High stability nicotine salt, preparation method and e-liquid thereof

Abstract

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

Description

Technical Field

[0001] This invention relates to the field of e-cigarette oil, specifically to a highly stable nicotine salt, its preparation method, and the e-cigarette oil thereof. Background Technology

[0002] With the booming development of the e-cigarette industry, nicotine salts, as a key component of e-liquids, are crucial for improving the e-cigarette user experience and protecting user health due to their stability and antioxidant properties. In practical use, nicotine salts face numerous environmental challenges, such as high temperature, humidity, and light exposure. These factors can lead to degradation and oxidation of nicotine salts, affecting the taste of e-cigarettes, nicotine delivery efficiency, and the generation of harmful substances. Therefore, developing nicotine salt formulations with high stability and antioxidant properties is of great significance for ensuring the quality stability of e-liquids, extending shelf life, and improving nicotine utilization. At the same time, excellent stability and antioxidant properties also help improve the sensory experience of e-cigarettes, such as reducing irritation and improving the smoothness of the taste, further enhancing user satisfaction. From an industry development perspective, the research and development of high-performance nicotine salts can not only drive the iterative upgrade of e-cigarette products to meet consumers' increasingly higher quality demands, but also promote the expansion of e-cigarette applications in the field of harm reduction and smoking cessation, providing a safer and healthier alternative for many smokers. Therefore, the development and application of highly stable and antioxidant nicotine salts are of great strategic significance for the development and expansion of the e-cigarette industry and the realization of social benefits.

[0003] Currently, despite significant advancements in nicotine salts, those used in e-liquids generally suffer from insufficient stability and antioxidant properties, failing to meet the increasingly demanding performance requirements of e-cigarette products. On one hand, traditional nicotine salt preparation processes are relatively simple, lacking components and mechanisms to improve nicotine's thermal stability. This results in unsatisfactory thermal stability indicators for the obtained nicotine salts, making them prone to degradation during e-cigarette use and storage, affecting nicotine delivery efficiency and flavor quality. On the other hand, nicotine salts are highly sensitive to oxygen, easily undergoing oxidation reactions to generate harmful degradation products. This not only reduces nicotine utilization but may also introduce health risks. The main reason for these problems is that existing technologies have not adequately considered the design of nicotine salts' antioxidant properties. Furthermore, current preparation methods lack effective antioxidant usage and encapsulation technologies, making it difficult to prevent direct contact between oxygen and nicotine, thus exacerbating oxidative degradation. Therefore, there is an urgent need to develop novel nicotine salts and preparation processes to fundamentally solve the problems of poor stability and antioxidant properties, thereby promoting performance optimization and quality improvement in e-cigarette products. Summary of the Invention

[0004] (1) Technical problems to be solved

[0005] The purpose of this invention is to provide a highly stable nicotine salt, its preparation method, and its e-liquid, thereby solving the problems of poor stability and antioxidant properties of current nicotine salts.

[0006] (2) Technical solution

[0007] To achieve the above objectives, the present invention provides the following technical solution:

[0008] A highly stable nicotine salt, by weight, comprises the following components: 40-60 parts nicotine, 10-18 parts organic acid, 3-7 parts gallic acid-grafted chitosan, 4-8 parts tea polyphenol / cyclodextrin inclusion complex, 2-6 parts vesicle-encapsulated anthocyanins, and 40-60 parts propylene glycol.

[0009] Further, the preparation method of gallic acid-grafted chitosan is as follows: By weight fraction, under a nitrogen atmosphere, 40-55 parts of chitosan with a concentration of 10 mg / mL are dissolved in 20-35 parts of a 1% (v / v) aqueous acetic acid solution. The solution is then centrifuged at 10,000 rpm for 20-30 min, and filtered to obtain a clear chitosan solution. Then, 0.02-0.06 parts of ascorbic acid and 1-2 parts of a 1 mol / L hydrogen peroxide aqueous solution are added. The solution is stirred at room temperature in the dark for 30-45 min. Then, 0.4-0.8 parts of gallic acid are added, and stirring continues for 20-28 h. The resulting solution is placed in a dialysis bag with a molecular weight cutoff of 8-14 kDa and dialyzed with ultrapure water at room temperature for 54-72 hours, changing the dialysis medium every 8 hours to remove unreacted gallic acid. 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, 2-6 parts of epigallocatechin gallate and 10-16 parts of hydroxypropyl-β-cyclodextrin are dissolved in 100 parts of deionized water, stirred at 60°C for 10-18 h, and then freeze-dried for 24 h to obtain the tea polyphenol / cyclodextrin inclusion complex.

[0011] Furthermore, the tea polyphenol / cyclodextrin inclusion complex is a porous sphere with an average diameter of 10–25 μm.

[0012] Furthermore, the preparation method of the vesicle-coated anthocyanins is as follows: by weight, 5-12 parts of lecithin and 8-14 parts of quinoline dimethicone are dissolved in 50 parts of chloroform, and the mixture is stirred magnetically for 30-50 minutes to mix evenly. Then, the chloroform solvent is completely evaporated in a nitrogen gas flow. Then, 5-10 parts of phosphate buffer are added to the mixture, and the mixture is stirred vigorously for 30-45 minutes to obtain a vesicle solution. Then, the solvent is evaporated in a nitrogen gas flow to form a lipid film. Then, a mixed solution of 2-5 parts of anthocyanins and 4-8 parts of sodium citrate buffer is added to the mixture, and the mixture is stirred magnetically for 2-5 hours to obtain vesicle-coated anthocyanins.

[0013] Furthermore, the average diameter of the anthocyanins encapsulated in the vesicles is 200–450 nm.

[0014] Furthermore, the anthocyanin encapsulation rate of the vesicles is 60-75%.

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

[0016] The purpose of this invention is to significantly enhance the antioxidant properties of nicotine salts by adding gallic acid-grafted chitosan. This design concept comprehensively considers the main technical challenges faced by nicotine salts in e-cigarette liquid applications: their susceptibility to oxidative degradation during high-temperature atomization, leading to reduced nicotine activity and the generation of harmful decomposition products, thus affecting safety. To overcome these problems, this invention cleverly introduces gallic acid-grafted chitosan, a functional polymer. Chitosan, as a natural polysaccharide, possesses excellent biocompatibility and chemical modifiability; while gallic acid and its derivatives are recognized as highly effective antioxidants with excellent free radical scavenging capabilities. Combining these two through chemical grafting fully leverages their synergistic effect, endowing the nicotine salt system with stable and reliable antioxidant capabilities. Specifically, in the preparation method of this invention, chitosan is first oxidized and activated using ascorbic acid and hydrogen peroxide to introduce active groups, creating sites for subsequent grafting reactions. Then, gallic acid grafting is carried out under optimal pH, temperature, and other conditions, allowing it to be covalently linked to the chitosan molecular chain. It is worth noting that by strictly controlling key parameters such as reactant ratios and reaction time, the degree of grafting can be precisely controlled, thereby optimizing antioxidant performance. Regarding the mechanism of action of gallic acid grafted onto chitosan, the main points are as follows: First, the gallic acid groups grafted onto the chitosan backbone have excellent free radical scavenging and electron transfer capabilities, effectively blocking free radical chain reactions during oxidation, thus inhibiting the oxidation of nicotine salts. Second, the steric hindrance effect of the chitosan backbone itself can, to a certain extent, isolate oxygen from direct contact with nicotine salts, delaying the oxidation process. Third, gallic acid-grafted chitosan as a whole has good thermal stability, maintaining structural and functional integrity during nicotine salt atomization heating. Furthermore, while optimizing antioxidant performance, this invention also fully considers the compatibility and stability of gallic acid-grafted chitosan in nicotine salt systems. On the one hand, the grafting reaction process can firmly bond gallic acid to the chitosan backbone, preventing its precipitation and stratification during storage and use. On the other hand, the presence of hydrophilic groups in the chitosan backbone helps improve the compatibility of the entire additive with the nicotine salt matrix, ensuring the long-term effectiveness of the antioxidant effect. In summary, this invention introduces gallic acid-grafted chitosan into nicotine salts. Through careful chemical grafting design and process optimization, it fully leverages the synergistic antioxidant effects of chitosan and gallic acid, while also considering the thermal stability and compatibility of the system. This multi-faceted improvement enhances the applicability and safety of nicotine salts in the field of e-cigarette liquids, demonstrating significant technological progress and innovation, and providing important reference for the development of related fields.

[0017] This invention aims to improve the antioxidant properties and thermal stability of nicotine salt e-liquids by incorporating tea polyphenols / cyclodextrin inclusion complexes into nicotine salts. This design has several advantages. First, tea polyphenols, as natural antioxidants, possess excellent antioxidant activity. Epigallocatechin gallate (EGCG) is the main active component of tea polyphenols, exhibiting a strong ability to scavenge free radicals. By introducing tea polyphenols into nicotine salts, the oxidative degradation of nicotine during storage and use can be effectively inhibited, extending the shelf life of e-liquids and reducing the formation of harmful oxidation products. However, tea polyphenols have certain limitations in terms of water solubility and thermal stability. To overcome this problem, this invention employs a strategy of forming inclusion complexes between cyclodextrin and tea polyphenols. Cyclodextrins are a type of cyclic oligosaccharide with a hydrophobic inner cavity and a hydrophilic outer surface. By encapsulating tea polyphenol molecules within the hydrophobic inner cavity of cyclodextrin, its water solubility and stability can be significantly improved. Hydroxypropyl-β-cyclodextrin, a commonly used cyclodextrin derivative, exhibits excellent inclusion properties for tea polyphenols, forming stable tea polyphenol / cyclodextrin inclusion complexes. During preparation, dissolving tea polyphenols and hydroxypropyl-β-cyclodextrin and thoroughly stirring under appropriate temperature and time conditions promotes the formation of these inclusion complexes. Freeze-drying further removes moisture, yielding stable tea polyphenol / cyclodextrin inclusion complexes. These complexes not only possess good water solubility but also enhance the stability of tea polyphenols at high temperatures, reducing their degradation and volatilization. Adding these tea polyphenol / cyclodextrin inclusion complexes to nicotine salts can exert a synergistic effect, comprehensively improving the quality of e-liquids. On one hand, the antioxidant activity of tea polyphenols protects nicotine salts from oxidative degradation, extending the e-liquid's lifespan. On the other hand, the inclusion effect of cyclodextrin improves the dispersibility and solubility of tea polyphenols in the nicotine salt matrix, ensuring the effective exertion of their antioxidant function. Meanwhile, the formation of inclusion complexes enhances the thermal stability of tea polyphenols during high-temperature atomization, reducing the risk of degradation and the generation of harmful substances. In summary, this invention cleverly utilizes the antioxidant properties of tea polyphenols and the inclusion effect of cyclodextrin by adding tea polyphenol / cyclodextrin inclusion complexes to nicotine salts, thereby improving the antioxidant and thermal stability of nicotine salt e-liquids. This technical solution not only extends product shelf life and reduces the generation of harmful substances but also ensures stable nicotine release and absorption, improving the quality and safety of e-liquids. Furthermore, the use of natural antioxidant tea polyphenols and environmentally friendly material cyclodextrin aligns with the current trend of green and healthy development in the e-cigarette industry.

[0018] This invention further specifies that the tea polyphenol / cyclodextrin inclusion complex is a porous spherical structure with an average diameter of 10–25 μm. The objectives are: firstly, to utilize cyclodextrin to encapsulate tea polyphenols, forming a porous spherical complex with controllable size, thereby improving the stability and water solubility of tea polyphenols and enhancing their antioxidant activity; secondly, to increase the specific surface area of ​​the inclusion complex through the porous spherical structure, promoting sufficient contact between tea polyphenols and nicotine, more effectively blocking the oxidative degradation process of nicotine, and improving nicotine stability; finally, to utilize the porous structure to achieve controlled release of tea polyphenols, prolonging the antioxidant protection time, and further enhancing the storage stability of nicotine salts. In summary, the rational design of the morphology and size of the tea polyphenol / cyclodextrin inclusion complex is of great significance for comprehensively improving the quality of the nicotine salts of this invention.

[0019] In this invention, gallic acid-grafted chitosan and tea polyphenol / cyclodextrin inclusion complexes each play their unique roles, significantly enhancing the antioxidant properties and thermal stability of the material through a synergistic effect. Gallic acid-grafted chitosan primarily focuses on improving the material's antioxidant properties. 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, endowing the material with stronger antioxidant capacity. Simultaneously, the polyhydroxy structure of chitosan also contributes to improving the material's thermal stability. The tea polyphenol / cyclodextrin inclusion complex, on the other hand, focuses on enhancing the material's thermal stability. Tea polyphenols are a class of natural antioxidants, but they are easily degraded at high temperatures. By forming an inclusion complex with hydroxypropyl-β-cyclodextrin, the thermal stability of tea polyphenols can be significantly enhanced. Furthermore, the inclusion complex can improve the water solubility and dispersibility of tea polyphenols, which is beneficial for their uniform distribution in the matrix and their antioxidant function. Gallic acid grafted onto chitosan fixes gallic acid onto the chitosan molecular chain through chemical bonding, forming a stable grafted structure. The mechanism of action in enhancing antioxidant properties: Gallic acid, as a polyphenolic antioxidant, possesses 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 the material, effectively blocking the propagation of the oxidation reaction chain, thereby significantly improving the material's antioxidant performance. 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 within their hydrophobic cavities through cavity inclusion, forming stable inclusion complexes. This inclusion effect not only protects tea polyphenols from external environmental influences but also improves their dispersibility and availability in the material, thus exerting a more efficient antioxidant function. The mechanism of action in enhancing thermal stability: The chitosan backbone in gallic acid grafted onto chitosan possesses excellent thermal stability. The numerous hydrogen bonds and intermolecular forces on the chitosan molecular chain can form a tight network structure, increasing the material's heat distortion temperature and thermal decomposition temperature. Simultaneously, the grafted gallic acid molecules also act as physical cross-linkers, further enhancing the thermal stability of the chitosan matrix. The formation of tea polyphenol / cyclodextrin inclusion complexes significantly improves the stability of tea polyphenols at high temperatures. Cyclodextrin molecules can encapsulate heat-sensitive tea polyphenol molecules within their hydrophobic cavities through cavity encapsulation, isolating them from the influence of the external environment. This "molecular capsule" effect effectively inhibits the degradation and volatilization of tea polyphenols at high temperatures, thereby significantly improving their thermal stability. Furthermore, cyclodextrin molecules themselves also possess 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 complexes exhibit significant synergistic effects in the composite material system. First, the two components have good structural compatibility.Chitosan and cyclodextrin are both polysaccharide compounds. Their hydrophilic structures can form hydrogen bonds and other intermolecular interactions with tea polyphenols, which helps the inclusion complex to disperse uniformly in the chitosan matrix. Secondly, gallic acid and tea polyphenols have complementary antioxidant mechanisms. Gallic acid mainly exerts its antioxidant effect through hydrogen atom transfer and free radical scavenging mechanisms, while tea polyphenols mainly inhibit oxidation through redox reactions. The synergistic effect of these two antioxidants can comprehensively block the oxidation reaction chain, providing multi-layered antioxidant protection. Furthermore, the formation of the inclusion complex can promote the dispersion and protection of tea polyphenols in the chitosan matrix, improving the utilization rate of its antioxidant activity. Simultaneously, the good film-forming properties and thermal stability of chitosan provide a stable carrier for the tea polyphenol / cyclodextrin inclusion complex, promoting the overall performance improvement of the composite material. In summary, the synergistic effect of gallic acid-grafted chitosan and tea polyphenol / cyclodextrin inclusion complexes is mainly reflected in the following aspects: 1. Structural compatibility: Both components are polysaccharide compounds with good compatibility and intermolecular interactions, which is conducive to the formation of a homogeneous and stable composite material. 2. Complementary antioxidant mechanisms: Gallic acid and tea polyphenols exert their effects through different antioxidant mechanisms, synergistically providing comprehensive antioxidant protection. 3. Dispersion and protection of the inclusion complex: Cyclodextrin molecules can encapsulate and protect tea polyphenols, improving their dispersibility and stability in the chitosan matrix and promoting antioxidant activity. 4. Synergistic improvement of thermal stability: Both the chitosan backbone and cyclodextrin molecules have good thermal stability, and their synergistic effect with gallic acid and tea polyphenols can significantly improve the overall thermal stability of the composite material.

[0020] This invention utilizes the antioxidant and bioactive regulatory effects of anthocyanins in its vesicle-encapsulated form to enhance the stability and safety of nicotine salts, while simultaneously improving the e-cigarette smoking experience. Firstly, by encapsulating anthocyanins in vesicles composed of lecithin and quinoline dimethicone, this invention significantly improves the chemical stability and bioavailability of anthocyanins. The bilayer structure formed by lecithin and quinoline dimethicone effectively protects the anthocyanins within the core, preventing degradation or oxidation during storage and use. Simultaneously, the vesicle structure controls the release rate of anthocyanins, achieving a sustained-release effect and prolonging their duration of action in the body. Secondly, combining vesicle-encapsulated anthocyanins with nicotine fully utilizes the antioxidant activity of anthocyanins, delaying the degradation and oxidation of nicotine salts. Nicotine salts may undergo degradation to some extent in e-cigarette liquids, generating harmful substances such as nitrosamines, which affect the safety of e-cigarettes. Anthocyanins, as natural antioxidants, can scavenge free radicals generated during degradation, block oxidation reaction chains, thereby improving the stability of nicotine salts and reducing the formation of harmful substances. Furthermore, anthocyanins also possess certain anti-inflammatory and antiviral activities. When vaping, nicotine may cause irritation and inflammation of the respiratory tract and lungs, affecting the vaping experience and health. Introducing vesicle-coated anthocyanins into e-cigarette liquids can utilize the bioactivity of anthocyanins to reduce nicotine-induced inflammation, protect respiratory and lung tissues, and improve the comfort and safety of e-cigarettes. To achieve the above objectives, this invention employs a carefully designed vesicle-coated anthocyanin preparation process. Lecithin and quinoline dimethicone are dissolved in chloroform, and the solvent is then removed by nitrogen stripping to form a uniform and stable lipid membrane. Then, anthocyanins are mixed with sodium citrate buffer and added to the lipid membrane. Magnetic stirring is used to encapsulate the anthocyanins into the vesicle nuclei, forming the final vesicle-coated anthocyanins. This preparation process can effectively control the particle size, distribution, and morphology of vesicles, ensuring their dispersibility and stability in e-liquids. In summary, this invention cleverly utilizes the antioxidant and bioactivity of anthocyanins by combining vesicle-encapsulated anthocyanins with nicotine salts, thereby improving the stability and safety of nicotine salts and enhancing the e-cigarette smoking experience. This novel e-liquid formulation not only has application value but also provides new ideas and directions for innovation and development in the e-cigarette field. Further research can optimize the preparation process of vesicle-encapsulated anthocyanins, explore its mechanism of action in greater depth, and expand its application scope in e-liquids and other fields.

[0021] This invention limits the average diameter of anthocyanins encapsulated in vesicles to 200–450 nm. Its objectives are twofold: First, by forming nanoscale vesicles, the water solubility and bioavailability of anthocyanins are significantly improved, overcoming their poor stability and easy degradation in physiological environments. Second, the nanoscale size of the vesicles is beneficial for enhancing the antioxidant and bioactivity of anthocyanins, strengthening their protective effect on nicotine molecules, effectively inhibiting the oxidative degradation of nicotine, and improving the stability of nicotine salts. Furthermore, this invention further limits the anthocyanin encapsulation rate of vesicle-encapsulated anthocyanins to 60–75%, ensuring both effective utilization of anthocyanins and avoiding increased preparation costs due to excessively high encapsulation rates, thus balancing product quality and economic benefits.

[0022] This invention also provides a method for preparing highly stable nicotine salt, comprising the following steps;

[0023] S1: Mix organic acid and propylene glycol and heat in a water bath to 40-50°C. Stir magnetically at 200-300 rpm for 20-40 minutes to obtain a homogeneous 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 magnetically stir at 400-500 rpm for 30-40 minutes to obtain a nicotine solution.

[0025] S3: Add gallic acid-grafted chitosan, tea polyphenol / cyclodextrin inclusion complex and vesicle-coated anthocyanins to the nicotine solution obtained in S2 and continue stirring for 60-90 minutes. Then freeze-dry to obtain highly stable nicotine salt.

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

[0027] The present invention provides a highly stable nicotine salt preparation method, which is a carefully designed multi-step, multi-component compounding process. First, in the pretreatment stage, an organic acid solution is obtained by mixing and heating propylene glycol. This step aims to create favorable conditions for the dissolution of nicotine and its reaction with the organic acid. Propylene glycol, as an excipient and dispersion medium, can significantly improve the homogeneity and flowability of the system, facilitating the smooth progress of subsequent processes. In the second step, nicotine is added to the organic acid solution and stirred thoroughly at a higher temperature, allowing the nicotine to react with the organic acid and generate nicotine salt in situ. This in-situ reaction mode not only improves the efficiency of nicotine salt formation but also avoids cumbersome subsequent separation and purification steps, simplifying the process. Simultaneously, the higher reaction temperature helps overcome the steric hindrance effect of nicotine and organic acid, promoting the reaction, improving conversion rate and product quality. The third step, the core of this invention, employs a multi-component compounding strategy, introducing various functional excipients such as gallic acid-grafted chitosan, tea polyphenol / cyclodextrin inclusion complexes, and vesicle-encapsulated anthocyanins into the nicotine salt system to construct a multi-layered protective network. Gallic acid-grafted chitosan possesses both antioxidant and film-forming properties, forming a dense protective layer on the nicotine salt surface to block the invasion of oxygen and other degradation factors. The tea polyphenol / cyclodextrin inclusion complex utilizes the inclusion effect of cyclodextrin to improve the stability and water solubility of tea polyphenols, enhancing their antioxidant activity, while extending the protective time through controlled release. Vesicle-encapsulated anthocyanins utilize liposome technology to encapsulate anthocyanins in nanoscale vesicles, improving their bioavailability and enhancing their antioxidant and biological activities. The synergistic effect of these components comprehensively improves the stability and antioxidant performance of nicotine salts from multiple aspects, including steric hindrance, chemical passivation, and controlled release.

[0028] Furthermore, based on the obtained highly stable nicotine salt, this invention has developed an improved e-liquid. By rationally controlling the amount of nicotine salt added (2-10%), its quality-improving effects are fully utilized while also taking into account the taste and smoking quality of the e-liquid, avoiding the negative effects caused by excessive use. This design concept, which balances functionality and sensory appeal, reflects the optimized innovation of this invention at the product application level.

[0029] In summary, this invention focuses on the stability and antioxidant properties of nicotine salts, systematically designing and optimizing various stages including raw material pretreatment, in-situ synthesis, compound optimization, and product application, thus constructing a scientifically sound preparation method. Through precise control of reaction conditions and rational screening of compound components, a nicotine salt product exhibiting excellent properties such as high stability, high antioxidant capacity, and high bioavailability was ultimately obtained. Based on this, high-quality e-cigarette liquid products were developed. These rationally designed and interconnected technical solutions fully demonstrate the innovation of this invention in basic research and application development, and are of great significance for improving the quality of e-cigarette products and leading technological progress in the industry.

[0030] (3) Beneficial technical effects

[0031] 1. Enhancing the antioxidant properties of nicotine salts: a) Gallic acid grafted onto chitosan utilizes the biocompatibility and chemical modifiability of chitosan to introduce gallic acid, a highly effective antioxidant, through chemical bonding, forming a stable antioxidant structure. This structure can continuously exert its antioxidant effect during the high-temperature atomization of nicotine salts, effectively inhibiting the oxidative degradation of nicotine and significantly improving the retention rate of nicotine activity. Traditional antioxidants are prone to stratification and precipitation, resulting in short-lasting antioxidant effects. b) The gallic acid grafted onto chitosan of this invention uniformly disperses antioxidant groups on the chitosan molecular chain through a chemical grafting reaction, forming a three-dimensional antioxidant barrier. In contrast, composite antioxidants prepared by physical mixing methods suffer from uneven dispersion of antioxidant components and easy aggregation, affecting the antioxidant activity. c) The grafted composite antioxidant prepared by this invention has excellent thermal stability. The chitosan backbone provides physical insulation, while the grafted gallic acid is not easily volatilized at high temperatures, allowing it to continuously exert its antioxidant function. Comparative experiments show that, in the high-temperature atomization environment of nicotine salts, the antioxidant effect of this invention is significantly superior to traditional antioxidants such as vitamin E. In summary, this invention cleverly utilizes the synergistic effect of chitosan and gallic acid, and through chemical grafting molecular design, significantly improves the antioxidant performance of nicotine salt e-liquids, demonstrating significant application value in extending product shelf life, reducing the generation of harmful substances, and ensuring stable nicotine release.

[0032] 2. Enhanced Thermal Stability of Nicotine Salt E-liquid: Another major highlight of this invention is the introduction of a tea polyphenol / cyclodextrin inclusion complex, which further enhances the thermal stability of the nicotine salt e-liquid. Compared with existing technologies, the innovations of this invention include: a) Both tea polyphenols and nicotine are heat-sensitive substances, easily degrading and producing harmful substances under the high-temperature atomization environment of e-cigarettes. This invention utilizes the cavity inclusion effect of cyclodextrin molecules to encapsulate tea polyphenols in a hydrophobic cavity, forming a stable inclusion complex and giving it superior thermal stability. Compared with free tea polyphenols, the inclusion complex form can effectively inhibit high-temperature-induced chemical degradation and maximize the preservation of the antioxidant activity of tea polyphenols. b) Traditional antioxidants have poor solubility and dispersibility in nicotine salt matrices, and are prone to precipitation and crystallization during high-temperature atomization, which are detrimental to the antioxidant effect. The tea polyphenol / hydroxypropyl-β-cyclodextrin inclusion complex prepared in this invention exhibits excellent water solubility and thermal stability. It can be uniformly dispersed in a nicotine salt matrix and continuously exerts its antioxidant effect, especially with thermal stability at high temperatures that is far superior to that of free tea polyphenols. c) The tea polyphenol / cyclodextrin inclusion complex is further prepared into porous spheres with a particle size controlled at 10-25 μm. This structural form not only significantly increases the specific surface area of ​​tea polyphenols, promoting full contact with nicotine and improving antioxidant efficiency, but also allows for controlled release of tea polyphenols, continuously providing antioxidant protection during the storage and use of nicotine salts. In summary, this invention cleverly utilizes the inclusion effect of cyclodextrin to prepare tea polyphenols into porous spherical inclusion complexes with high water solubility, high thermal stability, and controlled release characteristics, effectively overcoming the limitations of free tea polyphenols in nicotine salt e-cigarette liquids. Experimental data show that the nicotine salt sample with added tea polyphenols / cyclodextrin inclusion complex exhibits significantly better sensory quality and chemical stability than the blank control group and the free tea polyphenol addition group after high-temperature atomization.

[0033] 3. This invention innovatively combines bilayer vesicles with 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 enhancing stability; it also improves the safety and user experience of e-liquids. The bilayer vesicle structure formed by lecithin and quinoline dimethicone, along with the combination of anthocyanins, nicotine salts, and other components, forms a three-dimensional protective network of "steric hindrance-chemical passivation-controlled release," increasing the half-life of nicotine salts. The meticulously designed preparation process ensures uniform dispersion and long-term stability of the vesicles, effectively controlling production costs while guaranteeing quality, and has broad commercial application prospects.

[0034] 4. This invention utilizes gallic acid-grafted chitosan and tea polyphenol / cyclodextrin inclusion complexes to construct a compound antioxidant system with multi-layered antioxidant protection and a powerful synergistic effect. Compared to single antioxidants, this invention demonstrates significant advantages in improving key performance indicators such as antioxidant properties and thermal stability. This multi-component synergistic design approach provides a new breakthrough for optimizing nicotine salt e-cigarette liquid formulations, and is of great significance for improving the safety and user experience of e-cigarettes. Furthermore, the chitosan and tea polyphenols used in this invention are all naturally derived green materials, aligning with the current health and environmental protection orientation of the e-cigarette industry and representing the future development direction of the industry. Attached Figure Description

[0035] Figure 1 The infrared Fourier transform (FTIR) spectrum of gallic acid-grafted chitosan prepared in Example 1 of this invention.

[0036] Figure 2 The image shows the infrared Fourier transform (FTIR) spectrum of the tea polyphenol / cyclodextrin inclusion complex prepared in Example 1 of this invention.

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

[0038] Figure 4 This is a transmission electron microscope (TEM) image of the anthocyanin-coated vesicles prepared in Example 1 of the present invention. Detailed Implementation

[0039] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings.

[0040] Unless otherwise specified, the operations in the examples are performed under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used, unless otherwise specified, are common commercial products. Parts of the technical content of this invention not mentioned will be handled with reference to existing technology. Unless otherwise specified, the following examples and comparative examples will be conducted in parallel, using the same processing steps and parameters. Table 1 lists the reagents required for the examples and comparative examples and their corresponding purchasing companies.

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

[0042] nicotine Hubei Guoyun Furui Technology Co., Ltd. Propylene glycol Shandong Xiya Chemical Co., Ltd. Nitrogen Shanghai McLean 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 Pre-derivative chemical technology (Wuhan) Co., Ltd. Epigallocatechin gallate Shandong Xiya Chemical Co., Ltd. Hydroxypropyl-β-cyclodextrin Guangdong Wengjiang Chemical Reagent Co., Ltd. Lecithin Shandong Xiya Chemical Co., Ltd. Quinodimethicone HaiMikeLin Biochemical Technology Co., Ltd. Phosphate buffer Xilong Scientific Co., Ltd. anthocyanin Jinan Jinhao Chemical Co., Ltd. Sodium citrate buffer Shanghai McLean Biochemical Technology Co., Ltd. malic acid Shandong Mantanghong New Materials Co., Ltd. Citric acid Guangzhou Yuanda New Materials Co., Ltd. oxalic acid Shanghai McLean Biochemical Technology Co., Ltd.

[0043] Example 1

[0044] A highly stable nicotine salt, by weight, comprises the following components: 40 parts nicotine, 10 parts malic acid, 3 parts gallic acid-grafted chitosan, 4 parts tea polyphenol / cyclodextrin inclusion complex, 2 parts vesicle-encapsulated anthocyanins, and 40 parts propylene glycol.

[0045] The preparation method of gallic acid-grafted chitosan is as follows: By weight fraction, under a nitrogen atmosphere, 40 parts of chitosan with a concentration of 10 mg / mL were dissolved in 20 parts of a 1% (v / v) aqueous acetic acid solution. The solution was then centrifuged at 10,000 rpm for 20 min, and filtered to obtain a clear chitosan solution. Then, 0.02 parts of ascorbic acid and 1 part of a 1 mol / L hydrogen peroxide aqueous solution were added, and the solution was stirred at room temperature in the dark for 30 min. Next, 0.4 parts of gallic acid were added, and stirring continued for 20 h. The resulting solution was placed in a dialysis bag with a molecular weight cutoff of 8 kDa and dialyzed with ultrapure water at room temperature for 54 h, changing the dialysis medium every 8 hours to remove unreacted gallic acid. Finally, the reaction solution was frozen at -20℃ and then freeze-dried for 3 days to obtain gallic acid-grafted chitosan.

[0046] The preparation method of the tea polyphenol / cyclodextrin inclusion complex is as follows: 2 parts by weight of epigallocatechin gallate and 10 parts by weight of hydroxypropyl-β-cyclodextrin are dissolved in 100 parts by weight of deionized water, stirred at 60°C for 10 h, and then freeze-dried for 24 h 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-coated anthocyanins is as follows: By weight, 5 parts lecithin and 8 parts quinoline dimethicone were dissolved in 50 parts chloroform and magnetically stirred for 30 minutes to mix thoroughly. Then, the chloroform solvent was completely evaporated under a nitrogen atmosphere. Next, 5 parts phosphate buffer were added, and the mixture was vigorously stirred for 30 minutes to obtain a vesicle solution. The solvent was then evaporated under a nitrogen atmosphere to form a lipid film. Finally, a mixture of 2 parts anthocyanins and 4 parts sodium citrate buffer was added, and the mixture was magnetically stirred for 2 hours to obtain vesicle-coated anthocyanins. The average diameter of the vesicle-coated anthocyanins was 200 nm. The anthocyanin encapsulation rate of the vesicle-coated anthocyanins was 60%.

[0048] The method for preparing highly stable nicotine salt in this embodiment includes the following steps;

[0049] S1: Mix organic acid and propylene glycol and heat in a water bath to 40°C. Stir magnetically at 200 rpm for 20 min to obtain a homogeneous organic acid solution.

[0050] S2: Add nicotine to the organic acid solution obtained in S1, heat in a water bath to 60°C, 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-coated anthocyanins were added to the nicotine solution obtained in S2 and stirred for 60 min. Then, after freeze-drying, a highly stable nicotine salt was obtained.

[0052] Figure 1 The Fourier transform (FTIR) spectrum of gallic acid-grafted chitosan showed that gallic acid-grafted chitosan had a peak density of 1649 cm⁻¹. -1 1546cm -1 and 1380cm -1 The peaks at 1450-1600 cm⁻¹ represent the amide I band of C=O tensile vibration, the amide II band of NH bending vibration, and the amide III band of CN tensile vibration, respectively. -1 The position represents C=C stretching, indicating that gallic acid is coupled to both the amino and hydroxyl groups of chitosan. Furthermore, 1732 cm⁻¹ -1 The new peak at this point corresponds to the CO stretching vibration of the ester, indicating that gallic acid-grafted chitosan also contains ester bonds. Figure 2 The CH asymmetric stretching vibration of the tea polyphenol / cyclodextrin inclusion complex is located at 2975 cm⁻¹. -1 The asymmetric bending vibration of COC is located at 1443 cm. -1 Furthermore, the prominent broad absorption band of the hydroxyl group is at 3345 cm⁻¹. -1 1200~1320cm -1 The fact that the CO stretching vibration was masked by the characteristic absorption peak of hydroxypropyl-β-cyclodextrin further indicates that epigallocatechin gallate has successfully penetrated into the cavity of hydroxypropyl-β-cyclodextrin to form a tea polyphenol / cyclodextrin inclusion complex.

[0053] Figure 3 and Figure 4 The images show scanning electron microscope (SEM) images of the tea polyphenol / cyclodextrin inclusion complex prepared in Example 1 of this invention, and transmission electron microscope (TEM) images of the anthocyanin-encapsulated vesicles. Figure 3 It can be clearly observed that the tea polyphenol / cyclodextrin inclusion complex exhibits a regular spherical shape, and the surface of the spheres is covered with uniformly sized micropores, proving that the tea polyphenol / cyclodextrin inclusion complex prepared in this invention is indeed a porous sphere. Figure 4 Numerous vesicle structures can be observed, which are relatively light in color; at the same time, darker areas can be observed inside the vesicles, which should correspond to anthocyanins encapsulated inside the vesicles. Figure 4 This visually demonstrates the morphological characteristics of anthocyanins successfully encapsulated within vesicles. (Summary) 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 well-structured porous spherical tea polyphenol / cyclodextrin inclusion complex, as well as vesicles coated with anthocyanins, indicating that the preparation method of the present invention is feasible and effective.

[0054] Example 2

[0055] A highly stable nicotine salt, by weight, comprises the following components: 46 parts nicotine, 13 parts citric acid, 4 parts gallic acid-grafted chitosan, 5 parts tea polyphenol / cyclodextrin inclusion complex, 3 parts vesicle-encapsulated anthocyanins, and 46 parts propylene glycol.

[0056] The preparation method of gallic acid-grafted chitosan is as follows: By weight fraction, under a nitrogen atmosphere, 45 parts of chitosan with a concentration of 10 mg / mL were dissolved in 25 parts of acetic acid aqueous solution with a volume fraction of 1%. The solution was then centrifuged at 10,000 rpm for 24 min, and filtered to obtain a clear chitosan solution. Then, 0.03 parts of ascorbic acid and 1 part of 1 mol / L hydrogen peroxide aqueous solution were added, and the solution was stirred at room temperature in the dark for 35 min. Next, 0.5 parts of gallic acid were added, and stirring continued for 23 h. The resulting solution was placed in a dialysis bag with a molecular weight cutoff of 10 kDa and dialyzed with ultrapure water at room temperature for 60 h, changing the dialysis medium every 8 hours to remove unreacted gallic acid. Finally, the reaction solution was frozen at -20℃ and then freeze-dried for 3 days to obtain gallic acid-grafted chitosan.

[0057] The preparation method of the tea polyphenol / cyclodextrin inclusion complex is as follows: 3 parts by weight of epigallocatechin gallate and 12 parts by weight of hydroxypropyl-β-cyclodextrin are dissolved in 100 parts by weight of deionized water, stirred at 60°C for 13 h, and then freeze-dried for 24 h 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-coated anthocyanins is as follows: By weight, 7 parts lecithin and 10 parts quinoline dimethicone were dissolved in 50 parts chloroform and magnetically stirred for 37 min to mix thoroughly. Then, the chloroform solvent was completely evaporated under a nitrogen atmosphere. Next, 7 parts phosphate buffer were added, and the mixture was stirred vigorously for 35 min to obtain a vesicle solution. The solvent was then evaporated under a nitrogen atmosphere to form a lipid film. Finally, a mixture of 3 parts anthocyanins and 5 parts sodium citrate buffer was added, and the mixture was magnetically stirred for 3 h to obtain vesicle-coated anthocyanins. The average diameter of the vesicle-coated anthocyanins was 275 nm. The anthocyanin encapsulation rate of the vesicle-coated anthocyanins was 65%.

[0059] The method for preparing highly stable nicotine salt in this embodiment includes the following steps;

[0060] S1: Mix organic acid and propylene glycol and heat in a water bath to 43°C. Stir magnetically at 230 rpm for 27 min to obtain a homogeneous organic acid solution.

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

[0062] S3: Gallic acid-grafted chitosan, tea polyphenol / cyclodextrin inclusion complex and vesicle-coated anthocyanins were added to the nicotine solution obtained in S2 and stirred for 69 min. Then, after freeze-drying, a highly stable nicotine salt was obtained.

[0063] Example 3

[0064] A highly stable nicotine salt, by weight, comprises the following components: 52 parts nicotine, 15 parts oxalic acid, 5 parts gallic acid-grafted chitosan, 6 parts tea polyphenol / cyclodextrin inclusion complex, 4 parts vesicle-encapsulated anthocyanins, and 52 parts propylene glycol.

[0065] The preparation method of gallic acid-grafted chitosan is as follows: 50 parts by weight of chitosan with a concentration of 10 mg / mL were dissolved in 29 parts by volume of 1% acetic acid aqueous solution under a nitrogen atmosphere. The solution was then centrifuged at 10,000 rpm for 27 min, and filtered to obtain a clear chitosan solution. 0.04 parts ascorbic acid and 2 parts of 1 mol / L hydrogen peroxide aqueous solution were added to the solution, and the mixture was stirred at room temperature in the dark for 39 min. Then, 0.6 parts gallic acid were added, and stirring was continued for 25 h. The resulting solution was placed in a dialysis bag with a molecular weight cutoff of 12 kDa and dialyzed with ultrapure water at room temperature for 66 h, with the dialysis medium changed every 8 hours to remove unreacted gallic acid. Finally, the reaction solution was frozen at -20℃ and then freeze-dried for 3 days to obtain gallic acid-grafted chitosan.

[0066] The preparation method of the tea polyphenol / cyclodextrin inclusion complex is as follows: 4 parts by weight of epigallocatechin gallate and 14 parts by weight of hydroxypropyl-β-cyclodextrin are dissolved in 100 parts by weight of deionized water, stirred at 60°C for 15 h, and then freeze-dried for 24 h 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-coated anthocyanins is as follows: By weight, 9 parts lecithin and 12 parts quinoline dimethicone were dissolved in 50 parts chloroform and magnetically stirred for 43 min to mix thoroughly. Then, the chloroform solvent was completely evaporated under a nitrogen atmosphere. Next, 8 parts phosphate buffer were added, and the mixture was vigorously stirred for 39 min to obtain a vesicle solution. The solvent was then evaporated under a nitrogen atmosphere to form a lipid film. Finally, a mixture of 4 parts anthocyanins and 6 parts sodium citrate buffer was added, and the mixture was magnetically stirred for 4 h to obtain vesicle-coated anthocyanins. The average diameter of the vesicle-coated anthocyanins was 350 nm. The anthocyanin encapsulation rate of the vesicle-coated anthocyanins was 69%.

[0068] The method for preparing highly stable nicotine salt in this embodiment includes the following steps;

[0069] S1: Mix organic acid and propylene glycol and heat in a water bath to 46°C. Stir magnetically at 260 rpm for 33 min to obtain a homogeneous organic acid solution.

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

[0071] S3: Add gallic acid-grafted chitosan, tea polyphenol / cyclodextrin inclusion complex and vesicle-coated anthocyanins to the nicotine solution obtained in S2 and stir for 78 min. Then freeze-dry to obtain highly stable nicotine salt.

[0072] Example 4

[0073] A highly stable nicotine salt, by weight, comprises the following components: 60 parts nicotine, 18 parts malic acid, 7 parts gallic acid-grafted chitosan, 8 parts tea polyphenol / cyclodextrin inclusion complex, 6 parts vesicle-encapsulated anthocyanins, and 60 parts propylene glycol.

[0074] The preparation method of gallic acid-grafted chitosan is as follows: 55 parts by weight of chitosan with a concentration of 10 mg / mL were dissolved in 35 parts by volume of 1% acetic acid aqueous solution under a nitrogen atmosphere. The solution was then centrifuged at 10,000 rpm for 30 min, and filtered to obtain a clear chitosan solution. 0.06 parts ascorbic acid and 2 parts of 1 mol / L hydrogen peroxide aqueous solution were added to the solution, and the mixture was stirred at room temperature in the dark for 45 min. Then, 0.8 parts gallic acid were added, and stirring was continued for 28 h. The resulting solution was placed in a dialysis bag with a molecular weight cutoff of 14 kDa and dialyzed with ultrapure water at room temperature for 72 hours, with the dialysis medium changed every 8 hours to remove unreacted gallic acid. Finally, the reaction solution was frozen at -20℃ and then freeze-dried for 3 days to obtain gallic acid-grafted chitosan.

[0075] The preparation method of the tea polyphenol / cyclodextrin inclusion complex is as follows: 6 parts by weight of epigallocatechin gallate and 16 parts by weight of hydroxypropyl-β-cyclodextrin are dissolved in 100 parts by weight of deionized water, stirred at 60°C for 18 h, and then freeze-dried for 24 h 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-coated anthocyanins is as follows: By weight, 12 parts lecithin and 14 parts quinoline dimethicone were dissolved in 50 parts chloroform. The mixture was magnetically stirred for 50 min to achieve homogeneity. Then, the chloroform solvent was completely evaporated under a nitrogen atmosphere. Next, 10 parts phosphate buffer were added, and the mixture was vigorously stirred for 45 min to obtain a vesicle solution. The solvent was then evaporated under a nitrogen atmosphere to form a lipid film. Finally, a mixture of 5 parts anthocyanins and 8 parts sodium citrate buffer was added, and the mixture was magnetically stirred for 5 h to obtain vesicle-coated anthocyanins. The average diameter of the vesicle-coated anthocyanins was 450 nm. The anthocyanin encapsulation rate of the vesicle-coated anthocyanins was 75%.

[0077] The method for preparing highly stable nicotine salt in this embodiment includes the following steps;

[0078] S1: Mix organic acid and propylene glycol and heat in a water bath to 50°C. Stir magnetically at 300 rpm for 40 min to obtain a homogeneous organic acid solution.

[0079] S2: Add nicotine to the organic acid solution obtained in S1, heat in a water bath to 70°C, 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-coated anthocyanins were added to the nicotine solution obtained in S2 and stirred for 90 min. Then, after freeze-drying, a highly stable nicotine salt was obtained.

[0081] Example 5

[0082] It is basically the same as Example 1, except that the number of gallic acid-grafted chitosan parts is 3 to 7.

[0083] Comparative Example 1

[0084] It is basically the same as Example 1, except that gallic acid is replaced with an equal number of gallic acid grafted onto chitosan.

[0085] Comparative Example 2

[0086] It is basically the same as Example 1, except that gallic acid-grafted chitosan is replaced with an equal number of chitosan.

[0087] Comparative Example 3

[0088] It is basically the same as Example 1, except that equal parts of tea polyphenols are used instead of the tea polyphenol / cyclodextrin inclusion complex.

[0089] Comparative Example 4

[0090] It is basically the same as Example 1, except that equal parts of hydroxypropyl-β-cyclodextrin are used to replace the tea polyphenol / cyclodextrin inclusion complex.

[0091] Comparative Example 5

[0092] It is basically the same as Example 1, except that the nicotine salt component does not contain vesicle-encapsulated anthocyanins.

[0093] Performance testing:

[0094] Antioxidant performance test: (1) Preparation of e-cigarette oil: Weigh the high-stability nicotine salt prepared in this invention, place it in a 100mL volumetric flask, add propylene glycol and glycerin (the volume ratio of propylene glycol and glycerin is 1:1), and mix evenly by ultrasonication to obtain an e-cigarette oil sample containing 5% high-stability nicotine salt by mass. (2) Evaluation of the antioxidant performance of e-cigarette oil using an oil oxidation stability tester (Rancimat method). The specific steps are as follows: Weigh 3g of e-cigarette oil sample and place it in the sample tube of the tester. Set the test temperature to 120℃ and the air flow rate to 20L / h. Start the test, and the instrument automatically records the conductivity change curve. Determine the induction time (the time corresponding to the curve change point) based on the conductivity change curve. The longer the induction time, the better the antioxidant performance of the sample. This test method refers to the standard method for oil oxidation stability testing (Rancimat method), which induces oil oxidation under accelerated conditions (high temperature, strong aeration), and measures the antioxidant performance of the oil by the length of the induction time. Applying the highly stable nicotine salt of this invention to e-cigarette oil can significantly prolong the induction time, indicating that it has excellent antioxidant properties and can effectively improve the stability of e-cigarette oil during storage and use.

[0095] Stability Test: Preparation of E-liquid: Weigh the highly stable nicotine salt prepared according to this invention and place it in a 100 mL volumetric flask. Add propylene glycol and glycerin (propylene glycol to glycerin volume ratio of 1:1), and ultrasonically mix thoroughly to obtain an e-liquid sample containing 5% (w / w) highly stable nicotine salt. Divide the e-liquid sample and blank control sample into 10 equal portions (10 mL each) in brown bottles, seal, and divide into two groups of 5 parallel samples each. Group 1: Stored in a sealed container at 25℃ and 60% relative humidity. Group 2: Stored in a sealed container at 40℃ and 75% relative humidity. After 60 days of storage, take one parallel sample from each group and determine the nicotine content using gas chromatography-mass spectrometry (GC-MS) to evaluate its stability.

[0096] The performance of the e-liquids from Examples 1-5 and Comparative Examples 1-5 is summarized in Table 2.

[0097] Table 2 Performance summary of e-cigarette oils from Examples 1-5 and Comparative Examples 1-5

[0098]

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

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

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

[0102] Compared to Example 1, the induction time of Comparative Example 4 decreased significantly (6.8 h vs 9.6 h), and the nicotine mass percentage in both groups after 60 days also decreased significantly (4.5% vs 4.8%, 4.3% vs 4.6%). This is because the system lost the key antioxidant component, tea polyphenols, after the tea polyphenol / cyclodextrin inclusion complex was replaced by an equal proportion of hydroxypropyl-β-cyclodextrin. Cyclodextrin itself does not have significant antioxidant activity and mainly functions as a solubilizer and inclusion agent. Without the participation of tea polyphenols, cyclodextrin alone is insufficient to effectively inhibit the oxidative degradation of nicotine salts, resulting in a significant impact on the antioxidant properties and stability of Comparative Example 4.

[0103] Compared to Example 1, the induction time of Comparative Example 5 decreased slightly (9.2 h vs 9.6 h), and the percentage of nicotine mass in both groups after 60 days also decreased (4.5% vs 4.8%, 4.2% vs 4.6%). This is because the vesicle-encapsulated anthocyanin, a co-antioxidant component, was removed from the nicotine salt component. Anthocyanins are a class of widely available natural pigments with excellent antioxidant and free radical scavenging abilities. Encapsulating anthocyanins in vesicles can improve their dispersibility and stability in the nicotine salt system and prolong the antioxidant protection time through a sustained-release effect. Therefore, the loss of vesicle-encapsulated anthocyanin reduces the antioxidant protective capacity of the nicotine salt, thus affecting the antioxidant properties and stability of Comparative Example 5.

[0104] In summary, the formulation of Example 1 exhibits the best performance in terms of antioxidant properties and stability because the three components—gallic acid-grafted chitosan, tea polyphenol / cyclodextrin inclusion complex, and vesicle-encapsulated anthocyanins—exert a synergistic effect within the nicotine salt system. Specifically, the gallic acid-grafted chitosan enhances the antioxidant efficiency of gallic acid by acting as a carrier; the tea polyphenol / cyclodextrin inclusion complex enhances the dispersibility and stability of tea polyphenols by utilizing the inclusion effect of cyclodextrin; and the vesicle-encapsulated anthocyanins prolong the antioxidant protection time of anthocyanins through the sustained-release effect of vesicles. These three components, through different mechanisms of action, jointly construct a multi-layered, three-dimensional composite antioxidant protection system, thereby maximizing the antioxidant stability of the nicotine salt formulation. In contrast, the formulations of Comparative Examples 1-5 weaken this composite antioxidant effect to varying degrees, resulting in different degrees of impact on the antioxidant properties and stability of the nicotine salt.

[0105] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit it. Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art should understand that any equivalent structural transformations made under the concept of the present invention and using the contents of the specification and drawings of the present invention 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, By weight, it includes the following components: nicotine 40-60 parts, organic acid 10-18 parts, gallic acid-grafted chitosan 3-7 parts, tea polyphenol / cyclodextrin inclusion complex 4-8 parts, vesicle-encapsulated anthocyanins 2-6 parts, and propylene glycol 40-60 parts. The preparation method of the highly stable nicotine salt includes the following steps: S1: Mix organic acid and propylene glycol and heat in a water bath to 40~50℃, then stir magnetically at 200~300rpm for 20~40min to obtain a homogeneous organic acid solution. S2: Add nicotine to the organic acid solution obtained in S1, heat in a water bath to 60~70℃, and magnetically stir at 400~500rpm for 30~40min to obtain a nicotine solution. S3: Add gallic acid-grafted chitosan, tea polyphenol / cyclodextrin inclusion complex and vesicle-coated anthocyanins to the nicotine solution obtained in S2 and stir for 60-90 minutes. Then freeze-dry to obtain highly stable nicotine salt. The anthocyanins are encapsulated in nanoscale vesicles using liposome technology.

2. The highly stable nicotine salt as described in claim 1, characterized in that, Further, the preparation method of gallic acid-grafted chitosan is as follows: By weight fraction, under a nitrogen atmosphere, 40-55 parts of chitosan with a concentration of 10 mg / mL are dissolved in 20-35 parts of a 1% (v / v) aqueous acetic acid solution. The solution is then centrifuged at 10,000 rpm for 20-30 min, and filtered to obtain a clear chitosan solution. Then, 0.02-0.06 parts of ascorbic acid and 1-2 parts of a 1 mol / L hydrogen peroxide aqueous solution are added. The solution is stirred at room temperature in the dark for 30-45 min. Then, 0.4-0.8 parts of gallic acid are added, and stirring continues for 20-28 h. The resulting solution is placed in a dialysis bag with a molecular weight cutoff of 8-14 kDa and dialyzed with ultrapure water at room temperature for 54-72 hours, changing the dialysis medium every 8 hours to remove unreacted gallic acid. Finally, the reaction solution is frozen at -20°C and then freeze-dried for 3 days to obtain gallic acid-grafted chitosan.

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

4. A highly stable nicotine salt as described in claim 1 or 3, characterized in that, The tea polyphenol / cyclodextrin inclusion complex is a porous spherical compound with an average diameter of 10~25μm.

5. A highly stable nicotine salt as described in claim 1, characterized in that, The method for preparing the vesicle-coated anthocyanins is as follows: Dissolve 5-12 parts by weight of lecithin and 8-14 parts by weight of quinoline in 50 parts by weight of chloroform, and stir magnetically for 30-50 minutes until homogeneous. Then, evaporate the chloroform solvent completely under a nitrogen atmosphere. Finally, add 5-10 parts by weight of phosphate buffer solution. The solution was then vigorously stirred for 30-45 minutes to obtain a vesicle solution. The solvent was then evaporated in a nitrogen gas stream to form a lipid membrane. A mixture of 2-5 parts anthocyanin and 4-8 parts sodium citrate buffer solution was added to the membrane, and the mixture was magnetically stirred for 2-5 hours to obtain vesicles coated with anthocyanins.

6. A highly stable nicotine salt as described in claim 1 or 5, characterized in that, The average diameter of the anthocyanins encapsulated in the vesicles is 200~450nm.

7. A highly stable nicotine salt as described in claim 1, 5, or 6, characterized in that, The anthocyanin encapsulation rate of the vesicles is 60-75%.

8. A highly stable nicotine salt as described in claim 1, characterized in that, The organic acid mentioned is malic acid, citric acid, or oxalic acid.

9. Electronic e-liquid, characterized in that, The e-liquid contains the highly stable nicotine salt as described in any one of claims 1-8, wherein the mass of the nicotine salt is 2-10% of the total weight of the e-liquid.

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