A nicotine liquid formulation, and a method of preparing and using the same

Abstract

The present application relates to the technical field of electronic atomization, in particular to a nicotine liquid preparation, a preparation method and application thereof. The present application provides a nicotine liquid preparation, wherein the raw material components of the nicotine liquid preparation comprise nicotine, sparteine and lactic acid. Through the compounding of sparteine, lactic acid and nicotine, the three components can synergistically act to effectively improve the satisfaction of the electronic cigarette formula.

Description

Technical Field

[0001] This invention relates to the field of electronic atomization technology, specifically to a nicotine liquid formulation, its preparation method, and its application. Background Technology

[0002] Electronic atomization systems are smoking cessation products that deliver nicotine without tobacco smoke. Instead, they deliver nicotine into the bloodstream, effectively reducing tobacco intake and helping smokers quit, similar to nicotine replacement therapy. An electronic atomization system mainly consists of three parts: a cartridge, an atomizer, and a power source. The cartridge is the container for the liquid nicotine formulation, whose main components are nicotine, propylene glycol, glycerol, and flavorings. The atomizer, powered by a battery, atomizes the liquid nicotine in the cartridge into an aerosol with a specific aroma for the user.

[0003] The core ingredient in nicotine liquid formulations is nicotine. When the nebulizer is heated, the nicotine in the liquid formulation is atomized into an aerosol and inhaled, thus enhancing the feeling of satisfaction. To prevent nicotine abuse and protect public health and safety, various countries strictly regulate nicotine, generally limiting its content to 20mg / g or below. However, lower nicotine levels lead to a decrease in the feeling of satisfaction. To enhance consumer satisfaction, current technologies typically use nicotine salts. Benzoic acid is a commonly used organic acid in nicotine salt formation. The combination of nicotine and benzoic acid is used to enhance satisfaction, but the effect remains limited. Summary of the Invention

[0004] The purpose of this invention is to overcome the shortcomings of existing technologies that use nicotine and benzoic acid in combination to improve user satisfaction, and to provide a nicotine liquid formulation, its preparation method and application.

[0005] To achieve the above objectives, the present invention adopts the following technical solution:

[0006] This invention provides a nicotine liquid formulation, wherein the raw material components of the nicotine liquid formulation include nicotine, cytisine, and lactic acid.

[0007] Preferably, the mass ratio of nicotine to cytisine is 1:(0.05-2);

[0008] The total molar amount of nicotine and cytisine is used in a molar ratio of 1:(0.01-3.1) to lactic acid.

[0009] Optionally, in the nicotine liquid formulation, the nicotine and organic acid may be in the form of nicotine organic acid salts, and the cytisine and organic acid may be in the form of cytisine organic acid salts.

[0010] Preferably, the raw material components of the nicotine liquid preparation further include a second organic acid, which is selected from at least one of salicylic acid, citric acid, malic acid, benzoic acid, levulinic acid, tartaric acid, and succinic acid;

[0011] Preferably, the second organic acid is selected from at least one of salicylic acid, citric acid, and malic acid.

[0012] Preferably, the molar ratio of lactic acid to the second organic acid is 1:(0.2-2.1).

[0013] Preferably, the raw material components of the nicotine liquid formulation further include flavoring and / or atomizing solvent.

[0014] Preferably, the mass ratio of nicotine to flavoring is (1-2):(20-40);

[0015] The mass ratio of nicotine to atomizing solvent is (1-2):(30-100).

[0016] Preferably, the flavoring includes at least one of tobacco flavoring, fruit flavoring, compound tobacco flavoring, and mint flavoring.

[0017] Preferably, the fruit flavoring includes at least one of blueberry flavoring, strawberry flavoring, and watermelon flavoring;

[0018] The compound tobacco flavoring includes at least one of strawberry tobacco flavoring, mint tobacco flavoring, and creamy tobacco flavoring.

[0019] Optionally, the watermelon flavoring is watermelon ice flavoring.

[0020] Preferably, the atomizing solvent is at least one selected from propylene glycol, glycerol, water, ethanol, triacetyl ester, and sorbitol;

[0021] Preferably, the atomizing solvent is propylene glycol, glycerol, or ethanol.

[0022] Preferably, the mass ratio of propylene glycol, glycerol and ethanol is (5-50):(10-50):(1-5).

[0023] Preferably, the nicotine liquid preparation contains 10-20 mg / g of nicotine.

[0024] The nicotine liquid formulation described in this invention is used to enhance satisfaction, and further, to enhance consumer satisfaction.

[0025] This invention provides a method for preparing the above-described nicotine liquid formulation, comprising the following steps:

[0026] The mixture of nicotine, cytisine, lactic acid, and atomizing solvent is heated and stirred until homogeneous.

[0027] Preferably, the method for preparing the nicotine liquid formulation further includes the step of adding flavoring.

[0028] Preferably, the method for preparing the nicotine liquid formulation further includes the step of adding a second organic acid.

[0029] The present invention does not specifically limit the stirring method. Optionally, the stirring method can be selected from mechanical stirring, mechanical oscillation or ultrasonic oscillation.

[0030] The present invention also provides the above-described nicotine liquid formulation or the application of the above-described nicotine liquid formulation in an atomizing device.

[0031] Preferably, the atomizing device is an electronic atomizing device.

[0032] The beneficial effects of this invention are:

[0033] The nicotine liquid formulation provided by this invention comprises nicotine, cytisine, and lactic acid. Cytisine has a high affinity for the α4β2 subtype of nicotinic acetylcholine receptors and is a low-nonspecific partial agonist. However, cytisine has poor penetration into the human brain and a weak peripheral effect on the cardiovascular system. This invention, through the combination of nicotine and cytisine, helps to modify the penetration properties of cytisine into the human brain. Simultaneously, by combining specific lactic acid with the high binding capacity of cytisine to receptors, it can further increase the peak blood concentration of nicotine while reducing the time to peak concentration. The synergistic effect of these three factors helps to enhance user satisfaction. Attached Figure Description

[0034] To more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0035] Figure 1 Normalized heart rate graphs of Examples 8 and 13 and Comparative Examples 5 and 6 of this invention;

[0036] Figure 2 The mean normalized heart rate graphs of Examples 8 and 13 and Comparative Examples 5 and 6 of this invention. Detailed Implementation

[0037] The core ingredient in nicotine liquid formulations is nicotine. When the atomizer is heated, the nicotine in the liquid formulation is atomized into an aerosol, which is then inhaled. Part of this aerosol is transported to the throat, where acetylcholine receptors are located. Nicotine deposited in the throat binds to these receptors, creating the throat hit. The remaining aerosol enters the lungs and participates in pulmonary venous circulation, then enters arterial circulation, rapidly transporting nicotine to the brain. There, it binds to acetylcholine receptors, promoting the release of the neurotransmitter dopamine. Dopamine release is a pleasurable experience that enhances the brain's reward function, producing a feeling of euphoria and satisfaction. Satisfaction is a comprehensive evaluation of both euphoria and throat hit. A suitable throat hit contributes to an enhanced overall satisfaction, but an excessively strong throat hit can cause excessive irritation and physiological discomfort, thus reducing satisfaction. To prevent nicotine abuse and protect public health and safety, various countries strictly regulate nicotine in e-cigarette products, generally limiting nicotine content to 20mg / g or below. However, lower nicotine levels lead to a decrease in satisfaction. To enhance consumer satisfaction, current technologies typically use nicotine salts, with benzoic acid being a commonly used organic acid in this process. The combination of nicotine and benzoic acid is used to increase satisfaction, but the effect remains limited.

[0038] Cyathine was first isolated from *Chamaedorea elegans* in 1865 and used as a respiratory stimulant in Europe. Since 1964, cyathine has been shown to have a high affinity for the α4β2 subtype of acetylcholine receptors and is a low-nonspecific partial agonist. However, cyathine has low blood-brain barrier penetration (cyathine logP = -0.94, nicotine logP = 1.2), resulting in poor penetration into the human brain, but it has a high binding affinity to receptors in the brain; the dissociation constant (KD) of cyathine nAChRs in the rat brain is less than 1 nM.

[0039] The inventors unexpectedly discovered that combining nicotine with cytisine alters the penetrability of cytisine to the human brain. Combined with specific lactic acid and the high binding capacity of cytisine to receptors, this can further increase the peak blood concentration of nicotine while reducing the time to peak concentration. The synergistic effect of these three factors enhances user satisfaction, achieving or even surpassing the satisfaction of commercially available products with benzoic acid as the organic acid and a nicotine content of 30%.

[0040] This invention provides a nicotine liquid formulation, the raw material components of which include nicotine, cytisine, and lactic acid. The synergistic effect of the combination of nicotine, cytisine, and lactic acid helps to enhance user satisfaction.

[0041] In an optional embodiment, the mass ratio of nicotine to cytisine is 1:(0.05-2). For example, selectable mass ratios of nicotine to cytisine include 1:0.05, 1:0.1, 1:0.2, 1:0.3, 1:0.4, 1:0.5, 1:0.7, 1:0.9, 1:1, 1:1.1, 1:1.2, 1:1.4, 1:1.5, 1:1.7, 1:1.8, and 1:2.0. The inventors have found that when the amount of cytisine used is too small, its effect on enhancing satisfaction is limited; however, when the amount of cytisine used is too large, the aroma will interact with the characteristic aromas of different flavored e-cigarettes, resulting in a deterioration in taste.

[0042] In an optional embodiment, the total molar ratio of nicotine and cytisine to lactic acid is 1:(0.01-3.1). For example, selectable molar ratios of nicotine and cytisine to lactic acid include 1:0.01, 1:0.05, 1:0.1, 1:0.3, 1:0.5, 1:1, 1:1.2, 1:1.5, 1:1.8, 1:2.0, 1:2.3, 1:2.5, 1:2.7, 1:3.0, and 1:3.1. After adding the synergistic substance cytisine, the inventors further discovered that the molar ratio of the total molar ratio of nicotine and cytisine to lactic acid affects the feeling of satisfaction. The chemical structure of nicotine includes a six-membered pyridine ring and a five-membered pyrrole ring, and has two nitrogen atoms. Cytisine also contains two nitrogen atoms and has similar acid-base properties to nicotine. Changing the total molar ratio of nicotine and cytisine to lactic acid alters the acid-base environment of the throat, creating a throat hit during aerosol entry into the lungs. The inventors discovered that both the euphoria and throat hit during inhalation change when the molar ratio of nicotine and cytisine to lactic acid is 1:(0.01-3). When the molar ratio of lactic acid to the total amount of nicotine and cytisine is low (<0.01:1), the throat hit is strong, but nicotine and cytisine are primarily deposited in the throat, resulting in low lung entry efficiency, a strong pungent sensation in the smoke, and a low overall satisfaction. When the molar ratio of lactic acid to the total amount of nicotine and cytisine is high (>3:1), there is no throat hit, but the overall satisfaction is also weak.

[0043] In an optional embodiment, the raw material components of the nicotine liquid formulation further include a second organic acid. In this invention, the second organic acid is defined as an organic acid containing carboxyl groups, which can contain 1-3 carboxyl groups. The acidity of the organic compound is measured by its pKa value, which reflects the binding ability of different organic acids with nicotine and cytisine. Nicotine salts are formed by adding appropriate organic acids. Appropriate organic acids can be carboxylic acids. Examples of organic carboxylic acids include monocarboxylic acids, dicarboxylic acids (organic acids containing two carboxyl groups), aryl carboxylic acids (e.g., benzoic acid), hydroxycarboxylic acids, heterocyclic carboxylic acids, terpene acids, and sugar acids; for example, pectic acid, amino acids, cyclic fatty acids, aliphatic carboxylic acids, ketocarboxylic acids, and the like. In some nicotine liquid formulations provided by this invention, the second organic acid used is selected from at least one of salicylic acid, citric acid, malic acid, benzoic acid, levulinic acid, tartaric acid, and succinic acid; preferably, the second organic acid is selected from at least one of salicylic acid, citric acid, and malic acid. More preferably, the molar ratio of lactic acid to the second organic acid is 1:(0.2-2.1). For example, the molar ratio of lactic acid to the second organic acid can be selected as 1:0.2, 1:0.3, 1:0.5, 1:1, 1:1.2, 1:1.5, 1:1.8, 1:2.0, or 1:2.1.

[0044] This invention further ensures user satisfaction by adding specific organic acids to the raw material components.

[0045] In an optional embodiment, the raw material components of the nicotine liquid formulation further include flavoring and / or atomizing solvent. The flavoring can be a conventional flavoring material in the art, for example, it can be formulated from single flavoring raw materials or multiple extracts. This includes, but is not limited to, tobacco flavoring, fruit flavoring, compound tobacco flavoring, and mint flavoring. Further, the fruit flavoring includes at least one of blueberry flavoring, strawberry flavoring, and watermelon flavoring; the compound tobacco flavoring includes at least one of strawberry tobacco flavoring, mint tobacco flavoring, and creamy tobacco flavoring. Optionally, the mass ratio of nicotine to flavoring is (1-2):

[0046] (20-40), for example, the mass ratio of nicotine to flavoring can be selected as 1:20, 1:22, 1:24, 1:26, 1:28, 1:32, 1:34, 1:35, 1:37, 1:40, 2:20, 2:22, 2:24, 2:26, ​​2:28, 2:32, 2:34, 2:35, 2:37, 2:40.

[0047] In an optional embodiment, the atomizing solvent may be a conventional atomizing solvent in the art, including but not limited to propylene glycol and glycerol. Optionally, the atomizing solvent is at least one selected from propylene glycol, glycerol, water, ethanol, triacetin, and sorbitol; preferably, the atomizing solvent is propylene glycol, glycerol, and ethanol. Optionally, the mass ratio of nicotine to the atomizing solvent is (1-2):(30-100). For example, selectable mass ratios of nicotine to the atomizing solvent are 1:30, 1:40, 1:50, 1:60, 1:70, 1:80, 1:90, 1:100, 2:30, 2:40, 2:50, 2:60, 2:70, 2:80, 2:90, and 2:100. The mass ratio of propylene glycol, glycerol, and ethanol is (5-50):(10-50):(1-5). Alternatively, the mass ratio of propylene glycol, glycerol, and ethanol can be 5:10:1, 5:25:1, 5:50:1, 5:10:2, 5:10:5, 10:10:1, 10:15:1, 10:25:1, 10:50:1, 10:10:2, or 10:1. The atomizing solvents in this invention can better dissolve the raw material components, effectively improve the atomization efficiency of nicotine, and increase satisfaction. The possible ratios are: 0:5, 22:15:1, 22:25:1, 22:50:1, 22:10:5, 30:10:1, 30:15:1, 30:25:1, 30:50:1, 30:50:2, 30:50:5, 40:10:1, 40:15:1, 40:50:1, 40:15:5, 50:10:1, 50:30:4, 50:50:5.

[0048] In an optional embodiment, the atomizing solvent contains 0-15% water, 0-15% ethanol, 0-10% triacetin, 0-10% sorbitol, 10-80% propylene glycol, and 20-50% glycerol.

[0049] In one optional embodiment, the nicotine liquid preparation contains nicotine at a content of 10-20 mg / g, and optionally, the nicotine liquid preparation contains nicotine at contents of 10 mg / g, 11 mg / g, 12 mg / g, 13 mg / g, 14 mg / g, 15 mg / g, 17 mg / g, or 20 mg / g.

[0050] The present invention also provides a method for preparing the above-mentioned nicotine liquid preparation, comprising the following steps: mixing nicotine, cytisine, lactic acid and atomizing solvent, and then heating and stirring until uniform.

[0051] In an optional embodiment, the step of adding a second organic acid is also included.

[0052] In an optional implementation, a step of adding fragrance is also included.

[0053] This invention does not specifically limit the heating and stirring temperature and time, as long as the raw materials can be dissolved. Optionally, the dissolution temperature should not exceed 100℃. Optionally, the heating and stirring temperature is 40-65℃, and the heating and stirring time is 20-30 minutes. In this invention, all raw materials can be mixed and then heated to dissolve, or some raw materials can be mixed and dissolved first, and then the remaining raw materials can be mixed and dissolved. In an optional embodiment, the preparation method of the nicotine liquid preparation includes the following steps: mixing nicotine, cytisine, propylene glycol, and ethanol, heating at 40-65℃ for 20-30 minutes until the cytisine is completely dissolved, adding fragrance and glycerol after complete dissolution, and stirring at 10-35℃ for 5-40 minutes to mix evenly to obtain the nicotine liquid preparation.

[0054] The present invention also provides an application of the above-described nicotine liquid formulation or the nicotine liquid formulation prepared by the above-described preparation method in an atomizing device. Optionally, the atomizing device is an electronic atomizing device.

[0055] The following embodiments are provided to better understand the present invention and are not limited to the preferred embodiments described. They do not constitute a limitation on the content and scope of protection of the present invention. Any product that is the same as or similar to the present invention, derived by any person under the guidance of the present invention or by combining the features of the present invention with other prior art, falls within the protection scope of the present invention.

[0056] For experiments not specifically described in the examples, the procedures or conditions should be followed according to the conventional experimental procedures described in the literature in this field. Reagents or instruments whose manufacturers are not specified are all commercially available conventional reagent products.

[0057] Example 1

[0058] This embodiment provides a method for preparing a nicotine liquid formulation, including the following steps:

[0059] Mix 1.80g nicotine, 0.09g cytisine, 1.04g lactic acid, and 28.97g propylene glycol, add 2g ethanol to aid dissolution, and heat at 50°C for 20 minutes. After the cytisine is completely dissolved, add 16.1g watermelon ice flavoring and 50g glycerol, and stir at room temperature for 20 minutes to mix evenly, thus obtaining the nicotine liquid preparation.

[0060] Example 2

[0061] This embodiment provides a method for preparing a nicotine liquid formulation, including the following steps:

[0062] Mix 1.80g nicotine, 3.6g cytisine, 2.7g lactic acid, and 23.8g propylene glycol, add 2g ethanol to aid dissolution, and heat at 50°C for 20 minutes. After the cytisine is completely dissolved, add 16.1g watermelon ice flavoring and 50g glycerol, and stir at room temperature for 20 minutes to mix evenly, thus obtaining the nicotine liquid preparation.

[0063] Example 3

[0064] This embodiment provides a method for preparing a nicotine liquid formulation, including the following steps:

[0065] Mix 1.80g nicotine, 0.9g cytisine, 0.014g lactic acid, and 29.186g propylene glycol, add 2g ethanol to aid dissolution, and heat at 50°C for 20 minutes. After the cytisine is completely dissolved, add 16.1g watermelon ice flavoring and 50g glycerol, and stir at room temperature for 20 minutes to mix evenly, thus obtaining the nicotine liquid preparation.

[0066] Example 4

[0067] This embodiment provides a method for preparing a nicotine liquid formulation, including the following steps:

[0068] Mix 1.80g nicotine, 0.9g cytisine, 4.29g lactic acid, and 24.91g propylene glycol, add 2g ethanol to aid dissolution, and heat at 50°C for 20 minutes. After the cytisine is completely dissolved, add 16.1g watermelon ice flavoring and 50g glycerol, and stir at room temperature for 20 minutes to mix evenly, thus obtaining the nicotine liquid preparation.

[0069] Example 5

[0070] This embodiment provides a method for preparing a nicotine liquid formulation, including the following steps:

[0071] Mix 1.00g nicotine, 0.9g cytisine, 0.98g lactic acid, and 29.02g propylene glycol, add 2g ethanol to aid dissolution, and heat at 50°C for 20 minutes. After the cytisine is completely dissolved, add 16.1g watermelon ice flavoring and 50g glycerol, and stir at room temperature for 20 minutes to mix evenly, thus obtaining the nicotine liquid preparation.

[0072] Example 6

[0073] This embodiment provides a method for preparing a nicotine liquid formulation, including the following steps:

[0074] Mix 2g nicotine, 0.9g cytisine, 0.98g lactic acid, and 28.02g propylene glycol, add 2g ethanol to aid dissolution, and heat at 50°C for 20 minutes. After the cytisine is completely dissolved, add 16.1g watermelon ice flavoring and 50g glycerol, and stir at room temperature for 20 minutes to mix evenly, thus obtaining the nicotine liquid preparation.

[0075] Example 7

[0076] This embodiment provides a method for preparing a nicotine liquid formulation, including the following steps:

[0077] Mix 1.8g nicotine, 0.9g cytisine, 1.43g lactic acid, and 27.77g propylene glycol, add 2g ethanol to aid dissolution, and heat at 50°C for 20 minutes. After the cytisine is completely dissolved, add 16.1g watermelon ice flavoring and 50g glycerol, and stir at room temperature for 20 minutes to mix evenly, thus obtaining the nicotine liquid preparation.

[0078] Example 8

[0079] This embodiment provides a method for preparing a nicotine liquid formulation, including the following steps:

[0080] 1.8g nicotine, 0.45g cytisine, 1.21g lactic acid, and 28.44g propylene glycol were mixed, and 2g ethanol was added to aid dissolution. The mixture was heated at 50°C for 20 minutes. After the cytisine was completely dissolved, 16.1g watermelon ice flavoring and 50g glycerol were added, and the mixture was stirred at room temperature for 20 minutes to obtain a homogeneous nicotine liquid formulation. Example 9

[0081] This embodiment provides a method for preparing a nicotine liquid formulation, including the following steps:

[0082] Mix 1.8g nicotine, 0.225g cytisine, 1.11g lactic acid, and 28.765g propylene glycol, add 2g ethanol to aid dissolution, and heat at 50°C for 20 minutes. After the cytisine is completely dissolved, add 16.1g watermelon ice flavoring and 50g glycerol, and stir at room temperature for 20 minutes to mix evenly, thus obtaining the nicotine liquid preparation.

[0083] Example 10

[0084] This embodiment provides a method for preparing a nicotine liquid formulation, including the following steps:

[0085] Mix 1.8g nicotine, 0.9g cytisine, 1.19g lactic acid, 0.36g salicylic acid, and 27.65g propylene glycol, add 2g ethanol to aid dissolution, and heat at 50°C for 20 minutes. After the cytisine and salicylic acid are completely dissolved, add 16.1g watermelon ice flavoring and 50g glycerol, and stir at room temperature for 20 minutes to mix evenly, thus obtaining the nicotine liquid formulation.

[0086] Example 11

[0087] This embodiment provides a method for preparing a nicotine liquid formulation, including the following steps:

[0088] Mix 1.8g nicotine, 0.9g cytisine, 0.47g lactic acid, 1.46g salicylic acid, and 27.27g propylene glycol, add 2g ethanol to aid dissolution, and heat at 50°C for 20 minutes. After the cytisine and salicylic acid are completely dissolved, add 16.1g watermelon ice flavoring and 50g glycerol, and stir at room temperature for 20 minutes to mix evenly, thus obtaining the nicotine liquid formulation.

[0089] Example 12

[0090] This embodiment provides a method for preparing a nicotine liquid formulation, including the following steps:

[0091] Mix 1.8g nicotine, 0.9g cytisine, 0.53g lactic acid, 0.27g salicylic acid, and 28.4g propylene glycol, add 2g ethanol to aid dissolution, and heat at 50°C for 20 minutes. After the cytisine and salicylic acid are completely dissolved, add 16.1g watermelon ice flavoring and 50g glycerol, and stir at room temperature for 20 minutes to mix evenly, thus obtaining the nicotine liquid preparation.

[0092] Example 13

[0093] This embodiment provides a method for preparing a nicotine liquid formulation, including the following steps:

[0094] Mix 1.8g nicotine, 0.9g cytisine, 0.32g lactic acid, 0.16g salicylic acid, and 28.72g propylene glycol, add 2g ethanol to aid dissolution, and heat at 50°C for 20 minutes. After the cytisine and salicylic acid are completely dissolved, add 16.1g watermelon ice flavoring and 50g glycerol, and stir at room temperature for 20 minutes to mix evenly, thus obtaining the nicotine liquid preparation.

[0095] Example 14

[0096] This embodiment provides a method for preparing a nicotine liquid formulation, including the following steps:

[0097] Mix 1.8g nicotine, 0.9g cytisine, 0.21g lactic acid, 0.1g salicylic acid, and 38.89g propylene glycol, add 2g ethanol to aid dissolution, and heat at 50°C for 20 minutes. After the cytisine and salicylic acid are completely dissolved, add 16.1g watermelon ice flavoring and 40g glycerol, and stir at room temperature for 20 minutes to mix evenly, thus obtaining the nicotine liquid preparation.

[0098] Example 15

[0099] This embodiment provides a method for preparing a nicotine liquid formulation, including the following steps:

[0100] Mix 1.8g nicotine, 0.9g cytisine, 1.07g lactic acid, 0.76g citric acid, and 27.37g propylene glycol, add 2g ethanol to aid dissolution, and heat at 50°C for 20 minutes. After the cytisine and citric acid are completely dissolved, add 16.1g watermelon ice flavoring and 50g glycerol, and stir at room temperature for 20 minutes to mix evenly, thus obtaining the nicotine liquid preparation.

[0101] Example 16

[0102] This embodiment provides a method for preparing a nicotine liquid formulation, including the following steps:

[0103] Mix 1.8g nicotine, 0.9g cytisine, 1.07g lactic acid, 0.53g malic acid, and 27.6g propylene glycol, add 2g ethanol to aid dissolution, and heat at 50°C for 20 minutes. After the cytisine and malic acid are completely dissolved, add 16.1g watermelon ice flavoring and 50g glycerol, and stir at room temperature for 20 minutes to mix evenly, thus obtaining the nicotine liquid preparation.

[0104] Example 17

[0105] This embodiment provides a method for preparing a nicotine liquid formulation, including the following steps:

[0106] Mix 1.8g nicotine, 0.9g cytisine, 1.07g lactic acid, 0.55g salicylic acid, and 47.58g propylene glycol, add 2g ethanol to aid dissolution, and heat at 50°C for 20 minutes. After the cytisine and salicylic acid are completely dissolved, add 16.1g watermelon ice flavoring and 30g glycerol, and stir at room temperature for 20 minutes to mix evenly, thus obtaining the nicotine liquid formulation.

[0107] Comparative Example 1

[0108] This comparative example provides a method for preparing a nicotine liquid formulation, comprising the following steps:

[0109] Mix 2.93g of nicotine and 28.97g of propylene glycol, add 2g of ethanol to aid dissolution, and heat at 50°C for 20 minutes. Add 16.1g of watermelon ice flavoring and 50g of glycerol, and stir at room temperature for 20 minutes to mix evenly, to obtain the nicotine liquid formulation.

[0110] Comparative Example 2

[0111] This comparative example provides a method for preparing a liquid formulation, comprising the following steps:

[0112] Mix 2.93g of cytisine and 28.97g of propylene glycol, add 2g of ethanol to aid dissolution, and heat at 50°C for 20 minutes. Add 16.1g of watermelon ice flavoring and 50g of glycerol, and stir at room temperature for 20 minutes to mix evenly, to obtain the liquid formulation.

[0113] Comparative Example 3

[0114] This comparative example provides a method for preparing a liquid formulation, comprising the following steps:

[0115] Mix 2.93g of lactic acid and 28.97g of propylene glycol, add 2g of ethanol to aid dissolution, and heat at 50°C for 20 minutes. Add 16.1g of watermelon ice flavoring and 50g of glycerol, and stir at room temperature for 20 minutes to mix evenly, to obtain the liquid formulation.

[0116] Comparative Example 4

[0117] This comparative example provides a method for preparing a liquid formulation, comprising the following steps:

[0118] Mix 2g of ethanol and 31.9g of propylene glycol, add 2g of ethanol to aid dissolution, and heat at 50°C for 20 minutes. Add 16.1g of watermelon ice flavoring and 50g of glycerol, and stir at room temperature for 20 minutes to mix evenly, to obtain the liquid formulation.

[0119] Comparative Example 5

[0120] This comparative example provides a method for preparing a nicotine liquid formulation, comprising the following steps:

[0121] Mix 1.8g nicotine and 1.36g benzoic acid and dissolve them in 24.84g propylene glycol. Add 2g ethanol to aid dissolution and heat at 50°C for 20 minutes until the benzoic acid is completely dissolved. After complete dissolution, add 20g tobacco flavoring and 50g glycerol, and stir at room temperature for 20 minutes to mix evenly, thus obtaining the nicotine liquid formulation.

[0122] Comparative Example 6

[0123] This comparative example provides a method for preparing a nicotine liquid formulation, comprising the following steps:

[0124] Dissolve 3g of nicotine and 2.26g of benzoic acid in 22.74g of propylene glycol, add 2g of ethanol to aid dissolution, and heat at 50°C for 20 minutes until the benzoic acid is completely dissolved. After complete dissolution, add 20g of tobacco flavoring and 50g of glycerol, and stir at room temperature for 20 minutes to mix evenly, to obtain the nicotine liquid preparation.

[0125] Test Example 1

[0126] This invention employs a subjective vaping method to score various vaping indicators for Examples 1-17 and Comparative Examples 1-6. The vaping team consisted of 15 people, all with over 3 years of experience vaping traditional cigarettes and / or electronic atomizing devices, and all underwent nicotine withdrawal for 10 hours prior to the experiment. To eliminate the possibility that evaluators knew the specific proportions of different samples in advance, different examples and comparative examples were randomly coded with 3-digit numbers. Evaluators began testing at 10:00 AM and 3:00 PM, vaping one sample every half day. The device used was the RELX5 generation e-cigarette. The specific vaping process was as follows: 3 puffs, a brief pause of smoke in the mouth, followed by swallowing the smoke into the lungs, and then exhaling through the nose. A total of 3 puffs were taken, with a 30-second interval between each puff. After vaping, evaluators scored the effects of this vaping method on the head-throat sensation, throat hit, and satisfaction based on their physiological sensations over 15 minutes. After the satisfaction score was completed, the evaluator took three more puffs and evaluated the aroma. The specific puffing method was as follows: inhale for 3 seconds, hold the smoke briefly in the mouth, and then exhale through the nose, scoring the aroma. The scoring was based on the evaluation indicators in Table 1, and the test results are shown in Table 2 (the score is the average score).

[0127] Table 1 Evaluation Indicators

[0128]

[0129] Table 2. Smoking Scoring Data

[0130]

[0131]

[0132] Test Example 2

[0133] Heart rate tests were conducted during the smoking process for Examples 8 and 13, and Comparative Examples 5 and 6. The method was as follows: Participants underwent nicotine withdrawal the night before smoking, and heart rate tests were performed at 9:00 AM on the day of smoking. Before smoking, a heart rate monitoring device (Lepu Xin'anbao ER1) was worn, and real-time heart rate changes were monitored throughout the smoking process. After the device was properly worn and adjusted, a 2-minute baseline heart rate test was performed. Once the heart rate stabilized, heart rate monitoring during smoking began. Using the RELX5 nicotine mod (with different examples and comparative samples), five puffs of smoke were taken (each puff lasted 3 seconds, with a 27-second interval between puffs), for a total smoking time of approximately 2.5 minutes. The time of inhalation for each puff was recorded. After smoking, heart rate changes were monitored for another 1 minute, and then the experiment ended. After completing one sample, participants were required to abstain from nicotine for 2 hours before the next sample's heart rate test was conducted. The test results are as follows: Figure 1 and 2 As shown, the normalized heart rate is the ratio of the real-time monitored heart rate during the inhalation process to the average baseline heart rate over the aforementioned 2 minutes, while the average normalized heart rate is the ratio of the average monitored heart rate during the inhalation process to the average baseline heart rate. The data shows that, within the effective inhalation time range, Examples 8 and 13 have a higher average normalized heart rate than Comparative Examples 5 and 6.

[0134] In summary, this invention utilizes a compound of nicotine, cytisine, and lactic acid. The synergistic effect of these three compounds significantly enhances user satisfaction. Comparative Examples 1-3 demonstrate that adding only equal amounts of nicotine, cytisine, or lactic acid results in a substantial decrease in user satisfaction compared to adding all three. This indicates a synergistic effect between nicotine, cytisine, and lactic acid. The product described in Comparative Example 6 is a commercially available product. Compared to commercially available products with high nicotine content, this invention, through the synergistic effect of nicotine, cytisine, and lactic acid, significantly reduces nicotine content while achieving user satisfaction levels that essentially match or even exceed those of commercially available products.

[0135] Obviously, the above embodiments are merely illustrative examples for clear explanation and are not intended to limit the implementation. Those skilled in the art will recognize that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively list all possible implementations here. However, obvious variations or modifications derived therefrom are still within the scope of protection of this invention.

Claims

1. A nicotine liquid formulation characterised in that, The raw material components of the nicotine liquid preparation include nicotine, cytisine, and lactic acid; The mass ratio of nicotine to cytisine is 1:(0.05-2). The total molar amount of nicotine and cytisine is used in a molar ratio of 1:(0.01-3.1) to lactic acid.

2. The nicotine liquid formulation according to claim 1, characterized in that, The raw material components of the nicotine liquid preparation also include a second organic acid, which is selected from at least one of salicylic acid, citric acid, malic acid, benzoic acid, acetylpropionic acid, tartaric acid, and succinic acid.

3. The nicotine liquid formulation according to claim 2, characterised in that, The second organic acid is selected from at least one of salicylic acid, citric acid, and malic acid.

4. The nicotine liquid formulation according to claim 2, characterized in that, The molar ratio of lactic acid to the second organic acid is 1:(0.2-2.1).

5. The nicotine liquid formulation according to any one of claims 1 to 4, wherein, The raw material components of the nicotine liquid formulation also include flavorings and / or atomizing solvents.

6. The nicotine liquid formulation according to claim 5, characterised in that, The mass ratio of nicotine to flavoring is (1-2):(20-40); The mass ratio of nicotine to atomizing solvent is (1-2):(30-100).

7. The nicotine liquid formulation according to any one of claim 5, wherein, The flavorings include at least one of tobacco flavorings, fruit flavorings, compound tobacco flavorings, and mint flavorings.

8. The nicotine liquid formulation according to claim 7, characterised in that, The fruit flavoring includes at least one of blueberry flavoring, strawberry flavoring, and watermelon flavoring; The compound tobacco flavoring includes at least one of strawberry tobacco flavoring, mint tobacco flavoring, and creamy tobacco flavoring.

9. The nicotine liquid formulation of claim 5, wherein, The atomizing solvent is at least one of propylene glycol, glycerol, water, ethanol, triacetyl ester, and sorbitol.

10. The nicotine liquid formulation according to claim 9, characterised in that, The atomizing solvent is propylene glycol, glycerol, and ethanol.

11. The nicotine liquid formulation according to claim 10, characterized in that, The mass ratio of propylene glycol, glycerol and ethanol is (5-50):(10-50):(1-5).

12. The nicotine liquid formulation according to claim 1, characterized in that, The nicotine liquid preparation contains 10-20 mg / g of nicotine.

13. A method for preparing a nicotine liquid formulation according to any one of claims 1-12, characterized in that, Includes the following steps: The mixture of nicotine, cytisine, lactic acid, and atomizing solvent is heated and stirred until homogeneous.

14. The method for preparing the nicotine liquid formulation according to claim 13, characterized in that, It also includes the step of adding flavoring.

15. The method for preparing the nicotine liquid formulation according to claim 13 or 14, characterized in that, It also includes the step of adding a second organic acid.

16. The use of the nicotine liquid formulation according to any one of claims 1-12 or the nicotine liquid formulation according to any one of claims 13-15 in a nebulizing device.

17. The application according to claim 16, characterized in that, The atomizing device is an electronic atomizing device.

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