Nicotine-containing gel as well as preparation method and application thereof

Abstract

The invention provides a nicotine-containing gel and a preparation method thereof. The nicotine-containing gel comprises the following components: a nicotine microcapsule, a penetrant, a gel matrix, a flavoring agent and water. The gel has excellent biocompatibility and slow release performance through combination of the nicotine microcapsules and the gel matrix, the skin permeability of nicotine can be improved by adding the penetrant, and the gel has the advantages of freshening the oral cavity and keeping fragrance for a long time by adding the flavoring agent. Therefore, a new consumption choice can be provided for smoking cessation groups and patients needing nicotine medicine.

Description

Technical Field

[0001] The present invention belongs to the technical field of oral products, and in particular relates to a nicotine-containing gel and a preparation method and application thereof. Background Art

[0002] Years of research have shown that with the development of the tobacco industry, many smokers have become highly dependent on the nicotine in tobacco products. Nicotine-like chemicals can stimulate the sympathetic nerves, cause damage to the vascular endothelium, and pose certain hazards to people's health. Therefore, as consumers' pursuit of a healthy lifestyle grows, more and more nicotine replacement products have emerged to help smokers alleviate withdrawal symptoms and assist in quitting smoking.

[0003] WO1999015171A1 discloses a nicotine polar lipid formulation in a liquid crystal, a colloidal dispersion thereof, and a precursor or progeny thereof, which, when in contact with body fluids and / or affected by body temperature, is converted into a liquid crystal or a liquid crystal mixture, which is used as a controlled release matrix for nicotine and is suitable for smoking cessation and / or replacement therapy. The disclosed composition of the liquid crystal or its dispersion, its precursor or progeny contains nicotine and an anti-irritant or local analgesic, or any combination thereof to reduce the local irritation of nicotine and mask its taste. Applicable routes of administration and devices include oral cavity, chewing gum containing liquid crystal, its dispersion or its precursor or progeny, oral adhesives, gels and patches, using mucus to adhere liquid crystal, its dispersion or its precursor, and mouth spray using the liquid crystal dispersion, their precursors or progeny, nasal sprays and gels using the liquid crystal or its dispersion, their precursors or progeny, and adhesive patches and gels for topical application of the liquid crystal or its precursor or progeny.

[0004] CN106491569A discloses a smoking cessation hydrogel patch and its preparation method. The patch is made of nicotine, a copolymer of polyacrylic acid and sodium polyacrylate, aluminum glycolate, tartaric acid, glycerol, a high molecular weight polymer with a linear and / or network cross-linked structure, disodium edetate, azone, eucalyptus oil, castor oil, and purified water to form a hydrogel, which is then coated, covered with a film, and cured. The patch utilizes the special structure and composition of the material to achieve the purpose of preserving and releasing nicotine, thereby achieving the effect of quitting smoking. The patch has the advantages of rapid and sustained release, moisturizing, breathability, good skin permeability, low irritation, stability, aesthetics, and comfort.

[0005] However, the nicotine replacement products provided by the existing technology still have disadvantages such as unstable release rate, poor coating effect and irritation to the human body, which greatly affects the consumer experience. Summary of the Invention

[0006] In view of the deficiencies of the prior art, the present invention aims to provide a nicotine-containing gel and a preparation method and application thereof.

[0007] In order to achieve the purpose of the invention, the present invention adopts the following technical solutions:

[0008] In a first aspect, the present invention provides a nicotine-containing gel, wherein the components of the nicotine-containing gel include nicotine microcapsules, a permeabilizer, a gel matrix, a flavoring agent, and water.

[0009] The gel of the present invention, through the combination of nicotine microcapsules and a gel matrix, can have excellent biocompatibility and sustained-release properties. By adding a penetrant, the skin permeability of nicotine can be improved. By adding a flavoring agent, the gel can have the advantages of refreshing the mouth and lasting fragrance, thereby providing a new consumer option for people who want to quit smoking and patients who need nicotine for medical use.

[0010] Preferably, the components of the nicotine-containing gel include, by weight, 1-10 parts of nicotine microcapsules, 1-5 parts of osmotic agents, 5-20 parts of gel matrix, 1-5 parts of flavoring agents, and 60-95 parts of water.

[0011] The amount of nicotine microcapsules added to the nicotine-containing gel of the present invention can be 2 parts, 3 parts, 4 parts, 5 parts, 6 parts, 7 parts, 8 parts or 9 parts, etc.;

[0012] The amount of the penetrant added can be 1.5 parts, 2 parts, 2.5 parts, 3 parts, 3.5 parts, 4 parts or 4.5 parts, etc.;

[0013] The amount of the gel matrix added can be 6 parts, 8 parts, 10 parts, 12 parts, 14 parts, 16 parts or 18 parts, etc.;

[0014] The amount of the flavoring agent added can be 1.5 parts, 2 parts, 2.5 parts, 3 parts, 3.5 parts, 4 parts or 4.5 parts, etc.;

[0015] The amount of water added can be 65 parts, 70 parts, 75 parts, 80 parts, 85 parts or 90 parts, etc.

[0016] Preferably, the flavoring agent includes any one of menthol, lemon oil, apple ketone or sweet orange oil, or a combination of at least two thereof.

[0017] Preferably, the flavoring agent is a combination of menthol, malicone and sweet orange oil.

[0018] In the present invention, the flavoring agent is a combination of menthol, apple ketone and sweet orange oil, which can better mask the bitter taste of nicotine, thereby improving the user experience of the gel. The aroma and taste formed by the combination of the three can give the oral cavity a fresh and comfortable feeling.

[0019] Preferably, the mass ratio of menthol, apple ketone and sweet orange oil is (1-3):(0.1-1):(1-2).

[0020] Wherein "1-3" can be 1.1, 1.3, 1.5, 1.8, 2, 2.2, 2.5, 2.7 or 2.9, etc.;

[0021] “0.1-1” can be 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8 or 0.9, etc.;

[0022] “1-2” can be 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8 or 1.9, etc.

[0023] Preferably, the penetrant comprises any one or a combination of at least two of azone, ethanol or oleic acid;

[0024] Preferably, the penetrant is azone and ethanol.

[0025] As a preferred technical solution of the present invention, the synergistic combination of azone and ethanol can improve the transdermal penetration efficiency of nicotine, thereby further improving the satisfaction brought to consumers.

[0026] Preferably, the mass ratio of the azone to the ethanol is 1:(2-3), for example, it can be 1:2.1, 1:2.2, 1:2.3, 1:2.4, 1:2.5, 1:2.6, 1:2.7, 1:2.8 or 1:2.9, etc.

[0027] Preferably, the gel matrix comprises any one of sodium alginate, hyaluronic acid, polyvinyl alcohol, polypropylene alcohol or poly (N-isopropylacrylamide) or a combination of at least two thereof.

[0028] Preferably, the gel matrix is ​​a combination of sodium alginate, polyvinyl alcohol and poly (N-isopropylacrylamide).

[0029] Preferably, the mass ratio of the sodium alginate, polyvinyl alcohol and poly (N-isopropylacrylamide) is (2-5): (2-3): (1-3).

[0030] Wherein "2-5" can be 2.2, 2.5, 2.8, 3, 3.2, 3.5, 3.8, 4, 4.2, 4.5 or 4.8, etc.;

[0031] "2-3" can be 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8 or 2.9, etc.;

[0032] “1-3” can be 1.1, 1.3, 1.5, 1.8, 2, 2.2, 2.5, 2.7 or 2.9, etc.

[0033] In the present invention, the sodium alginate, polyvinyl alcohol and poly (N-isopropylacrylamide) serve as a gel matrix, which can improve the biocompatibility of the gel and also has a temperature / humidity response effect, thereby realizing the environmentally triggered release of the gel and improving the use effect of the gel.

[0034] Preferably, the raw materials for preparing the nicotine microcapsules include nicotine core material and wall material.

[0035] Preferably, the wall material comprises chitosan and / or polylactic acid.

[0036] Preferably, the mass ratio of the nicotine core material to the wall material is 1:(0.5-2), for example, it can be 1:0.6, 1:0.8, 1:1, 1:1.2, 1:1.5, 1:1.7 or 1:1.9.

[0037] Preferably, the preparation method of the nicotine microcapsules comprises dissolving chitosan and / or polylactic acid in water to form a wall material, adding nicotine, and mixing and homogenizing to obtain the nicotine microcapsules.

[0038] In the present invention, by coating nicotine to form nicotine microcapsules, the oxidation of nicotine can be prevented, its release time can be prolonged, its release rate can be slowed down, and the irritation and bitterness caused by nicotine can be reduced.

[0039] Preferably, the nicotine-containing gel further comprises a pH regulator and / or a moisturizer.

[0040] Preferably, the nicotine-containing gel further comprises 5-20 parts by weight of a moisturizer, for example, 6 parts, 8 parts, 10 parts, 12 parts, 14 parts, 16 parts or 18 parts.

[0041] Preferably, the pH adjuster comprises any one of citric acid, acetic acid, lactic acid or sodium bicarbonate, or a combination of at least two thereof;

[0042] Preferably, the moisturizing agent includes any one of glycerin, butylene glycol or propylene glycol, or a combination of at least two of them.

[0043] Preferably, the humectant is glycerin.

[0044] Other specific point values ​​within the above numerical ranges can be selected and will not be described in detail here.

[0045] In a second aspect, the present invention provides a method for preparing the nicotine-containing gel according to the first aspect, the method comprising: mixing nicotine microcapsules, a permeant, a gel matrix, a flavoring agent, and water to obtain the nicotine-containing gel.

[0046] Preferably, the preparation method comprises:

[0047] (1) Dissolve the gel matrix in water, add nicotine microcapsules and osmotic agent, and mix homogeneously;

[0048] (2) Then, a moisturizing agent and a flavoring agent are added, mixed and homogenized, and the pH is adjusted, and then a freeze-thaw cycle is performed to obtain the nicotine-containing gel.

[0049] Preferably, the mixing and homogenizing in step (1) is carried out by stirring, and the stirring speed is 500-1000 rpm (for example, it can be 600 rpm, 700 rpm, 800 rpm or 900 rpm, etc.), and the time is 10-30 min (for example, it can be 12 min, 15 min, 18 min, 20 min, 22 min, 25 min or 28 min, etc.).

[0050] Preferably, the mixing and homogenizing in step (2) is carried out by stirring, and the stirring speed is 500-1000 rpm (for example, it can be 600 rpm, 700 rpm, 800 rpm or 900 rpm, etc.), and the time is 10-30 min (for example, it can be 12 min, 15 min, 18 min, 20 min, 22 min, 25 min or 28 min, etc.).

[0051] Preferably, the pH is adjusted to 4-6, for example, 4.2, 4.5, 4.8, 5, 5.2, 5.5 or 5.8.

[0052] Preferably, the freeze-thaw cycle treatment in step (2) comprises freezing at -20°C to -30°C (for example, -21°C, -23°C, -25°C, -27°C or -29°C, etc.) for 5-10 minutes (for example, 6 minutes, 7 minutes, 8 minutes or 9 minutes, etc.), and then heating to 20-25°C (for example, 21°C, 22°C, 23°C or 24°C, etc.) for thawing;

[0053] Preferably, the number of freeze-thaw cycle treatments is 3-5 times, for example, 3 times, 4 times or 5 times.

[0054] Other specific point values ​​within the above numerical ranges can be selected and will not be described in detail here.

[0055] In a third aspect, the present invention provides a use of the nicotine-containing gel according to the first aspect in a smoking cessation product.

[0056] The gel of the present invention can be used as a nicotine replacement product such as a transdermal patch or an oral mucosal gel to assist in quitting smoking.

[0057] Compared with the prior art, the present invention has the following beneficial effects:

[0058] The gel of the present invention, through the combination of nicotine microcapsules and a gel matrix, can have excellent biocompatibility and sustained-release properties. By adding a penetrant, the skin permeability of nicotine can be improved. By adding a flavoring agent, the gel can have the advantages of refreshing the mouth and lasting fragrance, thereby providing a new consumer option for people who want to quit smoking and patients who need nicotine for medical use. DETAILED DESCRIPTION

[0059] The technical solution of the present invention is further described below by way of specific embodiments. It should be understood by those skilled in the art that the embodiments are merely to help understand the present invention and should not be regarded as specific limitations of the present invention.

[0060] The sources of some of the raw materials used in the examples or comparative examples of the present invention are as follows:

[0061]

[0062]

[0063] The rest of the raw materials can be used as long as they are purchased from regular dealers.

[0064] Example 1

[0065] This embodiment provides a nicotine-containing gel, wherein the nicotine-containing gel comprises 5 parts of nicotine microcapsules, 3 parts of a penetrant, 15 parts of a gel base, 3 parts of a flavoring agent, 20 parts of glycerin, and 1±0.5 parts of citric acid, and water is added to make up to 100 parts.

[0066] The flavoring agent is menthol, apple ketone and sweet orange oil in a mass ratio of 4:1:3;

[0067] The penetrant is azone and ethanol in a mass ratio of 2:5;

[0068] The gel matrix is ​​sodium alginate, polyvinyl alcohol and poly (N-isopropylacrylamide) in a mass ratio of 8:5:4.

[0069] The preparation method of the nicotine-containing gel is as follows:

[0070] (1) dissolving chitosan in water to form a wall material, adding nicotine (with a mass ratio of 1:1 to chitosan), and homogenizing at 1500 rpm for 20 minutes to obtain the nicotine microcapsules;

[0071] (2) Dissolve the gel matrix in water, add nicotine microcapsules and osmotic agent, and mix and homogenize at 800 rpm for 20 min;

[0072] (3) Then, the moisturizer and flavoring agent were added, mixed and homogenized at 800 rpm for 20 min, and then citric acid was added to adjust the pH to 5;

[0073] (4) The nicotine-containing gel was obtained after the mixture was frozen at -25°C for 8 minutes and then heated to 22°C for thawing. The cycle was repeated 4 times to obtain the nicotine-containing gel.

[0074] Example 2

[0075] This embodiment provides a nicotine-containing gel, wherein the nicotine-containing gel comprises 4 parts of nicotine microcapsules, 4 parts of osmotic agent, 20 parts of gel matrix, 2 parts of flavoring agent, 15 parts of glycerin, 1±0.5 parts of citric acid, and water is added to make up to 100 parts.

[0076] The flavoring agent is menthol, apple ketone and sweet orange oil in a mass ratio of 3:0.3:2;

[0077] The penetrant is azone and ethanol in a mass ratio of 1:2;

[0078] The gel matrix is ​​sodium alginate, polyvinyl alcohol and poly (N-isopropylacrylamide) in a mass ratio of 5:2:3.

[0079] The preparation method of the nicotine-containing gel is as follows:

[0080] (1) dissolving polylactic acid in water to form a wall material, adding nicotine (nicotine to polylactic acid at a mass ratio of 1:0.8), and homogenizing at 1000 rpm for 25 minutes to obtain the nicotine microcapsules;

[0081] (2) Dissolve the gel matrix in water, add nicotine microcapsules and osmotic agent, and mix and homogenize at 1000 rpm for 10 min;

[0082] (3) Then, the moisturizer and flavoring agent were added, mixed and homogenized at 500 rpm for 30 min, and then citric acid was added to adjust the pH to 6;

[0083] (4) The nicotine-containing gel was obtained by freezing the mixture at -20°C for 10 minutes and then heating the mixture to 25°C for thawing. The cycle was repeated three times.

[0084] Example 3

[0085] This embodiment provides a nicotine-containing gel, wherein the nicotine-containing gel comprises 8 parts of nicotine microcapsules, 5 parts of a penetrant, 18 parts of a gel base, 4 parts of a flavoring agent, 17 parts of glycerin, and 1±0.5 parts of citric acid, and water is added to make up to 100 parts.

[0086] The flavoring agent is menthol, apple ketone and sweet orange oil in a mass ratio of 1:1:1;

[0087] The penetrant is azone and ethanol in a mass ratio of 1:3;

[0088] The gel matrix is ​​sodium alginate, polyvinyl alcohol and poly (N-isopropylacrylamide) in a mass ratio of 2:3:1.

[0089] The preparation method of the nicotine-containing gel is as follows:

[0090] (1) dissolving chitosan in water to form a wall material, adding nicotine (with a mass ratio of 1:2 to chitosan), and homogenizing at 2000 rpm for 20 minutes to obtain the nicotine microcapsules;

[0091] (2) Dissolve the gel matrix in water, add nicotine microcapsules and osmotic agent, and mix and homogenize at 500 rpm for 30 min;

[0092] (3) Then, the moisturizer and flavoring agent were added, mixed and homogenized at 1000 rpm for 10 min, and then citric acid was added to adjust the pH to 5.5;

[0093] (4) The nicotine-containing gel was obtained after the mixture was frozen at -30°C for 5 minutes and then heated to 20°C for thawing. The cycle was repeated 5 times.

[0094] Example 4

[0095] This embodiment provides a nicotine-containing gel, which differs from Example 1 only in that glycerin is not included in the components, and the reduced amount is supplemented by water. The remaining components and preparation method are the same as those in Example 1.

[0096] Example 5

[0097] This embodiment provides a nicotine-containing gel. The only difference between this embodiment and Example 1 is that the gel matrix comprises sodium alginate and polyvinyl alcohol in a mass ratio of 8:5, and the amount of the gel matrix remains unchanged. The remaining components and preparation method are the same as those in Example 1.

[0098] Example 6

[0099] This example provides a nicotine-containing gel. The only difference from Example 1 is that the gel matrix comprises sodium alginate and poly (N-isopropylacrylamide) in a mass ratio of 2:1, and the amount of the gel matrix remains unchanged. The remaining components and preparation method are the same as those in Example 1.

[0100] Example 7

[0101] This example provides a nicotine-containing gel. The only difference from Example 1 is that the gel matrix comprises polyvinyl alcohol and poly (N-isopropylacrylamide) in a mass ratio of 5:4, and the amount of the gel matrix remains unchanged. The remaining components and preparation method are the same as those in Example 1.

[0102] Example 8

[0103] This embodiment provides a nicotine-containing gel, which differs from Example 1 only in that the penetrant is azone, and the amount of the penetrant remains unchanged. The remaining components and preparation method are the same as those in Example 1.

[0104] Example 9

[0105] This embodiment provides a nicotine-containing gel, which differs from Example 1 only in that the osmotic agent is ethanol and the amount of the osmotic agent remains unchanged. The remaining components and preparation method are the same as those in Example 1.

[0106] Example 10

[0107] This embodiment provides a nicotine-containing gel, which differs from Example 1 only in that the flavoring agents in the components are menthol and apple ketone in a mass ratio of 4:1, and the amount of the flavoring agents remains unchanged. The remaining components and preparation method are the same as those in Example 1.

[0108] Example 11

[0109] This embodiment provides a nicotine-containing gel. The only difference between this embodiment and Example 1 is that the flavoring agent is menthol and sweet orange oil in a mass ratio of 4:3, and the amount of the flavoring agent remains unchanged. The remaining components and preparation method are the same as those in Example 1.

[0110] Example 12

[0111] This example provides a nicotine-containing gel, which differs from Example 1 only in that the flavoring agents in the components are apple ketone and sweet orange oil in a mass ratio of 1:3, and the amount of the flavoring agents remains unchanged. The remaining components and preparation method are the same as those in Example 1.

[0112] Comparative Example 1

[0113] This comparative example provides a nicotine-containing gel, which differs from Example 1 only in that an equal amount of nicotine microcapsules in the components are replaced with pure nicotine, and the remaining components and preparation method are the same as those in Example 1.

[0114] Comparative Example 2

[0115] This comparative example provides a nicotine-containing gel, which differs from Example 1 only in that the osmotic agent is not included in the components, and the reduced amount is supplemented by water. The remaining components and preparation method are the same as those in Example 1.

[0116] Comparative Example 3

[0117] This comparative example provides a nicotine-containing gel, which differs from Example 1 only in that the flavoring agent is not included in the components, and the reduced amount is supplemented by water. The remaining components and preparation method are the same as those in Example 1.

[0118] Test Example 1 Sensory Evaluation

[0119] The evaluation method involved 10 sensory evaluators, each with an evaluation form, using a blind evaluation method. Each evaluator scored the nicotine-containing gels (used as oral mucosal gels) of Examples 1-12 and Comparative Examples 1-3 after experiencing them. The highest and lowest scores were removed, and the average was taken. The specific definitions of the sensory quality evaluation indicators are shown in Table 1, the scoring criteria are shown in Table 2, and the scoring results are shown in Table 3 (the average of each group was taken, rounded to one decimal place).

[0120] Table 1

[0121]

[0122] Table 2

[0123]

[0124] Table 3

[0125]

[0126] As can be seen from Table 3, the nicotine-containing gels obtained in Examples 1-3 of the present invention have substantially no irritation or bitterness after use, and can provide the satisfaction and comfort of nicotine, while also having the effect of freshening breath.

[0127] As can be seen from Example 4, when no moisturizer is added to the nicotine-containing gel, the comfort of the gel is poor;

[0128] As shown in Examples 5-7, the choice of gel matrix has a certain influence on the sustained release of nicotine. The use of the specific gel matrix of the present invention can reduce the irritation and bitterness caused by nicotine.

[0129] From Examples 8-9 and Comparative Example 2, it can be seen that the addition of a penetrant and the selection of azone and ethanol as a penetrant can make the gel more satisfying;

[0130] From Examples 10-12 and Comparative Example 3, it can be seen that the addition of flavoring agents and the selection of their types will also have a certain impact on the sensory experience of the gel;

[0131] As can be seen from Comparative Example 1, the use of nicotine microcapsules can better slowly release nicotine in the gel, thereby making the sensory experience of the oral spray more excellent.

[0132] Test Example 2 In vitro transdermal test

[0133] Test subjects: nicotine-containing gels of Examples 1, 8-9 of the present invention and Comparative Example 2.

[0134] Test method:

[0135] (1) Skin samples were obtained from the pig abdomen and stored at −20°C wrapped in aluminum foil until use. Before the experiment, the skin samples were thawed at room temperature for approximately 10 minutes, and 3 cm × 3 cm skin pieces were cut and washed to remove dirt and sebum. All pig skin samples were provided by Huilang Bio.

[0136] (2) A vertical Franz diffusion cell with an effective diffusion area of ​​1.77 cm2 and a receiving cell volume of 18 mL was used. A rotor was placed in the receiving cell. The treated pigskin was fixed to the Franz diffusion cell with the epidermis facing the dosing cell. 2 g of gel was added to the dosing cell. The receiving cell was filled with phosphate buffered saline (PBS) containing 2% Tween 80. The water temperature was 37°C and the rotation speed was 300 r / min.

[0137] (3) After 6 hours, the diffusion cell was dismantled, the suckling pig skin was removed, and a layer of the stratum corneum was removed with tape after being wiped clean. The pig skin was cut and soaked in an appropriate amount of methanol. Ultrasonic treatment (power 500W, frequency 40kHz) was performed for 30 minutes. An appropriate amount of the extract was taken and filtered through a 0.45μm microporous membrane. The filtrate was taken and the nicotine content was determined. The nicotine absorption per unit area of ​​skin was calculated. The results are shown in Table 4

[0138] Table 4

[0139] product <![CDATA[Nicotine absorption amount (μg / cm 2 )]]> Example 1 36.8 Example 8 25.7 Example 9 22.6 Comparative Example 2 5.5

[0140] As can be seen from Table 4, the amount of nicotine absorbed by the skin in the gel of Example 1 of the present invention is significantly higher, indicating that the gel provided by the present invention can effectively solve the problem of nicotine penetration.

[0141] It can be seen from Examples 8-9 and Comparative Example 2 that the addition of a penetrant and the combination of azone and ethanol as a penetrant can better enhance the skin permeability of nicotine.

[0142] The applicant states that the present invention uses the above-described embodiments to illustrate the nicotine-containing gel, its preparation method, and its application. However, the present invention is not limited to the above-described detailed methods, nor does it necessarily rely on the above-described detailed methods for implementation. Those skilled in the art should understand that any improvements to the present invention, equivalent substitutions for raw materials in the present invention, addition of auxiliary ingredients, and selection of specific methods, etc., fall within the scope of protection and disclosure of the present invention.

Claims

1. A gel containing nicotine, characterized in that: The components of the nicotine-containing gel include nicotine microcapsules, an osmotic agent, a gel matrix, a flavoring agent and water.

2. The nicotine-containing gel according to claim 1, characterized in that The components of the nicotine-containing gel include, by weight, 1-10 parts of nicotine microcapsules, 1-5 parts of permeants, 5-20 parts of gel bases, 1-5 parts of flavoring agents, and 60-95 parts of water.

3. The nicotine-containing gel according to claim 1 or 2, characterized in that The flavoring agent includes any one or a combination of at least two of menthol, lemon oil, apple ketone or sweet orange oil; Preferably, the penetrant comprises any one or a combination of at least two of azone, ethanol or oleic acid; Preferably, the penetrant is azone and ethanol.

4. The nicotine-containing gel according to any one of claims 1 to 3, characterized in that The gel matrix includes any one or a combination of at least two of sodium alginate, hyaluronic acid, polyvinyl alcohol, polypropylene alcohol or poly (N-isopropylacrylamide); Preferably, the gel matrix is ​​a combination of sodium alginate, polyvinyl alcohol and poly (N-isopropylacrylamide).

5. The nicotine-containing gel according to any one of claims 1 to 4, characterized in that The raw materials for preparing the nicotine microcapsules include nicotine core material and wall material; Preferably, the wall material comprises chitosan and / or polylactic acid; Preferably, the mass ratio of the nicotine core material to the wall material is 1:(0.5-2); Preferably, the preparation method of the nicotine microcapsules comprises dissolving chitosan and / or polylactic acid in water to form a wall material, adding nicotine, and mixing and homogenizing to obtain the nicotine microcapsules.

6. The nicotine-containing gel according to any one of claims 1 to 5, characterized in that The nicotine-containing gel further comprises a pH regulator and / or a moisturizer; Preferably, the pH adjuster comprises any one of citric acid, acetic acid, lactic acid or sodium bicarbonate, or a combination of at least two thereof; Preferably, the moisturizing agent includes any one of glycerin, butylene glycol or propylene glycol, or a combination of at least two of them.

7. A method for preparing a nicotine-containing gel according to any one of claims 1 to 6, characterized in that: The preparation method comprises: mixing nicotine microcapsules, a permeating agent, a gel matrix, a flavoring agent and water to obtain the nicotine-containing gel.

8. The preparation method according to claim 7, characterized in that The preparation method comprises: (1) Dissolve the gel matrix in water, add nicotine microcapsules and osmotic agent, and mix homogeneously; (2) Then, a moisturizing agent and a flavoring agent are added, mixed and homogenized, and the pH is adjusted, and then a freeze-thaw cycle is performed to obtain the nicotine-containing gel.

9. The preparation method according to claim 8, characterized in that The mixing and homogenization in step (1) is carried out by stirring at a speed of 500-1000 rpm for 10-30 min; Preferably, the mixing and homogenizing in step (2) is carried out by stirring at a speed of 1000-2000 rpm for 10-30 min; Preferably, the pH is adjusted to 4-6.

10. The preparation method according to claim 8 or 9, characterized in that: The freeze-thaw cycle treatment in step (2) includes freezing at -20°C to -30°C for 5-10 minutes and then heating to 20-25°C for thawing; Preferably, the number of freeze-thaw cycle treatments is 3-5 times.

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