6-methylnicotinium salt formulations, methods of making the same, oral products, atomizing substrates, and electronic atomizing devices

Abstract

The application discloses a 6-methyl-nicotine salt preparation and a preparation method, a mouth-containing product, an atomization substrate and an electronic atomization device thereof. The preparation method comprises the following steps: mixing 6-methyl-nicotine and an alicyclic hydrocarbon carboxylic acid, and reacting to obtain the 6-methyl-nicotine salt preparation at a reaction temperature of 30 DEG C to 80 DEG C, wherein the boiling point of the alicyclic hydrocarbon carboxylic acid is 200 DEG C to 265 DEG C. In the application, the 6-methyl-nicotine salt preparation is prepared by using the alicyclic hydrocarbon carboxylic acid and the 6-methyl-nicotine, and has the advantages of good taste, good safety and low corrosion.

Description

Technical Field

[0001] This application relates to the field of nicotine derivative preparation technology, and in particular to a 6-methylnicotine salt preparation and its preparation method, oral product, atomizing matrix and electronic atomizing device. Background Technology

[0002] Electronic atomizing devices are inhalation devices that mimic traditional tobacco products. They do not involve combustion; instead, they produce vapor by electrically heating a vaporizing matrix. On one hand, the usage of electronic atomizing devices is similar to that of traditional tobacco products, and they can achieve a similar level of satisfaction. On the other hand, by atomizing the matrix without combustion, electronic atomizing devices reduce the harm to users from harmful combustion byproducts such as tar, carbon monoxide, carbon dioxide, and acrolein. Therefore, electronic atomizing devices are gaining popularity. Nicotine is the main bioactive substance in the vaporizing matrix of electronic atomizing devices, which can alleviate cravings, provide a throat hit, and provide satisfaction. The finished vaporizing matrix primarily contains nicotine salts, which reduce the irritation of nicotine.

[0003] Currently, benzoic acid is commonly chosen to react with nicotine. However, benzoic acid is toxic to the lungs and has potential carcinogenic risks. Furthermore, the resulting nicotine salts have a strong smoky odor and oxidize and discolor rapidly. Lactic acid is also sometimes used to react with nicotine. This method produces nicotine salts with a good taste, but it has a significant corrosive effect on the heating coil, leading to an increase in heavy metal content in the smoke. Using single or compound acids such as malic acid, citric acid, or tartaric acid to react with nicotine often results in coil clogging and airway blockage during atomization.

[0004] In conclusion, there is a need to develop a better-performing and more promising alternative to nicotine salts. Summary of the Invention

[0005] The purpose of this application is to provide a 6-methylnicotine salt formulation, its preparation method and application, an atomizing matrix, and an electronic atomizing device.

[0006] The following technical solution is adopted in this application:

[0007] This application discloses a method for preparing a 6-methylnicotine salt preparation, comprising: mixing 6-methylnicotine and an alicyclic carboxylic acid, and reacting them at a reaction temperature of 30°C to 80°C to obtain the 6-methylnicotine salt preparation, wherein the boiling point of the alicyclic carboxylic acid is between 200°C and 265°C.

[0008] In one implementation of this application, the alicyclic carboxylic acid includes at least one of cyclopentyl, cyclohexyl, and cycloheptyl.

[0009] In one implementation of this application, the alicyclic carboxylic acid includes at least one of cyclohexanecarboxylic acid, cyclohexanoic acid, 2-methylcyclohexanecarboxylic acid, 3,4-dimethylcyclohexanecarboxylic acid, cyclopentanoic acid, and 1,3-cyclohexanoic acid.

[0010] In one implementation of this application, the molar ratio of the 6-methylnicotine to the carboxyl group in the alicyclic carboxylic acid is 1:0.5-2.

[0011] One implementation of this application includes: mixing the 6-methylnicotine and the alicyclic carboxylic acid in an organic solvent to react and obtain the 6-methylnicotine salt formulation; the organic solvent includes at least one of glycerol and propylene glycol.

[0012] This application discloses a 6-methylnicotine salt preparation containing a 6-methylnicotine alicyclic hydrocarbon carboxylate, wherein the alicyclic hydrocarbon carboxylate corresponding to the alicyclic hydrocarbon carboxyl group in the 6-methylnicotine alicyclic hydrocarbon carboxylate has a boiling point of 200℃ to 265℃, or the 6-methylnicotine salt preparation is prepared by the preparation method of the 6-methylnicotine salt preparation disclosed in this application.

[0013] This application discloses a mouthpiece containing the 6-methylnicotine salt formulation.

[0014] This application discloses an atomizing matrix containing the 6-methylnicotine salt formulation.

[0015] In one implementation of this application, the content of the 6-methylnicotine salt preparation in the atomizing matrix is ​​1 mg / g to 10 mg / g.

[0016] This application discloses an electronic atomizing device, wherein the electronic atomizing device contains the atomizing matrix.

[0017] The beneficial effects of this application are as follows:

[0018] In this application, alicyclic carboxylic acids and 6-methylnicotine are used to prepare a 6-methylnicotine salt formulation. The boiling point of the alicyclic carboxylic acid is close to that of 6-methylnicotine, resulting in good compatibility. Furthermore, the alicyclic carboxylic acid molecule does not contain a benzene ring, thus exhibiting low toxicity and safer application. Additionally, the alicyclic carboxylic acid has low acidity, minimizing corrosion to the heating wire of the atomizing device. In summary, the 6-methylnicotine salt formulation prepared using alicyclic carboxylic acids and 6-methylnicotine in this application offers advantages such as good taste, excellent safety, and low corrosiveness. Attached Figure Description

[0019] Figure 1This is a molecular structure diagram of 6-methylnicotine and six alicyclic carboxylic acids involved in this application.

[0020] Figure 2 This is a schematic diagram of the cytotoxicity test results of the 6-methylnicotine cyclohexane salt involved in this application.

[0021] Figure 3 This is a schematic diagram of the cytotoxicity test results of the 6-methylnicotine cyclohexanoate involved in this application.

[0022] Figure 4 This is a schematic diagram of the cytotoxicity test results of the 6-methylnicotine 2-methylcyclohexane carboxylate involved in this application.

[0023] Figure 5 This is a schematic diagram of the cytotoxicity test results of 6-methylnicotine 3,4-dimethylcyclohexane carboxylate involved in this application.

[0024] Figure 6 This is a schematic diagram of the cytotoxicity test results of 6-methylnicotine 1,3-cyclohexanediol involved in this application.

[0025] Figure 7 This is a schematic diagram of the cytotoxicity test results of the 6-methylnicotine benzoate involved in this application. Detailed Implementation

[0026] The present invention will now be described in further detail with reference to specific embodiments and accompanying drawings. In the following embodiments, many details are described to facilitate a better understanding of the present application. However, those skilled in the art will readily recognize that some features may be omitted in different situations, or may be replaced by other materials or methods. In some cases, certain operations related to the present application are not shown or described in the specification. This is to avoid obscuring the core parts of the present application with excessive description. For those skilled in the art, detailed description of these related operations is not necessary; they can fully understand the related operations based on the description in the specification and general technical knowledge in the art.

[0027] Furthermore, the features, operations, or characteristics described in the specification can be combined in any suitable manner to form various embodiments. At the same time, the steps or actions in the method description can be rearranged or adjusted in a manner obvious to those skilled in the art. Therefore, the various orders in the specification and drawings are only for the clear description of a particular embodiment and do not imply a necessary order, unless otherwise stated that a particular order must be followed.

[0028] The serial numbers assigned to components in this article, such as "first" and "second", are used only to distinguish the objects being described and have no sequential or technical meaning.

[0029] Nicotine is the main bioactive substance in the atomizing matrix of electronic vaping devices, providing relief from nicotine cravings, a throat hit, and a sense of satisfaction. Pre-made atomizing matrices primarily contain nicotine salts, which reduce the irritation of nicotine. In recent years, 6-methylnicotine has been used, offering advantages such as higher biological activity, lower toxicity, and a stronger throat hit and sense of satisfaction, making it a good alternative to nicotine. 6-methylnicotine is a weak organic base, and it typically reacts with weak organic acids in non-aqueous systems. Directly replacing the nicotine in current nicotine salts with 6-methylnicotine, for example, by reacting benzoic acid with 6-methylnicotine, is another option. The two nitrogen atoms in 6-methylnicotine have lone pairs of electrons, while the oxygen atom on the hydroxyl group of benzoic acid has an empty orbital. During the reaction, the nitrogen atom on the five-membered ring more readily donates electrons to form a coordinated covalent bond, resulting in the benzoate salt of 6-methylnicotine. However, benzoic acid is pulmonaryly toxic and carries potential carcinogenic risks. Furthermore, the resulting 6-methylnicotine salt still has a strong smoky odor and oxidizes and discolors quickly. Using lactic acid to react with 6-methylnicotine provides a good taste, but it has a significant corrosive effect on the heating coil, leading to increased heavy metal content in the smoke. Using single or compound acids such as malic acid, citric acid, or tartaric acid to react with 6-methylnicotine is also an option, but the boiling points of these acids differ greatly from 6-methylnicotine, causing acid crystallization during atomization, potentially leading to coil burn-in and airway blockage.

[0030] In view of this, this application creatively proposes a 6-methylnicotine salt preparation, its preparation method and application, atomizing matrix and electronic atomizing device. In this application, an alicyclic carboxylic acid and 6-methylnicotine are used to prepare a 6-methylnicotine salt formulation. The selected alicyclic carboxylic acid has a boiling point of 200℃-265℃, which is close to that of 6-methylnicotine, indicating good compatibility with 6-methylnicotine. Furthermore, the alicyclic carboxylic acid has low toxicity, does not contain a benzene ring in its molecule, and is therefore less toxic, making its application safer and avoiding potential health problems. The alicyclic carboxylic acid and the formed salt have no obvious odor. The alicyclic carboxylic acid and the formed salt have high stability and are not easily oxidized or decomposed. The alicyclic carboxylic acid has low acidity and will not cause significant corrosion to the heating wire of the atomizing device. Compared with acids such as acetic acid, propionic acid, and lactic acid, the 6-methylnicotine salt prepared using alicyclic carboxylic acid is less corrosive and has a lower content of heavy metals in the flue gas. The formed salt has good solubility in the PG (Propylene Glycol) and VG (Vegetable Glycerin) systems. Subsequent tests on 6-methylnicotine salt or atomizing matrices containing 6-methylnicotine salt, including taste, oxidation discoloration rate, toxicity, and heavy metal content, showed that the salt has good application performance and promising application prospects.

[0031] This application relates to a method for preparing a 6-methylnicotine salt formulation (hereinafter sometimes referred to as the "preparation method"), a 6-methylnicotine salt formulation, a lozenge, an atomizing matrix, and an electronic atomizing device.

[0032] In one specific embodiment, the preparation method of the 6-methylnicotine salt formulation includes: mixing 6-methylnicotine and an alicyclic carboxylic acid, and reacting to obtain the 6-methylnicotine salt formulation. It should be noted that the 6-methylnicotine salt formulation contains 6-methylnicotine alicyclic carboxylic acid. Alicyclic carboxylic acids are a class of organic compounds that contain one or more cyclic carbon skeletons (alicyclic hydrocarbons) and one or more carboxylic acid groups (-COOH), with the carboxylic acid groups directly attached to the cyclic structure.

[0033] In one specific embodiment, the alicyclic carboxylic acid has a boiling point of 200°C to 265°C. It should be noted that the alicyclic carboxylic acid has a boiling point close to that of 6-methylnicotine (6-methylnicotine has a boiling point of approximately 250°C), which facilitates its simultaneous release during atomization and entry into the user's oral cavity.

[0034] In one specific embodiment, the alicyclic carboxylic acid may include at least one selected from cyclohexyl, cyclopentyl, and cycloheptyl. It should be noted that the cyclohexyl, cyclopentyl, or cycloheptyl group may have one or more substituents, such as methyl (-CH3), ethyl (-CH2CH3), and propyl (-CH2CH2CH3).

[0035] In one specific embodiment, the alicyclic carboxylic acid may include at least one of cyclohexanecarboxylic acid (cyclohexanecarboxylic acid, CAS Registry No.: 98-89-5), cyclohexanoic acid (cyclohexylacetic acid, CAS Registry No.: 5292-21-7), 2-methylcyclohexanecarboxylic acid (2-methyl-1-cyclohexanecarboxylic acid, CAS Registry No.: 56586-13-1), 3,4-dimethylcyclohexanecarboxylic acid (CAS Registry No.: 681448-23-7), cyclopentanoic acid (cyclopentanoic acid, CAS Registry No.: 3400-45-1), and 1,3-cyclohexanoic acid. Figure 1 This is a molecular structure diagram of 6-methylnicotine and six alicyclic carboxylic acids involved in this application. The structural formulas of 6-methylnicotine and some alicyclic carboxylic acids can be found in [reference needed]. Figure 1In 6-methylnicotine, both nitrogen atoms have lone pairs of electrons, and the oxygen atom on the hydroxyl group of the alicyclic carboxylic acid has an empty orbital. During the reaction, the nitrogen atom on the five-membered ring more readily donates electrons to form a coordinate covalent bond with the oxygen atom of the carboxyl group, thus yielding the alicyclic carboxylic acid salt of 6-methylnicotine. The boiling points of 6-methylnicotine are 256.6℃, cyclohexanecarboxylic acid is 232.5℃, cyclohexanoic acid is 242℃, 2-methylcyclohexanecarboxylic acid is 241℃, 3,4-dimethylcyclohexanecarboxylic acid is 244℃, cyclopentanoic acid is 216℃, and 1,3-cyclohexadionic acid is 258.1℃.

[0036] In one specific embodiment, the alicyclic carboxylic acid can also be cyclohexanepropionic acid, cyclohexanebutyric acid, cycloheptanecarboxylic acid, etc.

[0037] In one specific embodiment, the molar ratio of the carboxyl groups in 6-methylnicotine and alicyclic carboxylic acids during the reaction can be 1:0.5 to 2. For example, the molar ratio of the carboxyl groups in 6-methylnicotine and alicyclic carboxylic acids can be 1:0.5, 1:1, 1:1.5, or 1:2.

[0038] In one specific embodiment, the reaction is carried out in a non-aqueous system. For example, it can be carried out in ethanol, glycerol, and / or propylene glycol.

[0039] In one specific embodiment, 6-methylnicotine and alicyclic carboxylic acids are mixed in an organic solvent to react and obtain a 6-methylnicotine salt formulation.

[0040] In one specific embodiment, the organic solvent includes at least one of glycerol and propylene glycol. It should be noted that the solvent made from glycerol and / or propylene glycol has a better match with the boiling point and other characteristics of 6-methylnicotine and alicyclic carboxylic acids. During atomization, the aerosol formed by the solvent synergistically carries 6-methylnicotine and the acid into the user's mouth, hindering their separation. This solvent can effectively protect against the release of 6-methylnicotine and alicyclic carboxylic acids from the atomization matrix. Furthermore, glycerol and propylene glycol are also major components of the atomization matrix; therefore, using them as organic solvents facilitates the direct application of the 6-methylnicotine salt formulation of this application to e-liquid.

[0041] In one specific embodiment, 1 to 90 parts by weight of 6-methylnicotine and 1 to 90 parts by weight of alicyclic carboxylic acid can be mixed in 1 to 50 parts by weight of propylene glycol to react and obtain a 6-methylnicotine salt preparation.

[0042] In one specific embodiment, 40 parts by weight of 6-methylnicotine and 40 parts by weight of alicyclic carboxylic acid can be mixed in 20 parts by weight of propylene glycol to react and obtain a 6-methylnicotine salt formulation.

[0043] In one specific embodiment, the reaction is carried out at 30°C to 80°C. Preferably, the reaction is carried out at 60°C.

[0044] In one specific embodiment, the mixture of 6-methylnicotine, alicyclic carboxylic acid, and organic solvent is stirred during the reaction.

[0045] In one specific embodiment, the reaction time is 1 hour to 6 hours.

[0046] In one specific embodiment, preferably, the mixture is stirred at 60°C for 3 hours to react and obtain a 6-methylnicotine alicyclic carboxylate preparation.

[0047] This embodiment also relates to a 6-methylnicotine salt preparation, which contains a 6-methylnicotine alicyclic hydrocarbon carboxylate, wherein the alicyclic hydrocarbon carboxylate corresponding to the alicyclic hydrocarbon carboxyl group in the 6-methylnicotine alicyclic hydrocarbon carboxylate has a boiling point of 200℃ to 265℃, or is prepared by the above preparation method.

[0048] This embodiment also relates to a mouth-sucking product containing 6-methylnicotine salt or a 6-methylnicotine salt preparation. It should be noted that the mouth-sucking product can refer to a cigarette, specifically a candy or chewing gum containing hexamethylnicotine salt or a 6-methylnicotine salt preparation. The mouth-sucking product of this application contains 6-methylnicotine alicyclic carboxylate, which has a better taste and better safety.

[0049] In one specific embodiment, the oral product may also contain at least one of flavoring, sweetener and cooling agent.

[0050] This embodiment also relates to the application of a 6-methylnicotine salt formulation in an atomizing matrix. It should be noted that, in this application, the application of the 6-methylnicotine salt formulation to the atomizing matrix offers advantages such as good taste, excellent safety, slow oxidation rate, and low corrosivity.

[0051] This embodiment also relates to an atomizing matrix containing 6-methylnicotine salt or a 6-methylnicotine salt preparation. It should be noted that the atomizing matrix of this application has the advantages of good taste, excellent safety, slow oxidation rate, and low corrosivity.

[0052] In one specific embodiment, the atomizing matrix may also contain at least one of the following: flavoring, sweetener, cooling agent, preservative, antioxidant, glycerin, and propylene glycol.

[0053] In one specific embodiment, the atomizing matrix may contain 0.3 mg / g to 30 mg / g of 6-methylnicotine salt. Preferably, the atomizing matrix may contain 1 mg / g to 10 mg / g of 6-methylnicotine salt. More preferably, the atomizing matrix may contain 4 mg / g of 6-methylnicotine salt.

[0054] The present application will be further described in detail below through specific embodiments and comparative examples. The following embodiments and comparative examples are only for further illustration of the present application and should not be construed as limiting the present application. In this embodiment or comparative example, unless otherwise specified, the reagents and instruments used are all commercially available, and the experimental operations are all performed in accordance with the product instructions and conventional experimental procedures.

[0055] (1) Preparation of 6-methylnicotine salt formulations and atomizing matrix in the examples and comparative examples:

[0056] Example 1: 40g of cyclohexanecarboxylic acid was poured into a flat-bottomed flask and heated in a water bath to 50°C to melt the cyclohexanecarboxylic acid into a liquid. 40g of 6-methylnicotine and 20g of propylene glycol were slowly added, and the mixture was stirred for 3 hours. After the reaction was complete, the salt was a light yellow viscous liquid. Thus, a 6-methylnicotine cyclohexanecarboxylate preparation was obtained.

[0057] Subsequently, the obtained 6-methylnicotine cyclohexane carboxylate formulation was used to prepare an atomizing matrix according to the following formula, by weight: 20 parts strawberry flavoring, 10 parts green strawberry flavoring, 2 parts sweetener (neotame and sucralose), 5 parts cooling agent (WS-23), 1 part 6-methylnicotine cyclohexane carboxylate, 40 parts glycerin, and 22 parts propylene glycol. This yielded the atomizing matrix of Example 1, which contained 4 mg / g of 6-methylnicotine salt and had a density of 1.12 g / cm³. 3 The pH value is 5.7.

[0058] Example 2: Cyclohexanoic acid in Example 1 was replaced with cyclohexanoic acid, with all other steps remaining the same as in Example 1, to prepare a 6-methylnicotine cyclohexanoic acid salt formulation and the atomizing matrix of Example 2. The atomizing matrix contained 4 mg / g of 6-methylnicotine salt and had a density of 1.12 g / cm³. 3 The pH value is 5.7.

[0059] Example 3: The cyclohexanecarboxylic acid in Example 1 was replaced with 2-methylcyclohexanecarboxylic acid, while all other procedures remained the same as in Example 1. This yielded a 6-methylnicotine 2-methylcyclohexanecarboxylate formulation and the atomizing matrix of Example 3. The atomizing matrix contained 4 mg / g of 6-methylnicotine salt and had a density of 1.13 g / cm³. 3 The pH value is 5.8.

[0060] Example 4: The cyclohexanecarboxylic acid in Example 1 was replaced with 3,4-dimethylcyclohexanecarboxylic acid, while all other procedures remained the same as in Example 1. This yielded a 6-methylnicotine 3,4-dimethylcyclohexanecarboxylate formulation and the atomizing matrix of Example 4. The atomizing matrix contained 4 mg / g of 6-methylnicotine salt and had a density of 1.13 g / cm³. 3The pH value is 5.7.

[0061] Example 5: The cyclohexanecarboxylic acid in Example 1 was replaced with 1,3-cyclohexanediol, and all other procedures remained the same as in Example 1. This yielded a 6-methylnicotine 1,3-cyclohexanediol salt formulation and the atomizing matrix of Example 5. The atomizing matrix contained 4 mg / g of 6-methylnicotine salt and had a density of 1.14 g / cm³. 3 It has a pH value of 5.4 and is a light yellow viscous liquid, which is lighter in color than that of Example 1.

[0062] Comparative Example 1: A 6-methylnicotine benzoate formulation was prepared using the same method as in Example 1. The 6-methylnicotine benzoate was a deep yellow viscous liquid with a more pronounced smoky odor. The 6-methylnicotine benzoate was then prepared into an atomizing matrix with a 6-methylnicotine salt content of 4 mg / g using the same method as in Example 1; this is the atomizing matrix of Comparative Example 1.

[0063] Comparative Example 2: A 6-methylnicotine lactate formulation was prepared using the same method as in Example 1. 6-methylnicotine lactate has a lighter color and a weaker smoky odor compared to 6-methylnicotine benzoate. The 6-methylnicotine lactate was then used to prepare an atomizing matrix with a 6-methylnicotine salt content of 4 mg / g, which is the atomizing matrix of Comparative Example 2, using the same method as in Example 1.

[0064] Comparative Example 3: Pure 6-methylnicotine was prepared into an atomizing matrix with a free 6-methylnicotine concentration of 4 mg / g using the same method as in Example 1, which is the atomizing matrix of Comparative Example 3.

[0065] (2) Suction feel test:

[0066] The taste evaluation was conducted by 6 people. The evaluation dimensions included: throat hit (1-10 points, the higher the score, the stronger the impact on the throat); smoothness (1-10 points, the higher the score, the less uncomfortable the irritation); satisfaction (1-10 points); off-flavor (1-10 points); and overall aroma (1-10 points).

[0067] The evaluation results are shown in the table below:

[0068] Table 1. Results of Atomized Matrix Suction Taste Test in Example 1

[0069]

[0070] Table 2. Results of Atomized Matrix Suction Taste Test in Example 2

[0071]

[0072] Table 3. Results of Atomized Matrix Suction Taste Test in Example 3

[0073]

[0074] Table 4. Results of Atomized Matrix Suction Taste Test in Example 4

[0075]

[0076] Table 5. Results of Atomized Matrix Suction Taste Test in Example 5

[0077]

[0078]

[0079] Table 6. Results of the atomized matrix inhalation taste test for Comparative Example 1.

[0080]

[0081] Table 7. Comparative Example 2: Results of Atomized Matrix Inhalation Taste Test

[0082]

[0083] Table 8. Comparative Example 3: Results of Atomized Matrix Inhalation Taste Test

[0084]

[0085] By comparing the evaluation results, we can see that:

[0086] The order of throat hit sensation is: free 6-methylnicotine > 6-methylnicotine benzoate > 6-methylnicotine alicyclic carboxylate > 6-methylnicotine lactate.

[0087] Compliance ranking: 6-methylnicotine alicyclic carboxylate > 6-methylnicotine lactate > 6-methylnicotine benzoate > free 6-methylnicotine.

[0088] Satisfaction ranking: Overall, there is not much difference.

[0089] Odor ranking (from best to worst): 6-methylnicotine alicyclic carboxylate > 6-methylnicotine lactate > 6-methylnicotine benzoate > free 6-methylnicotine.

[0090] Overall aroma performance ranking: 6-methylnicotine alicyclic carboxylate > 6-methylnicotine benzoate > 6-methylnicotine lactate > free 6-methylnicotine.

[0091] Taste evaluation shows that 6-methylnicotine alicyclic carboxylate can significantly reduce throat irritation and increase smoothness without affecting the satisfaction; it also has a milder off-flavor and better aroma. This is also related to the fact that the boiling point of alicyclic carboxylate is close to that of 6-methylnicotine, resulting in a more even release after acid and alkali decomposition during atomization.

[0092] (3) Oxidation discoloration rate test:

[0093] By placing the nicotine at room temperature for three months and comparing the results, the colors were observed and recorded weekly, with the intensity of the color recorded as a score (water was 0 points, and nicotine benzoate, which had been stored for one year, was 10 points). At the beginning of the experiment, 6-methylnicotine cyclohexane carboxylate was light yellow (1 point), 6-methylnicotine benzoate was dark yellow (3 points), and 6-methylnicotine lactate was light yellow (1 point).

[0094] The color changes are shown in the table below:

[0095] Table 8. Test results of oxidation discoloration rate of various 6-methylnicotine salts

[0096]

[0097] The oxidation color change rate test results show that 6-methylnicotine alicyclic carboxylate has the lowest oxidation color change rate, followed by 6-methylnicotine lactate, and 6-methylnicotine benzoate has the highest oxidation color change rate. After 3 months of storage, 6-methylnicotine alicyclic carboxylate is dark yellow, roughly the same color as freshly prepared 6-methylnicotine benzoate; 6-methylnicotine lactate is light brown; and 6-methylnicotine benzoate is dark brown.

[0098] (4) Toxicity testing:

[0099] Beas-2B cells were selected. Beas-2B cells are a cell line derived from normal human lung epithelial cells. The 6-methylnicotine salt preparations of Examples 1-5 and Comparative Examples 1-2 were subjected to in vitro cell proliferation and toxicity tests and analyses, respectively. The results are as follows: Figures 2 to 7 As shown, where Figure 2 This is a schematic diagram of the cytotoxicity test results of the 6-methylnicotine cyclohexane salt involved in this application. Figure 3 This is a schematic diagram of the cytotoxicity test results of the 6-methylnicotine cyclohexanoate involved in this application. Figure 4 This is a schematic diagram of the cytotoxicity test results of the 6-methylnicotine-2-methylcyclohexane carboxylate involved in this application. Figure 5 This is a schematic diagram of the cytotoxicity test results for 6-methylnicotine 3,4-dimethylcyclohexane carboxylate, which is involved in this application. Figure 6This is a schematic diagram of the cytotoxicity test results for the 6-methylnicotine 1,3-cyclohexanediol salt involved in this application. Figure 7 This is a schematic diagram of the cytotoxicity test results of the 6-methylnicotine benzoate involved in this application.

[0100] IC50 (half-maximal inhibitory concentration) refers to the concentration at which a substance inhibits certain biological processes by 50%. In the context of cell proliferation, it can be understood as the concentration at which the inhibitory effect on cell proliferation reaches 50% of the normal cell proliferation level. The lower the IC50 value, the greater the killing power of the substance and the greater its toxicity to cells. Based on the above results, it can be seen that the toxicity of 6-methylnicotine alicyclic hydrocarbon carboxylate is lower than that of 6-methylnicotine benzoate, indicating that 6-methylnicotine alicyclic hydrocarbon carboxylate is safer and more reliable in use, and has a reduced toxicity and harm effect.

[0101] (5) Heavy metal testing in flue gas:

[0102] Inductively coupled plasma mass spectrometry (ICP-MS) was used to test the heavy metal content in the flue gas of the atomized matrices of Examples 1-5 and Comparative Examples 1-2. The test instruments, conditions, and results are shown in the table below.

[0103] Table 9 ICP-MS Detection Parameters

[0104]

[0105]

[0106] Table 10 Heavy Metal Test Results

[0107]

[0108] The results of the flue gas heavy metal test show that the heavy metal content is as follows: 6-methylnicotine alicyclic hydrocarbon carboxylate < 6-methylnicotine benzoate < 6-methylnicotine lactate. The heavy metal content of 6-methylnicotine cyclohexane carboxylate and 6-methylnicotine benzoate are within the TPD reference limit, while the nickel and chromium content of lactate exceeds the limit (the limit for nickel is 5 ug / 200 puffs, and the limit for chromium is 3 ug / 200 puffs).

[0109] In summary, 6-methylnicotine alicyclic carboxylate has the following advantages: ① It has a better taste and reduces throat irritation; ② Compared with commonly used benzoates and lactates, alicyclic carboxylate has a lower rate of oxidation and discoloration; ③ Cytotoxicity tests show that alicyclic carboxylate is less toxic than lactates and benzoates; ④ Heavy metal experiments show that, during flue gas release, the heavy metal content of alicyclic carboxylate is lower than that of lactates and benzoates, and the heavy metal content in the flue gas is far below the TPD reference limit. Therefore, 6-methylnicotine alicyclic carboxylate has good application prospects.

[0110] The above description, in conjunction with specific embodiments, provides a further detailed explanation of this application and should not be construed as limiting the specific implementation of this application to these descriptions. Those skilled in the art to which this application pertains can make several simple deductions or substitutions without departing from the concept of this application.

Claims

1. A method for preparing a 6-methylnicotine salt formulation, characterized in that, include: 6-methylnicotine and alicyclic carboxylic acid are mixed and reacted at a reaction temperature of 30°C to 80°C to obtain the 6-methylnicotine salt preparation, wherein the boiling point of the alicyclic carboxylic acid is 200°C to 265°C.

2. The preparation method according to claim 1, characterized in that, The alicyclic carboxylic acid includes at least one of cyclopentyl, cyclohexyl, and cycloheptyl.

3. The preparation method according to claim 1, characterized in that, The alicyclic carboxylic acids include at least one of cyclohexanecarboxylic acid, cyclohexanoic acid, 2-methylcyclohexanecarboxylic acid, 3,4-dimethylcyclohexanecarboxylic acid, cyclopentanoic acid, and 1,3-cyclohexanoic acid.

4. The preparation method according to any one of claims 1-3, characterized in that, The molar ratio of the 6-methylnicotine and the carboxyl group in the alicyclic carboxylic acid is 1:0.5-2.

5. The preparation method according to claim 1, characterized in that, include: The 6-methylnicotine and the alicyclic carboxylic acid are mixed in an organic solvent to react and obtain the 6-methylnicotine salt formulation; the organic solvent includes at least one of glycerol and propylene glycol.

6. A 6-methylnicotine salt formulation, characterized in that, The 6-methylnicotine salt preparation contains a 6-methylnicotine alicyclic carboxylate, wherein the alicyclic carboxyl group of the 6-methylnicotine alicyclic carboxylate has a boiling point of 200°C to 265°C; or the 6-methylnicotine salt preparation is prepared by the preparation method according to any one of claims 1 to 5.

7. A mouth-held product, characterized in that, The oral product contains the 6-methylnicotine salt formulation as described in claim 6.

8. An atomizing matrix, characterized in that, The atomizing matrix contains the 6-methylnicotine salt formulation as described in claim 6.

9. The atomizing matrix according to claim 8, characterized in that, In the atomizing matrix, the content of the 6-methylnicotine salt preparation is 1 mg / g to 10 mg / g.

10. An electronic atomizing device, characterized in that, The electronic atomizing device contains the atomizing matrix as described in claim 8 or 9.

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