A nicotine-tartrate complex, preparation method and application

Abstract

The present invention discloses a nicotine-tartrate complex, a preparation method and an application, which relate to the technical field of chemical synthesis. The preparation method provided by the present invention includes: Step 1: Completely dissolve tartaric acid in a protic solvent to obtain a tartaric acid solution; Step 2: Dropwise add nicotine to the solution obtained in Step 1, and stir at room temperature until a white solid precipitates. Then, add an aprotic solvent to the reaction system, and the amount of the precipitated solid increases. Continue to stir for 16-24 hours. When the amount of the white solid no longer increases, filter, and wash the filter cake with the aprotic solvent 2-3 times to obtain a white solid; Step 3: Vacuum-dry the white solid obtained in Step 2 to obtain a white solid powder of tartaric acid-nicotine salt complex. This method well solves the problems that the nicotine-tartrate complex is not easy to form a solid and the solid is not easy to dry. The obtained nicotine-tartrate complex solid is a uniform white fluffy powder, which is more convenient to use.

Description

Technical Field

[0001] The present invention relates to the technical field of chemical synthesis, and in particular to a nicotine-tartrate complex, a preparation method and an application thereof. Background Art

[0002] Nicotine, commonly known as nicotine, has the chemical formula C10H 14 N2, is an alkaloid present in Solanaceae plants (Solanum) and is also an important component of tobacco. Since directly adding nicotine to tobacco products will cause excessive irritation and discomfort to the throat and nasal cavity of smokers, nicotine salts have emerged. Nicotine salts are mainly composed of nicotine and other organic compounds, and are easier to be absorbed and excreted by the human body compared to nicotine, cause less irritation to the throat and nasal cavity, are less volatile, and are more likely to bring a sense of pleasure.

[0003] Nicotine-tartrate has potential application value in the research and development of new tobacco products due to its mild and non-irritating characteristics. In the prior art, Chinese Patent Application CN108329296A discloses a preparation method of nicotine-tartrate complex crystals, which uses water as a solvent and obtains white solid powder by freeze-drying. This method requires freeze-drying, with harsh conditions and high costs, and is not suitable for large-scale production. Chinese Patent Application CN113880802A discloses a preparation method of nicotine-tartrate, which uses propylene glycol as a solvent to prepare solid nicotine salt. However, the nicotine salt obtained by this method is not easy to form a solid, and the crystallization operation is relatively difficult. Summary of the Invention

[0004] The present invention aims at the deficiencies and defects existing in the prior art, and provides a nicotine-tartrate complex with good crystallization and properties, a preparation method and an application thereof.

[0005] In order to solve the above problems, the present invention proposes the following technical solutions:

[0006] In the first aspect, the present invention provides a preparation method of a nicotine-tartrate complex, comprising the following steps:

[0007] Step 1: Dissolve tartaric acid completely in a protic solvent to obtain a tartaric acid solution;

[0008] Step 2: Dropwise add nicotine to the solution obtained in Step 1, stir at room temperature until a white solid precipitates, then add an aprotic solvent to the reaction system, the amount of precipitated solid increases, continue to stir for 16 - 24 hours, when the white solid no longer increases, filter, and wash the filter cake with the aprotic solvent 2 - 3 times to obtain a white solid;

[0009] Step 3: Vacuum dry the white solid obtained in Step 2 to obtain a white solid powder of tartaric acid-nicotine salt complex;

[0010] Among them, the molar ratio of nicotine to tartaric acid is 1:0.7-1.1.

[0011] More preferably, the molar ratio of nicotine to tartaric acid is 1:0.8-0.95.

[0012] A further technical solution thereof is that in the Step 1, the protic solvent is 1-8 times the mass of tartaric acid; more preferably, the protic solvent is 3-5 times the mass of tartaric acid.

[0013] A further technical solution thereof is that in the Step 2, the aprotic solvent added to the reaction system is 10-50 times the mass of tartaric acid; more preferably, in the Step 2, the aprotic solvent added to the reaction system is 20-30 times the mass of tartaric acid.

[0014] A further technical solution thereof is that in the Step 3, the aprotic solvent used for washing the filter cake each time is 1-8 times the mass of tartaric acid; more preferably, the aprotic solvent used for washing the filter cake each time is 3-5 times the mass of tartaric acid.

[0015] A further technical solution thereof is that in the Step 3, the temperature of vacuum drying is 30-75 °C; more preferably, in the Step 3, the temperature of vacuum drying is 40-50 °C.

[0016] A further technical solution thereof is that the protic solvent is selected from low-boiling protic solvents, such as ethanol.

[0017] A further technical solution thereof is that the aprotic solvent is selected from low-boiling aprotic solvents, such as ethyl acetate.

[0018] In the second aspect, the present invention provides a nicotine-tartrate complex prepared by the preparation method described in the first aspect.

[0019] In the third aspect, the present invention also provides the application of the nicotine-tartrate complex in the preparation of non-combustible tobacco products.

[0020] A further technical solution thereof is that the non-combustible tobacco products include atomized liquid and oral tobacco.

[0021] Compared with the prior art, the technical effects that the present invention can achieve include:

[0022] The preparation method provided by the present invention uses a protic solvent as the reaction solvent and an aprotic solvent as the purification solvent, which well solves the problems that the nicotine-tartrate complex is not easy to form a solid and the solid is not easy to dry. The obtained nicotine-tartrate complex solid is a uniform white fluffy powder, which is more convenient to use. The preparation method provided by the present invention is simple in operation, low in production cost, high in the degree of salification of the obtained product, good in quality, and suitable for industrial production.

[0023] The nicotine-tartrate complex provided by the present invention is a uniform fluffy white powder, which is convenient for storage and transportation, and can be directly applied to non-combustible tobacco products such as oral tobacco and atomized liquid. The picture of the nicotine-tartrate complex after crystallization for one week is a yellow oily liquid. Brief Description of the Drawings

[0024] Figure 1 The product prepared by the method of Example 3 of the present invention is a white solid powder;

[0025] Figure 2 The product prepared by the method of Comparative Example 1 of the present invention is still a yellow oily liquid after crystallization for one week. Detailed Description of the Embodiments

[0026] The technical solutions in the embodiments will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention. Obviously, the embodiments described below are only a part of the embodiments of the present invention, rather than all of the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without making creative efforts shall fall within the protection scope of the present invention.

[0027] It should be understood that when used in this specification and the appended claims, the terms "comprises" and "comprising" indicate the presence of the described features, wholes, steps, operations, elements and / or components, but do not preclude the presence or addition of one or more other features, wholes, steps, operations, elements, components and / or their combinations.

[0028] It should also be understood that the terms used in the description of the embodiments of the present invention herein are only for the purpose of describing specific embodiments and are not intended to limit the embodiments of the present invention. As used in the description of the embodiments of the present invention and the appended claims, unless the context clearly indicates otherwise, the singular forms "a", "an" and "the" are intended to include the plural forms.

[0029] Example 1

[0030] This example provides a nicotine-tartrate complex and a preparation method, which are specifically introduced as follows:

[0031] Prepare materials according to a nicotine to tartaric acid molar ratio of 1:0.8, with ethanol being 3 times the mass of tartaric acid.

[0032] Add tartaric acid to ethanol and stir until dissolved at room temperature to obtain a tartaric acid solution. Dropwise add nicotine to the tartaric acid solution and stir at room temperature for 2 hours. White solids start to precipitate. At this time, add ethyl acetate that is 20 times the mass of tartaric acid. The amount of precipitated solids increases. Continue to stir for 16 hours. When the amount of white solids no longer increases, filter. Wash the filter cake twice with ethyl acetate that is 4 times the mass of tartaric acid to obtain white solids. The obtained white solids are dried under vacuum at 45 °C to obtain white solid powder.

[0033] The total nicotine content of the obtained white solid powder is detected to be 50.8%, which is within the theoretical value range of nicotine and tartaric acid forming a salt in a molar ratio of 1:1. The product yield is 95.6%.

[0034] Example 2

[0035] This example provides a nicotine-tartrate complex and its preparation method, which is specifically introduced as follows:

[0036] Prepare materials according to a nicotine to tartaric acid molar ratio of 1:0.9, with ethanol being 3 times the mass of tartaric acid.

[0037] Add tartaric acid to ethanol and stir until dissolved at room temperature to obtain a tartaric acid solution. Dropwise add nicotine to the tartaric acid solution and stir at room temperature for 3 hours. White solids start to precipitate. At this time, add ethyl acetate that is 25 times the mass of tartaric acid. The amount of precipitated solids increases. Continue to stir for 16 hours. When the amount of white solids no longer increases, filter. Wash the filter cake three times with ethyl acetate that is 5 times the mass of tartaric acid to obtain white solids. The obtained white solids are dried under vacuum at 50 °C to obtain white solid powder.

[0038] The total nicotine content of the obtained white solid powder is detected to be 51.0%, which is within the theoretical value range of nicotine and tartaric acid forming a salt in a molar ratio of 1:1. The product yield is 96.3%.

[0039] Example 3

[0040] This example provides a nicotine-tartrate complex and its preparation method, which is specifically introduced as follows:

[0041] Prepare materials according to a nicotine to tartaric acid molar ratio of 1:0.95, with ethanol being 4 times the mass of tartaric acid.

[0042] Add tartaric acid to ethanol and stir until dissolved at room temperature to obtain a tartaric acid solution; add nicotine dropwise to the tartaric acid solution and stir at room temperature for 3 hours. White solids start to precipitate. At this time, add ethyl acetate 30 times the mass of tartaric acid, and the amount of precipitated solids increases. Continue to stir for 16 hours. When the amount of white solids no longer increases, filter. Wash the filter cake 3 times with ethyl acetate 4 times the mass of tartaric acid to obtain white solids; the obtained white solids are vacuum dried at 45 °C to obtain white solid powder, see Figure 1 。

[0043] The total nicotine content of the obtained white solid powder is detected to be 51.7%, which is within the theoretical value range of the salt formation of nicotine and tartaric acid in a molar ratio of 1:1. The product yield is 96.8%.

[0044] Comparative Example 1

[0045] Prepare materials according to a nicotine to tartaric acid molar ratio of 1:0.95, and propylene glycol is 4 times the mass of tartaric acid;

[0046] Add tartaric acid to propylene glycol and heat and stir until dissolved at room temperature to obtain a tartaric acid solution; add nicotine dropwise to the tartaric acid solution and stir at room temperature for 3 hours. No white solids appear. Continue to stir for 2 hours, and still no solids appear. Add ethyl acetate 30 times the mass of tartaric acid, and still no solids appear. The obtained solution is concentrated by rotary evaporation under reduced pressure at 45 °C to obtain a yellow oily liquid. Crystallize at room temperature for 1 week, and still no solids are formed, see Figure 2 。

[0047] Comparative Example 2

[0048] Prepare materials according to a nicotine to tartaric acid molar ratio of 1:0.5, and ethanol is 3 times the mass of tartaric acid;

[0049] Add tartaric acid to ethanol and stir until dissolved at room temperature to obtain a tartaric acid solution; add nicotine dropwise to the tartaric acid solution and stir at room temperature for 2 hours. White solids start to precipitate. At this time, add ethyl acetate 20 times the mass of tartaric acid, and the amount of precipitated solids increases. Continue to stir for 16 hours. When the amount of white solids no longer increases, filter. Wash the filter cake 2 times with ethyl acetate 4 times the mass of tartaric acid to obtain white solids; the obtained white solids are vacuum dried at 45 °C to obtain white solid powder.

[0050] The total nicotine content of the obtained white solid powder is detected to be 51.3%, which is within the theoretical value range of the salt formation of nicotine and tartaric acid in a molar ratio of 1:1. The product yield is 65.6%.

[0051] Comparative Example 3

[0052] Prepare materials according to a nicotine to tartaric acid molar ratio of 1:1.5, and ethanol is 3 times the mass of tartaric acid;

[0053] Tartaric acid was added to ethanol and stirred until dissolved at room temperature to obtain a tartaric acid solution. Nicotine was added dropwise to the tartaric acid solution and stirred at room temperature for 2 hours. White solids began to precipitate. At this time, ethyl acetate 20 times the mass of tartaric acid was added, and the amount of precipitated solids increased. Stirring was continued for 16 hours. When the amount of white solids no longer increased, filtration was carried out. The filter cake was washed twice with ethyl acetate 4 times the mass of tartaric acid to obtain white solids. The obtained white solids were dried under vacuum at 45 °C to obtain white solid powder.

[0054] The total nicotine content of the obtained white solid powder was detected to be 33.8%, which did not meet the theoretical value range of the salt formation of nicotine and tartaric acid in a molar ratio of 1:1.

[0055] Comparative Example 4

[0056] Materials were prepared according to a molar ratio of nicotine to tartaric acid of 1:0.8, with ethanol being 10 times the mass of tartaric acid.

[0057] Tartaric acid was added to ethanol and stirred until dissolved at room temperature to obtain a tartaric acid solution. Nicotine was added dropwise to the tartaric acid solution and stirred at room temperature for 2 hours. No solids appeared. Ethyl acetate 20 times the mass of tartaric acid was added, and stirring was continued for 16 hours. White solids began to precipitate. Filtration was carried out. The filter cake was washed twice with ethyl acetate 4 times the mass of tartaric acid to obtain a small amount of white solids. The obtained white solids were dried under vacuum at 45 °C to obtain white solid powder.

[0058] The total nicotine content of the obtained white solid powder was detected to be 50.3%, which met the theoretical value range of the salt formation of nicotine and tartaric acid in a molar ratio of 1:1, and the product yield was 25.6%.

[0059] Comparative Example 5

[0060] Materials were prepared according to a molar ratio of nicotine to tartaric acid of 1:0.8, with ethanol being 3 times the mass of tartaric acid.

[0061] Tartaric acid was added to ethanol and stirred until dissolved at room temperature to obtain a tartaric acid solution. Nicotine was added dropwise to the tartaric acid solution and stirred at room temperature for 2 hours. White solids began to precipitate. At this time, ethyl acetate 5 times the mass of tartaric acid was added, and stirring was continued for 16 hours. The amount of white solids precipitated was very small. Filtration was carried out. The filter cake was washed twice with ethyl acetate 4 times the mass of tartaric acid to obtain white solids. The obtained white solids were dried under vacuum at 45 °C to obtain a small amount of white solid powder.

[0062] The total nicotine content of the obtained white solid powder was detected to be 51.1%, which met the theoretical value range of the salt formation of nicotine and tartaric acid in a molar ratio of 1:1, and the product yield was 18.3%.

[0063] Comparing Comprehensive Examples 1-3 with Comparative Examples 1-5, the method for preparing the solid nicotine-tartrate complex provided by the present invention is convenient to operate, has a stable nicotine content, is easy to use, and is suitable for industrial production.

[0064] The nicotine-tartrate complex prepared by the preparation method provided by the present invention can be directly applied to the preparation of non-combustible tobacco products.

[0065] In the above embodiments, the descriptions of each embodiment have their own focuses. For parts not described in detail in a certain embodiment, reference may be made to the relevant descriptions of other embodiments.

[0066] The above is the specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any person skilled in the art within the technical scope disclosed by the present invention can easily think of various equivalent modifications or substitutions, and these modifications or substitutions should all be covered within the protection scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.

Claims

1. A method for preparing a nicotine-tartrate complex, characterized in that, It includes the following steps: Step 1: Completely dissolve tartaric acid in ethanol with a mass 3 - 5 times that of tartaric acid to obtain a tartaric acid solution; Step 2: Drop nicotine into the solution obtained in Step 1. When a white solid precipitates after stirring at room temperature, add ethyl acetate with a mass 20 - 30 times that of tartaric acid to the reaction system. The amount of the precipitated solid increases. Continue to stir for 16 - 24 hours. When the amount of the white solid no longer increases, filter. Wash the filter cake with ethyl acetate with a mass 1 - 8 times that of tartaric acid for 2 - 3 times to obtain a white solid; Step 3: Vacuum-dry the white solid obtained in Step 2 at a temperature of 30 - 75 °C to obtain a white solid powder of tartaric acid-nicotine salt complex; Among them, the molar ratio of nicotine to tartaric acid is 1:0.7 - 1.

1.

2. The preparation method of the nicotine-tartrate complex according to claim 1, characterized in that, In the said Step 3, the temperature of the vacuum drying is 40 - 50 °C.

3. The method for preparing the nicotine-tartrate complex according to claim 1, wherein Application of the said nicotine tartrate complex in the preparation of a non-combustible tobacco product.

4. The method for preparing the nicotine-tartrate complex according to claim 3, wherein The said non-combustible tobacco product includes an atomization liquid and a smokeless tobacco product.

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