A mint flavored aerosol containing a salt of sparteine and a method of making

Abstract

The present application relates to the technical field of electronic atomization, in particular to a menthol-flavored atomized product containing a salt of cytisine and a preparation method thereof. The atomized product comprises 1-10 parts of nicotine salt, 1-5 parts of cytisine salt, 0.5-5 parts of cooling agent, 0.1-2 parts of sour agent, 0.1-2 parts of sweet agent, 1-10 parts of menthol-flavored essence, and 60-90 parts of essence solvent. The cytisine salt is added to replace part of the nicotine salt on the basis of the existing atomized product. By reducing the content of the nicotine salt, the effect of smoking cessation is gradually achieved, and the user's withdrawal reaction is not significant. At the same time, the addition of the cytisine salt gives the atomized liquid a richer aroma, a good taste, a reduced oral irritation, and a better acceptance by consumers.

Description

Technical Field

[0001] This invention relates to the field of electronic atomizing agent technology, specifically to a mint-flavored atomizing agent containing cypress alkaloid salt and its preparation method. Background Technology

[0002] Currently available smoking cessation products include e-cigarettes, oral cigarettes, and chewing gum, but their effects are not significant and cannot eliminate nicotine at its source. Cyperine, a natural product, is a quinolone alkaloid extracted from the seeds of plants in the genus *Sophora* (legumes). It possesses antitumor activity. Cyperine has a similar chemical structure to nicotine and can replace nicotine in binding to brain receptors. Therefore, in recent years, cyperine has attracted considerable attention as a partial antagonist of nicotine acetylcholine receptors and has a strong affinity for the α4β2 receptor.

[0003] The cytisine used in this invention has a certain degree of toxicity, and users may experience symptoms such as headache, bloating, and vomiting. Natural peppermint oil mainly contains flavonoids, phenolic acids, polysaccharides, volatile components, various free amino acids, and trace elements, and has effects such as treating exogenous wind-heat, headache, red eyes, and detoxification.

[0004] This invention achieves smoking cessation by reducing the nicotine content in e-cigarette vapors and gradually replacing some nicotine salts with cypermine salts. The addition of naturally extracted peppermint oil reduces the side effects of cypermine salts, resulting in minimal withdrawal symptoms and a significant smoking cessation effect. Summary of the Invention

[0005] The purpose of this invention is to use organic acid to react with cytisine, and the reaction product cytisine salt replaces nicotine salt to achieve the purpose of smoking cessation. Furthermore, this invention proposes a mint-flavored atomized product containing cytisine salt and its preparation method.

[0006] To achieve the above objectives, the technical solution of the present invention is as follows:

[0007] A mint-flavored atomized product containing cypress alkaloid salt and its preparation method, comprising the following components: nicotine salt, cypress alkaloid salt, cooling agent, acidulant, sweetener, mint flavoring, and flavoring solvent.

[0008] The method for preparing a peppermint-flavored atomized product containing cypress alkaloid salt and the atomized product thereof are characterized in that the preparation of the peppermint flavoring includes the following steps: S1. Wash and sterilize fresh mint leaves, then freeze-dry the washed mint leaves (-35℃; 24h) at a vacuum degree of 10-20 Pa until the moisture content is 5-10%. S2. The dried peppermint leaves are then subjected to ultra-fine grinding (910 r / min; 350 W) to obtain peppermint leaf powder; S3. After mixing peppermint leaf powder with ethanol, extract the mixture using an ultrasonic-coupled negative pressure vacuum method. The ultrasonic temperature is 25℃, the negative pressure vacuum is -0.8MPa, and the extraction time is 120S. S4. The extract was centrifuged (25℃; 6000 rpm / min; 15 min), and the supernatant after centrifugation was purified by vacuum distillation (50 min; 45℃) to obtain peppermint extract.

[0009] The aforementioned peppermint-flavored atomized product containing cypress alkaloid salt and its preparation method are characterized in that the preparation of cypress alkaloid salt includes the following steps: S1. Cyperine was isolated from plants such as *Sophora japonica*, *Sophora* (Fabaceae), *Cassia* (Spartina*), *Salvia lanceolata*, and *Cassia microphylla*. S2. A cytisine salt is prepared by reacting the alkalinity of cytisine with an organic acid, wherein the organic acid is one of gallic acid, ferulic acid, succinic acid, malic acid, glycyrrhizic acid, and acetylsalicylic acid; preferably, the organic acid is ferulic acid. S3. In a 50 mL dry round-bottom flask, add 1.17 g (0.005 mol) of cytisine and 0.97 g (0.005 mol) of ferulic acid, then add 25 mL of acetone solution, reflux at 40 °C for 4 h, concentrate to dryness, and add acetone, ethyl acetate and petroleum ether in sequence (acetone:ethyl acetate:petroleum ether = 4:12:35). A precipitate forms, which is filtered to obtain a white powder, mp: 66.8-68.8 °C. S4, TLC detection: Spot the sample on a thin-layer silica gel G plate, develop with anhydrous ethanol:ethyl acetate = 1:1 (volume ratio) as the developing solvent, spray with modified bismuth potassium iodide reagent for color development, and obtain a single spot with an Rf value of 0.35.

[0010] The cooling agent includes one or more of WS-23, WS-3, WS-5, borneol, menthol, camphor, carbamate, menthol, and eugenol.

[0011] The sweetener is one or more of xylitol, erythritol, mannitol, sorbitol, maltitol, lactitol, dihydrochalcone derivatives, stevia, sucralose, alicite, acesulfame potassium, advantran, neotame, aspartame, cyclamate, sematrandez, sucrose, glucose, fructose, lactose, cyclohexyl glycosides, strawberry sugar alcohol, saccharin, sodium saccharin, lactulose, steviol glucoside, glucose oxidase, and cellulase.

[0012] The nicotine salt mentioned is one or more of the following: benzoic acid nicotine salt, malic acid nicotine salt, propionic acid nicotine salt, succinic acid nicotine salt, glycine nicotine salt, oxalic acid nicotine salt, and oxalic acid nicotine salt.

[0013] The acidulant is one or more of the following: citric acid, malic acid, lactic acid, oxalic acid, succinic acid, acetic acid, gluconic acid, linolenic acid, citric anhydride, sorbic acid, tartaric acid, malonic acid, benzoic acid, cardamomic acid, succinic anhydride, polyfructic acid, coumaric acid, and succinic acid.

[0014] A mint-flavored atomized product containing cypress alkaloid salt and its preparation method, comprising the following components in 100 parts by weight: 1-10 parts nicotine salt, 1-5 parts cypress alkaloid salt, 0.5-5 parts cooling agent, 0.1-2 parts acidulant, 0.1-2 parts sweetener, 1-10 parts mint flavoring, and 60-90 parts flavoring solvent.

[0015] Preferably, the cypress alkaloid salt is ferulic acid cypress alkaloid salt, and the dosage is 2 parts.

[0016] Preferably, the nicotine salt is nicotine tartrate salt, and the dosage is 1 part.

[0017] Preferably, the cooling agent is WS-23, and the dosage is 2 parts.

[0018] Preferably, the acidulant is citric acid, and the dosage is 0.5 parts.

[0019] Preferably, the sweetener is neotame, and the dosage is 1.5 parts.

[0020] Preferably, the peppermint flavoring is peppermint oil, and the dosage is 8 parts.

[0021] Preferably, the fragrance solvent is glycerin and propylene glycol in a ratio of 35:50, and the amount used is 85 parts.

[0022] This invention discloses a peppermint-flavored atomized product containing cytisine salt and its preparation method. The peppermint extract is first prepared by vacuum freeze-drying, which avoids excessive loss of nutrients and active substances while effectively preserving the unique flavor and aroma components of peppermint. Then, ultra-fine pulverization is used to disrupt the cell structure of peppermint leaves, promoting the release of intracellular active substances and facilitating subsequent extraction. Finally, ultrasonic-coupled negative pressure vacuum extraction technology is used to extract the unique aroma components from the peppermint powder, maximizing the preservation and extraction of volatile aroma components and avoiding their loss. By modifying the structure of cytisine, a cytisine salt with better smoking cessation effects and lower toxicity is sought to achieve effective smoking cessation. The strong alkalinity of cytisine combines with the carboxyl group in ferulic acid to form cytisine salt. Ferulic acid has anti-inflammatory, sedative, and cardiovascular disease-regulating effects. The combination of peppermint extract and ferulic acid-cytisine salt achieves a synergistic effect. Detailed Implementation

[0023] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer shall apply. 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. [Example 1] The preparation method of a peppermint-flavored broom salt atomized product in the implementation case includes the following steps: (1) Peppermint flavoring: Fresh peppermint leaves were washed and sterilized, and then the washed peppermint leaves were freeze-dried (-35℃; 24h) with a vacuum degree of 10-20 Pa until the moisture content was 5-10%. The dried peppermint leaves were then subjected to ultrafine grinding (910 r / min; 350 W) to obtain peppermint leaf powder. The peppermint leaf powder was mixed with ethanol and then extracted by ultrasonic coupling negative pressure vacuum method. The ultrasonic temperature was 25℃, the negative pressure vacuum was -0.8 MPa, and the extraction time was 120 s. The extract was centrifuged (25℃; 6000 rpm / min; 15 min), and the supernatant after centrifugation was purified by vacuum distillation (50 min; 45℃) to obtain peppermint extract. (2) Synthesis of cycad alkaloid salt: Cycad alkaloid was isolated from plants such as *Sophora japonica*, *Sophora* (Fabaceae), *Senna* (Senna), *Senna lanceolate*, and *Senna microphylla*. Cycad alkaloid salt was prepared by reacting its basicity with an acid, ferulic acid. In a 50 mL dry round-bottom flask, 1.17 g (0.005 mol) of cycad alkaloid and 0.97 g (0.005 mol) of ferulic acid were added, followed by the addition of 25 mL of... L of acetone solution was refluxed at 40℃ for 4 hours, concentrated to dryness, and then acetone, ethyl acetate, and petroleum ether were added sequentially (acetone:ethyl acetate:petroleum ether = 4:12:35). A precipitate was formed, filtered, and a white powder was obtained, mp: 66.8-68.8℃. For the verification of the synthesis, the sample was spotted on a thin-layer silica gel G plate, developed with anhydrous ethanol:ethyl acetate = 1:1 (volume ratio), and sprayed with modified bismuth potassium iodide reagent for color development, resulting in a single spot with an Rf value of 0.35. (3) Preparation of atomized material: including nicotine salt, cypress alkaloid salt, cooling agent, acidulant, sweetener, mint flavoring, and flavoring solvent, wherein the weight percentages of each component are as follows: nicotine salt 1-10 parts, cypress alkaloid salt 1-5 parts, cooling agent 0.5-5 parts, acidulant 0.1-2 parts, sweetener 0.1-2 parts, mint flavoring 1-10 parts, and flavoring solvent is glycerol and propylene glycol (35:50) 60-90 parts. The aforementioned peppermint-flavored atomized product containing cypress alkaloid salt and its preparation method include nicotine salt, cypress alkaloid salt, cooling agent, acidulant, sweetener, peppermint flavoring, glycerin, and propylene glycol, wherein, by weight, the weight proportions of each component are: 1 part nicotine salt, 2 parts cypress alkaloid salt, 2 parts cooling agent, 0.5 parts acidulant, 1.5 parts sweetener, 8 parts peppermint flavoring, and 85 parts glycerin and propylene glycol, which are mixed evenly to prepare the product. [Example 2] The aforementioned peppermint-flavored atomized product containing cypress alkaloid salt and its preparation method include nicotine salt, cypress alkaloid salt, cooling agent, acidulant, sweetener, peppermint flavoring, glycerin, and propylene glycol, wherein, by weight, the weight proportions of each component are: 2 parts nicotine salt, 1 part cypress alkaloid salt, 2 parts cooling agent, 0.5 parts acidulant, 1.5 parts sweetener, 8 parts peppermint flavoring, and 85 parts glycerin and propylene glycol, which are mixed evenly to prepare the product. The preparation method of Example 2 is the same as that of Example 1, except that the weight proportions of the above components are different. The atomized material of Example 2 is prepared according to the preparation method of Example 1. [Comparative Example 1] No cypress alkaloid salts are added. The product includes nicotine salts, cooling agents, acidulants, sweeteners, mint flavoring, glycerin, and propylene glycol, by weight. The weight proportions of each component are: 3 parts nicotine salt, 2 parts cooling agent, 0.5 parts acidulant, 1.5 parts sweetener, 8 parts mint flavoring, and 85 parts glycerin and propylene glycol, mixed thoroughly. The preparation method of Comparative Example 1 is the same as that of Example 1, except that no cytisine salt is added. The atomized material of Comparative Example 1 is prepared according to the preparation method of Example 1. [Comparative Example 2] No mint flavoring added. The product includes nicotine salt, cypress alkaloid salt, cooling agent, acidulant, sweetener, watermelon flavoring, glycerin, and propylene glycol, by weight. The weight proportions of each component are: 3 parts nicotine salt, 2 parts cooling agent, 0.5 parts acidulant, 1.5 parts sweetener, 8 parts watermelon flavoring, and 85 parts glycerin and propylene glycol, mixed thoroughly. The preparation method of Comparative Example 2 is the same as that of Example 1, except that the mint flavoring is replaced with fruit flavoring. The atomized material of Comparative Example 2 is prepared according to the preparation method of Example 1.

[0024] Sensory flavor evaluation:

[0025] To demonstrate the technical effectiveness of the present invention, sensory evaluations were conducted on the atomized products of Examples 1-2 and Comparative Examples 1-2. The sensory quality evaluation was performed by an evaluation panel of 20 personnel trained in electronic cigarette atomization evaluation. Table 1 Sensory Flavor Evaluation of Microcapsules Table 2. Evaluation of atomized substances in different implementations and control examples

[0026] The results in Table 2 show that, preferably, Example 1 is the best embodiment of the present invention. The weight parts of each component are as follows: 1 part nicotine salt, 2 parts cypress alkaloid salt, 2 parts cooling agent, 0.5 parts acidulant, 1.5 parts sweetener, 8 parts mint flavoring, and 85 parts glycerin and propylene glycol. These components are mixed evenly to produce an atomized product containing mint-flavored cypress alkaloid salt. It has a rich aroma, low irritation, high satisfaction after inhalation, no obvious discomfort after stopping smoking, minimal withdrawal symptoms, good smoking cessation effect, and a good user experience.

[0027] Acute inhalation toxicity test: 1. Selection of atomizing agent: The atomizing agent used in this experiment was the same as that in Example 1, consisting of 1 part nicotine salt, 2 parts cypress alkaloid salt, 2 parts cooling agent, 0.5 parts acidulant, 1.5 parts sweetener, 8 parts mint flavoring, and 85 parts glycerin and propylene glycol. 2. Selection of experimental animals: Healthy adult rats, aged 8-12 weeks and weighing between 200-300 grams, are typically selected, ensuring they are free from disease or abnormal behavior. Before the experiment begins, the rats need to be housed in a laboratory environment for at least 5 days to acclimatize, provided with standard laboratory animal feed and water. 3. Experimental preparation: Dosage selection: Based on the expected toxicity of the chemical substance, a series of escalating concentrations are selected for testing, typically using dose escalation studies, to determine the LC50 value. Exposure device: Use specially designed inhalation exposure devices, such as whole-body exposure chambers or head exposure devices, to ensure that rats inhale the test substance evenly throughout the experiment. Exposure time: Rats were continuously exposed to the aerosol of the test substance for 4 hours. The temperature, humidity and airflow of the exposure chamber were controlled to ensure consistency of experimental conditions. 4. Experimental Procedure: Baseline assessment: Check and record the health status and weight of rats before the start of the experiment. Administration methods: Administration can be administered via nasal or head contact, or whole-body contact within a dosing cabinet. A constant airflow, aerosol concentration, temperature, and humidity should be maintained within the dosing cabinet. Observation and recording: During and after exposure, rats were observed for 14 consecutive days, and their clinical symptoms and behavioral changes were recorded at least once a day. Data Analysis: During the 4-hour exposure period, the actual concentration of aerosol in this example was 5.63 ± 0.17 mg / L. No abnormalities were observed in the rats during the exposure period. 12 hours after the exposure ended, some rats showed reduced activity, but quickly recovered to normal within 12 hours. During the observation periods of days 1, 3, 7, and 14, no obvious clinical symptoms such as dyspnea, reduced activity, weight changes, or food intake changes were observed. After 14 days of observation, no rat deaths occurred, and the weight of all rats showed an increasing trend. 6. Pathological examination: After all rats were euthanized at the end of the experiment, no abnormalities were found in the autopsy results. 7. Interpretation of results: The experimental results showed no rat deaths or obvious poisoning symptoms. According to Appendix 3d of "Chemical Testing Methods 4: Health Effects (Second Edition)": 436 Acute Inhalation Toxicity Test: Hierarchical Approach to Acute Toxicity Tests, the GSH classification of the atomized matrix in this embodiment for acute inhalation toxicity in rats is unclassified, i.e., the LC50 limit is ∞.

[0028] The above are merely preferred embodiments of the present invention and do not limit the patent scope of the present invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the patent protection scope of the present invention.

Claims

1. A peppermint-flavored atomized product containing cypress alkaloid salt and its preparation method, characterized in that, include: Nicotine salts, broom salts, cooling agents, acidulants, sweeteners, mint flavorings, and flavoring solvents.

2. The peppermint-flavored atomized material containing cypress alkaloid salt and its preparation method according to claim 1, characterized in that, The preparation of mint flavoring includes the following steps: S1. Wash and sterilize fresh mint leaves, then freeze-dry the washed mint leaves (-35℃; 24h) at a vacuum degree of 10-20 Pa until the moisture content is 5-10%. S2. The dried peppermint leaves are then subjected to ultra-fine grinding (910 r / min; 350 W) to obtain peppermint leaf powder; S3. After mixing peppermint leaf powder with ethanol, extract the mixture using an ultrasonic-coupled negative pressure vacuum method. The ultrasonic temperature is 25℃, the negative pressure vacuum is -0.8MPa, and the extraction time is 120S. S4. The extract was centrifuged (25℃; 6000 rpm / min; 15 min), and the supernatant after centrifugation was purified by vacuum distillation (50 min; 45℃) to obtain peppermint extract—peppermint oil.

3. The peppermint-flavored atomized material containing cypress alkaloid salt and its preparation method according to claim 1, characterized in that, Includes the following steps: S1. Cyperine was isolated from plants such as *Sophora japonica*, *Sophora* (Fabaceae), *Cassia* (Spartina*), *Salvia lanceolata*, and *Cassia microphylla*. S2. The cytisine salt is prepared by reacting the alkalinity of cytisine with an organic acid, wherein the organic acid is one of gallic acid, ferulic acid, succinic acid, malic acid, glycyrrhizic acid, or acetylsalicylic acid. S3. Taking ferulic acid as an example: In a 50 mL dry round-bottom flask, add 1.17 g (0.005 mol) of cytisine and 0.97 g (0.005 mol) of ferulic acid, then add 25 mL of acetone solution, reflux at 40 °C for 4 h, concentrate to dryness, and add acetone, ethyl acetate and petroleum ether in sequence (acetone: ethyl acetate: petroleum ether = 4:12:35). A precipitate is formed, filtered, and a white powder is obtained, mp: 66.8-68.8 °C. S4, TLC detection: Spot the sample on a thin-layer silica gel G plate, develop with anhydrous ethanol:ethyl acetate = 1:1 (volume ratio) as the developing solvent, spray with modified bismuth potassium iodide reagent for color development, and obtain a single spot with an Rf value of 0.

35.

4. The peppermint-flavored atomized product containing cypress alkaloid salt and its preparation method according to claim 1, characterized in that, Cooling agents include one or more of WS-23, WS-3, WS-5, borneol, menthol, camphor, carbamate, menthol, and eugenol.

5. The peppermint-flavored atomized material containing cypress alkaloid salt and its preparation method according to claim 1, characterized in that, The acidulant is one or more of the following: citric acid, malic acid, lactic acid, oxalic acid, succinic acid, acetic acid, gluconic acid, linolenic acid, citric anhydride, sorbic acid, tartaric acid, malonic acid, benzoic acid, cardamomic acid, chitosanic acid, succinic anhydride, polyfructic acid, coumaric acid, and succinic acid.

6. The peppermint-flavored atomized material containing cypress alkaloid salt and its preparation method according to claim 1, characterized in that, The sweetener is one or more of the following: xylitol, erythritol, mannitol, sorbitol, maltitol, lactitol, dihydrochalcone derivatives, stevia, sucralose, alicate, acesulfame potassium, advantran, neotame, aspartame, cyclamate, sematrandez, sucrose, glucose, fructose, lactose, cyclohexyl glycosides, strawberry sugar alcohol, saccharin, sodium saccharin, lactulose, steviol glucoside, glucose oxidase, and cellulase.

7. The peppermint-flavored atomized material containing cypress alkaloid salt and its preparation method according to claim 1, characterized in that, Nicotine salts are one or more of the following: benzoic acid nicotine salt, malic acid nicotine salt, propionic acid nicotine salt, succinic acid nicotine salt, glycine nicotine salt, oxalic acid nicotine salt, and oxalic acid nicotine salt.

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