Nasal electronic atomized liquid and preparation method thereof

Abstract

The invention discloses a snorting electronic atomized liquid and a preparation method thereof, and the snorting electronic atomized liquid comprises the following raw materials: 1-8 wt% of a nicotine-cyclodextrin inclusion compound solution, a solute is nicotine-cyclodextrin, and the weight ratio of nicotine to cyclodextrin to the solvent is 1: 1.1-1.9: 2.1-2.9; 20 wt% to 35 wt% of a temperature sensitive type gel carrier; 0 wt%-15 wt% of a perfume; 0 wt%-8.7 wt% of a composite additive; and 10 wt%-70 wt% of a buffer solution. Due to the adoption of the host-guest inclusion structure of the nicotine-cyclodextrin inclusion compound, the release of nicotine is delayed, the peak reaching time is prolonged, the burst release stimulation is reduced, dizziness is not easily caused, and the bioavailability is improved; moreover, the temperature-sensitive gel carrier is added, so that the mucous membrane of a user can be protected, the nasal mucous membrane is prevented from being burnt and dried due to stimulation of propylene glycol and nicotine free alkali, the cilia function of the nasal mucous membrane is not easily damaged even if the temperature-sensitive gel carrier is used for a long time, and the cilia removal rate is not obviously reduced; and the bioavailability of the snuffing electronic atomized liquid can also be improved.

Description

Technical Field

[0001] This invention relates to the field of nebulized inhalation technology, specifically to a nasal electronic nebulizer and its preparation method. Background Technology

[0002] Electronic cigarettes mainly consist of four parts: e-liquid (containing nicotine, flavorings, solvent propylene glycol, etc.), heating system, power supply, and filter. They produce aerosols with specific odors through heating and atomization for smokers to use.

[0003] Nasal e-cigarettes, a variant of e-cigarettes that involve inhaling vaporized smoke through the nasal cavity, combine the traditional snuff usage method with modern electronic atomization technology.

[0004] While the nasal inhalation modules of nasal e-cigarettes can provide a stimulating effect by adding stimulants such as camphor, menthol, and borneol, traditional solvents (e.g., propylene glycol) and free nicotine base (the form of nicotine used in e-liquids, where nicotine is not bound to any other substance) can easily cause burning and dryness of the nasal mucosa. Long-term use of such nasal e-cigarettes may damage the nasal mucosal ciliary function, leading to a decrease in ciliary clearance rate (e.g., <70%). Furthermore, the burst release of nicotine results in insufficient bioavailability (i.e., low utilization rate, approximately 48%), and the short time to peak nicotine release can easily cause dizziness in users. Summary of the Invention

[0005] To address at least one of the aforementioned problems, according to one aspect of the present invention, a nasal electronic atomizing liquid is provided.

[0006] The nasal inhalation e-nebulizer liquid contains the following ingredients:

[0007] Nicotine-cyclodextrin inclusion complex solution 1wt%~8wt%, the solute in the nicotine-cyclodextrin inclusion complex solution is nicotine-cyclodextrin, and the weight ratio of nicotine, cyclodextrin and solvent is 1:1.1~1.9:2.1~2.9;

[0008] Temperature-sensitive gel carrier 20wt%~35wt%;

[0009] Fragrances 0wt%~15wt%;

[0010] Composite additives: 0 wt% to 8.7 wt%;

[0011] Buffer solution 10wt%–70wt%.

[0012] The use of a nicotine-cyclodextrin inclusion complex, a host-guest inclusion structure, delays nicotine release, prolongs the time to peak concentration, reduces burst release stimulation, is less likely to cause dizziness, and can alleviate mucosal irritation. Because the hollow cylindrical structure of cyclodextrin has an upper saturation limit for nicotine, controlling the weight ratio of cyclodextrin to nicotine at 1.1–1.5 fully utilizes the hydrophobic cavity of cyclodextrin and ensures that nicotine molecules enter the cyclodextrin cavity to the maximum extent, reducing the content of free nicotine and maintaining an encapsulation efficiency of over 90%. This reduces the stinging sensation caused by free nicotine irritating the nasal mucosa, achieving a sustained-release effect. Furthermore, when the weight ratio of cyclodextrin to nicotine is controlled between 1.1 and 1.5, the host-guest structure remains stable, allowing for delayed nicotine release through a physical barrier effect. If the weight ratio is too low, insufficient encapsulation may lead to a sudden release of nicotine, causing problems such as rapid absorption and dizziness. If the weight ratio is too high, the increased viscosity of the system due to cyclodextrin may affect the flowability of the nebulizer. Moreover, due to the addition of a temperature-sensitive gel carrier, the encapsulation effect of cyclodextrin on nicotine and... The temperature-sensitive gel carrier provides dual protection by physically encapsulating nicotine. While significantly improving nicotine stability and ensuring sustained release, the temperature-sensitive gel carrier can control the nicotine release rate through temperature changes. Together with cyclodextrin, the temperature-sensitive gel carrier allows for more precise control of nicotine release. Furthermore, because cyclodextrin improves nicotine solubility and permeability, and the temperature-sensitive gel carrier prolongs the residence time of nicotine at the site of action, the combination significantly improves nicotine bioavailability. Simultaneously, the cyclodextrin encapsulation reduces the chemical irritation of nicotine, and the gel state of the temperature-sensitive gel carrier reduces discomfort caused by liquid flow; the combination significantly reduces nicotine irritation to the mucous membranes. In addition, the temperature-sensitive gel carrier protects the user's mucous membranes, preventing burning and dryness caused by propylene glycol and free nicotine alkali. Even with long-term use, it is unlikely to damage the nasal mucosal ciliary function, does not significantly reduce the ciliary clearance rate, and can also improve the bioavailability of nasal e-cigarette liquid.

[0013] A nicotine-cyclodextrin inclusion complex solution of 1 wt% to 8 wt% ensures that the bioavailability of nicotine is increased from the traditional 48% to 75% to 82% due to the dual effects of cyclodextrin inclusion and gel carrier retention. If the ratio is too high, it may aggravate mucosal burning; if the ratio is too low, it may not be effectively absorbed, affecting the user experience.

[0014] A temperature-sensitive gel carrier ratio of 20wt%–35wt% ensures that it remains a low-viscosity liquid (viscosity ≤10mPa·s) at 25℃, facilitating the delivery of the nebulized liquid within the device. Upon contact with the nasal cavity temperature (above 36.5℃), it rapidly transforms into a high-viscosity gel (viscosity ≥1000mPa·s), forming a physical barrier to achieve dynamic state regulation and mucosal protection. If the ratio is below 20wt%, the gel carrier is insufficient, failing to effectively isolate the buffer solution and free nicotine from irritating the mucosa, leading to a decrease in the ciliary clearance rate recovery rate. If the ratio is above 35wt%, the system viscosity may be too high at low temperatures, affecting delivery smoothness, and excessive gel may cause a foreign body sensation in the nasal cavity.

[0015] In some embodiments, the temperature-sensitive gel carrier is a temperature-sensitive gel carrier with a viscosity ≤10 mPa·s at a contact temperature of 25°C and a viscosity ≥1000 mPa·s at a contact temperature above 36.5°C; and / or the temperature-sensitive gel carrier is a temperature-sensitive gel carrier that is a liquid at a contact temperature of 25°C and a gel at a contact temperature above 36.5°C.

[0016] Therefore, it can protect the user's mucous membranes, preventing the nasal mucosa from burning and dryness caused by the stimulation of propylene glycol and nicotine free alkali. Even with long-term use, it is not easy to damage the nasal mucosal ciliary function, and will not lead to a significant decrease in the ciliary clearance rate recovery rate. It can also improve the bioavailability of nasal electronic atomizing liquid.

[0017] In some embodiments, the temperature-sensitive gel carrier is prepared by mixing physiological saline, poloxamer 407 and hydroxypropyl chitosan in a weight ratio of 4:3 to 5:1.

[0018] Because it is liquid at 25°C (viscosity ≤10 mPa·s) and rapidly forms a gel (viscosity ≥1000 mPa·s) upon contact with the nasal cavity temperature (36.5°C), using poloxamer 407 as the main component of a temperature-sensitive gel carrier facilitates the delivery of the atomized liquid in nasal e-cigarettes at 25°C. When this nasal e-cigarette liquid comes into contact with the user's skin (e.g., nasal mucosa), poloxamer 407 allows mucosal adhesives such as hydroxypropyl chitosan to adhere to the user's skin surface (e.g., nasal mucosa). Furthermore, hydroxypropyl chitosan can prolong the retention time of nicotine by binding to nasal mucosal glycoproteins, acting as a mucosal adsorbent. The effect is to prolong the residence time of the nebulized solution in the nasal cavity, thereby increasing bioavailability from approximately 48% to approximately 79%, and improving the recovery rate of nasal mucosal ciliary clearance from less than 70% to over 95%. Furthermore, maintaining a weight ratio of physiological saline, poloxamer 407, and hydroxypropyl chitosan of 4:3 to 5:1 ensures good fluidity of the nasal electronic nebulized solution at low temperatures, while rapidly gelling at body temperature, balancing convenient delivery and effective retention. At this ratio, the two work synergistically: poloxamer 407 provides the gelling structure, and hydroxypropyl chitosan enhances adhesion, prolonging the action time of the nebulized solution in the nasal cavity and improving nicotine bioavailability. A temperature-sensitive gel carrier at a ratio of 20wt% to 35wt% ensures sufficient binding of hydroxypropyl chitosan to nasal mucosal glycoproteins, prolonging the residence time of the nebulized solution in the nasal cavity, and synergistically achieving precise sustained release with the nicotine-cyclodextrin inclusion complex, thus achieving a synergistic effect of sustained release and enhanced retention.

[0019] In some embodiments, the cyclodextrin is at least one of α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin. Therefore, the release of nicotine can be delayed by encapsulating it with cyclodextrin, prolonging the time to peak release, reducing burst-release stimulation, and thus lessening the likelihood of dizziness in the user. When the cyclodextrin is β-cyclodextrin, since β-cyclodextrin is a cyclic oligosaccharide composed of 7 glucose units linked by α-1,4-glycosidic bonds, it has a hollow cylindrical structure, with a hydrophilic exterior and a hydrophobic interior. Nicotine, as an alkaloid, is highly irritating; its hydrophobic portion can enter the hydrophobic cavity of the β-cyclodextrin, forming a stable inclusion complex through non-covalent interactions such as van der Waals forces and hydrogen bonds.

[0020] In some embodiments, the fragrance includes at least one of tobacco extract, menthol-based fragrances, and floral fragrances. This reduces irritation to the user's nasal mucosa while enhancing the experience through aroma.

[0021] In some embodiments, the compound additive includes at least one of a cooling agent, a sweetener, a mucosal repair agent, an osmotic pressure regulator, and a stabilizer. Thus, the osmotic pressure of the nasal e-vaporizer can be adjusted by the osmotic pressure regulator to be consistent with the osmotic pressure of the nasal mucosal tissue fluid (isotonic). This allows the cooling agent, mucosal repair agent, and osmotic pressure regulator to reduce nasal stinging for the user. The sweetener balances the bitter taste, and the stabilizer maintains the stability of the nasal e-vaporizer's form, preventing stratification, sedimentation, or abnormal viscosity, thereby ensuring stable efficacy.

[0022] In some implementations, peppermint flavorings include at least one of peppermint leaf extract and spearmint essential oil to activate the user's sense of coolness and reduce the stinging sensation in the user's nasal cavity.

[0023] In some embodiments, floral fragrances include at least one of lavender essential oil and chamomile extract to achieve soothing and anti-inflammatory effects, reducing the release of IL-8 inflammatory factor by 82%.

[0024] In some embodiments, the cooling agent includes at least one of menthol, peppermint oil, Icilin, and WS-3 (WilkinsonSword-3) to give the nasal e-vaporizer a longer-lasting cooling sensation and further reduce the user's nasal irritation.

[0025] In some embodiments, the sweetener includes at least one of maltol and ethyl maltol to balance the bitterness of nicotine.

[0026] In some implementations, the mucosal repair agent includes at least one of sodium hyaluronate and trehalose to prevent damage to the nasal mucosa by maintaining its hydration.

[0027] In some embodiments, the osmotic pressure regulator includes at least one of sodium chloride and sorbitol to adjust the nasal e-liquid to be isotonic with the nasal cavity, thereby reducing the irritation of the nasal e-liquid to the user's nasal cavity.

[0028] In some embodiments, the stabilizer includes at least one of xanthan gum and sodium carboxymethyl cellulose to form a three-dimensional network structure, preventing the nasal e-liquid from stratifying and affecting its quality stability.

[0029] As a natural high-molecular-weight polysaccharide, xanthan gum possesses excellent thickening and suspending properties, enabling it to form high-viscosity solutions at low concentrations. It also exhibits good temperature resistance (stable performance within the temperature range of atomization liquid preparation), effectively encapsulating dispersed phase particles (such as nicotine-β-cyclodextrin inclusion complexes and flavoring components) and preventing their aggregation. Furthermore, sodium carboxymethyl cellulose has good water solubility, excellent adhesion and water retention, and can form a complementary three-dimensional network structure with xanthan gum, enhancing the system's stability. It is also gentle and non-irritating to mucous membranes, exhibiting excellent compatibility with other components in the formulation (such as hydroxypropyl chitosan and sodium hyaluronate) without interfering with the mucous membrane protective function.

[0030] In some embodiments, the buffer and / or solvent includes at least one of propylene glycol and 3-methyl-2-butanol. This allows for the generation of smoke, dissolution and delivery of components, adjustment of throat hit sensation, viscosity adjustment, and moisturizing, all achieved using the buffer. The irritation of propylene glycol primarily stems from its penetrating effect and chemical irritation upon direct contact with the nasal mucosa. The temperature-sensitive gel carrier added in this application forms a dynamic protective barrier, rapidly transforming into a gel state (viscosity ≥1000 mPa·s) upon contact with nasal cavity temperatures (above 36.5°C), tightly adhering to the nasal mucosa surface and forming a physical barrier layer, reducing the contact area and time between propylene glycol and the mucosa. When the temperature-sensitive gel carrier contains hydroxypropyl chitosan, the hydroxypropyl chitosan, through specific binding to nasal mucosal glycoproteins, prolongs the residence time of the gel carrier in the nasal cavity, further blocking the penetrating irritation of propylene glycol, while maintaining a moist environment on the mucosal surface and alleviating dryness. Furthermore, because cyclodextrin encapsulates nicotine molecules through hollow hydrophobic cavities, forming nicotine-cyclodextrin inclusion complexes, it significantly reduces the content of free nicotine. With reduced free nicotine, its synergistic stimulating effect with propylene glycol is greatly weakened, reducing the risk of mucosal burning at the source. When the mucosal repair agent is at least one of sodium hyaluronate and trehalose, it can maintain mucosal hydration, promote epithelial cell repair, counteract the dryness and damage caused by propylene glycol, and enhance the mucosal barrier function. When the osmotic pressure regulator is at least one of sodium chloride and sorbitol, it can adjust the osmotic pressure of the nebulized solution to (isotonic with nasal mucosal tissue fluid), avoiding mucosal cell dehydration and shrinkage caused by osmotic pressure imbalance that may be due to propylene glycol, thus reducing irritation.

[0031] In some embodiments, the tobacco extract comprises 0 wt% to 12 wt%, the peppermint flavoring comprises 0 wt% to 5 wt%, and the floral flavoring comprises 0 wt% to 1.5 wt%. Thus, by using appropriate proportions of tobacco extract, peppermint flavoring, and floral flavoring, the user's cold receptors can be activated and the nerves can be soothed. Furthermore, the nasal e-vaporizer can have an anti-inflammatory effect; moreover, increasing the proportion of floral flavoring to 1.5 wt% results in a milder aroma.

[0032] In some embodiments, the weight percentages of the cooling agent are 0 wt% to 3 wt%, the sweetener is 0 wt% to 4 wt%, the mucosal repair agent is 0 wt% to 4 wt%, the osmotic pressure regulator is 0 wt% to 3 wt%, and the stabilizer is 0 wt% to 0.7 wt%. Thus, by using appropriate proportions of cooling agent, sweetener, mucosal repair agent, osmotic pressure regulator, and stabilizer, the nasal inhalation e-nebulizer can be made more stimulating, less bitter, less irritating to the nasal mucosa, and more stable in quality.

[0033] In some embodiments, the weight percentages of menthol are 0 wt% to 2 wt%, peppermint oil is 0 wt% to 1 wt%, icilin is 0 wt% to 3 wt%, WS-3 is 0 wt% to 3 wt%, maltol is 0 wt% to 2 wt%, ethyl maltol is 0 wt% to 2 wt%, sodium hyaluronate is 0 wt% to 2 wt%, trehalose is 0 wt% to 2 wt%, xanthan gum is 0 wt% to 0.4 wt%, and sodium carboxymethyl cellulose is 0 wt% to 0.3 wt%. Therefore, by using appropriate proportions of menthol, peppermint oil, icilin, WS-3, maltol, ethyl maltol, sodium hyaluronate, trehalose, xanthan gum, and sodium carboxymethyl cellulose, the nasal inhalation e-nebulizer can be made more stimulating, less bitter, less irritating to the nasal mucosa, and more stable in quality.

[0034] Since xanthan gum and sodium carboxymethyl cellulose are both biocompatible natural polymers, when added at low concentrations within the range specified in this application, they are gentle and non-irritating to the nasal mucosa. They can also work synergistically with mucosal repair agents such as sodium hyaluronate and trehalose in the formula to maintain mucosal hydration. While ensuring that the stabilizer is effective, they do not increase the burden on the nasal cavity. Moreover, they are compatible with osmotic pressure regulators and sweeteners in the compound additives and do not affect osmotic pressure regulation and flavor balance. If the specified ratio is exceeded, excessive polymer materials may cause a foreign body sensation in the mucosa or interfere with the normal physiological function of the nasal mucosa.

[0035] In some preferred embodiments, xanthan gum and sodium carboxymethyl cellulose are combined in a weight ratio of 2:1 to obtain a stabilizer. This results in a denser three-dimensional network structure, effectively preventing system delamination.

[0036] In some implementations, the tobacco extract in the flavoring is obtained by supercritical CO2 extraction, which retains aroma-producing components such as megalotrienone and removes tar. This preserves the core aroma-producing components, optimizing the aroma experience; removes harmful components such as tar, reducing health risks; and adapts to the specific needs of nasal inhalation, resulting in a milder aroma.

[0037] According to one aspect of the present invention, a method for preparing a nasal inhalation electronic atomizing liquid is provided.

[0038] The preparation method of this nasal inhalation electronic atomizing liquid includes the following steps:

[0039] S10: Mixing nicotine with cyclodextrin yields a first mixture containing nicotine-cyclodextrin inclusion complexes;

[0040] S20: Poloxamer 407, hydroxypropyl chitosan and physiological saline were added to the first mixture in proportion to obtain the second mixture;

[0041] S30: Add fragrance, compound additive and buffer solution to the second mixture in proportion to obtain the third mixture;

[0042] S40: Heat the third mixture to 28°C for 1 min to 5 min, and stir at 150 rpm to 300 rpm for 30 min to 60 min to obtain the fourth mixture;

[0043] S50: Let the fourth mixture stand for 5h to 48h to obtain the fifth mixture.

[0044] In existing technologies, the main technical challenges in mixing nicotine-cyclodextrin inclusion complexes with temperature-sensitive gel carriers are as follows:

[0045] 1. Compatibility differences: Nicotine-cyclodextrin inclusion complexes are solid particles (or semi-solids), while temperature-sensitive gel carriers (such as a mixture of poloxamer 407 and hydroxypropyl chitosan) are liquid at low temperatures and gel at body temperature. The difference in their physical states may lead to uneven dispersion, particle aggregation, or stratification.

[0046] 2. Viscosity compatibility issues: Cyclodextrin inclusion complexes may increase the initial viscosity of the system (at low temperatures), affecting the flowability of the gel carrier and making it difficult to deliver the atomized liquid in the equipment; if not properly dispersed, it may also damage the gelling ability of the gel carrier at body temperature (e.g., the viscosity cannot reach ≥1000 mPa·s), weakening the sustained-release effect.

[0047] 3. Interference of component interactions: Cyclodextrin in the inclusion complex may non-specifically bind to components in the gel carrier (such as hydroxypropyl chitosan), affecting the sustained release control of nicotine by the inclusion complex or the mucosal adhesion of the gel carrier, and reducing the functional stability of the overall system.

[0048] This solution achieves efficient mixing of nicotine-cyclodextrin inclusion complexes and temperature-sensitive gel carriers through the following process design and parameter optimization:

[0049] I. Stepwise dissolution and low-temperature dispersion:

[0050] 1.1. First, the temperature-sensitive gel carrier (poloxamer 407 + hydroxypropyl chitosan) is stirred at a low temperature in physiological saline at 18℃~25℃ (e.g., 20℃) for 20min~60min (e.g., 60min). The low temperature can reduce the viscosity of the solution and make the solution more fluid. During the stirring process, the molecular movement is relatively smooth, which is conducive to the more uniform dispersion of poloxamer 407 and hydroxypropyl chitosan in physiological saline, forming a homogeneous mixture, improving the mixing effect and product quality stability, and ensuring that it is completely dissolved into a low-viscosity liquid (viscosity ≤10mPa·s at 25℃), providing a good carrier for the dispersion of inclusion complex.

[0051] 1.2. After the inclusion complex of nicotine-cyclodextrin is completed, it is added to the above-mentioned low-temperature liquid gel carrier. The low viscosity of the low-temperature carrier is used to reduce particle agglomeration and achieve preliminary uniform dispersion.

[0052] II. Gradient heating and synergistic stirring:

[0053] 2.1. After mixing, heat to 28℃ and stir (150 rpm to 300 rpm for 30 min to 60 min). This temperature is lower than the gelation temperature of the gel carrier (36.5℃). This can avoid premature gelation that hinders dispersion, and the moderate heating can promote the affinity and mobility of the inclusion complex and the carrier molecules, thereby enhancing compatibility and ensuring the stability of the gel carrier's performance.

[0054] 2.2. Optimization of stirring parameters (speed and time) ensures that the dispersed phase particles (such as inclusion complexes and fragrance components) are uniformly distributed in the gel carrier, avoiding problems such as system instability, irritation, or functional imbalance caused by excessively high local concentrations; and the stirring time is controlled between 30 min and 60 min, which can ensure that all components are completely dispersed (avoiding stratification or precipitation) without introducing too many air bubbles due to excessive stirring (air bubbles may damage the subsequent gel structure or affect the atomization effect); combined with the three-dimensional network structure formed by xanthan gum and sodium carboxymethyl cellulose, the stability of the system can be further maintained, so that the atomized liquid remains in a homogeneous state during storage.

[0055] III. Aging process enhances fusion:

[0056] After stirring, let it stand at 25℃ for 5h to 1h (aging) to promote the intermolecular interaction (such as van der Waals forces and hydrogen bonds) between the nicotine-cyclodextrin inclusion complex and the gel carrier, so that the two form a stable dispersion system, while avoiding interference of the inclusion complex on the gelling performance of the carrier (the final system can still form a gel with a viscosity ≥1000mPa·s after contact with body temperature).

[0057] This ensures the uniformity of the mixing of nicotine-cyclodextrin inclusion complex, temperature-sensitive gel carrier, fragrance, and compound additives. Furthermore, the host-guest inclusion structure of the nicotine-cyclodextrin inclusion complex delays nicotine release, prolongs peak time, reduces burst-release stimulation, and is less likely to cause dizziness. The temperature-sensitive gel carrier also protects the user's mucous membranes, preventing burning and dryness caused by propylene glycol and nicotine free base. Even with long-term use, it does not easily damage the nasal mucosal ciliary function, does not significantly reduce the ciliary clearance rate, and improves the bioavailability of the nasal e-nebulizer solution.

[0058] In some embodiments, the first mixture in step S10 is obtained by ultrasonication at 20 kHz to 60 kHz for 10 to 30 minutes in a solvent with pH = 6 to 7, with nicotine, cyclodextrin, and solvent in a weight ratio of 1:1.1 to 1.9:2.1 to 2.9. This allows for an encapsulation rate of over 90% of nicotine by cyclodextrin, controlling the nicotine release rate and extending the peak release time from the usual 3 to 5 minutes to 8 to 12 minutes, reducing burst release stimulation and minimizing dizziness. Furthermore, by maintaining a neutral pH of 6 to 7, nicotine and cyclodextrin are kept in a relatively stable chemical state, avoiding degradation of nicotine or changes in the structure of cyclodextrin due to excessively high or low pH, thus ensuring the smooth preparation of the mixture. Ultrasonic treatment accelerates molecular motion and collisions, increasing the rate of the inclusion reaction.

[0059] In some preferred embodiments, the weight ratio of nicotine to cyclodextrin and solvent is 1:1.5:2.5. Nicotine has low solubility in pure water, while propylene glycol can significantly improve its solubility; simultaneously, cyclodextrin (especially β-cyclodextrin) also has higher solubility in the propylene glycol-water mixture than in pure water. The presence of propylene glycol can increase the solubility and dispersibility of nicotine and cyclodextrin, reduce agglomeration, and allow them to come into full contact, indirectly promoting the inclusion reaction.

[0060] In some preferred embodiments, the buffer solution is propylene glycol.

[0061] In some embodiments, in step S20, the second mixture is obtained by adding poloxamer 407, hydroxypropyl chitosan, and physiological saline to the first mixture in proportion and stirring at a temperature of 18°C ​​to 25°C for 20 to 60 minutes. This allows the nicotine-cyclodextrin inclusion complex to be completely dispersed in a temperature-sensitive gel carrier, thereby increasing the bioavailability from approximately 48% to approximately 79%.

[0062] In some preferred embodiments, the weight ratio of physiological saline, poloxamer 407, and hydroxypropyl chitosan is 4:3 to 5:1. At this ratio, physiological saline acts as a solvent, allowing poloxamer 407 and hydroxypropyl chitosan to dissolve fully and mix uniformly. The components exhibit good compatibility, preventing stratification, precipitation, or other phenomena, thus ensuring the stability of the entire system.

[0063] In some embodiments, when adding the composite additive in step S30, the osmotic pressure of the third mixture needs to be adjusted to 280 mOsm / kg to 320 mOsm / kg. This allows the nasal inhalation e-nebulizer to be adjusted to be isotonic with the nasal cavity, reducing irritation to the user's nasal cavity.

[0064] In some implementations, the following step is included after step S50:

[0065] S60: The fifth mixture is sterilized by ultrafiltration at a depth of 0.1μm to 0.22μm to obtain the sixth mixture. This ensures the sterility of the nasal e-needle solution and reduces potential harm to the user.

[0066] In some implementations, the following step is included after step S60:

[0067] S70: The sixth mixture is filled with nitrogen and sealed in a brown, light-proof bottle. This prevents oxidation of the nasal e-liquid and ensures its effectiveness. Attached Figure Description

[0068] Figure 1 This is a schematic flowchart of a method for preparing a nasal electronic atomizing liquid according to an embodiment of this application.

[0069] Figure 2 This is a schematic flowchart illustrating a method for preparing a nasal electronic atomizing liquid according to another embodiment of this application.

[0070] Figure 3 This is a schematic flowchart of a method for preparing a nasal electronic atomizing liquid according to another embodiment of this application. Detailed Implementation

[0071] It should be noted that, unless otherwise specified, the embodiments and features described in this application can be combined with each other.

[0072] It should also be noted that, in this document, relational terms such as "first" and "second" are used only to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising" or "including" include not only those elements but also other elements not expressly listed, or elements inherent to such a process, method, article, or apparatus. Unless otherwise specified, an element defined by the phrase "comprising..." does not exclude the presence of other identical elements in the process, method, article, or apparatus that includes said element. The terminology used herein is generally that commonly used by those skilled in the art; in case of any discrepancy with commonly used terminology, the terminology used herein shall prevail.

[0073] Furthermore, for ease of description, spatial relative terms such as “below,” “under,” “lower,” “above,” and “upper” may be used herein to describe the relationship between one element or component and another (or other) element or component as shown in the figure. In addition to the orientation shown in the figure, spatial relative terms are intended to include different orientations of the device during use or operation. The device may be oriented in other ways (rotated 90 degrees or in other orientations), and the spatial relative descriptors used herein can be interpreted accordingly.

[0074] In this paper, the term "temperature-sensitive gel carrier" refers to a class of smart materials that can undergo reversible physical state transitions (such as sol-gel phase transitions) in response to changes in ambient temperature. Its core characteristic is temperature-triggered gelation. It exhibits temperature responsiveness, remaining in a liquid state (sol state) at low temperatures, and rapidly transforming into a semi-solid gel when the temperature rises to a critical value (such as body temperature), adhering to the site of action.

[0075] In this article, the term "nicotine burst release" refers to the phenomenon of an abnormally rapid release of nicotine within a short period of time in e-cigarettes, nicotine replacement therapies (such as patches, lozenges), or other delivery systems, causing a sudden increase in blood nicotine concentration beyond the safe threshold. This phenomenon not only reduces product effectiveness but also poses health risks, and is most common in e-cigarettes.

[0076] In this article, the term "bioavailability" refers to the relative amount of a drug absorbed into the systemic bloodstream after administration via an extravascular route.

[0077] In this article, the term "time to peak concentration" refers to the time required for a drug to reach its highest blood concentration in the human body.

[0078] In this paper, the term "menthol" refers to a cyclic monoterpene alcohol naturally found in peppermint, a classic agonist of TRPM8 that triggers conformational changes by binding to the transmembrane domains (S1-S4) of the channel.

[0079] In this article, the term "Icilin" refers to a synthetically produced, super-potent TRPM8 agonist with a structure different from menthol but with higher activation potency (EC). 50 (Approximately 0.1 μM).

[0080] In this article, the term "WS-3" refers to a synthetic menthol derivative, a highly effective cooling agent, also known as mentholamide (N-ethyl-2-isopropyl-5-methylcyclohexanecarboxamide).

[0081] 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. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0082] According to one aspect of the present invention, a nasal electronic atomizing liquid is provided.

[0083] The nasal inhalation e-nebulizer liquid contains the following ingredients:

[0084] Nicotine-cyclodextrin inclusion complex solution 1wt%~8wt%, the solute in the nicotine-cyclodextrin inclusion complex solution is nicotine-cyclodextrin, and the weight ratio of nicotine, cyclodextrin and solvent is 1:1.1~1.9:2.1~2.9;

[0085] Temperature-sensitive gel carrier 20wt%~35wt%;

[0086] Fragrances 0wt%~15wt%;

[0087] Composite additives: 0 wt% to 8.7 wt%;

[0088] Buffer solution 10wt%–70wt%.

[0089] Because the use of a nicotine-cyclodextrin inclusion complex, a host-guest inclusion structure, delays nicotine release, prolongs the time to peak concentration, reduces burst-release stimulation, and is less likely to cause dizziness; moreover, the addition of a temperature-sensitive gel carrier can protect the user's mucous membranes, preventing burning and dryness of the nasal mucosa due to irritation from propylene glycol and nicotine free alkali. Even with long-term use, it is not likely to damage the nasal mucosal ciliary function, will not lead to a significant decrease in the ciliary clearance rate, and can also improve the bioavailability of the nasal inhalation e-nebulizer liquid.

[0090] In some embodiments, the temperature-sensitive gel carrier is a temperature-sensitive gel carrier with a viscosity ≤10 mPa·s at a contact temperature of 25°C and a viscosity ≥1000 mPa·s at a contact temperature above 36.5°C; and / or the temperature-sensitive gel carrier is a temperature-sensitive gel carrier that is a liquid at a contact temperature of 25°C and a gel at a contact temperature above 36.5°C.

[0091] Therefore, it can protect the user's mucous membranes, preventing the nasal mucosa from burning and dryness caused by the stimulation of propylene glycol and nicotine free alkali. Even with long-term use, it is not easy to damage the nasal mucosal ciliary function, and will not lead to a significant decrease in the ciliary clearance rate recovery rate. It can also improve the bioavailability of nasal electronic atomizing liquid.

[0092] In some embodiments, the temperature-sensitive gel carrier is prepared by mixing physiological saline, poloxamer 407, and hydroxypropyl chitosan in a weight ratio of 4:3 to 5:1. This allows the poloxamer 407 to enable mucosal adhesives such as hydroxypropyl chitosan to adhere to the user's skin surface (e.g., nasal mucosa) upon contact. Furthermore, hydroxypropyl chitosan can prolong the retention time of nicotine by binding to nasal mucosal glycoproteins, thereby increasing bioavailability from approximately 48% to approximately 79% and improving the nasal mucosal ciliary clearance rate recovery rate from less than 70% to over 95%.

[0093] In some embodiments, the cyclodextrin is at least one of α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin. Therefore, by encapsulating nicotine with cyclodextrin, the release of nicotine can be delayed, the time to peak concentration can be prolonged, and the burst release stimulation can be reduced, thus making it less likely to cause dizziness in the user.

[0094] In some embodiments, the fragrance includes at least one of tobacco extract, menthol-based fragrances, and floral fragrances. This reduces irritation to the user's nasal mucosa while enhancing the experience through aroma.

[0095] In some embodiments, the compound additive includes at least one of a cooling agent, a sweetener, a mucosal repair agent, an osmotic pressure regulator, and a stabilizer. Thus, the cooling agent, mucosal repair agent, and osmotic pressure regulator can reduce the user's nasal irritation, the sweetener can balance the bitterness, and the stabilizer can maintain the stability of the form of the nasal e-nebulizer liquid, thereby ensuring stable efficacy.

[0096] In some implementations, peppermint flavorings include at least one of peppermint leaf extract and spearmint essential oil to activate the user's sense of coolness and reduce the stinging sensation in the user's nasal cavity.

[0097] In some implementations, floral fragrances include at least one of lavender essential oil and chamomile extract to achieve soothing and anti-inflammatory effects.

[0098] In some embodiments, the cooling agent includes at least one of menthol, peppermint oil, icilin, and WS-3 to give the nasal e-liquid a longer-lasting cooling sensation and further reduce the stinging sensation in the user's nasal cavity.

[0099] In some embodiments, the sweetener includes at least one of maltol and ethyl maltol to balance the bitterness of nicotine.

[0100] In some embodiments, the mucosal repair agent includes at least one of sodium hyaluronate and trehalose to prevent damage to the nasal mucosa by maintaining mucosal hydration and keeping the nasal mucosa moist.

[0101] In some embodiments, the osmotic pressure regulator includes at least one of sodium chloride and sorbitol to adjust the nasal e-liquid to be isotonic with the nasal cavity, thereby reducing the irritation of the nasal e-liquid to the user's nasal cavity.

[0102] In some embodiments, the stabilizer includes at least one of xanthan gum and sodium carboxymethyl cellulose to form a three-dimensional network structure, preventing the nasal e-liquid from stratifying and affecting its quality stability.

[0103] In some embodiments, the buffer and / or solvent includes at least one of propylene glycol and 3-methyl-2-butanol.

[0104] In some embodiments, the tobacco extract comprises 0 wt% to 12 wt%, the peppermint flavoring comprises 0 wt% to 5 wt%, and the floral flavoring comprises 0 wt% to 1.5 wt%. Thus, by using appropriate proportions of tobacco extract, peppermint flavoring, and floral flavoring, the user's cold receptors can be activated and the nerves can be soothed, and the nasal e-vaporizer can also have an anti-inflammatory effect.

[0105] In some embodiments, the weight percentages of the cooling agent are 0 wt% to 3 wt%, the sweetener is 0 wt% to 4 wt%, the mucosal repair agent is 0 wt% to 4 wt%, the osmotic pressure regulator is 0 wt% to 3 wt%, and the stabilizer is 0 wt% to 0.7 wt%. Thus, by using appropriate proportions of cooling agent, sweetener, mucosal repair agent, osmotic pressure regulator, and stabilizer, the nasal inhalation e-nebulizer can be made more stimulating, less bitter, less irritating to the nasal mucosa, and more stable in quality.

[0106] In some embodiments, the weight percentages of menthol are 0 wt% to 2 wt%, peppermint oil is 0 wt% to 1 wt%, icilin is 0 wt% to 3 wt%, WS-3 is 0 wt% to 3 wt%, maltol is 0 wt% to 2 wt%, ethyl maltol is 0 wt% to 2 wt%, sodium hyaluronate is 0 wt% to 2 wt%, trehalose is 0 wt% to 2 wt%, xanthan gum is 0 wt% to 0.4 wt%, and sodium carboxymethyl cellulose is 0 wt% to 0.3 wt%. Therefore, by using appropriate proportions of menthol, peppermint oil, icilin, WS-3, maltol, ethyl maltol, sodium hyaluronate, trehalose, xanthan gum, and sodium carboxymethyl cellulose, the nasal inhalation e-nebulizer can be made more stimulating, less bitter, less irritating to the nasal mucosa, and more stable in quality.

[0107] In some preferred embodiments, xanthan gum and sodium carboxymethyl cellulose are combined in a weight ratio of 2:1 to obtain a stabilizer. This results in a denser three-dimensional network structure, effectively preventing system delamination.

[0108] In some embodiments, the tobacco extract in the flavoring is obtained by supercritical CO2 extraction to retain aroma-producing components such as megalotrienone and remove tar.

[0109] The nasal e-cigarette liquid formulated as described above not only delays nicotine release, prolongs peak time, and reduces burst-release stimulation, making it less likely to cause dizziness in users, but also protects the user's mucous membranes, preventing burning and dryness caused by propylene glycol and nicotine free alkali. Even with long-term use, it is less likely to damage the nasal mucosal ciliary function, increasing bioavailability from approximately 48% to approximately 79%, and improving the nasal mucosal ciliary clearance rate recovery rate from less than 70% to over 95%. Furthermore, it reduces irritation to the user's nasal mucosa through tobacco extracts, mint-like flavorings, and floral fragrances, and optimizes the experience by providing aroma. Simultaneously, it reduces nasal stinging through cooling agents, mucosal repair agents, and osmotic pressure regulators, balances bitterness with sweeteners, and maintains the stability of the nasal e-cigarette liquid's form with stabilizers, thus ensuring stable effects. Ultimately, it reduces the nasal stinging score to below 2.2.

[0110] Figure 1 An exemplary method for preparing a nasal electronic atomizing liquid according to a first embodiment of the present invention is shown.

[0111] like Figure 1 As shown, the preparation method of this nasal inhalation electronic atomizing liquid includes the following steps:

[0112] S10: Mixing nicotine with cyclodextrin yields a first mixture containing nicotine-cyclodextrin inclusion complexes;

[0113] S20: Poloxamer 407, hydroxypropyl chitosan and physiological saline were added to the first mixture in proportion to obtain the second mixture;

[0114] S30: Add fragrance, compound additives and buffer to the second mixture in proportion to obtain the third mixture;

[0115] S40: Heat the third mixture to 28°C for 1 min to 5 min, and stir at 150 rpm to 300 rpm for 30 min to 60 min to obtain the fourth mixture;

[0116] S50: Let the fourth mixture stand for 5h to 48h to obtain the fifth mixture.

[0117] This ensures the uniformity of the mixture of nicotine-cyclodextrin inclusion complex, temperature-sensitive gel carrier, fragrance, and compound additives. Furthermore, the host-guest inclusion structure of the nicotine-cyclodextrin inclusion complex delays nicotine release, prolongs peak time, reduces burst release stimulation, and is less likely to cause dizziness. The temperature-sensitive gel carrier also protects the user's mucous membranes, preventing burning and dryness caused by propylene glycol and nicotine free base. Even with long-term use, it does not easily damage the nasal mucosal ciliary function, does not significantly reduce the ciliary clearance rate, and improves the bioavailability of the nasal e-cigarette liquid. Long-term static placement also promotes the full integration of fragrance and temperature-sensitive gel carrier, ensuring slow and long-lasting fragrance release.

[0118] In some embodiments, the first mixture in step S10 is obtained by treating nicotine, cyclodextrin, and solvent in a weight ratio of 1:1.1-1.9:2.1-2.9 in a solvent with pH 6-7 with ultrasonication at 20 kHz-60 kHz for 10-30 minutes. This allows the cyclodextrin to achieve an encapsulation rate of over 90% for nicotine, controlling the nicotine release rate and extending the peak release time from the usual 3-5 minutes to 8-12 minutes, reducing burst release stimulation and minimizing dizziness. Furthermore, by controlling the pH at 6-7, acid-base damage to the nasal mucosa can be avoided.

[0119] In some preferred embodiments, the buffer solution is propylene glycol.

[0120] In some embodiments, in step S20, the second mixture is obtained by adding poloxamer 407, hydroxypropyl chitosan, and physiological saline in proportion and stirring at a temperature of 18°C ​​to 25°C for 20 to 60 minutes. This allows the nicotine-cyclodextrin inclusion complex to be completely dispersed in a temperature-sensitive gel carrier, thereby increasing the bioavailability from approximately 48% to approximately 79%.

[0121] In some preferred embodiments, the weight ratio of physiological saline, poloxamer 407, and hydroxypropyl chitosan is 4:3 to 5:1.

[0122] In some embodiments, when adding the composite additive in step S30, the osmotic pressure of the third mixture needs to be adjusted to 280 mOsm / kg to 320 mOsm / kg. This allows the nasal inhalation e-nebulizer to be adjusted to be isotonic with the nasal cavity, reducing irritation to the user's nasal cavity.

[0123] Figure 2 An exemplary method for preparing a nasal electronic atomizing liquid according to a second embodiment of the present invention is shown.

[0124] like Figure 2 As shown, this embodiment further includes the following content based on the first embodiment: specifically, after step S50, it further includes the following steps:

[0125] S60: The fifth mixture is sterilized by ultrafiltration at a depth of 0.1μm to 0.22μm to obtain the sixth mixture. This ensures the sterility of the nasal e-needle solution and reduces potential harm to the user.

[0126] Figure 3 An exemplary method for preparing a nasal electronic atomizing liquid according to a third embodiment of the present invention is shown.

[0127] like Figure 3 As shown, this embodiment further includes the following content based on the second embodiment: specifically, after step S60, it further includes the following steps:

[0128] S70: The sixth mixture is filled with nitrogen and sealed in a brown, light-proof bottle. This prevents oxidation of the nasal e-liquid and ensures its effectiveness.

[0129] In some embodiments, the peppermint leaf extract is American peppermint leaf extract.

[0130] In some embodiments, menthol is DL-menthol.

[0131] The preparation method of the nasal inhalation electronic atomizing liquid of this application is illustrated below with specific embodiments. The total amount of experimental sample is 100g.

[0132]

[0133]

[0134] Example 1

[0135] Preparation process:

[0136] The first step involves encapsulating nicotine and β-cyclodextrin with a solvent (e.g., propylene glycol) in a ratio of 1:1.1–1.9:2.1–2.9 in a solvent at pH 6.5 using ultrasonication at 40 kHz for 30 min to obtain the first mixture.

[0137] The second step involves mixing poloxamer 407 with hydroxypropyl chitosan and physiological saline at a mass ratio of 3:1:4, stirring at 20°C for 1 hour, and then adding the first mixture to obtain the second mixture.

[0138] The third step involves adding fragrance and compound additives to the second mixture in a specific ratio, and adjusting the osmotic pressure to 280 mOsm / kg to obtain the third mixture.

[0139] Fourth step: Heat the third mixture to 28°C and stir at 150 rpm for 60 minutes to obtain the fourth mixture;

[0140] The fifth step is to let the fourth mixture stand for 48 hours to obtain the fifth mixture.

[0141] Example 2

[0142] The main difference between Example 2 and Example 1 is that: instead of using peppermint flavorings, trehalose, and sodium chloride, floral flavorings and sorbitol are used, and the cooling agent is Icilin (TRPM8 agonist), which makes the cooling sensation last longer; and the proportion of floral flavorings is increased to 1.5%, making the aroma more mellow.

[0143] Example 3

[0144] The main differences between Example 3 and Example 2 are: the amount of poloxamer 407 and hydroxypropyl chitosan solution added is increased, and the amount of nasal mucosa protective gel is increased; spearmint essential oil and menthol are used; and lavender essential oil is not used.

[0145] Example 4

[0146] The main difference between Example 4 and Example 3 is that the amount of nicotine-cyclodextrin inclusion complex solution added was further increased, which increased the nicotine content and enhanced the irritant effect; peppermint leaf extract, trehalose, and sodium chloride were used; and chamomile extract and sorbitol were not used.

[0147] Example 5

[0148] Preparation process:

[0149] The first step involves encapsulating nicotine and β-cyclodextrin with a solvent (e.g., propylene glycol) in a ratio of 1:1.1–1.9:2.1–2.9 in a solvent at pH 6 using ultrasonication at 20 kHz for 30 min to obtain the first mixture.

[0150] The second step involves mixing poloxamer 407 with hydroxypropyl chitosan and physiological saline at a mass ratio of 3:1:4, stirring at 18°C ​​for 1 hour, and then adding the first mixture to obtain the second mixture.

[0151] The third step involves adding fragrance and compound additives to the second mixture in a specific ratio, and adjusting the osmotic pressure to 320 mOsm / kg to obtain the third mixture.

[0152] Fourth step: Heat the third mixture to 28°C and stir at 300 rpm for 30 minutes to obtain the fourth mixture;

[0153] The fifth step is to let the fourth mixture stand for 5 hours to obtain the fifth mixture.

[0154] Step 6: Sterilize the fifth mixture by passing it through 0.1μm ultrafiltration to obtain the sixth mixture.

[0155] Example 6

[0156] Preparation process:

[0157] The first step involves encapsulating nicotine and β-cyclodextrin with a solvent (e.g., propylene glycol) in a ratio of 1:1.1–1.9:2.1–2.9 in a solvent at pH 7 using ultrasonication at 60 kHz for 10 min to obtain the first mixture.

[0158] The second step involves mixing poloxamer 407 with hydroxypropyl chitosan and physiological saline at a mass ratio of 3:1:4, stirring at 25°C for 20 minutes, and then adding the first mixture to obtain the second mixture.

[0159] The third step involves adding fragrance and compound additives to the second mixture in a specific ratio, and adjusting the osmotic pressure to 280 mOsm / kg to obtain the third mixture.

[0160] Fourth step: Heat the third mixture to 28°C and stir at 150 rpm for 60 minutes to obtain the fourth mixture;

[0161] The fifth step is to let the fourth mixture stand for 48 hours to obtain the fifth mixture.

[0162] The sixth step is to sterilize the fifth mixture by passing it through 0.22μm ultrafiltration to obtain the sixth mixture.

[0163] Step 7: Fill the sixth mixture with nitrogen and seal it in a brown light-proof bottle.

[0164] Comparative Example 1

[0165] Preparation process

[0166] The first step is to add the flavoring ingredients in sequence;

[0167] The second step is to add nicotine and propylene glycol solvent;

[0168] The third step is to stir at 150 rpm for 60 minutes;

[0169] The main difference from Examples 1 to 4 is that:

[0170] Only the main flavoring ingredients (tobacco extract, peppermint leaf extract, spearmint essential oil, menthol, maltol, ethyl maltol) are selected, and pure nicotine is added according to the nicotine content in the nicotine-cyclodextrin inclusion complex solution.

[0171] Comparative Example 2

[0172] The main difference between Comparative Example 2 and Comparative Example 1 is:

[0173] Only the main flavoring ingredients are selected, and pure nicotine is added according to the nicotine content in the nicotine-cyclodextrin inclusion complex solution. Poloxamer 407 and hydroxypropyl chitosan solution are also added to protect the nasal mucosa and reduce the irritation of atomization.

[0174] The table below is a rating table for traditional nasal inhalation products, the product of the present invention, and the comparative product.

[0175]

[0176] The above descriptions are merely some embodiments of the present invention. Those skilled in the art can make various modifications and improvements without departing from the inventive concept of the present invention, and these all fall within the scope of protection of the present invention.

Claims

1. A nasal inhalation electronic atomizing liquid, characterized in that, Including the following raw materials: Nicotine-cyclodextrin inclusion complex solution 1wt%~8wt%, the solute in the nicotine-cyclodextrin inclusion complex solution is nicotine-cyclodextrin, and the weight ratio of nicotine, cyclodextrin and solvent is 1:1.1~1.9:2.1~2.9; Temperature-sensitive gel carrier 20wt%~35wt%; Fragrances 0wt%~15wt%; Composite additives: 0 wt% to 8.7 wt%; Buffer solution 10wt%–70wt%.

2. The nasal inhalation electronic atomizing liquid according to claim 1, characterized in that, The temperature-sensitive gel carrier adopts a viscosity ≤10 mPa·s at a contact temperature of 25℃ and a viscosity ≥1000 mPa·s at a contact temperature above 36.5℃; and / or The temperature-sensitive gel carrier is a type of temperature-sensitive gel carrier that is liquid when the contact temperature is 25°C and gel when the contact temperature is above 36.5°C.

3. The nasal inhalation electronic atomizing liquid according to claim 2, characterized in that, The temperature-sensitive gel carrier is composed of physiological saline, poloxamer 407, and hydroxypropyl chitosan in a weight ratio of 4:3 to 5:1; and / or The cyclodextrin is at least one of α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin.

4. The nasal electronic atomizing liquid according to any one of claims 1 to 3, characterized in that, The flavoring includes at least one of tobacco extract, mint-based flavorings, and floral flavorings; and / or The compound additive includes at least one of a cooling agent, a sweetener, a mucosal repair agent, an osmotic pressure regulator, and a stabilizer.

5. The nasal inhalation electronic atomizing liquid according to claim 4, characterized in that, The peppermint flavorings include at least one of peppermint leaf extract and spearmint essential oil; The floral fragrance includes at least one of lavender essential oil and chamomile extract; and / or The cooling agent includes at least one of menthol, peppermint oil, icilin, and WS-3; The sweetener includes at least one of maltol and ethyl maltol; The mucosal repair agent includes at least one of sodium hyaluronate and trehalose; The osmotic pressure regulator includes at least one of sodium chloride and sorbitol; The stabilizer includes at least one of xanthan gum and sodium carboxymethyl cellulose; and / or The buffer and / or solvent includes at least one of propylene glycol and 3-methyl-2-butanol.

6. The nasal inhalation electronic atomizing liquid according to claim 4, characterized in that, The tobacco extract has a weight percentage of 0 wt% to 12 wt%, the peppermint flavoring has a weight percentage of 0 wt% to 5 wt%, and the floral flavoring has a weight percentage of 0 wt% to 1.5 wt%. and / or The cooling agent comprises 0 wt% to 3 wt% by weight, the sweetener comprises 0 wt% to 4 wt% by weight, the mucosal repair agent comprises 0 wt% to 4 wt% by weight, the osmotic pressure regulator comprises 0 wt% to 3 wt% by weight, and the stabilizer comprises 0 wt% to 0.7 wt% by weight.

7. The nasal inhalation electronic atomizing liquid according to claim 5, characterized in that, The stabilizer comprises, by weight percentage, 0 wt% to 2 wt% of menthol, 0 wt% to 1 wt% of peppermint oil, 0 wt% to 3 wt% of icilin, 0 wt% to 3 wt% of WS-3, 0 wt% to 2 wt% of maltol, 0 wt% to 2 wt% of ethyl maltol, 0 wt% to 2 wt% of sodium hyaluronate, 0 wt% to 2 wt% of trehalose, 0 wt% to 0.4 wt% of xanthan gum, and 0 wt% to 0.3 wt% of sodium carboxymethyl cellulose; preferably, xanthan gum and sodium carboxymethyl cellulose are compounded in a weight ratio of 2:1 to obtain the stabilizer; and / or The tobacco extract in the fragrance is obtained by supercritical CO2 extraction to retain aroma-producing components such as megalotrienone and remove tar.

8. The method for preparing the nasal inhalation electronic atomizing liquid according to any one of claims 1 to 7, characterized in that, Includes the following steps: S10: Mixing nicotine with cyclodextrin yields a first mixture containing nicotine-cyclodextrin inclusion complexes; S20: Poloxamer 407, hydroxypropyl chitosan and physiological saline were added to the first mixture in proportion and mixed to obtain the second mixture; S30: Add fragrance, compound additive and buffer solution to the second mixture in proportion to obtain the third mixture; S40: Heat the third mixture to 28°C for 1 min to 5 min, and stir at 150 rpm to 300 rpm for 30 min to 60 min to obtain the fourth mixture; S50: Let the fourth mixture stand for 5h to 48h to obtain the fifth mixture.

9. The method for preparing the nasal electronic atomizing liquid according to claim 8, characterized in that, The first mixture in step S10 is obtained by treating nicotine and cyclodextrin with solvent in a weight ratio of 1:1.1-1.9:2.1-2.9 in a solvent with pH=6-7 by sonication at 20kHz-60kHz for 10-30 minutes; and / or In step S20, the second mixture is obtained by adding poloxamer 407, hydroxypropyl chitosan and physiological saline to the first mixture in proportion and stirring at a temperature of 18°C ​​to 25°C for 20 min to 60 min; preferably, the weight ratio of physiological saline, poloxamer 407 and hydroxypropyl chitosan is 4:3 to 5:

1.

10. The method for preparing the nasal inhalation electronic atomizing liquid according to claim 8, characterized in that, In step S30, when adding the composite additive, the osmotic pressure of the third mixture needs to be adjusted to 280 mOsm / kg to 320 mOsm / kg; and / or The following steps are included after step S50: S60: Sterilize the fifth mixture by ultrafiltration at 0.1μm–0.22μm to obtain the sixth mixture; and / or The following steps are included after step S60: S70: Fill the sixth mixture with nitrogen and seal it in a brown light-proof bottle.

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