerin is present at 50% (w / w), propylene glycol at 40% (w / w), and water at 10% (w / w), there is a decrease in the amount of vapor produced by the electron liquid. Vegetable glycerin is the main vapor "cloud" generating substance in the mixture, and it is preferable to maintain the amount of vegetable glycerin at 50% (w / w) or higher.

[0062] Heating coil systems such as JUUL use a resistive coil wire to heat the electron liquid to approximately 215°C (Talih et al.). At this temperature (above 200°C), nicotine salts undergo a process called disproportionation, producing one diprotonated nicotine molecule and one aprotonated (free radical) nicotine molecule from two monoprotonated nicotine molecules (Seeman et al.).

[0063] For a compound to be considered biologically active, it must have an effect on living organisms. Protonated nicotine cannot easily pass through the lipid bilayer of cell membranes, making it difficult for it to enter the bloodstream, travel to the brain, and bind to nicotinic acetylcholine receptors in the brain to exert biological effects on humans. Therefore, protonated nicotine is considered to have no biological activity. Because protonated nicotine is not very soluble in lipids, it does not easily pass through the alveoli in the lungs and enter the bloodstream. Furthermore, when diprotonated nicotine is produced, the amount of nicotine that can be rapidly delivered into the bloodstream decreases even further. In contrast, free nicotine is considered to have physiological activity. Free nicotine is easily absorbed into the bloodstream.

[0064] When protonated nicotine enters the lungs, it deposits in the mucous membrane lining the alveoli. The pH of this mucous membrane is approximately 7.4. At this pH, protonated nicotine slowly deprotonates. Typically, 18% to 22% of protonated nicotine forms free nicotine, which easily enters the bloodstream. The remaining 78% to 82% of protonated nicotine remains in a monoprotonated form. This monoprotonated form also enters the bloodstream, but not as readily as free nicotine.

[0065] Nicotine generated in the disproportionation process of the heating coil system travels through a similar pulmonary process to the lungs and ultimately into the bloodstream. Free radical nicotine is more volatile than protonated nicotine, and as a result, it "off-gasifies" from the aerosolized droplets and deposits in the mouth and larynx of the upper respiratory tract. Because free radical nicotine deposits in the mouth and larynx of the upper respiratory tract, its absorption into the bloodstream is twice as slow as absorption from the alveoli. In contrast, less volatile protonated nicotine remains in the aerosolized droplets and can be inhaled deep into the lungs.

[0066] In one embodiment of the present invention, an ultrasonic device may be used to achieve aerosolization. Several non-limiting examples of such ultrasonic devices are provided in PCT application no. PCT / IB2019 / 060810. A typical ultrasonic device consists of a liquid reservoir structure including a liquid chamber that receives the liquid to be atomized, an ultrasonic processing chamber, and a capillary element positioned between the liquid chamber and the ultrasonic processing chamber. The ultrasonic device does not heat the electron liquid to achieve aerosolization. Instead, the ultrasonic device atomizes the electron liquid using both acoustic cavitation and capillary waves.

[0067] Acoustic cavitation is a phenomenon in which tiny bubbles in a liquid grow and implode. The size of the bubbles formed depends on many factors, including frequency and the liquid itself, and therefore the size of the formed bubbles varies. Generally, the size of the bubbles is on the nanometer to micrometer scale. The phenomenon of acoustic cavitation is caused by high-frequency sound waves (20 kHz to several MHz). These sound waves generate extremely high pressure waves of several hundred atmospheres and low pressure waves in the liquid, allowing bubbles to grow and collapse very quickly. Bubbles usually collapse within microseconds. After several acoustic cycles, when the bubble reaches a critical size, it collapses rapidly. The critical size and the number of cycles usually vary depending on the characteristics of the system, such as the liquid used. This implosion releases heat rapidly along with a shock wave.

[0068] Acoustic cavitation occurs on the nano to micro scale, so all physical properties occur on the same scale. Acoustic cavitation occurs at distances of nanometers or micrometers, in nanoseconds or microseconds.

[0069] Heat release is effectively an adiabatic process. 9 K / s (plus or minus) It is dissipated into the cooler surrounding liquid at a speed of the order of single digits.

[0070] Shock waves are crucial in the ultrasonic aerosolization process. They facilitate the formation of capillary waves at the liquid surface. Capillary waves propagate very quickly. The propagation speed of capillary waves depends on the system, such as the liquid being used. This high propagation speed creates millions of tiny droplets. These tiny droplets break the liquid's surface tension and are released into the air, resulting in droplet aerosolization.

[0071] The droplet size is typically 0.25 to 0.5 microns. The droplets form an aerosol, which can be absorbed by the user through respiration.

[0072] In some embodiments of the present invention, non-thermal aerosolization (i.e., ultrasonic aerosolization) allows nicotine salts in the electron liquid to remain in the electron liquid as nicotine salts without imbalance (as experienced in heating coil systems). The nicotine salts may be inhaled deep into the lungs. In some embodiments of the present invention, because less nicotine accumulates in the upper respiratory tract, the concentration of nicotine salts inhaled into the lungs is higher compared to the concentration of nicotine salts inhaled into the lungs from the use of heating coil devices.

[0073] Upon entering the lungs, the nicotine component of nicotine salts is deprotonated through disproportionation, potentially forming one diprotonated nicotine molecule and one unprotonated (free base) molecule from two monoprotonated nicotine molecules. The free base nicotine is more easily absorbed into the bloodstream. The remaining protonated nicotine also passes through the bloodstream, but it is less effective than the free base nicotine.

[0074] After entering the bloodstream, nicotine travels to the brain. Once in the brain, nicotine binds to nicotinic acetylcholine receptors (nAchRs), promoting the flow of sodium and potassium ions through these receptors. This flow of sodium and potassium ions stimulates the neurons associated with those ions. When nerve cells are stimulated, neurotransmitters such as dopamine are released, producing the "buzz" effect that nicotine users desire.

[0075] By using ultrasound and nicotine salts, the nicotine salts can be inhaled deep into the lungs, generating free nicotine within the lungs and making it easier for them to enter the bloodstream. By using an ultrasound device in combination with an electron liquid containing nicotine salts, users can experience an enhanced nicotine effect (compared to the same concentration of nicotine salts in an electron liquid vaporized using a heating coil method). In other words, a synergistic effect is achieved by using an ultrasound device and nicotine salts (in an electron liquid) together.

[0076] While I don't want to be bound by theory, the synergistic effect arises, at least, from the fact that using nicotine salts in an electron liquid in combination with an ultrasonic device allows for an increase in the level of nicotine delivered to the lungs with relatively low levels of nicotine salts in the electron liquid, without the user experiencing sensory irritation (as in the case of a heating coil system). The nicotine salts then enter the lungs without depositing in the upper respiratory tract, such as the mouth or Adam's apple, due to the use of the ultrasonic device, forming free basic nicotine. Free nicotine quickly and easily enters the user's bloodstream. Because the level of nicotine that quickly enters the user's bloodstream increases, the user may experience an enhanced nicotine effect with minimized and / or reduced "sore throat." [Examples]

[0077] The following is a non-limiting example discussing the advantages of using ultrasonic aerosolization with electron liquids containing nicotine salts.

[0078] Example 1: Use of nicotine levulinate as a nicotine salt In a non-limiting example, four exemplary compositions of the electron liquid consist of nicotine, propylene glycol, vegetable glycerin, water, and fragrance. The percentage concentrations of each component in the electron liquid are shown in Tables 1, 2, 3, and 4.

[0079] [Table 1]

[0080] [Table 2]

[0081] [Table 3]

[0082] [Table 4]

[0083] In non-specific examples, nicotine in a solution is all or part in the form of nicotine levulinate.

[0084] Levulinic acid nicotine salt is formed by the bonding of nicotine and levulinic acid in solution. As a result, levulinic acid nicotine salt is formed, consisting of a levulinic acid anion and a nicotine cation.

[0085] The percentage concentrations of nicotine in the electronic liquid shown in Tables 1, 2, 3, and 4 are approximately equivalent to 17 mg / ml.

[0086] The electrolyzed liquid is placed in an ultrasonic device. In this non-limiting example, the ultrasonic device is one described in PCT / IB2019 / 060810. The electrolyzed liquid is then aerosolized and inhaled into the lungs by the user. The user experiences the desired nicotine "buzz" effect with minimal or no "throat hit".

[0087] For nicotine to enter the bloodstream, the nicotine component of nicotine salts must be deprotonated. As explained in Chemistry of Nicotine / Levulinic Acid (BN: 511034204-511034215), levulinic acid nicotine protonates only the pyrrolidine nitrogen of the nicotine molecule. This protonation results in the formation of a monoprotonated nicotine molecule. Some of the monoprotonated nicotine is deprotonated and enters the bloodstream as free nicotine, while other parts enter the bloodstream as monoprotonated nicotine. Monoprotonated nicotine does not enter the bloodstream as effectively as free nicotine (Lippiello et al.).

[0088] Referring to the different compositions in Tables 2, 3, and 4, all three examples provide a beneficial reduction in "throat hit." Therefore, any composition containing levulinic acid (or other organic acid) in a molar ratio of 1:1, 2:1, or 3:1 to nicotine provides a beneficial effect.

[0089] The nicotine molecule contains two nitrogen atoms, one on the pyridine ring and the other on the pyrrolidine ring. Both nitrogen atoms are in a free base form, possessing free electron pairs. These two nitrogen atoms can accept a proton donor molecule, such as a proton from the hydroxyl group of levulinic acid (or other organic acids). The nitrogen atom on the pyrrolidine ring is the first to accept a proton from levulinic acid (or other organic acids), followed by the nitrogen atom on the pyridine ring. Two molar equivalents of levulinic acid (or other organic acids) are required to protonate both nitrogen atoms on the nicotine molecule.

[0090] The different ratios of levulinic acid and nicotine shown in Tables 2, 3, and 4 were tested to see if different levels of equivalent acid produced different effects. Users reported that compositions with a 1:1 molar ratio (i.e., the compositions in Table 3) still provided a reduced throat hit. However, 2:1 molar ratios (i.e., the compositions in Table 2) and 3:1 molar ratios (i.e., the compositions in Table 4) provided a further reduction in throat irritation. This result indicates that using a 1:1 molar ratio (or higher amount) of levulinic acid (or other organic acid) to nicotine yields a beneficial effect (i.e., levulinic acid is a larger component at ratios higher than 1:1).

[0091] Advantageously, nicotine levulinate contains a levulinate anion. The levulinate anion (as a component of nicotine levulinate) has an octanol:water partition coefficient (P) of 0.69, as illustrated in Table 5, which is 500 times higher than that of levulinic acid (P=0.00145).

[0092] [Table 5]

[0093] The partition coefficient can be used as an indicator of lipid solubility. Because levulinate anions have high lipid solubility, they enter the bloodstream along with nicotine.

[0094] When nicotine and levulinate anions enter the bloodstream, they travel to the brain.

[0095] The presence of additional levulinate ions increases the amount of nicotine that binds to receptors in the brain (Lippiello et al.). Levulinate anions increase nicotine binding to brain receptors in two ways: firstly, by increasing the affinity of receptor sites for nicotine molecules; and secondly, by inducing positive binding cooperation of nicotine at an additional class of receptor sites.

[0096] Therefore, the presence of levulinate anions results in greater nicotine binding to receptors in the brain. As discussed by Lippello et al., when nicotine levulinate is inhaled, the proportion of nicotine binding sites can increase by 20–50% compared to other nicotine salts such as nicotine salicylate.

[0097] The use of ultrasonic devices to aerosolize nicotine salt electron liquids containing nicotine levulinate leads to enhanced nicotine effects for the user at relatively low concentrations of nicotine in the electron liquid (compared to heating coil devices).

[0098] Using an ultrasonic device to aerosolize a nicotine salt electron liquid containing nicotine levulinate results in a nicotine experience that is unmatched by any currently available heated coil ENDS devices.

[0099] Similar effects are observed when all or part of nicotine levulinate is replaced by another nicotine salt, including but not limited to nicotine benzoate, nicotine maleate, nicotine ditartarate, nicotine salicylate, nicotine citrate, and nicotine lactate.

[0100] As used herein and in the claims, the terms “equipped with” and “equipped with” and their variations mean that the specified feature, step or integer is included. This term shall not be construed to exclude the presence of other features, steps or components.

[0101] The features disclosed in the preceding description, or in the following claims, or in the accompanying drawings, may be expressed as appropriate in their specific forms, or in terms of means for performing the disclosed functions, or methods or processes for achieving the disclosed results, and may be used separately or in any combination of those features to realize the invention in its various forms.

[0102] Bibliographic information The following references, by their inclusion, are incorporated into this book.

[0103] Lippiello, PM, Fernandes, KG, Reynolds, JH, & Hayes, AW (1989, September 25). Enhancement of nicotine binding to nicotinic receptors by nicotine levulinate and levulinic acid. RJ Reynolds. Bates No. 509336913-509336640. http: / / tobacco- Excerpt from documents.org / product_design / 509336913-6940.html.

[0104] Talih S, Salman R, El-Hage R, et al. Characteristics and toxicant emissions of JUUL electronic cigarettes. Tob Control. 2019. doi: 10.1136 / tobaccocontrol-2018-054616

[0105] Seeman J., Fournier J., Paine III J., Waymack B. The Form of Nicotine in Tobacco. Thermal Transfer of Nicotine and Nicotine Acid Salts to Nicotine in the Gas Phase. Journal of Agricultural Food Chemistry. 1999.

[0106] RJ Reynolds Records. Chemistry of Nicotine / Levulinic Acid. 1992. BN: 511034204-511034215. Retrieved from https: / / www.industrydocuments.ucsf.edu / docs / hfdy0046

Claims

1. A step of providing an electronic liquid composition comprising nicotine and / or a nicotine salt, propylene glycol, vegetable glycerin, water, and at least one of a fragrance, A step of placing an electron liquid composition inside an ultrasonic device, A process of aerosolizing the electron liquid composition inside the ultrasonic device and A method for delivering nicotine to a user, characterized by including [a certain element].

2. The method according to claim 1, characterized by comprising propylene glycol, vegetable glycerin, water, and two, three, or four fragrances.

3. A. The relative amount of vegetable glycerin in the composition is 55-80% (w / w). B. The relative amount of propylene glycol in the composition is 5-30% (w / w), C. The relative amount of water in the composition is 5-15% (w / w), and, D. The amount of nicotine and / or nicotine salt in the composition is 0.1 to 80 mg / ml. The method according to feature 2.

4. A. The relative amount of vegetable glycerin in the composition is 60-80% (w / w). B. The relative amount of propylene glycol in the composition is 10-30% (w / w), C. The relative amount of water in the composition is 5-15% (w / w), and D. The amount of nicotine and / or nicotine salt in the composition is 0.1 to 80 mg / ml. The method according to feature 2.

5. A. The relative amount of vegetable glycerin in the composition is 65-75% (w / w). B. The relative amount of propylene glycol in the composition is 15-25% (w / w), C. The relative amount of water in the composition is 7-12% (w / w), and / or D. The amount of nicotine and / or nicotine salt in the composition is 0.1 to 80 mg / ml. The method according to feature 2.

6. The aforementioned composition has the following composition (in % (w / w) units): Propylene glycol 10-20 Vegetable glycerin 65-75 Wed 5-15 Nicotine 1-5 Organic acid 0.1-5.0 fragrance residue Includes, The organic acids include at least one of benzoic acid, levulinic acid, malic acid, tartaric acid, salicylic acid, citric acid, or lactic acid, or any combination of two, three, four, five, six, or seven of these organic acids. The method according to any one of claims 2 to 5, characterized by the following:

7. The method according to any one of claims 2 to 6, characterized in that the composition contains 0.1 to 5.0% (w / w) of an organic acid.

8. The method according to any one of claims 2 to 6, characterized in that the composition contains 1.0 to 4.0% (w / w) of an organic acid.

9. The method according to any one of claims 2 to 6, characterized in that the composition contains 0.1 to 2.0% (w / w) of an organic acid.

10. The method according to any one of claims 2 to 9, characterized in that the composition comprises at least one organic acid selected from the group consisting of benzoic acid, levulinic acid, malic acid, tartaric acid, salicylic acid, citric acid, or lactic acid, or any combination of two, three, four, five, six, or seven of these organic acids.

11. The method according to 10, characterized in that the organic acid is selected from the group consisting of benzoic acid, levulinic acid, or a combination thereof.

12. The method according to 10 or 11, characterized in that the nicotine and organic acid are present in a molar ratio of 1 part nicotine to 1 or more parts organic acid.

13. The method according to 10 or 11, characterized in that the nicotine and organic acid are present in a molar ratio of 1 part nicotine to 2 or more parts organic acid.

14. The method according to 10 or 11, characterized in that the nicotine and organic acid are present in a molar ratio of 1 part nicotine to 1 to 4 parts organic acid.

15. The method according to 10 or 11, characterized in that the nicotine and organic acid are present in a molar ratio of 1 part nicotine to 1 to 3 parts organic acid.

16. The method according to any one of claims 1 to 15, further comprising the step of inhaling an aerosolized composition.

17. The ultrasonic device is - A liquid reservoir structure including a liquid chamber adapted to receive the liquid to be atomized, - An ultrasonic irradiation chamber that is in fluid communication with a liquid chamber, - Capillary elements placed between the liquid chamber and the ultrasonic processing chamber The method according to 16, characterized in that it is an ultrasonic mist inhaler containing [a specific component].

18. The capillary element is 38 g / m 2 From 48 g / m 2 The method according to 17, characterized by having a density between [a certain value].

19. The method according to 17, characterized in that the peripheral portion has an L-shaped cross-section that extends to the liquid chamber.

20. The method according to 17, characterized in that the central portion has a U-shaped cross-section that extends to the ultrasonic processing chamber.

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