Neotame salt preparation method, neotame salt and application

Abstract

The invention discloses a preparation method of neotame salt, neotame salt and application. The preparation method of the neotame salt comprises the following steps: adding neotame and organic acid into an auxiliary solvent, and stirring and mixing to obtain liquid neotame salt, and carrying out spray drying treatment on the liquid neotame salt to obtain the solid neotame salt. According to the technical scheme, an imino group in neotame and organic acid are subjected to an acid-base neutralization reaction through a simple preparation process to generate neotame salt, and the prepared neotame salt is more stable in a polar solvent and is not prone to reacting with other components in essence, so that in the application of the electronic cigarette atomized liquid, the stability of neotame can be improved, and the service life of the electronic cigarette atomized liquid is prolonged. The solubility of the neotame in the polar solvent is increased, and when the neotame is finally atomized to generate aerosol, the smoking experience feeling of a user is improved.

Description

Technical Field

[0001] This application relates to the field of chemical synthesis technology, and particularly relates to a preparation method of neotame salt, neotame salt and applications thereof. Background Art

[0002] Electronic atomization is one of the most direct inhalation methods that people come into daily contact with, and the fields of use are also very extensive. For example, in the field of medical technology, e-cigarette technology, etc. Especially in the field of e-cigarette technology, it is a kind of atomization inhalation method that people often use to solve nicotine addiction.

[0003] In the field of e-cigarette technology, including e-cigarette atomization liquid, neotame is added to the existing technology of e-cigarette atomization liquid. Specifically, after neotame is diluted in concentration, it is directly added or used in combination with sweeteners such as sucralose, sodium saccharin, acesulfame potassium, and stevioside. In the existing technology, when the e-cigarette atomization liquid is atomized into an aerosol, the performance of the aerosol in the user's mouth is as follows: the sweetness is low when the taste enters the mouth, the sweetening speed is slow, the sweet feeling lags, and the aftertaste is too long and too sweet and greasy. Summary of the Invention

[0004] This application provides a preparation method of neotame salt, neotame salt and applications thereof, aiming to solve the problem that the application performance of neotame in e-cigarette atomization liquid in the existing technology is not good.

[0005] To achieve the above object, this application proposes a preparation method of neotame salt. The preparation method of this neotame salt includes:

[0006] Adding neotame and organic acid to an auxiliary solvent, and stirring and mixing to obtain a liquid neotame salt;

[0007] Performing spray drying treatment on the liquid neotame salt to obtain a solid neotame salt.

[0008] In some embodiments, the molar ratio of neotame to the organic acid is 0.5 - 3:1.

[0009] In some embodiments, the organic acid is one of citric acid, tartaric acid, malic acid, lactic acid, 2-furoic acid, levulinic acid, and benzoic acid.

[0010] In some embodiments, the auxiliary solvent is one of water, ethanol, methanol, and ethyl acetate.

[0011] In some embodiments, during the stirring process, the stirring temperature is normal temperature or the stirring temperature is 30 - 50 °C, and the stirring time is 0.5 - 4 h.

[0012] In some embodiments, in the spray drying treatment, the inlet air temperature is 60 - 90 °C, and the outlet air temperature is 40 - 70 °C.

[0013] The present application also proposes a neotame salt, which is prepared using the above-mentioned method for preparing the neotame salt.

[0014] The present application also proposes a use of the neotame salt as described above in an electronic cigarette aerosol liquid.

[0015] The technical solution of the present application proposes a method for preparing neotame salt, neotame salt and application. The method for preparing the neotame salt comprises: adding neotame and an organic acid to an auxiliary solvent, stirring and mixing to obtain a liquid neotame salt; spray drying the liquid neotame salt to obtain a solid neotame salt. The technical solution of the present application uses a simple process to cause the imino group in neotame to react with an organic acid to generate a neotame salt by an acid-base neutralization reaction. The prepared neotame salt is more stable in polar solvents and is not easy to react with other ingredients in flavors. Therefore, in the application of electronic cigarette atomizer liquid, the stability of neotame in the electronic cigarette atomizer liquid can be improved, the solubility of neotame in polar solvents can be increased, and finally when atomized to generate an aerosol, the user's smoking experience can be improved. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings required for use in the embodiments or the prior art descriptions are briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application. For those of ordinary skill in the art, other drawings can be obtained based on these drawings without creative work, among which:

[0017] Figure 1 This is a schematic diagram of the preparation process of neotame salt in this application;

[0018] Figure 2 This is a state diagram of the aerosol atomization device of this application after use. Figure 2 In the figure, (a) is a schematic diagram of the carbon deposition state of the heating wire after the electronic cigarette atomizer liquid is used in the embodiment of the present application (roughly schematically), and (b) is a schematic diagram of the carbon deposition state of the heating wire after the electronic cigarette atomizer liquid is used in the comparative example of the present application (roughly schematically). DETAILED DESCRIPTION

[0019] The following will be combined with the drawings in the embodiments of the present application to clearly and completely describe the technical solutions in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of this application.

[0020] See also Figure 1 As shown, the present application proposes a method for preparing neotame salt. The method for preparing neotame salt comprises:

[0021] Step S10: Add neotame and organic acid to an auxiliary solvent, and stir and mix them to obtain a liquid neotame salt.

[0022] Neotame, that is, N-[N-(3,3-dimethylbutyl)-L-α-aspartyl]-L-phenylalanine-1-methyl ester, is a high-intensity sweetener with the characteristics of high sweetness and low calories. However, the original neotame is unstable in some polar solvents and is prone to react with other components, affecting the persistence of its sweetness and aroma. This step aims to utilize the property that the imino group in neotame can undergo an acid-base neutralization reaction with organic acid to prepare a liquid neotame salt.

[0023] In the preparation process of the liquid neotame salt, adding neotame and organic acid together to a selected auxiliary solvent can dissolve and mix these two substances through the auxiliary solvent. Among them, the molar ratio of neotame to organic acid is 0.5 - 3:1. This ratio range ensures the full progress of the reaction, while avoiding the use of excessive organic acid, and optimizing the cost and performance of the product. During the further stirring process, a suitable stirring device, such as a mechanical stirrer, can be used to fully stir the mixture to ensure that neotame and organic acid can fully react and be evenly dispersed in the auxiliary solvent. Exemplarily, the stirring parameter settings include: the stirring temperature is room temperature or the stirring temperature is 30 - 50 °C, and the stirring time is 0.5 - 4 h. Thus, by heating and stirring for an appropriate time, the reaction rate can be accelerated to ensure the full progress of the reaction, and at the same time, preventing the temperature from being too high can avoid side reactions or degradation caused by high temperature.

[0024] Exemplarily, the organic acid is one of citric acid, tartaric acid, malic acid, lactic acid, 2-furoic acid, levulinic acid, and benzoic acid. These organic acids have different chemical structures and properties, and can form different types of salts with neotame, thereby endowing the product with different solubility, stability, and taste characteristics. The auxiliary solvent is one of water, ethanol, methanol, and ethyl acetate, all of which have good solubility for neotame and organic acid, and at the same time do not affect the reaction between them.

[0025] Step S20: Perform spray drying treatment on the liquid neotame salt to obtain a solid neotame salt.

[0026] In this step, a spray dryer is used for drying treatment. A spray dryer usually consists of a feeding system, an atomization system, a drying chamber, a collection system, and a control system. The specific drying steps include:

[0027] Feed the liquid neotame salt prepared in step S10 into the feeding system (liquid delivery pump) of a spray dryer. The liquid delivery pump feeds the liquid neotame salt into the atomization system, where it is dispersed into tiny droplets through the atomization system. Then the atomized droplets enter the drying chamber and exchange heat with hot air. The moisture in the droplets is evaporated to form solid neotame salt particles. Furthermore, the dried neotame salt particles are collected through the collection system to obtain the desired product. In this way, most of the auxiliary solvent can be evaporated in a very short time through spray drying, and the obtained neotame salt particles have uniform size and high quality.

[0028] Among them, in the spray drying process, control the inlet air temperature of the drying chamber to be 60 - 90 °C and the outlet air temperature to be 40 - 70 °C. It can be understood that the level of the inlet air temperature determines the energy of the hot air in the drying chamber, and the outlet air temperature reflects the temperature of the hot air in the drying chamber after taking away the moisture. By comprehensively considering the settings of the inlet air temperature and the outlet air temperature, it is possible to ensure minimizing energy consumption while obtaining high-quality solid neotame salt.

[0029] In summary, solid neotame salt can be prepared through simple steps. In this solid neotame salt, the amino group in neotame is neutralized by an acid, thereby reducing the activity of free nucleophilic attack and making the neotame salt more stable in a polar solvent environment.

[0030] Furthermore, when further applying this solid neotame salt to e-liquid, since the carboxyl group or hydroxyl group of the acid replaces the amino group of neotame, the neotame salt is not likely to react with other components in the e-liquid, thus making the aroma of the e-liquid stable, not easily volatile, reducing the attenuation of sweetness and aroma, improving the quality of the e-liquid, and extending its shelf life.

[0031] This application further presents specific examples of the preparation of neotame salt and the preparation of the corresponding e-liquid. It includes:

[0032] Example 1

[0033] Add 378 g of neotame and 384 g of citric acid (the molar ratio of neotame to citric acid is 0.5:1) to 1000 g of ethyl acetate, heat and stir at 35 °C for 2 hours to obtain liquid neotame salt. During spray drying, preset the drying conditions: the inlet air temperature at the air inlet is 80 °C, the outlet air temperature at the air outlet is 60 °C, and the rotational speed of the liquid delivery pump is 20 rpm. Spray dry the liquid neotame salt to obtain solid neotame citrate salt.

[0034] Weigh according to parts by weight: 0.806% of neotame citrate salt (the unified added amount of neotame converted is 0.4%), 40% of glycerol, 27.194% of propylene glycol, 2% of nicotine, 30% of watermelon essence, stir at room temperature for 30 min, with a rotational speed of 600 r / min, to prepare the e-liquid.

[0035] Example 2

[0036] 756 g of neotame and 180 g of lactic acid (the molar ratio of neotame to lactic acid is 1:1) were added to 600 g of water, and stirred at 40 °C for 3 hours to obtain liquid neotame salt. During spray drying, the preset drying conditions were: the inlet air temperature at the air inlet was 90 °C, the outlet air temperature at the air outlet was 65 °C, and the rotation speed of the liquid delivery pump was 30 rpm. The liquid neotame salt was spray-dried to obtain solid neotame lactate salt.

[0037] Weighed according to parts by weight: 0.495% of neotame lactate salt (the unified addition amount of neotame converted is 0.4%), 40% of glycerol, 27.505% of propylene glycol, 2% of nicotine, and 30% of watermelon essence. Stirred at room temperature for 30 min at a rotation speed of 600 r / min to prepare an e-cigarette atomization liquid.

[0038] Example 3

[0039] 756 g of neotame and 268 g of malic acid (the molar ratio of neotame to malic acid is 1:1) were added to 500 g of ethanol, and heated and stirred at 30 °C for 4 hours to obtain liquid neotame salt. During spray drying, the preset drying conditions were: the inlet air temperature at the air inlet was 60 °C, the outlet air temperature at the air outlet was 50 °C, and the rotation speed of the air flow liquid delivery pump was 20 rpm. The liquid neotame salt was spray-dried to obtain solid neotame salt.

[0040] Weighed according to parts by weight: 0.542% of neotame malate salt (the unified addition amount of neotame converted is 0.4%), 40% of glycerol, 27.458% of propylene glycol, 2% of nicotine, and 30% of watermelon essence. Stirred at room temperature for 30 min at a rotation speed of 600 r / min to prepare an e-cigarette atomization liquid.

[0041] Example 4

[0042] 756 g of neotame and 150 g of tartaric acid (the molar ratio of neotame to tartaric acid is 2:1) were added to 500 g of ethanol, and heated and stirred at 50 °C for 1 hour to obtain liquid neotame salt. During spray drying, the preset drying conditions were: the inlet air temperature at the air inlet was 60 °C, the outlet air temperature at the air outlet was 40 °C, and the rotation speed of the liquid delivery pump was 20 rpm. The liquid neotame salt was spray-dried to obtain solid neotame tartrate salt.

[0043] Weighed according to parts by weight: 0.479% of neotame tartrate salt (the unified addition amount of neotame converted is 0.4%), 40% of glycerol, 27.521% of propylene glycol, 2% of nicotine, and 30% of watermelon essence. Stirred at room temperature for 30 min at a rotation speed of 600 r / min to prepare an e-cigarette atomization liquid.

[0044] Example 5

[0045] 567 g of neotame and 56 g of 2-furoic acid (the molar ratio of neotame to 2-furoic acid is 3:1) were added to 450 g of methanol, and the mixture was heated and stirred at 35 °C for 3 hours to obtain a liquid neotame salt. During spray drying, the preset drying conditions were as follows: the inlet air temperature at the air inlet was 70 °C, the outlet air temperature at the air outlet was 40 °C, and the rotational speed of the liquid delivery pump was 20 rpm. The liquid neotame salt was spray-dried to obtain a solid 2-furoate neotame salt.

[0046] Weigh according to parts by weight: 0.440% of 2-furoate neotame salt (the unified addition amount of neotame converted is 0.4%), 40% of glycerol, 27.560% of propylene glycol, 2% of nicotine, and 30% of watermelon essence. Stir at room temperature for 30 min at a rotational speed of 600 r / min to prepare an e-cigarette atomization liquid.

[0047] Example 6

[0048] 756 g of neotame and 232 g of levulinic acid (the molar ratio of neotame to levulinic acid is 1:1) were added to 450 g of ethanol, and the mixture was heated and stirred at 35 °C for 3 hours to obtain a liquid neotame salt. During spray drying, the preset drying conditions were as follows: the inlet air temperature at the air inlet was 70 °C, the outlet air temperature at the air outlet was 40 °C, and the rotational speed of the liquid delivery pump was 20 rpm. Under the preset drying conditions, the liquid neotame salt was spray-dried to obtain a solid levulinate neotame salt.

[0049] Weigh according to parts by weight: 0.523% of levulinate neotame salt (the unified addition amount of neotame converted is 0.4%), 40% of glycerol, 27.477% of propylene glycol, 2% of nicotine, and 30% of watermelon essence. Stir at room temperature for 30 min at a rotational speed of 600 r / min to prepare an e-cigarette atomization liquid.

[0050] Example 7

[0051] 756 g of neotame and 244 g of benzoic acid (the molar ratio of neotame to benzoic acid is 1:1) were added to 450 g of ethanol, and the mixture was heated and stirred at 35 °C for 3 hours to obtain a liquid neotame salt. During spray drying, the preset drying conditions were as follows: the inlet air temperature at the air inlet was 70 °C, the outlet air temperature at the air outlet was 40 °C, and the rotational speed of the liquid delivery pump was 20 rpm. Under the preset drying conditions, the liquid neotame salt was spray-dried to obtain a solid benzoate neotame salt.

[0052] Weigh according to parts by weight: 0.529% of benzoate neotame salt (the unified addition amount of neotame converted is 0.4%), 40% of glycerol, 27.471% of propylene glycol, 2% of nicotine, and 30% of watermelon essence. Stir at room temperature for 30 min at a rotational speed of 600 r / min to prepare an e-cigarette atomization liquid.

[0053] The above are only partial embodiments of this application. Any modifications made within the parameter range proposed in this application are within the protection scope of this application. To further demonstrate the performance differences between the e-liquid configured with the neotame salt prepared by this application and the traditional e-liquid, the following comparative examples are further proposed in this application, including:

[0054] Comparative Example 1

[0055] Weigh by weight parts: 0.4% of neotame, 0.406% of citric acid, 40% of glycerol, 27.194% of propylene glycol, 2% of nicotine, 30% of watermelon essence, stir at room temperature for 30 min, rotation speed 600 r / min, and prepare the e-liquid.

[0056] Comparative Example 2

[0057] Weigh by weight parts: 0.4% of neotame, 0.095% of lactic acid, 40% of glycerol, 27.505% of propylene glycol, 2% of nicotine, 30% of watermelon essence, stir at room temperature for 30 min, rotation speed 600 r / min, and prepare the e-liquid.

[0058] Comparative Example 3

[0059] Weigh by weight parts: 0.4% of neotame, 0.142% of malic acid (the unified added amount of neotame is 0.4%), 40% of glycerol, 27.458% of propylene glycol, 2% of nicotine, 30% of watermelon essence, stir at room temperature for 30 min, rotation speed 600 r / min, and prepare the e-liquid.

[0060] Comparative Example 4

[0061] Weigh by weight parts: 0.4% of neotame, 0.079% of tartaric acid (the unified added amount of neotame is 0.4%), 40% of glycerol, 27.521% of propylene glycol, 2% of nicotine, 30% of watermelon essence, stir at room temperature for 30 min, rotation speed 600 r / min, and prepare the e-liquid.

[0062] Comparative Example 5

[0063] Weigh by weight parts: 0.4% of neotame, 0.040% of 2-furoic acid (the unified added amount of neotame is 0.4%), 40% of glycerol, 27.560% of propylene glycol, 2% of nicotine, 30% of watermelon essence, stir at room temperature for 30 min, rotation speed 600 r / min, and prepare the e-liquid.

[0064] Comparative Example 6

[0065] Weigh according to weight: 0.4% neotame, 0.123% levulinic acid (the unified addition amount of neotame is 0.4%), 40% glycerol, 27.477% propylene glycol, 2% nicotine, 30% watermelon flavor, stir at room temperature for 30 minutes at a speed of 600 r / min to prepare an electronic cigarette atomizer liquid.

[0066] Comparative Example 7

[0067] Weigh according to weight: 0.4% neotame, 0.129% benzoic acid (0.4% uniform addition amount of neotame), 40% glycerol, 27.471% propylene glycol, 2% nicotine, 30% watermelon flavor, stir at room temperature for 30 minutes at a speed of 600 r / min to prepare an electronic cigarette atomizer liquid.

[0068] The following is a further detailed description combined with specific experiments:

[0069] Test 1: Taste Test

[0070] An aerosol atomization device with the same basic parameters, i.e., an electronic cigarette atomizer, was used to inject the electronic cigarette atomizer liquids prepared by Examples 1 to 7 and Comparative Examples 1 to 7, respectively. Then, 40 testers tried it out, and the evaluation results of sweetness, aroma fullness, sweetness fusion, smoothness, and sweetness remaining in the mouth were obtained (full score is 5 points). After that, the average value of each evaluation result of the 30 testers was taken. The taste evaluation results are shown in Table 1.

[0071] Table 1

[0072]

[0073]

[0074] It can be seen from the results in Table 1 that the aroma fullness, sweetness fusion, smoothness, sweetness and greasy feeling in the mouth (the shorter the sweetness lingering time and the weaker the sweetness and greasy feeling, the higher the score) and the total score of the neotame salt in Examples 1 to 7 are all higher than those in Comparative Examples 1 to 7, indicating that the neotame salt in the present application can effectively improve the aroma fullness, sweetness fusion and smoothness of the sweetener electronic cigarette atomizer liquid, and reduce the sweetness and greasy feeling in the mouth.

[0075] Test 2: Bitterness Test

[0076] Two aerosol atomization devices (atomization device A and atomization device B), i.e., electronic cigarette atomizers, with the same basic parameters were used, and the electronic cigarette atomizer liquids prepared in Examples 1 to 7 and Comparative Examples 1 to 7 were respectively injected. The atomizer devices injected with the electronic cigarette atomizer liquid were sealed and placed in a refrigerator at 4° C. for 2 hours. Ten testers conducted a trial use, and the number of people who inhaled bitter taste was recorded. The bitterness test evaluation results are shown in Table 2.

[0077] Table 2

[0078]

[0079]

[0080] As can be seen from the results in Table 2, the situation of bitterness during the suction of neotame salts in Examples 1 to 7 of the two aerosol atomization devices (Atomization Device A and Atomization Device B) is significantly lower than that in Comparative Examples 1 to 7, indicating that the neotame salts in the present application can effectively reduce the risk of bitterness of neotame.

[0081] Experiment 3: Carbon deposition test on the wick

[0082] After injecting the prepared e-cigarette atomization liquid of Examples 1 to 7 and Comparative Examples 1 to 7 into aerosol atomization devices with the same basic parameters, under the preset suction parameters of a suction volume of 45 ml, a suction time of 2 s, and a pause time of 15 s, after continuously sucking 200 puffs, 400 puffs, 600 puffs, 800 puffs, 1000 puffs, and 1200 puffs of the e-cigarettes injected with the e-cigarette atomization liquid, 5 testers were used for trial, and the situation of sucking a burnt taste and the carbon deposition situation of the heating wire were recorded. The data are shown in Table 3.

[0083] Table 3

[0084]

[0085] As can be seen from the results in Table 3, the situation of sucking a burnt taste and the carbon deposition situation of the heating wire in Examples 1 to 7 are significantly lower than those in Comparative Examples 1 to 7. As Figure 2 shown in the schematic diagram of the carbon deposition state of the heating wire. It indicates that the neotame salts in the present application can effectively reduce the risk of carbon deposition on the wick of neotame.

[0086] The above are only partial or preferred embodiments of the present application. Whether in terms of text or drawings, the scope of protection of the present application cannot be limited thereby. Any equivalent structural transformation made under the overall concept of the present application by using the content of the specification and drawings of the present application, or any direct / indirect application in other related technical fields is included in the scope of protection of the present application.

Claims

1. A method for preparing neotame salt, characterized in that: include: Adding neotame and organic acid into the auxiliary solvent, stirring and mixing to obtain liquid neotame salt; The liquid neotame salt is spray-dried to obtain solid neotame salt.

2. The method for preparing neotame salt according to claim 1, characterized in that: The molar ratio of the neotame to the organic acid is 0.5-3:

1.

3. The method for preparing neotame salt according to claim 2, characterized in that: The organic acid is one of citric acid, tartaric acid, malic acid, lactic acid, 2-furancarboxylic acid, levulinic acid and benzoic acid.

4. The method for preparing neotame salt according to claim 3, characterized in that: The auxiliary solvent is one of water, ethanol, methanol and ethyl acetate.

5. The method for preparing neotame salt according to claim 1, characterized in that: During the stirring process, the stirring temperature is room temperature or a stirring temperature of 30 to 50°C, and the stirring time is 0.5 to 4 hours.

6. The method for preparing neotame salt according to claim 1, characterized in that: During the spray drying process, the inlet air temperature is 60-90°C and the outlet air temperature is 40-70°C.

7. A neotame salt, characterized in that: The product is prepared by the method for preparing neotame salt according to any one of claims 1 to 6.

8. Use of the neotame salt as claimed in claim 7 in electronic cigarette atomizer liquid.

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