High-stability nicotine salt, preparation method and electronic cigarette liquid thereof

Abstract

The invention relates to the field of electronic cigarette liquid, and provides high-stability nicotine salt, a preparation method and electronic cigarette liquid thereof, and the nicotine salt is prepared from the following components in parts by weight: 40-60 parts of nicotine, 10-18 parts of organic acid, 3-7 parts of gallic acid grafted chitosan, 4-8 parts of a tea polyphenol / cyclodextrin inclusion compound, 2-6 parts of vesicle coated anthocyanin and 40-60 parts of propylene glycol. The preparation method of the nicotine salt comprises the following steps: mixing organic acid and propylene glycol, heating in a water bath, and stirring to prepare a uniform solution; adding nicotine into the solution, heating and strongly stirring to prepare a nicotine solution; and then adding gallic acid grafted chitosan, a tea polyphenol / cyclodextrin inclusion compound and vesicle coated anthocyanin, uniformly stirring, and freeze-drying to obtain the high-stability nicotine salt. The gallic acid grafted chitosan, the tea polyphenol / cyclodextrin inclusion compound and the vesicle coated anthocyanin solve the problems of insufficient stability and inoxidizability of nicotine salt.

Description

Technical Field

[0001] The present invention relates to the field of electronic cigarette oil, and in particular to a high-stability nicotine salt, a preparation method and electronic cigarette oil thereof. Background Art

[0002] With the booming development of the e-cigarette industry, nicotine salt, as a key component of e-cigarette oil, its stability and antioxidant properties are crucial to improving the e-cigarette experience and protecting the health of users. In actual use, nicotine salt faces many environmental challenges, such as high temperature, humidity, light, etc. These factors may cause nicotine salt to undergo degradation, oxidation and other adverse reactions, thereby affecting the taste of e-cigarettes, nicotine delivery efficiency, and the production of harmful substances. Therefore, the development of nicotine salt formulas with high stability and antioxidant properties is of great significance for ensuring the quality stability of e-cigarette oil, extending shelf life, and improving nicotine utilization. At the same time, excellent stability and antioxidant properties can also help improve the sensory experience of e-cigarettes, such as reducing irritation, improving the smoothness of the taste, etc., and further enhance user satisfaction. From the perspective of industry development, the research and development of high-performance nicotine salts can not only promote the iterative upgrading of e-cigarette products and meet consumers' increasing quality needs, but also promote the application and expansion of e-cigarettes in the field of harm reduction and replacement, providing many smokers with safer and healthier alternatives. Therefore, the development and application of highly stable and antioxidant nicotine salts are of great strategic significance for the development and growth of the e-cigarette industry and the realization of social benefits.

[0003] At present, although nicotine salts have made great progress, the nicotine salts used in electronic cigarette oils generally have the problem of insufficient stability and antioxidant properties, which makes it difficult to meet the increasingly improved performance requirements of electronic cigarette products. On the one hand, the traditional nicotine salt preparation process is relatively simple, lacking the components and mechanisms to improve the thermal stability of nicotine, resulting in unsatisfactory thermal stability indicators of the obtained nicotine salts, which are prone to degradation during the use and storage of electronic cigarettes, affecting the nicotine delivery efficiency and taste quality. On the other hand, nicotine salts are more sensitive to oxygen and are prone to oxidation reactions, generating harmful degradation products, which not only reduces the utilization rate of nicotine, but also may introduce health risks. The main reason for the above problems is that the existing technology has not fully considered the design of the antioxidant properties of nicotine salts; at the same time, the existing preparation method also lacks effective antioxidant use and packaging technology, making it difficult to block the direct contact between oxygen and nicotine, thereby exacerbating the occurrence of oxidative degradation. Therefore, it is urgent to develop new nicotine salts and preparation processes to fundamentally solve the problems of poor stability and antioxidant properties, so as to promote the performance optimization and quality improvement of electronic cigarette products. Summary of the invention

[0004] (1) Technical issues solved

[0005] The purpose of the present invention is to provide a highly stable nicotine salt, a preparation method and an electronic cigarette oil thereof, so as to solve the problem that the current nicotine salt has poor stability and oxidation resistance.

[0006] (2) Technical solution

[0007] In order to achieve the above object, the present invention provides the following technical solutions:

[0008] A high-stability nicotine salt comprises the following components, measured by weight: 40-60 parts of nicotine, 10-18 parts of organic acid, 3-7 parts of gallic acid grafted chitosan, 4-8 parts of tea polyphenol / cyclodextrin inclusion compound, 2-6 parts of vesicle-coated anthocyanidin, and 40-60 parts of propylene glycol.

[0009] Furthermore, the preparation method of the gallic acid grafted chitosan is as follows: by weight, in a nitrogen atmosphere, 40 to 55 parts of chitosan with a concentration of 10 mg / mL are dissolved in 20 to 35 parts of an acetic acid aqueous solution with a volume fraction of 1%, and then centrifuged at 10000 rpm for 20 to 30 minutes, and then a clear chitosan solution is obtained by filtration, and then 0.02 to 0.06 parts of ascorbic acid and 1 to 2 parts of a 1 mol / L hydrogen peroxide aqueous solution are added thereto, and stirred for 30 to 45 minutes in a dark environment at room temperature, and then 0.4 to 0.8 parts of gallic acid are added, and stirring is continued for 20 to 28 hours, and the resulting solution is loaded into a dialysis bag with a molecular weight cutoff of 8 to 14 kDa, and dialyzed with ultrapure water at room temperature for 54 to 72 hours, during which the dialysis medium is replaced every 8 hours to remove unreacted gallic acid, and finally, the reaction solution is frozen at -20°C, and then freeze-dried for 3 days to obtain gallic acid grafted chitosan.

[0010] Furthermore, the preparation method of the tea polyphenol / cyclodextrin inclusion complex is as follows: by weight, 2 to 6 parts of epigallocatechin gallate and 10 to 16 parts of hydroxypropyl-β-cyclodextrin are dissolved in 100 parts of deionized water, stirred at 60° C. for 10 to 18 hours, and then freeze-dried for 24 hours to obtain the tea polyphenol / cyclodextrin inclusion complex.

[0011] Furthermore, the tea polyphenol / cyclodextrin inclusion compound is in the form of porous spheres with an average diameter of 10 to 25 μm.

[0012] Furthermore, the preparation method of the vesicle-coated anthocyanidin is as follows: by weight, 5 to 12 parts of lecithin and 8 to 14 parts of quinoline dimethacrylate are dissolved in 50 parts of chloroform, and magnetically stirred for 30 to 50 minutes to mix evenly, then the chloroform solvent is completely evaporated in a nitrogen gas stream, and then 5 to 10 parts of phosphate buffer are added thereto, followed by vigorous stirring for 30 to 45 minutes to obtain a vesicle solution, and then the solvent is completely evaporated in a nitrogen gas stream to form a lipid film, and then 2 to 5 parts of anthocyanidin and 4 to 8 parts of a mixed solution of sodium citrate buffer are added thereto, and magnetic stirring is performed for 2 to 5 hours to obtain vesicle-coated anthocyanidin.

[0013] Furthermore, the average diameter of the vesicle-encapsulated anthocyanin is 200-450 nm.

[0014] Furthermore, the anthocyanin coating rate of the vesicle-coated anthocyanin is 60-75%.

[0015] Furthermore, the organic acid is malic acid, citric acid or oxalic acid.

[0016] The design purpose of the technical solution of the present invention is to significantly improve the antioxidant properties of nicotine salt by adding gallic acid grafted chitosan to nicotine salt. The proposal of this design concept comprehensively considers the main technical challenges faced by nicotine salt in the application of electronic cigarette oil, that is, oxidative degradation is very likely to occur during the high-temperature atomization process, resulting in reduced nicotine activity and the production of harmful decomposition products, which affects the safety of use. In order to overcome the above problems, the present invention cleverly introduces the functional polymer of gallic acid grafted chitosan. Among them, chitosan, as a natural polysaccharide material, has excellent biocompatibility and chemical modifiability; and gallic acid and its derivatives are recognized as highly efficient antioxidants with good free radical scavenging ability. Combining the two through chemical grafting can give full play to the synergistic effect and give the nicotine salt system a stable and reliable antioxidant ability. Specifically, in the preparation method of the present invention, chitosan is firstly oxidized and activated by ascorbic acid and hydrogen peroxide to introduce active groups to create sites for subsequent grafting reactions; then, gallic acid is grafted under the optimum pH, temperature and other conditions to connect it to the chitosan molecular chain through covalent bonds. It is worth noting that by strictly controlling key parameters such as reactant ratio and reaction time, the degree of grafting can be precisely controlled, thereby optimizing the antioxidant performance. In terms of the mechanism of action of chitosan grafted with gallic acid, there are mainly the following points: first, the gallic acid group grafted onto the chitosan skeleton has excellent free radical scavenging ability and electron transfer ability, which can effectively block the free radical chain reaction in the oxidation process, thereby inhibiting the oxidation of nicotine salts; secondly, the steric hindrance effect of the chitosan skeleton itself can isolate oxygen from direct contact with nicotine salts to a certain extent, delaying the oxidation process; furthermore, chitosan grafted with gallic acid has good thermal stability as a whole, and can maintain the integrity of structure and function during the atomization and heating process of nicotine salts. In addition, while optimizing the antioxidant performance, the present invention also fully considers the compatibility and stability of gallic acid grafted chitosan in the nicotine salt system. On the one hand, the grafting reaction process can firmly bond gallic acid to the chitosan skeleton to avoid its precipitation and stratification during storage and use; on the other hand, the presence of hydrophilic groups in the chitosan skeleton helps to improve the compatibility of the entire additive with the nicotine salt matrix, ensuring the long-term antioxidant effect. In short, the present invention introduces gallic acid grafted chitosan into nicotine salt. After careful chemical grafting design and process optimization, the synergistic antioxidant effect of chitosan and gallic acid is fully exerted, while taking into account the thermal stability and compatibility of the system, which improves the applicability and safety of nicotine salt in the field of electronic cigarette oil from multiple angles, embodies a clear technological advancement and innovation, and has important reference significance for the development of related fields.

[0017] The technical solution of the present invention aims to improve the antioxidant and thermal stability of nicotine salt electronic cigarette oil by adding tea polyphenols / cyclodextrin inclusion complex to nicotine salt. This design has many considerations and advantages. First, tea polyphenols, as a natural antioxidant, have excellent antioxidant activity. Among them, epigallocatechin gallate (EGCG) is the main active ingredient of tea polyphenols and has a strong ability to scavenge free radicals. By introducing tea polyphenols into nicotine salt, the oxidative degradation of nicotine during storage and use can be effectively inhibited, the shelf life of electronic cigarette oil can be extended, and the generation of harmful oxidation products can be reduced. However, tea polyphenols have certain limitations in water solubility and thermal stability. In order to overcome this problem, the present invention adopts a strategy of forming an inclusion complex between cyclodextrin and tea polyphenols. Cyclodextrin is a type of cyclic oligosaccharide with a hydrophobic inner cavity and a hydrophilic outer surface. By encapsulating tea polyphenol molecules in the hydrophobic inner cavity of cyclodextrin, its water solubility and stability can be significantly improved. Hydroxypropyl-β-cyclodextrin, as a commonly used cyclodextrin derivative, has a good inclusion effect on tea polyphenols and can form a stable tea polyphenol / cyclodextrin inclusion complex. In the preparation process, the formation of the inclusion complex can be promoted by dissolving tea polyphenols and hydroxypropyl-β-cyclodextrin and stirring them fully under appropriate temperature and time conditions. The application of freeze-drying technology further removes moisture and obtains a stable tea polyphenol / cyclodextrin inclusion complex. This inclusion complex not only has good water solubility, but also improves the stability of tea polyphenols in high temperature environments and reduces its degradation and volatilization. Adding tea polyphenol / cyclodextrin inclusion complex to nicotine salt can play a synergistic role and comprehensively improve the quality of electronic cigarette oil. On the one hand, the antioxidant activity of tea polyphenols can protect nicotine salt from oxidative degradation and extend the service life of electronic cigarette oil. On the other hand, the inclusion of cyclodextrin can improve the dispersibility and solubility of tea polyphenols in the nicotine salt matrix, ensuring the effective performance of its antioxidant function. At the same time, the formation of the inclusion complex can also enhance the thermal stability of tea polyphenols during high-temperature atomization, reducing the risk of degradation and generation of harmful substances. In summary, the present invention cleverly utilizes the antioxidant effect of tea polyphenols and the inclusion effect of cyclodextrin by adding tea polyphenol / cyclodextrin inclusion complex to nicotine salt, thereby improving the antioxidant effect and thermal stability of nicotine salt electronic cigarette oil. This technical solution can not only extend the shelf life of the product and reduce the generation of harmful substances, but also ensure the stable release and absorption of nicotine, and improve the quality and safety of electronic cigarette oil. At the same time, the use of natural antioxidant tea polyphenols and environmentally friendly material cyclodextrin is also in line with the current green and healthy development trend of the electronic cigarette industry.

[0018] The present invention further defines the tea polyphenol / cyclodextrin inclusion compound as a porous spherical compound with an average diameter of 10 to 25 μm, and its purpose is: first, using cyclodextrin to include tea polyphenols to form a porous spherical inclusion compound with controllable size, thereby improving the stability and water solubility of tea polyphenols and enhancing its antioxidant activity; second, increasing the specific surface area of ​​the inclusion compound through the porous spherical structure, promoting full contact between tea polyphenols and nicotine, more effectively blocking the oxidative degradation process of nicotine, and improving the stability of nicotine; finally, using the porous structure to achieve controlled release of tea polyphenols, prolong the antioxidant protection time, and further enhance the storage stability of nicotine salt. In summary, the reasonable design of the morphology and size of the tea polyphenol / cyclodextrin inclusion compound is of great significance for comprehensively improving the quality of the nicotine salt of the present invention.

[0019] In the present invention, gallic acid grafted chitosan and tea polyphenol / cyclodextrin inclusion complex play their own unique roles and significantly improve the antioxidant and thermal stability of the material through synergistic effect. Gallic acid grafted chitosan mainly focuses on improving the antioxidant property of the material. Chitosan is a natural polysaccharide with excellent biocompatibility and chemical modification potential. By grafting gallic acid, its strong antioxidant activity can be introduced into the chitosan molecular chain, giving the material stronger antioxidant capacity. At the same time, the polyhydroxy structure of chitosan also helps to improve the thermal stability of the material. Tea polyphenol / cyclodextrin inclusion complex focuses on improving the thermal stability of the material. Tea polyphenol is a natural antioxidant, but it is easily degraded at high temperature. By forming an inclusion complex with hydroxypropyl-β-cyclodextrin, the thermal stability of tea polyphenol can be significantly enhanced. In addition, the inclusion complex can also improve the water solubility and dispersibility of tea polyphenol, which is conducive to its uniform distribution in the matrix and the antioxidant function. Gallic acid grafted chitosan fixes gallic acid on the chitosan molecular chain through chemical bonding to form a stable grafted structure. Mechanism of improving antioxidant properties: Gallic acid, as a polyphenol antioxidant, has excellent free radical scavenging ability and redox activity. After grafting onto chitosan, gallic acid can form a dense antioxidant network on the surface and inside of the material, effectively blocking the propagation of the oxidation reaction chain, thereby greatly improving the antioxidant properties of the material. Tea polyphenol components in tea polyphenol / cyclodextrin inclusion complexes, such as epigallocatechin gallate (EGCG), are also potent antioxidants. Cyclodextrin molecules can bind tea polyphenol molecules in their hydrophobic inner cavities through cavity inclusion to form stable inclusion complexes. This inclusion complex can not only protect tea polyphenols from the influence of the external environment, but also improve their dispersibility and availability in the material, thereby exerting a more efficient antioxidant function. Mechanism of improving thermal stability: The chitosan skeleton in gallic acid grafted chitosan has excellent thermal stability. A large number of hydrogen bonds and intermolecular forces on the chitosan molecular chain can form a tight network structure and increase the thermal deformation temperature and thermal decomposition temperature of the material. At the same time, the grafted gallic acid molecules can also play a role in physical cross-linking, further enhancing the thermal stability of the chitosan matrix. The formation of tea polyphenol / cyclodextrin inclusion complex significantly improves the stability of tea polyphenol at high temperature. Cyclodextrin molecules can encapsulate heat-sensitive tea polyphenol molecules in their hydrophobic inner cavity through cavity inclusion, isolating them from the influence of the external environment. This "molecular capsule" effect can effectively inhibit the degradation and volatilization of tea polyphenol at high temperature, thereby greatly improving its thermal stability. In addition, the cyclodextrin molecule itself also has good thermal stability, which can enhance the overall thermal stability of the composite material to a certain extent. Gallic acid grafted chitosan and tea polyphenol / cyclodextrin inclusion complex show significant synergistic effects in the composite material system. First, the two components have good compatibility in structure.Chitosan and cyclodextrin are both polysaccharide compounds. Their hydrophilic structures can form intermolecular interactions such as hydrogen bonds with tea polyphenols, which helps to evenly disperse the inclusion complex in the chitosan matrix. Secondly, gallic acid and tea polyphenols are complementary in antioxidant mechanism. Gallic acid mainly exerts antioxidant effects through hydrogen atom transfer and free radical scavenging mechanisms, while tea polyphenols mainly inhibit oxidation through redox reaction mechanisms. The synergistic effect of the two antioxidants can completely block the oxidation reaction chain and provide multi-level antioxidant protection. In addition, the formation of the inclusion complex can also promote the dispersion and protection of tea polyphenols in the chitosan matrix and improve the utilization rate of its antioxidant activity. At the same time, the good film-forming property and thermal stability of chitosan also provide a stable carrier for the tea polyphenol / cyclodextrin inclusion complex, which promotes the improvement of the overall performance of the composite material. In general, the synergistic effect of gallic acid grafted chitosan and tea polyphenols / cyclodextrin inclusion complex is mainly reflected in the following aspects: 1. Structural compatibility: Both components are polysaccharide compounds with good compatibility and intermolecular interactions, which are conducive to the formation of a uniform and stable composite material. 2. Complementary antioxidant mechanisms: Gallic acid and tea polyphenols act through different antioxidant mechanisms, respectively, and synergistically provide comprehensive antioxidant protection. 3. Dispersion and protection of inclusion complexes: Cyclodextrin molecules can encapsulate and protect tea polyphenols, improve their dispersibility and stability in the chitosan matrix, and promote the antioxidant activity. 4. Synergistic improvement of thermal stability: Both chitosan skeletons and cyclodextrin molecules have good thermal stability. Their synergistic effect with gallic acid and tea polyphenols can significantly improve the overall thermal stability of the composite material.

[0020] The vesicle-coated anthocyanidin designed by the present invention fully utilizes the antioxidant and bioactivity regulating effects of anthocyanidin, improves the stability and safety of nicotine salt, and improves the smoking experience of electronic cigarettes. First, the present invention significantly improves the chemical stability and bioavailability of anthocyanidin by coating anthocyanidin in a vesicle composed of lecithin and quinoline dimethacrylate. The bilayer structure formed by lecithin and quinoline dimethacrylate can effectively protect the anthocyanidin in the core and prevent it from being degraded or oxidized during storage and use. At the same time, the vesicle structure can also control the release rate of anthocyanidin, achieve its sustained release effect, and prolong its action time in the body. Secondly, compounding the vesicle-coated anthocyanidin with nicotine can make full use of the antioxidant activity of anthocyanidin and delay the degradation and oxidation process of nicotine salt. Nicotine salt may be degraded to a certain extent in the electronic cigarette liquid to generate harmful substances such as nitrosamines, affecting the safety of electronic cigarettes. As a natural antioxidant, anthocyanins can remove free radicals generated during the degradation process, block the oxidation reaction chain, thereby improving the stability of nicotine salts and reducing the generation of harmful substances. In addition, anthocyanins also have certain anti-inflammatory and antiviral activities. When smoking electronic cigarettes, nicotine may cause irritation and inflammatory reactions to the respiratory tract and lungs, affecting the smoking experience and health. By introducing vesicle-coated anthocyanins into electronic cigarette liquid, the biological activity of anthocyanins can be utilized to reduce the inflammatory reaction caused by nicotine, protect the respiratory tract and lung tissues, and improve the comfort and safety of electronic cigarettes. In order to achieve the above purpose, the present invention adopts a carefully designed vesicle-coated anthocyanin preparation process. By dissolving lecithin and quinoline dimethyl methacrylate in chloroform, and then blowing off the solvent with nitrogen, a uniform and stable lipid film is formed. Then, anthocyanins are mixed with sodium citrate buffer, added to the lipid film, and anthocyanins are coated into the vesicle core by magnetic stirring to form the final vesicle-coated anthocyanins. This preparation process can effectively control the particle size, distribution and morphology of the vesicles, ensuring their dispersibility and stability in the electronic cigarette liquid. In summary, the present invention cleverly utilizes the antioxidant activity and biological activity of anthocyanins by compounding vesicle-coated anthocyanins with nicotine salts, improves the stability and safety of nicotine salts, and improves the smoking experience of electronic cigarettes. This new electronic cigarette liquid formula not only has application value, but also provides new ideas and directions for innovation and development in the field of electronic cigarettes. In subsequent research, the preparation process of vesicle-coated anthocyanins can be further optimized, its mechanism of action can be further explored, and its application range in electronic cigarette liquids and other fields can be expanded.

[0021] The present invention limits the average diameter of the vesicle-coated anthocyanidin to 200-450nm, and its purpose is: first, by forming nano-scale vesicles, the water solubility and bioavailability of anthocyanidin are significantly improved, and its defects such as poor stability and easy degradation in the physiological environment are overcome; secondly, the nano-size of the vesicle is conducive to improving the antioxidant activity and biological activity of anthocyanidin, enhancing its protective effect on nicotine molecules, effectively inhibiting the oxidative degradation of nicotine, and improving the stability of nicotine salts. In addition, the present invention further limits the anthocyanidin coating rate of the vesicle-coated anthocyanidin to 60-75%, which not only ensures the effective utilization of anthocyanidin, but also avoids the increase in preparation cost caused by too high a coating rate, and takes into account both product quality and economic benefits.

[0022] The present invention also provides a method for preparing a high-stability nicotine salt, comprising the following steps:

[0023] S1: After mixing the organic acid and propylene glycol, heat the mixture in a water bath to 40-50° C. and stir the mixture with a magnetic stirrer at 200-300 rpm for 20-40 minutes to obtain a uniform organic acid solution.

[0024] S2: Add nicotine to the organic acid solution obtained in S1, heat in a water bath to 60-70° C., and stir magnetically at 400-500 rpm for 30-40 min to obtain a nicotine solution.

[0025] S3: Gallic acid grafted chitosan, tea polyphenol / cyclodextrin inclusion complex and vesicle-encapsulated anthocyanidin are continuously added to the nicotine solution obtained in S2, and stirring is continued for 60 to 90 minutes, and then freeze-dried to obtain a highly stable nicotine salt.

[0026] The present invention also provides an electronic cigarette oil, characterized in that it comprises the high-stability nicotine salt described in the above scheme, and the mass fraction of the nicotine salt accounts for 2-10% of the total mass fraction of the electronic cigarette oil.

[0027] The method for preparing a highly stable nicotine salt provided by the present invention is a well-designed multi-step, multi-component compounding process. First, in the pretreatment stage, an organic acid is mixed with propylene glycol and heated and stirred to obtain a uniform organic acid solution. The purpose of this step is to create favorable conditions for the dissolution of nicotine and the reaction with the organic acid. Propylene glycol, as an excipient and a dispersion medium, can significantly improve the uniformity and fluidity of the system, which is conducive to the smooth progress of subsequent processes. In the second step, nicotine is added to the organic acid solution and fully stirred at a high temperature to react with the organic acid to generate nicotine salt in situ. This in-situ reaction mode can not only improve the generation efficiency of nicotine salt, but also avoid the cumbersome steps of subsequent separation and purification, and simplify the process flow. At the same time, a higher reaction temperature helps to overcome the steric hindrance effect of nicotine and organic acid, promote the reaction, and improve the conversion rate and product quality. The third step is the core link of the present invention. A multi-component compounding strategy is adopted to introduce various functional excipients such as gallic acid grafted chitosan, tea polyphenol / cyclodextrin inclusion complex and vesicle-coated anthocyanidin into the nicotine salt system to construct a multiple protection network. Among them, gallic acid grafted chitosan has both antioxidant and film-forming properties, and can form a dense protective layer on the surface of nicotine salt to block the invasion of oxygen and other degradation factors. The tea polyphenol / cyclodextrin inclusion complex uses the inclusion effect of cyclodextrin to improve the stability and water solubility of tea polyphenols, enhance its antioxidant activity, and extend the protection time through controlled release. The vesicle-coated anthocyanidin uses liposome technology to encapsulate anthocyanidin in nano-scale vesicles, which not only improves its bioavailability, but also enhances its antioxidant and biological activity. The synergistic effect of these components comprehensively improves the stability and antioxidant properties of nicotine salt from multiple aspects such as steric hindrance, chemical passivation, and controlled release.

[0028] In addition, the present invention has also developed an improved electronic cigarette oil based on the obtained high-stability nicotine salt. By reasonably controlling the addition amount of nicotine salt (2-10%), while giving full play to its quality improvement effect, the taste and smoking quality of the electronic cigarette oil are taken into account, avoiding the negative effects caused by excessive use. This design concept that takes into account both functionality and sensory properties reflects the optimization and innovation of the present invention at the product application level.

[0029] In summary, the present invention takes the stability and antioxidant properties of nicotine salt as a breakthrough, systematically designs and optimizes the links of raw material pretreatment, in-situ synthesis, compounding optimization, product application, etc., and constructs a set of scientific and complete preparation methods. By precisely controlling the reaction conditions and rationally screening the compounding components, a nicotine salt product with excellent properties such as high stability, high antioxidant properties, and high bioavailability is finally obtained, and based on this, an electronic cigarette oil product with excellent quality is developed. These rationally designed and interlocking technical solutions fully demonstrate the innovation of the present invention in basic research and application development, and are of great significance for improving the quality of electronic cigarette products and leading the technological progress of the industry.

[0030] (3) Beneficial technical effects

[0031] 1. Improving the antioxidant properties of nicotine salts: a) Gallic acid grafted chitosan utilizes the biocompatibility and chemical modifiability of chitosan to introduce gallic acid high-efficiency antioxidants through chemical bonding to form a stable antioxidant structure, which can continuously exert antioxidant effects during the high-temperature atomization process of nicotine salts, effectively inhibit the oxidative degradation of nicotine, and greatly improve the retention rate of nicotine activity. However, traditional antioxidants are prone to stratification and precipitation, and the antioxidant effect is not long-lasting. b) The gallic acid grafted chitosan of the present invention uniformly disperses the antioxidant groups on the chitosan molecular chain through a chemical grafting reaction to form a three-dimensional antioxidant barrier. In contrast, the composite antioxidant prepared by the physical mixing method has the problem of uneven dispersion of antioxidant components and easy agglomeration, which affects the antioxidant activity. c) The grafted composite antioxidant prepared by the present invention has excellent thermal stability. The chitosan skeleton can provide physical insulation, and the grafted gallic acid is not easy to volatilize at high temperatures and can continuously exert antioxidant functions. Comparative experiments show that the present invention has significantly better antioxidant effect than traditional antioxidants such as vitamin E in the high-temperature atomization environment of nicotine salt. In summary, the present invention ingeniously utilizes the synergistic effect of chitosan and gallic acid, and significantly improves the antioxidant performance of nicotine salt electronic cigarette oil through chemical grafting molecular design, showing great application value in extending the shelf life of the product, reducing the generation of harmful substances, and ensuring the stable release of nicotine.

[0032] 2. Enhance the thermal stability of nicotine salt e-cigarette oil: Another highlight of the present invention is the introduction of tea polyphenol / cyclodextrin inclusion complex, which further enhances the thermal stability of nicotine salt e-cigarette oil. Compared with the prior art, the innovations of the present invention include: a) Tea polyphenols and nicotine are both heat-sensitive substances, which are prone to degradation and produce harmful substances under the high-temperature atomization environment of electronic cigarettes. The present invention utilizes the cavity inclusion effect of cyclodextrin molecules to encapsulate tea polyphenols in a hydrophobic inner cavity to form a stable inclusion complex, giving it better thermal stability. Compared with free tea polyphenols, the inclusion complex form can effectively inhibit chemical degradation caused by high temperature and maintain the antioxidant activity of tea polyphenols to the greatest extent. b) Traditional antioxidants have poor solubility and dispersibility in the nicotine salt matrix, and are prone to precipitation and crystallization during high-temperature atomization, which are not conducive to the antioxidant effect. The tea polyphenol / hydroxypropyl-β-cyclodextrin inclusion complex prepared by the present invention has excellent water solubility and thermal stability, can be evenly dispersed in the nicotine salt matrix and continuously exert antioxidant effects, especially the thermal stability under high temperature environment is much better than that of free tea polyphenols. c) The tea polyphenol / cyclodextrin inclusion complex is further prepared into a porous spherical shape, and the particle size is controlled at 10-25μm. This structural form not only greatly increases the specific surface area of ​​tea polyphenols, promotes its full contact with nicotine, and improves the antioxidant efficiency; but also the porous structure can realize the controlled release of tea polyphenols, and continuously provide antioxidant protection during the storage and use of nicotine salt. In summary, the present invention cleverly utilizes the inclusion effect of cyclodextrin to prepare tea polyphenols into a porous spherical inclusion complex with high water solubility, high thermal stability and controlled release characteristics, which effectively overcomes the limitations of the application of free tea polyphenols in nicotine salt electronic cigarette oil. Experimental data show that the sensory quality and chemical stability of nicotine salt samples added with tea polyphenols / cyclodextrin inclusion complex after high-temperature atomization are significantly better than those of the blank control group and the group added with free tea polyphenols.

[0033] 3. The present invention innovatively combines bilayer vesicles to encapsulate anthocyanins and nicotine salts, significantly improving the chemical stability and bioavailability of anthocyanins, effectively reducing the generation of harmful substances during nicotine degradation, and significantly improving stability; at the same time, it improves the safety and smoking experience of electronic cigarette liquids. The bilayer vesicle structure formed by lecithin and quinoline dimethacrylate, anthocyanins, nicotine salts and other multi-components form a three-dimensional protection network of "steric hindrance-chemical passivation-controlled release", which increases the half-life of nicotine salts. The carefully designed preparation process ensures the uniform dispersion and long-term stability of the vesicles, effectively controls the production cost while ensuring quality, and has broad prospects for commercial application.

[0034] 4. The present invention is based on gallic acid grafted chitosan and tea polyphenol / cyclodextrin inclusion complex to construct a composite antioxidant system with multi-level antioxidant protection and super synergistic effect. Compared with a single antioxidant, the present invention shows great advantages in improving key performance indicators such as antioxidant properties and thermal stability. This multi-component synergistic design concept provides a new breakthrough for the formulation optimization of nicotine salt electronic cigarette oil, which is of great significance for improving the safety and user experience of electronic cigarettes. At the same time, the chitosan, tea polyphenols, etc. used in the present invention are all green materials of natural origin, which are in line with the health and environmental protection orientation of the current electronic cigarette industry and represent the future development direction of the industry. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 This is the infrared Fourier transform FTIR spectrum of the gallic acid grafted chitosan prepared in Example 1 of the present invention.

[0036] Figure 2 This is the infrared Fourier transform FTIR spectrum of the tea polyphenols / cyclodextrin inclusion complex prepared in Example 1 of the present invention.

[0037] Figure 3 This is a scanning electron microscope morphology image of the tea polyphenols / cyclodextrin inclusion complex prepared in Example 1 of the present invention.

[0038] Figure 4 This is a transmission electron microscopy morphology of vesicles coated with anthocyanins prepared in Example 1 of the present invention. DETAILED DESCRIPTION

[0039] To make the purpose, technical solution and advantages of the embodiments of the present invention more clear, the technical solution in the embodiments of the present invention will be clearly and completely described below in conjunction with the accompanying drawings in the embodiments of the present invention.

[0040] In the case of not specifying specific conditions, the operation in the embodiment is carried out according to conventional conditions or the conditions recommended by the manufacturer. The reagents or instruments used, if the manufacturer is not indicated, are all common products on the market. The parts not mentioned in the technical content of the present invention will be processed with reference to the prior art. Unless otherwise specified, the following examples and comparative examples will be tested in parallel and use the same processing steps and parameters. Table 1 shows the reagents required for the examples and comparative examples and the corresponding purchasing companies.

[0041] Table 1 Reagents required for the examples and comparative examples and the corresponding purchasing companies

[0042] Reagents company nicotine Hubei Guoyun Furui Technology Co., Ltd. Propylene glycol Shandong West Asia Chemical Co., Ltd. Nitrogen Shanghai MacLean Biochemical Technology Co., Ltd. Chitosan Suzhou Qihang Biotechnology Co., Ltd. acetic acid Shanghai Titan Technology Co., Ltd. ascorbic acid Guangzhou Haoyu International Trade Co., Ltd. Hydrogen Peroxide Zhejiang Hangyu Pharmaceutical Technology Co., Ltd. gallic acid Qianyan Chemical Technology (Wuhan) Co., Ltd. Epigallocatechin gallate Shandong West Asia Chemical Co., Ltd. Hydroxypropyl-β-cyclodextrin Guangdong Wengjiang Chemical Reagent Co., Ltd. Lecithin Shandong West Asia Chemical Co., Ltd. Quinoline dimethacrylate Himaclin Biochemical Technology Co., Ltd. Phosphate buffered saline Xilong Scientific Co., Ltd. anthocyanin Jinan Jinhao Chemical Co., Ltd. Sodium citrate buffer Shanghai MacLean Biochemical Technology Co., Ltd. Malic Acid Shandong Mantanghong New Materials Co., Ltd. Citric Acid Guangzhou Yuanda New Materials Co., Ltd. Oxalic acid Shanghai MacLean Biochemical Technology Co., Ltd.

[0043] Example 1

[0044] A high-stability nicotine salt comprises the following components, measured by weight: 40 parts of nicotine, 10 parts of malic acid, 3 parts of gallic acid grafted chitosan, 4 parts of tea polyphenol / cyclodextrin inclusion compound, 2 parts of vesicle-coated anthocyanidins, and 40 parts of propylene glycol.

[0045] The preparation method of chitosan grafted with gallic acid is as follows: by weight fraction, in a nitrogen atmosphere, 40 parts of chitosan with a concentration of 10 mg / mL are dissolved in 20 parts of an acetic acid aqueous solution with a volume fraction of 1%, and then centrifuged at 10000 rpm for 20 minutes, and then a clear chitosan solution is obtained by filtration, and then 0.02 parts of ascorbic acid and 1 part of a 1 mol / L hydrogen peroxide aqueous solution are added thereto, and stirred for 30 minutes in the dark at room temperature, and then 0.4 parts of gallic acid are added, and stirring is continued for 20 hours, and the resulting solution is loaded into a dialysis bag with a molecular weight cutoff of 8 kDa, and dialyzed with ultrapure water at room temperature for 54 hours, during which the dialysis medium is replaced every 8 hours to remove unreacted gallic acid, and finally, the reaction solution is frozen at -20°C and then freeze-dried for 3 days to obtain chitosan grafted with gallic acid.

[0046] The preparation method of the tea polyphenol / cyclodextrin inclusion complex is as follows: by weight, 2 parts of epigallocatechin gallate and 10 parts of hydroxypropyl-β-cyclodextrin are dissolved in 100 parts of deionized water, stirred at 60° C. for 10 hours, and then freeze-dried for 24 hours to obtain the tea polyphenol / cyclodextrin inclusion complex. The tea polyphenol / cyclodextrin inclusion complex is a porous spherical compound with an average diameter of 10 μm.

[0047] The preparation method of vesicle-encapsulated anthocyanidin is as follows: by weight, 5 parts of lecithin and 8 parts of quinoline dimethacrylate are dissolved in 50 parts of chloroform, magnetically stirred for 30 minutes to mix evenly, then the chloroform solvent is completely evaporated in a nitrogen gas stream, and then 5 parts of phosphate buffer are added thereto, followed by vigorous stirring for 30 minutes to obtain a vesicle solution, and then the solvent is completely evaporated in a nitrogen gas stream to form a lipid film, and then 2 parts of anthocyanidin and 4 parts of a mixed solution of sodium citrate buffer are added thereto, and magnetically stirred for 2 hours to obtain vesicle-encapsulated anthocyanidin. The average diameter of the vesicle-encapsulated anthocyanidin is 200nm. The anthocyanidin coverage rate of the vesicle-encapsulated anthocyanidin is 60%.

[0048] The method for preparing the high-stability nicotine salt of this embodiment comprises the following steps:

[0049] S1: After mixing the organic acid and propylene glycol, heat the mixture in a water bath to 40°C and stir the mixture with a magnetic stirrer at 200 rpm for 20 min to obtain a uniform organic acid solution.

[0050] S2: Add nicotine to the organic acid solution obtained in S1, heat to 60° C. in a water bath, and stir magnetically at 400 rpm for 30 min to obtain a nicotine solution.

[0051] S3: Gallic acid grafted chitosan, tea polyphenol / cyclodextrin inclusion complex and vesicle-encapsulated anthocyanidin are continuously added to the nicotine solution obtained in S2, and stirring is continued for 60 minutes, and then freeze-dried to obtain a highly stable nicotine salt.

[0052] Figure 1 The infrared Fourier transform infrared (FTIR) spectrum of gallic acid grafted chitosan showed that gallic acid grafted chitosan had a -1 、1546cm -1 and 1380cm -1 There are characteristic peaks at 1450-1600cm, representing the amide I band of C=O stretching vibration, the amide II band of NH bending vibration, and the amide III band of CN stretching vibration. -1 represents C=C stretching, which indicates that gallic acid is coupled to both the amino and hydroxyl groups of chitosan. In addition, 1732 cm -1 The new peak at corresponds to the ester CO stretching vibration, indicating that the gallic acid-grafted chitosan also contains ester bonds. Figure 2 The CH asymmetric stretching vibration of tea polyphenols / cyclodextrin inclusion complex is located at 2975 cm -1 and the COC asymmetric bending vibration is located at 1443 cm -1 In addition, the prominent broad absorption band of hydroxyl is at 3345 cm -1 , 1200~1320cm -1 The CO stretching vibration was masked by the characteristic absorption peak of hydroxypropyl-β-cyclodextrin, which further indicated that epigallocatechin gallate had successfully penetrated into the cavity of hydroxypropyl-β-cyclodextrin to form a tea polyphenol / cyclodextrin inclusion complex.

[0053] Figure 3 and Figure 4 The following are the scanning electron microscope morphology of the tea polyphenol / cyclodextrin inclusion complex prepared in Example 1 of the present invention and the transmission electron microscope morphology of the vesicle-encapsulated anthocyanin. Figure 3 It can be clearly observed that the tea polyphenols / cyclodextrin inclusion complex presents a regular spherical shape, and the spherical surface is covered with microporous structures of uniform size, proving that the tea polyphenols / cyclodextrin inclusion complex prepared by the present invention is indeed a porous spherical shape. Figure 4 In the image, a large number of vesicle structures can be found, which are relatively light in color; at the same time, darker areas can be observed inside the vesicles. These dark areas should correspond to the anthocyanins encapsulated inside the vesicles. Figure 4 The morphological characteristics of anthocyanins successfully encapsulated in vesicles are intuitively demonstrated. Figure 3 and Figure 4Based on the electron microscopy characterization results, it can be concluded that Example 1 of the present invention successfully prepared a porous spherical tea polyphenol / cyclodextrin inclusion complex with a regular structure, as well as vesicles-encapsulated anthocyanins with anthocyanins encapsulated inside, indicating that the preparation method of the present invention is feasible and effective.

[0054] Example 2

[0055] A high-stability nicotine salt comprises the following components, measured by weight: 46 parts of nicotine, 13 parts of citric acid, 4 parts of gallic acid grafted chitosan, 5 parts of tea polyphenol / cyclodextrin inclusion compound, 3 parts of vesicle-coated anthocyanidins, and 46 parts of propylene glycol.

[0056] The preparation method of chitosan grafted with gallic acid is as follows: by weight fraction, in a nitrogen atmosphere, 45 parts of chitosan with a concentration of 10 mg / mL are dissolved in 25 parts of an acetic acid aqueous solution with a volume fraction of 1%, and then centrifuged at 10000 rpm for 24 minutes, and then a clear chitosan solution is obtained by filtration, and then 0.03 parts of ascorbic acid and 1 part of a 1 mol / L hydrogen peroxide aqueous solution are added thereto, and stirred for 35 minutes in the dark at room temperature, and then 0.5 parts of gallic acid are added, and stirring is continued for 23 hours, and the resulting solution is loaded into a dialysis bag with a molecular weight cutoff of 10 kDa, and dialyzed with ultrapure water at room temperature for 60 hours, during which the dialysis medium is replaced every 8 hours to remove unreacted gallic acid, and finally, the reaction solution is frozen at -20°C and then freeze-dried for 3 days to obtain chitosan grafted with gallic acid.

[0057] The preparation method of the tea polyphenol / cyclodextrin inclusion complex is as follows: by weight, 3 parts of epigallocatechin gallate and 12 parts of hydroxypropyl-β-cyclodextrin are dissolved in 100 parts of deionized water, stirred at 60° C. for 13 hours, and then freeze-dried for 24 hours to obtain the tea polyphenol / cyclodextrin inclusion complex. The tea polyphenol / cyclodextrin inclusion complex is a porous spherical compound with an average diameter of 15 μm.

[0058] The preparation method of vesicle-encapsulated anthocyanidins is as follows: by weight, 7 parts of lecithin and 10 parts of quinoline dimethacrylate are dissolved in 50 parts of chloroform, magnetically stirred for 37 minutes to mix evenly, then the chloroform solvent is completely evaporated in a nitrogen gas stream, and then 7 parts of phosphate buffer are added thereto, followed by vigorous stirring for 35 minutes to obtain a vesicle solution, and then the solvent is completely evaporated in a nitrogen gas stream to form a lipid film, and then 3 parts of anthocyanidins and 5 parts of a mixed solution of sodium citrate buffer are added thereto, and magnetically stirred for 3 hours to obtain vesicle-encapsulated anthocyanidins. The average diameter of the vesicle-encapsulated anthocyanidins is 275nm. The anthocyanidin coverage rate of the vesicle-encapsulated anthocyanidins is 65%.

[0059] The method for preparing the high-stability nicotine salt of this embodiment comprises the following steps:

[0060] S1: After mixing the organic acid and propylene glycol, heat the mixture in a water bath to 43°C and stir the mixture with a magnetic stirrer at 230 rpm for 27 min to obtain a uniform organic acid solution.

[0061] S2: Add nicotine to the organic acid solution obtained in S1, heat to 63° C. in a water bath, and stir magnetically at 430 rpm for 33 min to obtain a nicotine solution.

[0062] S3: Gallic acid grafted chitosan, tea polyphenol / cyclodextrin inclusion complex and vesicle-encapsulated anthocyanidin were added to the nicotine solution obtained in S2, and the mixture was stirred for 69 minutes, and then freeze-dried to obtain a highly stable nicotine salt.

[0063] Example 3

[0064] A high-stability nicotine salt comprises the following components, measured by weight: 52 parts of nicotine, 15 parts of oxalic acid, 5 parts of gallic acid-grafted chitosan, 6 parts of tea polyphenol / cyclodextrin inclusion compound, 4 parts of vesicle-coated anthocyanidins, and 52 parts of propylene glycol.

[0065] The preparation method of chitosan grafted with gallic acid is as follows: by weight fraction, in a nitrogen atmosphere, 50 parts of chitosan with a concentration of 10 mg / mL are dissolved in 29 parts of an acetic acid aqueous solution with a volume fraction of 1%, and then centrifuged at 10000 rpm for 27 minutes, and then a clear chitosan solution is obtained by filtration, and then 0.04 parts of ascorbic acid and 2 parts of a 1 mol / L hydrogen peroxide aqueous solution are added thereto, and stirred for 39 minutes in the dark at room temperature, and then 0.6 parts of gallic acid are added, and stirring is continued for 25 hours, and the resulting solution is loaded into a dialysis bag with a molecular weight cutoff of 12 kDa, and dialyzed with ultrapure water at room temperature for 66 hours, during which the dialysis medium is replaced every 8 hours to remove unreacted gallic acid, and finally, the reaction solution is frozen at -20°C and then freeze-dried for 3 days to obtain chitosan grafted with gallic acid.

[0066] The preparation method of the tea polyphenol / cyclodextrin inclusion complex is as follows: by weight, 4 parts of epigallocatechin gallate and 14 parts of hydroxypropyl-β-cyclodextrin are dissolved in 100 parts of deionized water, stirred at 60° C. for 15 hours, and then freeze-dried for 24 hours to obtain the tea polyphenol / cyclodextrin inclusion complex. The tea polyphenol / cyclodextrin inclusion complex is a porous spherical compound with an average diameter of 19 μm.

[0067] The preparation method of vesicle-encapsulated anthocyanidins is as follows: 9 parts of lecithin and 12 parts of quinoline dimethacrylate are dissolved in 50 parts of chloroform by weight, and magnetically stirred for 43 minutes to mix evenly, then the chloroform solvent is completely evaporated in a nitrogen gas stream, and then 8 parts of phosphate buffer are added thereto, followed by vigorous stirring for 39 minutes to obtain a vesicle solution, and then the solvent is completely evaporated in a nitrogen gas stream to form a lipid film, and then 4 parts of anthocyanidins and 6 parts of a mixed solution of sodium citrate buffer are added thereto, and magnetic stirring is performed for 4 hours to obtain vesicle-encapsulated anthocyanidins. The average diameter of the vesicle-encapsulated anthocyanidins is 350nm. The anthocyanidin coverage rate of the vesicle-encapsulated anthocyanidins is 69%.

[0068] The method for preparing the high-stability nicotine salt of this embodiment comprises the following steps:

[0069] S1: After mixing the organic acid and propylene glycol, heat the mixture in a water bath to 46°C and stir with a magnetic stirrer at 260 rpm for 33 min to obtain a uniform organic acid solution.

[0070] S2: Add nicotine to the organic acid solution obtained in S1, heat to 66° C. in a water bath, and stir magnetically at 460 rpm for 36 min to obtain a nicotine solution.

[0071] S3: Gallic acid grafted chitosan, tea polyphenol / cyclodextrin inclusion complex and vesicle-encapsulated anthocyanidin are continuously added to the nicotine solution obtained in S2, and stirring is continued for 78 minutes, and then freeze-dried to obtain a highly stable nicotine salt.

[0072] Example 4

[0073] A high-stability nicotine salt comprises the following components, measured by weight: 60 parts of nicotine, 18 parts of malic acid, 7 parts of gallic acid grafted chitosan, 8 parts of tea polyphenol / cyclodextrin inclusion compound, 6 parts of vesicle-coated anthocyanidins, and 60 parts of propylene glycol.

[0074] The preparation method of chitosan grafted with gallic acid is as follows: by weight fraction, in a nitrogen atmosphere, 55 parts of chitosan with a concentration of 10 mg / mL are dissolved in 35 parts of an acetic acid aqueous solution with a volume fraction of 1%, and then centrifuged at 10000 rpm for 30 minutes, and then a clear chitosan solution is obtained by filtration, and then 0.06 parts of ascorbic acid and 2 parts of 1 mol / L hydrogen peroxide aqueous solution are added thereto, and stirred at room temperature in the dark for 45 minutes, and then 0.8 parts of gallic acid are added, and stirring is continued for 28 hours, and the resulting solution is loaded into a dialysis bag with a molecular weight cutoff of 14 kDa, and dialyzed with ultrapure water at room temperature for 72 hours, during which the dialysis medium is replaced every 8 hours to remove unreacted gallic acid, and finally, the reaction solution is frozen at -20°C, and then freeze-dried for 3 days to obtain chitosan grafted with gallic acid.

[0075] The preparation method of the tea polyphenol / cyclodextrin inclusion complex is as follows: by weight, 6 parts of epigallocatechin gallate and 16 parts of hydroxypropyl-β-cyclodextrin are dissolved in 100 parts of deionized water, stirred at 60° C. for 18 hours, and then freeze-dried for 24 hours to obtain the tea polyphenol / cyclodextrin inclusion complex. The tea polyphenol / cyclodextrin inclusion complex is a porous spherical compound with an average diameter of 25 μm.

[0076] The preparation method of vesicle-encapsulated anthocyanidin is as follows: by weight, 12 parts of lecithin and 14 parts of quinoline dimethacrylate are dissolved in 50 parts of chloroform, magnetically stirred for 50 minutes to mix evenly, then the chloroform solvent is completely evaporated in a nitrogen gas stream, and then 10 parts of phosphate buffer are added thereto, followed by vigorous stirring for 45 minutes to obtain a vesicle solution, and then the solvent is completely evaporated in a nitrogen gas stream to form a lipid film, and then 5 parts of anthocyanidin and 8 parts of a mixed solution of sodium citrate buffer are added thereto, and magnetically stirred for 5 hours to obtain vesicle-encapsulated anthocyanidin. The average diameter of the vesicle-encapsulated anthocyanidin is 450nm. The anthocyanidin coverage rate of the vesicle-encapsulated anthocyanidin is 75%.

[0077] The method for preparing the high-stability nicotine salt of this embodiment comprises the following steps:

[0078] S1: After mixing the organic acid and propylene glycol, heat the mixture in a water bath to 50°C and stir the mixture with a magnetic stirrer at 300 rpm for 40 min to obtain a uniform organic acid solution.

[0079] S2: Add nicotine to the organic acid solution obtained in S1, heat to 70° C. in a water bath, and stir magnetically at 500 rpm for 40 min to obtain a nicotine solution.

[0080] S3: Gallic acid grafted chitosan, tea polyphenol / cyclodextrin inclusion complex and vesicle-encapsulated anthocyanidin are continuously added to the nicotine solution obtained in S2, and stirring is continued for 90 minutes, and then freeze-dried to obtain a highly stable nicotine salt.

[0081] Example 5

[0082] The method is basically the same as Example 1, except that the amount of gallic acid grafted chitosan is 3 to 7 parts.

[0083] Comparative Example 1

[0084] The method is substantially the same as Example 1, except that an equal amount of gallic acid is used to replace the gallic acid-grafted chitosan.

[0085] Comparative Example 2

[0086] The method is substantially the same as Example 1, except that an equal amount of chitosan is used to replace the gallic acid grafted chitosan.

[0087] Comparative Example 3

[0088] The method is basically the same as Example 1, except that tea polyphenols / cyclodextrin inclusion complex is replaced by tea polyphenols in equal parts.

[0089] Comparative Example 4

[0090] The method is basically the same as Example 1, except that the tea polyphenol / cyclodextrin inclusion complex is replaced by an equal amount of hydroxypropyl-β-cyclodextrin.

[0091] Comparative Example 5

[0092] The method is substantially the same as Example 1, except that the nicotine salt component does not contain vesicle-encapsulated anthocyanidins.

[0093] Performance Testing:

[0094] Antioxidant test: (1) Preparation of electronic cigarette oil: Weigh the high-stability nicotine salt prepared by the present invention, place it in a 100mL volumetric flask, add propylene glycol and glycerol (the volume ratio of propylene glycol and glycerol is 1:1), mix them evenly by ultrasonication, and obtain an electronic cigarette oil sample containing 5% high-stability nicotine salt by mass fraction. (2) Use an oil oxidation stability tester (Rancimat method) to evaluate the antioxidant properties of electronic cigarette oil. The specific steps are as follows: Weigh 3g of electronic cigarette oil sample and place it in the sample tube of the tester. Set the test temperature to 120°C and the air flow rate to 20L / h. Start the test, and the instrument automatically records the conductivity change curve. According to the conductivity change curve, determine the induction time (the time corresponding to the curve mutation point). The longer the induction time, the better the antioxidant property of the sample. This test method refers to the standard method for oil oxidation stability test (Rancimat method), and induces oil oxidation under accelerated conditions (high temperature, strong aeration), and measures the antioxidant property of the oil by the length of the induction time. The high-stability nicotine salt of the present invention is applied to electronic cigarette oil, which can significantly prolong the induction time, indicating that it has excellent antioxidant effect and can effectively improve the stability of electronic cigarette oil during storage and use.

[0095] Stability test: Preparation of electronic cigarette oil: Weigh the high-stability nicotine salt prepared by the present invention, place it in a 100mL volumetric flask, add propylene glycol and glycerol (the volume ratio of propylene glycol and glycerol is 1:1), and mix them evenly by ultrasonication to obtain an electronic cigarette oil sample containing a mass fraction of 5% high-stability nicotine salt. The electronic cigarette oil sample and the blank control sample were equally divided into 10 brown bottles, 10mL per bottle, and divided into two groups after sealing, with 5 parallel samples in each group. The first group: airtight storage at 25°C and relative humidity of 60%. The second group: airtight storage at 40°C and relative humidity of 75%. After 60 days of storage, a parallel sample was taken from each group, and the nicotine content was determined by gas chromatography-mass spectrometry (GC-MS) for evaluating its stability test.

[0096] The properties of the electronic cigarette oils of Examples 1 to 5 and Comparative Examples 1 to 5 are summarized in Table 2.

[0097] Table 2 Performance of electronic cigarette oils in Examples 1 to 5 and Comparative Examples 1 to 5

[0098]

[0099] Compared with Example 1, the induction time of Comparative Example 1 was slightly decreased (9.2h vs 9.6h), and the mass percentage of nicotine in the first and second groups after 60 days was also reduced (4.5% vs 4.8%, 4.3% vs 4.6%). This is because after the gallic acid grafted chitosan was replaced by an equal amount of gallic acid, although gallic acid itself has antioxidant activity, its compatibility and dispersibility with nicotine salts may not be as good as gallic acid grafted onto chitosan. Chitosan, as a carrier, can enhance the interaction between gallic acid and nicotine salts and improve its antioxidant efficiency. Therefore, the antioxidant properties and stability of Comparative Example 1 are reduced to a certain extent.

[0100] Compared with Example 1, the induction time of Comparative Example 2 was significantly reduced (7.2h vs 9.6h), and the mass percentage of nicotine in the first group decreased slightly after 60 days (4.6% vs 4.8%), and the mass percentage of nicotine in the second group decreased more significantly (4.4% vs 4.6%). This is because after the gallic acid grafted chitosan was replaced by an equal amount of chitosan, the system lost the key antioxidant component. Although chitosan has good biocompatibility and drug sustained release, its own antioxidant capacity is weak. Without the modification of gallic acid, chitosan is difficult to effectively inhibit the oxidative degradation of nicotine salts, resulting in a significant impact on the antioxidant and stability of Comparative Example 2.

[0101] Compared with Example 1, the induction time of Comparative Example 3 is basically the same (9.5h vs 9.6h), but after 60 days, the mass percentage of nicotine in the first and second groups decreased (4.4% vs 4.8%, 4.0% vs 4.6%). This is because after the tea polyphenol / cyclodextrin inclusion complex is replaced by an equal number of tea polyphenols, although tea polyphenols themselves are an excellent natural antioxidant, the dispersibility and stability of free tea polyphenols in the nicotine salt system may not be as good as the inclusion complex formed with cyclodextrin. Cyclodextrin can improve the water solubility and bioavailability of tea polyphenols through cavity inclusion, and control its release rate and delay oxidative degradation. Therefore, although the tea polyphenols without cyclodextrin inclusion maintain good antioxidant properties, the stability protection effect on nicotine salts is weakened.

[0102] Compared with Example 1, the induction time of Comparative Example 4 was greatly reduced (6.8h vs 9.6h), and the mass percentage of nicotine in the first and second groups was also significantly reduced after 60 days (4.5% vs 4.8%, 4.3% vs 4.6%). This is because after the tea polyphenol / cyclodextrin inclusion complex was replaced by an equal number of hydroxypropyl-β-cyclodextrin, the system lost the key antioxidant component tea polyphenol. Cyclodextrin itself does not have obvious antioxidant activity, and mainly plays a solubilizing and inclusion role. Without the participation of tea polyphenols, cyclodextrin alone is difficult to effectively inhibit the oxidative degradation of nicotine salts, resulting in significant effects on the antioxidant properties and stability of Comparative Example 4.

[0103] Compared with Example 1, the induction time of Comparative Example 5 was slightly decreased (9.2h vs 9.6h), and the mass percentage of nicotine in the first and second groups after 60 days was also reduced (4.5% vs 4.8%, 4.2% vs 4.6%). This is because the auxiliary antioxidant component of the vesicle-coated anthocyanidin was removed from the nicotine salt component. Anthocyanidins are a type of natural pigment with a wide range of sources and have excellent antioxidant and free radical scavenging abilities. Encapsulating anthocyanidins in vesicles can improve their dispersibility and stability in the nicotine salt system and extend the antioxidant protection time through a sustained release effect. Therefore, after losing the vesicle-coated anthocyanidins, the antioxidant protection ability of nicotine salts decreased, resulting in a certain impact on the antioxidant and stability of Comparative Example 5.

[0104] In summary, the reason why the formula of Example 1 performs best in terms of antioxidant properties and stability is that the three components of gallic acid grafted chitosan, tea polyphenols / cyclodextrin inclusion complex and vesicle-coated anthocyanidins play a synergistic role in the nicotine salt system. Among them, gallic acid grafted chitosan utilizes the carrier effect of chitosan to improve the antioxidant efficiency of gallic acid; tea polyphenols / cyclodextrin inclusion complex utilizes the inclusion effect of cyclodextrin to enhance the dispersibility and stability of tea polyphenols; vesicle-coated anthocyanidins utilize the sustained release effect of vesicles to extend the antioxidant protection time of anthocyanidins. The three components jointly construct a multi-level, three-dimensional composite antioxidant protection system through different mechanisms of action, thereby maximizing the antioxidant stability of nicotine salt preparations. In contrast, the formulas of Comparative Examples 1-5 more or less weakened this composite antioxidant effect, resulting in varying degrees of influence on the antioxidant properties and stability of nicotine salts.

[0105] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention rather than to limit it. Although the present invention has been described in detail with reference to the above embodiments, ordinary technicians in the relevant field should understand that all equivalent structural changes made under the concept of the present invention and using the contents of the present invention specification and drawings should be covered within the scope of protection of the claims of the present invention.

Claims

1. A highly stable nicotine salt, characterized in that: The invention comprises the following components in parts by weight: 40-60 parts of nicotine, 10-18 parts of organic acid, 3-7 parts of gallic acid grafted chitosan, 4-8 parts of tea polyphenol / cyclodextrin inclusion compound, 2-6 parts of vesicle-coated anthocyanidin and 40-60 parts of propylene glycol.

2. A highly stable nicotine salt according to claim 1, characterized in that: Furthermore, the preparation method of the gallic acid grafted chitosan is as follows: by weight, in a nitrogen atmosphere, 40 to 55 parts of chitosan with a concentration of 10 mg / mL are dissolved in 20 to 35 parts of an acetic acid aqueous solution with a volume fraction of 1%, and then centrifuged at 10000 rpm for 20 to 30 minutes, and then a clear chitosan solution is obtained by filtration, and then 0.02 to 0.06 parts of ascorbic acid and 1 to 2 parts of a 1 mol / L hydrogen peroxide aqueous solution are added thereto, and stirred for 30 to 45 minutes in a dark environment at room temperature, and then 0.4 to 0.8 parts of gallic acid are added, and stirring is continued for 20 to 28 hours, and the resulting solution is loaded into a dialysis bag with a molecular weight cutoff of 8 to 14 kDa, and dialyzed with ultrapure water at room temperature for 54 to 72 hours, during which the dialysis medium is replaced every 8 hours to remove unreacted gallic acid, and finally, the reaction solution is frozen at -20°C, and then freeze-dried for 3 days to obtain gallic acid grafted chitosan.

3. The high stability nicotine salt according to claim 1, characterized in that: The preparation method of the tea polyphenol / cyclodextrin inclusion compound is as follows: by weight, 2 to 6 parts of epigallocatechin gallate and 10 to 16 parts of hydroxypropyl-β-cyclodextrin are dissolved in 100 parts of deionized water, stirred at 60° C. for 10 to 18 hours, and then freeze-dried for 24 hours to obtain the tea polyphenol / cyclodextrin inclusion compound.

4. A high stability nicotine salt according to claim 1 or 3, characterized in that: The tea polyphenol / cyclodextrin inclusion compound is in the shape of porous spheres with an average diameter of 10 to 25 μm.

5. The high stability nicotine salt according to claim 1, characterized in that: The preparation method of the vesicle-encapsulated anthocyanidin is as follows: by weight, 5 to 12 parts of lecithin and 8 to 14 parts of quinoline dimethacrylate are dissolved in 50 parts of chloroform, and magnetic stirring is performed for 30 to 50 minutes to mix evenly, and then the chloroform solvent is completely evaporated in a nitrogen gas flow, and then 5 to 10 parts of phosphate buffer are added thereto. Subsequently, the vesicle solution is obtained by vigorous stirring for 30 to 45 minutes, and then the solvent is evaporated in a nitrogen gas stream to form a lipid membrane, and then a mixed solution of 2 to 5 parts of anthocyanins and 4 to 8 parts of sodium citrate buffer is added thereto, and magnetic stirring is performed for 2 to 5 hours to obtain vesicles coated with anthocyanins.

6. A high stability nicotine salt according to claim 1 or 5, characterized in that: The average diameter of the vesicle-coated anthocyanin is 200-450 nm.

7. A high stability nicotine salt according to claim 1, 5 or 6, characterized in that: The anthocyanin coating rate of the vesicle-coated anthocyanin is 60-75%.

8. The high stability nicotine salt according to claim 1, characterized in that: The organic acid is malic acid, citric acid or oxalic acid.

9. A method for preparing a high-stability nicotine salt according to any one of claims 1 to 8, characterized in that: The following steps are involved: S1: After mixing the organic acid and propylene glycol, heat the mixture in a water bath to 40-50°C, and stir the mixture magnetically at 200-300 rpm for 20-40 min to obtain a uniform organic acid solution; S2: Add nicotine to the organic acid solution obtained in S1, heat in a water bath to 60-70°C, and stir magnetically at 400-500 rpm for 30-40 min to obtain a nicotine solution; S3: Gallic acid grafted chitosan, tea polyphenol / cyclodextrin inclusion complex and vesicle-encapsulated anthocyanidin are continuously added to the nicotine solution obtained in S2, and stirring is continued for 60 to 90 minutes, and then freeze-dried to obtain a highly stable nicotine salt.

10. Electronic cigarette oil, characterized in that The electronic cigarette oil comprises the high-stability nicotine salt according to any one of claims 1 to 8 or the high-stability nicotine salt prepared by the preparation method according to claim 9, wherein the mass of the nicotine salt is 2 to 10% of the total weight of the electronic cigarette oil.

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