Nicotine buccal product capable of rapidly inhibiting taste and moistening and clearing throat and preparation method of nicotine buccal product

Abstract

The invention provides a nicotine buccal product capable of rapidly inhibiting odor and moistening throat and clearing heat from throat and a preparation method thereof. The nicotine buccal product comprises a core layer, and a throat protecting layer, an odor inhibiting layer and a sweet aftertaste layer which are sequentially coated from inside to outside, the components of the core layer comprise nicotine salt and silicon dioxide nanoparticles; the throat protection layer is prepared from the following components: polylactic acid-glycolic acid copolymer microspheres loaded with nicotine salt, a cyclodextrin inclusion compound of dipotassium glycyrrhizinate and hyaluronic acid; the odor-inhibiting layer comprises the following components: nicotine salt, a cyclodextrin microcapsule loaded with a freshener and zinc zeolite particles loaded with plant essential oil; the sweet aftertaste layer comprises nicotine salt, a hydrophilic polymer material, a sweetening agent and an acidulant. The four-layer structure synergistically controls the nicotine release rate within a reasonable range, the palatability of the nicotine preparation is effectively improved through the multi-layer compound flavoring agent and the plant essential oil, and the nicotine preparation has the effects of freshening breath and clearing throat and is suitable for people with sensitive oral cavity and social scenes.

Description

Technical Field

[0001] This invention belongs to the field of smokeless tobacco products technology, specifically relating to a nicotine lozenge that quickly suppresses taste and soothes the throat, and its preparation method. Background Technology

[0002] Currently, commercially available nicotine preparations can easily cause dizziness, vomiting, and other discomfort due to rapid nicotine intake. Furthermore, nicotine salts are highly irritating to the oral mucosa, causing a strong stinging sensation at the application site. Additionally, the interaction of nicotine with saliva can easily lead to dehydration and dryness of the oral and pharyngeal mucosa, often resulting in discomfort such as a dry and itchy throat. Long-term use can also cause bad breath, especially exacerbating the bad breath of long-term smokers.

[0003] CN116585279A discloses a controlled-release nicotine lozenge product, comprising the following components by weight: 1-30 parts of compound nicotine salt, 10-30 parts of sweetener, 1-5 parts of cooling agent, 1-5 parts of lubricant, 1-5 parts of flavoring agent, 20-50 parts of diluent, and 1-15 parts of flavoring; the compound nicotine salt is a mixture of nicotine benzoate, resin nicotine salt, and lactic acid nicotine salt. By utilizing the different release rates of nicotine salts formed by nicotine with different organic acids during oral administration, the product is compounded to ensure a stable effect over a longer period, allowing for a uniform, slow, and sustained release of nicotine in the mouth. However, nicotine salt constitutes a very small proportion of nicotine preparations, and the difficulty in mixing multiple nicotine salts and their slow release means that a significant portion will flow with saliva into the gastrointestinal tract during the oral administration process, entering the digestive system and reducing nicotine bioavailability.

[0004] CN116649576A discloses a nicotine lozenge containing an antibacterial and antioxidant composition, comprising an antibacterial and antioxidant composition, wherein the antibacterial and antioxidant composition is a mixture of Hericium erinaceus polysaccharide, proanthocyanidins, resveratrol, ellagic acid, rosmarinic acid, and hyperoside; and further comprising one or more of nicotine and / or nicotine salts, sweeteners, flavoring agents, fillers, disintegrants, preservatives, humectants, and distilled water. By adding an antibacterial and antioxidant composition to existing nicotine lozenges, the nicotine lozenges can provide the satisfaction of nicotine while also possessing antibacterial and antioxidant effects, which can improve oral hygiene problems and have certain health benefits in scavenging free radicals and inhibiting inflammation.

[0005] Existing nicotine lozenges, designed to meet consumer demand for nicotine, typically offer unpleasant tastes such as irritation, spiciness, and bitterness, along with a limited flavor profile, poor comfort, and a tendency to cause oral inflammation. Therefore, there is an urgent need to develop a nicotine lozenge that combines multi-stage sustained-release nicotine with the function of maintaining oral hygiene. Summary of the Invention

[0006] In view of the shortcomings of the prior art, the purpose of this invention is to provide a nicotine lozenge and its preparation method that can quickly suppress taste and soothe the throat. The nicotine lozenge provided by this invention meets the physiological needs of nicotine for "instant gratification + long-term maintenance", has good palatability, and has the effects of freshening breath and soothing the throat. It is suitable for people with oral sensitivities and for use in social situations.

[0007] To achieve this objective, the present invention employs the following technical solution:

[0008] In a first aspect, the present invention provides a nicotine lozenge that quickly suppresses taste and soothes the throat, the nicotine lozenge comprising a core layer and a throat-protecting layer, a taste-suppressing layer and a sweet aftertaste layer that are sequentially wrapped from the inside out;

[0009] The core layer consists of nicotine salts and silica nanoparticles.

[0010] The throat protection layer comprises polylactic acid-glycolic acid copolymer microspheres loaded with nicotine salts, dipotassium glycyrrhizate cyclodextrin inclusion complexes, and hyaluronic acid;

[0011] The components of the flavor-suppressing layer include nicotine salts, cyclodextrin microcapsules loaded with a cooling agent, and zinc zeolite particles loaded with plant essential oils.

[0012] The components of the aftertaste layer include nicotine salts, hydrophilic polymers, sweeteners, and acidulants.

[0013] This invention features a four-layer sustained-release structure that synergistically controls the release of nicotine within a reasonable range. It offers low oral irritation and high taste characteristics, satisfying both immediate and maintenance needs for nicotine. It also freshens breath and soothes the throat, reduces the total concentration of volatile sulfur compounds in breath, and maintains oral health. It is suitable for people with sensitive mouths and for use in social settings.

[0014] The cooling agent, encapsulated by cyclodextrin and the plant essential oils loaded by zinc zeolite, allows for slow release throughout the oral phase, effectively suppressing bad breath caused by nicotine salts. Polylactic acid-glycolic acid copolymer encapsulates the nicotine salts, ensuring sustained nicotine release while reducing irritation. Dipotassium glycyrrhizate possesses anti-inflammatory and anti-allergic properties, soothing discomfort caused by nicotine. Hyaluronic acid forms a moisturizing film in the mouth, relieving dryness. Nicotine salts are introduced into the pores of silica nanoparticles, maintaining a long-term sustained release of nicotine salts in the core layer during the later stages of oral absorption.

[0015] Preferably, the particle size of the silica nanoparticles is 50-1000nm, for example, it can be 50nm, 100nm, 200nm, 300nm, 400nm, 500nm, 600nm, 700nm, 800nm, 900nm or 1000nm, etc.

[0016] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0017] Preferably, the core layer comprises, by weight, 1-10 parts of nicotine salt and 15-30 parts of silica nanoparticles.

[0018] The nicotine salt can be in parts by weight of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

[0019] The weight percentages of the silica nanoparticles can be 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 parts, etc.

[0020] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0021] Preferably, the components of the throat protection layer, by weight, include 20-40 parts of polylactic acid-glycolic acid copolymer microspheres loaded with nicotine salt, 0.1-5 parts of dipotassium glycyrrhizate cyclodextrin inclusion complex, and 0.1-5 parts of hyaluronic acid.

[0022] The weight parts of the polylactic acid-glycolic acid copolymer microspheres loaded with nicotine salt can be 20 parts, 22 parts, 25 parts, 27 parts, 30 parts, 33 parts, 35 parts, 38 parts, or 40 parts, etc.

[0023] The weight parts of the dipotassium glycyrrhizate cyclodextrin inclusion complex can be 0.1 parts, 0.2 parts, 0.5 parts, 0.7 parts, 1 part, 1.3 parts, 1.5 parts, 1.8 parts, 2 parts, 2.5 parts, 3 parts, 3.5 parts, 4 parts, 4.5 parts, or 5 parts, etc.

[0024] The weight percentage of the hyaluronic acid can be 0.1 parts, 0.2 parts, 0.5 parts, 0.7 parts, 1 part, 1.3 parts, 1.5 parts, 1.8 parts, 2 parts, 2.5 parts, 3 parts, 3.5 parts, 4 parts, 4.5 parts, or 5 parts, etc.

[0025] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0026] Preferably, the components of the flavor-suppressing layer include, by weight, 15-25 parts of nicotine salt, 0.1-3 parts of cyclodextrin microcapsules loaded with a cooling agent, and 0.1-2 parts of zinc zeolite particles loaded with plant essential oils.

[0027] The nicotine salt can be in the following weight proportions: 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 parts.

[0028] The weight parts of the cyclodextrin microcapsules loaded with the cooling agent can be 0.1 parts, 0.2 parts, 0.5 parts, 0.7 parts, 1 part, 1.3 parts, 1.5 parts, 1.8 parts, 2 parts, 2.5 parts, or 3 parts, etc.

[0029] The weight percentage of the zinc zeolite particles loaded with plant essential oils can be 0.1 parts, 0.2 parts, 0.5 parts, 0.7 parts, 1 part, 1.3 parts, 1.5 parts, 1.8 parts, or 2 parts, etc.

[0030] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0031] Preferably, the components of the aftertaste layer include, by weight, 15-30 parts of nicotine salt, 20-60 parts of hydrophilic polymer material, 1-10 parts of sweetener and 1-10 parts of acidulant.

[0032] The nicotine salt can be in the following weight proportions: 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 parts.

[0033] The weight percentages of the hydrophilic polymer material can be 20, 22, 25, 27, 30, 33, 35, 38, 40, 45, 50, 55, or 60 parts, etc.

[0034] The sweetener can be present in parts by weight of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 parts, etc.

[0035] The acidulant can be present in parts by weight of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

[0036] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0037] Preferably, the mass ratio of the core layer, throat-protecting layer, flavor-suppressing layer and aftertaste layer is (1-10):(20-40):(15-30):(5-20).

[0038] The specific point values ​​in (1-10) can be 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, etc.

[0039] The specific point values ​​in (20-40) can be 20, 22, 25, 27, 30, 33, 35, 38 or 40, etc.

[0040] The specific point values ​​in (15-30) can be 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30, etc.

[0041] The specific point values ​​in (5-20) can be 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20, etc.

[0042] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0043] Preferably, the nicotine salt-loaded polylactic acid-glycolic acid copolymer microspheres are prepared by a method comprising the following steps:

[0044] Polylactic acid-glycolic acid copolymer and organic solvent were mixed to obtain a mixture; nicotine salt aqueous solution was mixed with the mixture, ultrasonically emulsified, and then mixed with polyvinyl alcohol aqueous solution, stirred, the organic solvent was evaporated, solid-liquid separation was performed, microspheres were collected, and freeze-dried to obtain the nicotine salt-loaded polylactic acid-glycolic acid copolymer microspheres.

[0045] Preferably, the polylactic acid-glycolic acid copolymer has a mass percentage content of 3-6% in the mixture, for example, it can be 3%, 3.2%, 3.5%, 3.8%, 4%, 4.3%, 4.5%, 4.7%, 5%, 5.5% or 6%, etc.

[0046] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0047] Preferably, the organic solvent includes any one or a combination of at least two of dichloromethane, ethyl acetate, chloroform, or isopropanol.

[0048] Preferably, the mass ratio of the polylactic acid-glycolic acid copolymer to the nicotine salt is (2-5):1.

[0049] The specific point values ​​in (2-5) can be 2, 2.2, 2.5, 2.7, 3, 3.3, 3.5, 3.8, 4, 4.5 or 5, etc.

[0050] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0051] Preferably, the power of the ultrasound is 200-500W, for example, 200W, 220W, 250W, 270W, 300W, 330W, 350W, 380W, 400W, 450W, or 500W; the duration is 3-8 minutes, for example, 3 minutes, 3.5 minutes, 4 minutes, 4.5 minutes, 5 minutes, 5.5 minutes, 6 minutes, 6.5 minutes, 7 minutes, 7.5 minutes, or 8 minutes.

[0052] Preferably, the stirring speed is 2000-3000 rpm, for example, 2000 rpm, 2100 rpm, 2200 rpm, 2300 rpm, 2400 rpm, 2500 rpm, 2600 rpm, 2700 rpm, 2800 rpm, 2900 rpm, or 3000 rpm; the stirring time is 2-5 hours, for example, 2 hours, 2.2 hours, 2.5 hours, 2.7 hours, 3 hours, 3.3 hours, 3.5 hours, 3.8 hours, 4 hours, 4.5 hours, or 5 hours.

[0053] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0054] Preferably, the solvent is evaporated by vacuum distillation.

[0055] Preferably, the process of collecting the microspheres further includes a washing step with water.

[0056] Preferably, the dipotassium glycyrrhizate cyclodextrin inclusion complex is prepared by a method comprising the following steps:

[0057] Dipotassium glycyrrhizate, cyclodextrin, and water were mixed, stirred, and spray-dried to obtain the cyclodextrin inclusion complex of dipotassium glycyrrhizate.

[0058] Preferably, the mass ratio of dipotassium glycyrrhizate, cyclodextrin and water is (1-3):(1-3):(3-6).

[0059] The specific point values ​​in (1-3) can be 1, 1.2, 1.5, 1.7, 2, 2.3, 2.5, 2.8 or 3, etc.

[0060] The specific point values ​​in (1-3) can be 1, 1.2, 1.5, 1.7, 2, 2.3, 2.5, 2.8 or 3, etc.

[0061] The specific point values ​​in (3-6) can be 3, 3.2, 3.5, 3.7, 4, 4.3, 4.5, 4.8, 5, 5.5 or 6, etc.

[0062] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0063] Preferably, the stirring speed is 1000-3000 rpm, for example, 1000 rpm, 1200 rpm, 1500 rpm, 1700 rpm, 2000 rpm, 2300 rpm, 2500 rpm, 2800 rpm or 3000 rpm; the stirring time is 0.5-2 hours, for example, 0.5 hours, 0.6 hours, 0.7 hours, 0.8 hours, 0.9 hours, 1 hour, 1.2 hours, 1.5 hours, 1.7 hours or 2 hours.

[0064] Preferably, the stirring temperature is 50-70℃, for example, it can be 50℃, 52℃, 55℃, 57℃, 60℃, 63℃, 65℃, 68℃ or 70℃, etc.

[0065] Preferably, the inlet air temperature of the spray dryer is 80-140℃, for example, it can be 80℃, 85℃, 90℃, 95℃, 100℃, 105℃, 110℃, 115℃, 120℃, 125℃, 130℃, 135℃ or 140℃, etc.

[0066] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0067] Preferably, the cyclodextrin microcapsules loaded with the cooling agent are prepared by a method comprising the following steps:

[0068] The cooling agent and organic solvent were mixed, then mixed with an aqueous solution of cyclodextrin, stirred, and spray-dried to obtain the cyclodextrin microcapsules loaded with the cooling agent.

[0069] Preferably, the cooling agent comprises any one or a combination of at least two of menthol, menthone, ethyl menthane formamide, or menthyl acetate.

[0070] Preferably, the organic solvent includes any one or a combination of at least two of ethanol, acetone, or diethyl ether.

[0071] Preferably, the mass ratio of the cooling agent to the organic solvent is (2-20):(98-80).

[0072] The specific point values ​​in (2-20) can be 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20, etc.

[0073] The specific point values ​​in (98-80) can be 98, 97, 96, 95, 94, 93, 92, 91, 90, 89, 88, 87, 86, 85, 84, 83, 82, 81 or 80, etc.

[0074] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0075] Preferably, the mass ratio of the cooling agent to cyclodextrin is (1-2):(2-5).

[0076] The specific point values ​​in (1-2) can be 1, 1.1, 1.2, 1.3, 1.4, 1.5, 16, 1.7, 1.8, 1.9 or 2, etc.

[0077] The specific point values ​​in (2-5) can be 2, 2.2, 2.5, 2.7, 3, 3.3, 3.5, 3.8, 4, 4.5 or 5, etc.

[0078] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0079] Preferably, the stirring speed is 1000-3000 rpm, for example, 1000 rpm, 1200 rpm, 1500 rpm, 1700 rpm, 2000 rpm, 2300 rpm, 2500 rpm, 2800 rpm or 3000 rpm; the stirring time is 0.5-3 hours, for example, 0.5 hours, 0.6 hours, 0.7 hours, 0.8 hours, 0.9 hours, 1 hour, 1.5 hours, 2 hours, 2.5 hours or 3 hours.

[0080] Preferably, the inlet air temperature for spray drying is 80-160℃, for example, it can be 80℃, 85℃, 90℃, 95℃, 100℃, 105℃, 110℃, 115℃, 120℃, 125℃, 130℃, 135℃, 140℃, 150℃ or 160℃, etc.

[0081] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0082] Preferably, the zinc zeolite particles loaded with plant essential oils are prepared by a method comprising the following steps:

[0083] Plant essential oils are mixed with organic solvents, then mixed with zinc zeolite, stirred, and spray-dried to obtain zinc zeolite particles loaded with plant essential oils.

[0084] Preferably, the plant essential oil includes any one or a combination of at least two of eucalyptus oil, patchouli oil, bergamot oil, or carrot seed oil.

[0085] Preferably, the plant essential oils include eucalyptus leaf essential oil, patchouli essential oil, bergamot essential oil, and carrot seed essential oil.

[0086] In the four-layer composite structure system of the present invention, eucalyptus oil, patchouli oil, bergamot oil and carrot seed oil are preferably used to load zinc zeolite particles. In the sustained-release system of nicotine oral preparations, the four essential oils work synergistically to exert excellent odor-suppressing effects.

[0087] The aforementioned plant essential oils can be added simultaneously during the loading process of zinc zeolite particles, or they can be prepared separately as zinc zeolite particles loaded with plant essential oils and then used in combination. Both methods have the same effect and do not affect the odor suppression effect.

[0088] Preferably, the mass ratio of the eucalyptus oil, patchouli oil, bergamot oil and carrot seed oil is (1-10):(1-10):(1-10):(1-10).

[0089] The specific point values ​​in the first (1-10) can be 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, etc.

[0090] The specific point values ​​in the second (1-10) can be 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, etc.

[0091] The specific point values ​​in the third (1-10) can be 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, etc.

[0092] The specific point values ​​in the fourth (1-10) can be 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, etc.

[0093] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0094] Preferably, the organic solvent is ethanol.

[0095] Preferably, the particle size of the zinc zeolite particles is 0.1-1 nm, for example, it can be 0.1 nm, 0.2 nm, 0.3 nm, 0.4 nm, 0.5 nm, 0.6 nm, 0.7 nm, 0.8 nm, 0.9 nm or 1 nm.

[0096] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0097] Preferably, the mass ratio of the plant essential oil to zinc zeolite is (4-5):1.

[0098] The specific point values ​​in (4-5) can be 4, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9 or 5, etc.

[0099] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0100] Preferably, the stirring temperature is 35-45℃, for example, 35℃, 36℃, 37℃, 38℃, 39℃, 40℃, 41℃, 42℃, 43℃, 44℃ or 45℃, etc.; the stirring time is 22-26h, for example, 22h, 22.5h, 23h, 23.5h, 24h, 24.5h, 25h, 25.5h or 26h, etc.

[0101] Preferably, the inlet air temperature for spray drying is 140-170℃, for example, it can be 140℃, 142℃, 145℃, 147℃, 150℃, 153℃, 155℃, 158℃, 160℃, 165℃ or 170℃, etc.

[0102] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0103] Preferably, the nicotine salt includes any one or a combination of at least two of nicotine malate, nicotine tartrate, nicotine citrate, nicotine lactate, nicotine benzoate, or nicotine levulinate.

[0104] Preferably, the hydrophilic polymeric material includes any one or a combination of at least two of sodium alginate, hyaluronic acid, chitosan, or gelatin.

[0105] Preferably, the sweetener comprises any one or a combination of at least two of the following: mogroside, stevia, erythritol, xylitol, sorbitol, sucralose, isomaltitol, aspartame, acesulfame potassium, neotame, saccharin, sucrose, glucose, maltose, or fructose.

[0106] Preferably, the acidulant comprises any one or a combination of at least two of malic acid, citric acid, tartaric acid, acetic acid, benzoic acid, butyric acid, lactic acid, fumaric acid, succinic acid, ascorbic acid, adipic acid, or phosphoric acid.

[0107] In a second aspect, the present invention provides a method for preparing a nicotine lozenge as described in the first aspect, the method comprising:

[0108] Nicotine salt and silica nanoparticles were mixed in water, sonicated, and dried to obtain the core layer material; nicotine salt-loaded polylactic acid-glycolic acid copolymer microspheres, dipotassium glycyrrhizate cyclodextrin inclusion complexes, and hyaluronic acid were mixed to obtain the throat-protecting layer material; nicotine salt, cyclodextrin microcapsules loaded with cooling agents, and zinc zeolite particles loaded with plant essential oils were mixed to obtain the flavor-suppressing layer material; and nicotine salt, hydrophilic polymer materials, sweeteners, and acidulants were mixed to obtain the aftertaste layer material.

[0109] The core layer material is sequentially coated with a throat-protecting layer material, a taste-suppressing layer material, and a sweet aftertaste layer material, and then compressed into tablets to obtain the nicotine lozenge.

[0110] Preferably, the power of the ultrasound is 100-300W, for example, 100W, 120W, 150W, 170W, 200W, 230W, 250W, 280W or 300W; the duration is 10-30min, for example, 10min, 12min, 15min, 17min, 20min, 23min, 25min, 28min or 30min.

[0111] Preferably, the drying temperature is 40-80℃, for example, 40℃, 42℃, 45℃, 47℃, 50℃, 53℃, 55℃, 58℃, 60℃, 70℃ or 80℃, etc.; the time is 0.5-3h, for example, 0.5h, 0.6h, 0.7h, 0.8h, 0.9h, 1h, 1.5h, 2h, 2.5h or 3h, etc.

[0112] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0113] Compared with the prior art, the present invention has the following beneficial effects:

[0114] This invention features a four-layer sustained-release structure that synergistically controls the release of nicotine within a reasonable range. It offers low oral irritation and high taste characteristics, satisfying both immediate and maintenance needs for nicotine. It also freshens breath and soothes the throat, reduces the total concentration of volatile sulfur compounds in breath, and maintains oral health. It is suitable for people with sensitive mouths and for use in social settings. Detailed Implementation

[0115] To further illustrate the technical means and effects of the present invention, the following describes the technical solution of the present invention in conjunction with preferred embodiments of the present invention. However, the present invention is not limited to the scope of the embodiments.

[0116] Where specific techniques or conditions are not specified in the examples, they shall be performed in accordance with the techniques or conditions described in the literature in this field, or in accordance with the product instructions. Reagents or instruments whose manufacturers are not specified are all conventional products that can be purchased through legitimate channels.

[0117] The sources of materials used in the following specific embodiments are as follows:

[0118] Raw material name Purchase manufacturer model Polylactic acid-glycolic acid copolymer Jilin Zhongke Kang Technology Co., Ltd. High-purity polylactic acid-glycolic acid copolymer Polyvinyl alcohol Shaanxi Jinyang Pharmaceutical Excipients Co., Ltd. 1788 Medium Viscosity Polyvinyl Alcohol Cyclodextrin Zhejiang Yuanfeng Biotechnology Co., Ltd. Food-grade cyclodextrin Zinc zeolite Taizhou Mingrui Teaching Equipment Co., Ltd. Zinc zeolite Silica nanoparticles Wuxi Taipeng New Materials Co., Ltd. High-purity hydrophilic silica nanoparticles Hyaluronic acid Guangzhou Huilong Biotechnology Co., Ltd. Food-grade hyaluronic acid Sodium alginate Zhongyuan Biotechnology Co., Ltd. Food-grade sodium alginate Chitosan Zhejiang Yuanfeng Biotechnology Co., Ltd. Food-grade chitosan

[0119] Preparation Example 1

[0120] This preparation example provides polylactic acid-glycolic acid copolymer microspheres loaded with nicotine salts, which are prepared by a method comprising the following steps:

[0121] 100g of 5wt% nicotine malate aqueous solution was mixed with 400g of 5wt% polylactic acid-glycolic acid copolymer in dichloromethane solution and ultrasonically emulsified at 300W for 5min; then 1000g of 6wt% polyvinyl alcohol aqueous solution was added and stirred at 2500rpm for 3h; the organic solvent was evaporated by vacuum distillation at 45℃, the microspheres were collected by centrifugation, washed three times with water, and freeze-dried to obtain the nicotine salt-loaded polylactic acid-glycolic acid copolymer microspheres.

[0122] Preparation Example 2

[0123] This preparation example provides polylactic acid-glycolic acid copolymer microspheres loaded with nicotine salts, which are prepared by a method comprising the following steps:

[0124] 100g of 5wt% nicotine tartrate aqueous solution was mixed with 830g of 3wt% polylactic acid-glycolic acid copolymer in ethyl acetate solution and ultrasonically emulsified at 200W for 8min; then 1500g of 4wt% polyvinyl alcohol aqueous solution was added and stirred at 2000rpm for 5h; the organic solvent was evaporated by vacuum distillation at 45℃, the microspheres were collected by centrifugation, washed three times with water, and freeze-dried to obtain the nicotine salt-loaded polylactic acid-glycolic acid copolymer microspheres.

[0125] Preparation Example 3

[0126] This preparation example provides polylactic acid-glycolic acid copolymer microspheres loaded with nicotine salts, which are prepared by a method comprising the following steps:

[0127] 100g of 5wt% nicotine citrate aqueous solution was mixed with 167g of 6wt% polylactic acid-glycolic acid copolymer in chloroform solution and ultrasonically emulsified at 500W for 3min; then 750g of 4wt% polyvinyl alcohol aqueous solution was added and stirred at 3000rpm for 2h; the organic solvent was evaporated by vacuum distillation at 45℃, the microspheres were collected by centrifugation, washed three times with water, and freeze-dried to obtain the nicotine salt-loaded polylactic acid-glycolic acid copolymer microspheres.

[0128] Preparation Example 4

[0129] This preparation example provides a cyclodextrin inclusion complex of dipotassium glycyrrhizate, which is prepared by a method comprising the following steps:

[0130] Dipotassium glycyrrhizate, cyclodextrin, and water were mixed in a mass ratio of 2:2:5, stirred at 2000 rpm for 1 hour at 60°C, and spray-dried at an inlet air temperature of 100°C to obtain the cyclodextrin inclusion complex of dipotassium glycyrrhizate.

[0131] Preparation Example 5

[0132] This preparation example provides a cyclodextrin inclusion complex of dipotassium glycyrrhizate, which is prepared by a method comprising the following steps:

[0133] Dipotassium glycyrrhizate, cyclodextrin, and water were mixed in a mass ratio of 1:3:6, stirred at 1000 rpm for 2 hours at 50°C, and spray-dried at an inlet air temperature of 140°C to obtain the cyclodextrin inclusion complex of dipotassium glycyrrhizate.

[0134] Preparation Example 6

[0135] This preparation example provides a cyclodextrin inclusion complex of dipotassium glycyrrhizate, which is prepared by a method comprising the following steps:

[0136] Dipotassium glycyrrhizate, cyclodextrin, and water were mixed in a mass ratio of 3:1:3, stirred at 3000 rpm for 0.5 h at 70 °C, and spray-dried at an inlet air temperature of 80 °C to obtain the cyclodextrin inclusion complex of dipotassium glycyrrhizate.

[0137] Preparation Example 7

[0138] This preparation example provides a cyclodextrin microcapsule loaded with menthol, which is prepared by a method comprising the following steps:

[0139] 100g of an ethanolic solution of 10wt% menthol was mixed with 300g of an aqueous solution of 10wt% cyclodextrin, stirred at 2000rpm for 2h, and spray-dried at an inlet air temperature of 130℃ to obtain the cyclodextrin microcapsules loaded with menthol.

[0140] Preparation Example 8

[0141] This preparation example provides a cyclodextrin microcapsule loaded with menthone, which is prepared by a method comprising the following steps:

[0142] 100g of an acetone solution containing 20wt% menthone was mixed with 400g of an aqueous solution containing 10wt% cyclodextrin, stirred at 1000rpm for 3h, and spray-dried at an inlet air temperature of 160℃ to obtain the cyclodextrin microcapsules loaded with menthone.

[0143] Preparation Example 9

[0144] This preparation example provides a cyclodextrin microcapsule loaded with menthyl acetate, which is prepared by a method comprising the following steps:

[0145] 100g of a 2wt% menthol acetate ether solution was mixed with 500g of a 2wt% cyclodextrin aqueous solution, stirred at 3000rpm for 0.5h, and spray-dried at an inlet air temperature of 80℃ to obtain the cyclodextrin microcapsules loaded with menthol acetate.

[0146] Preparation Example 10

[0147] This preparation example provides zinc zeolite particles loaded with eucalyptus oil, which are prepared by a method comprising the following steps:

[0148] 1000g of an ethanol solution of 4.5wt% eucalyptus oil was mixed with 10g of zinc zeolite, stirred at 40°C for 24h, and spray-dried at an inlet air temperature of 155°C to obtain the zinc zeolite particles loaded with eucalyptus oil.

[0149] Preparation Example 11

[0150] This preparation example provides zinc zeolite particles loaded with patchouli essential oil, which are prepared by a method including the following steps:

[0151] 1000g of an ethanol solution of 4wt% patchouli essential oil was mixed with 10g of zinc zeolite, stirred at 35°C for 26h, and spray-dried at an inlet air temperature of 140°C to obtain the zinc zeolite particles loaded with patchouli essential oil.

[0152] Preparation Example 12

[0153] This preparation example provides zinc zeolite particles loaded with bergamot essential oil, which are prepared by a method comprising the following steps:

[0154] 1000g of 5wt% bergamot essential oil in ethanol solution was mixed with 10g of zinc zeolite, stirred at 45℃ for 22h, and spray dried at an inlet air temperature of 170℃ to obtain the zinc zeolite particles loaded with bergamot essential oil.

[0155] Preparation Example 13

[0156] This preparation example provides zinc zeolite particles loaded with carrot seed oil, which differs from preparation example 10 only in that eucalyptus oil is replaced with carrot seed oil, while the other steps and raw materials remain unchanged.

[0157] Example 1

[0158] This embodiment provides a nicotine lozenge, which is prepared by a method comprising the following steps:

[0159] (1) Preparation of core layer material: By weight, 3 parts of nicotine malate and 20 parts of silica nanoparticles are mixed in water, ultrasonicated at 200W for 20 min, and dried at 60℃ for 2 h to obtain the core layer material.

[0160] Preparation of the throat protection layer material: by weight, 30 parts of the polylactic acid-glycolic acid copolymer microspheres loaded with nicotine salt provided in Preparation Example 1, 2 parts of the cyclodextrin inclusion complex of dipotassium glycyrrhizate provided in Preparation Example 4 and 2 parts of hyaluronic acid are mixed to obtain the material.

[0161] Preparation of the flavor-suppressing layer material: By weight, 20 parts of nicotine tartrate, 1 part of cyclodextrin microcapsules loaded with menthol provided in Preparation Example 7, 0.1 parts of zinc zeolite particles loaded with eucalyptus oil provided in Preparation Example 10, 0.3 parts of zinc zeolite particles loaded with patchouli oil provided in Preparation Example 11, 0.2 parts of zinc zeolite particles loaded with bergamot oil provided in Preparation Example 12, and 0.6 parts of zinc zeolite particles loaded with carrot seed oil provided in Preparation Example 13 are mixed to obtain the product.

[0162] Preparation of the sweet aftertaste layer material: By weight, 20 parts of nicotine citrate, 40 parts of sodium alginate, 5 parts of mogroside and 5 parts of malic acid are mixed to obtain the sweet aftertaste layer material.

[0163] (2) The throat-protecting layer material, the flavor-suppressing layer material, and the aftertaste layer material are sequentially coated on the outside of the core layer material in a mass ratio of 1:30:20:10, and then compressed into tablets to obtain the nicotine oral product.

[0164] Example 2

[0165] This embodiment provides a nicotine lozenge, which is prepared by a method comprising the following steps:

[0166] (1) Preparation of core layer material: By weight, 1 part of nicotine malate and 15 parts of silica nanoparticles are mixed in water, ultrasonicated at 100W for 30 min, and dried at 40℃ for 3 h to obtain the core layer material.

[0167] Preparation of the throat protection layer material: By weight, 20 parts of the polylactic acid-glycolic acid copolymer microspheres loaded with nicotine salt provided in Preparation Example 2, 5 parts of the cyclodextrin inclusion complex of dipotassium glycyrrhizate provided in Preparation Example 5, and 0.1 parts of hyaluronic acid are mixed to obtain the material.

[0168] Preparation of the flavor-suppressing layer material: By weight, 15 parts of nicotine tartrate, 3 parts of cyclodextrin microcapsules loaded with menthone provided in Preparation Example 8, 0.3 parts of zinc zeolite particles loaded with eucalyptus oil provided in Preparation Example 10, 0.3 parts of zinc zeolite particles loaded with patchouli oil provided in Preparation Example 11, 0.1 parts of zinc zeolite particles loaded with bergamot oil provided in Preparation Example 12, and 0.4 parts of zinc zeolite particles loaded with carrot seed oil provided in Preparation Example 13 are mixed to obtain the product.

[0169] Preparation of the sweet aftertaste layer material: By weight, mix 30 parts of nicotine citrate, 60 parts of hyaluronic acid, 10 parts of stevia and 1 part of citric acid to obtain the sweet aftertaste layer material;

[0170] (2) The core layer material is coated with the throat-protecting layer material, the flavor-suppressing layer material and the aftertaste layer material in sequence, with a mass ratio of 2:40:15:5, and then compressed into tablets to obtain the nicotine oral product.

[0171] Example 3

[0172] This embodiment provides a nicotine lozenge, which is prepared by a method comprising the following steps:

[0173] (1) Preparation of core layer material: By weight, 10 parts of nicotine malate and 30 parts of silica nanoparticles are mixed in water, ultrasonicated at 300W for 10 min, and dried at 80℃ for 0.5 h to obtain the core layer material.

[0174] Preparation of the throat protection layer material: by weight, 40 parts of the polylactic acid-glycolic acid copolymer microspheres loaded with nicotine salt provided in Preparation Example 3, 0.1 parts of the cyclodextrin inclusion complex of dipotassium glycyrrhizate provided in Preparation Example 6, and 5 parts of hyaluronic acid are mixed to obtain the material.

[0175] Preparation of the flavor-suppressing layer material: By weight, 25 parts of nicotine tartrate, 0.1 parts of the cyclodextrin microcapsules loaded with menthyl acetate provided in Preparation Example 9, 0.5 parts of zinc zeolite particles loaded with eucalyptus oil provided in Preparation Example 10, 0.3 parts of zinc zeolite particles loaded with patchouli oil provided in Preparation Example 11, 0.4 parts of zinc zeolite particles loaded with bergamot oil provided in Preparation Example 12, and 0.3 parts of zinc zeolite particles loaded with carrot seed oil provided in Preparation Example 13 are mixed to obtain the product.

[0176] Preparation of the aftertaste layer material: By weight, 15 parts of nicotine citrate, 20 parts of chitosan, 1 part of erythritol and 10 parts of lactic acid are mixed to obtain the material.

[0177] (2) The core layer material is coated with the throat-protecting layer material, the flavor-suppressing layer material and the aftertaste layer material in sequence, with a mass ratio of 1:20:30:20, and then compressed into tablets to obtain the nicotine oral product.

[0178] Example 4

[0179] This embodiment provides a nicotine lozenge, which differs from Embodiment 1 only in that: the zinc zeolite particles loaded with eucalyptus oil are not added to the flavor-suppressing layer, but are proportionally distributed to the zinc zeolite particles loaded with patchouli oil, bergamot oil, and carrot seed oil, while the other raw materials and steps remain unchanged.

[0180] Example 5

[0181] This embodiment provides a nicotine lozenge, which differs from Embodiment 1 only in that: the flavor-suppressing layer does not contain zinc zeolite particles loaded with patchouli essential oil, but its proportion is reduced and distributed proportionally to zinc zeolite particles loaded with eucalyptus essential oil, zinc zeolite particles loaded with bergamot essential oil, and zinc zeolite particles loaded with carrot seed essential oil, while the other raw materials and steps remain unchanged.

[0182] Example 6

[0183] This embodiment provides a nicotine lozenge, which differs from Embodiment 1 only in that: the zinc zeolite particles loaded with bergamot essential oil are not added to the flavor-suppressing layer, but are proportionally distributed to the zinc zeolite particles loaded with eucalyptus essential oil, the zinc zeolite particles loaded with patchouli essential oil, and the zinc zeolite particles loaded with carrot seed essential oil, while the other raw materials and steps remain unchanged.

[0184] Example 7

[0185] This embodiment provides a nicotine lozenge, which differs from Embodiment 1 only in that: the zinc zeolite particles loaded with carrot seed oil are not added to the flavor-suppressing layer, but are proportionally distributed to the zinc zeolite particles loaded with eucalyptus oil, the zinc zeolite particles loaded with patchouli oil, and the zinc zeolite particles loaded with bergamot oil, while the other raw materials and steps remain unchanged.

[0186] Comparative Example 1

[0187] This comparative example provides a nicotine oral product, which differs from Example 1 only in that: in step (2), "the throat-protecting layer material, the flavor-suppressing layer material, and the aftertaste layer material are sequentially coated on the outside of the core layer material in a mass ratio of 1:30:20:10" is replaced with "the flavor-suppressing layer material, the aftertaste layer material, and the core layer material are sequentially coated on the outside of the throat-protecting layer material in a mass ratio of 1:30:20:10", while the other raw materials and steps remain unchanged.

[0188] Comparative Example 2

[0189] This comparative example provides a nicotine lozenge, which differs from Example 1 only in that: in step (2), "the core layer material is wrapped with the throat-protecting layer material, the flavor-suppressing layer material, and the aftertaste layer material in sequence with a mass ratio of 1:30:20:10" is replaced with "the flavor-suppressing layer material is wrapped with the aftertaste layer material, the core layer material, and the throat-protecting layer material in sequence with a mass ratio of 1:30:20:10", while the other raw materials and steps remain unchanged.

[0190] Comparative Example 3

[0191] This comparative example provides a nicotine oral product, which differs from Example 1 only in that: in step (2), "the core layer material, the throat-protecting layer material, the flavor-suppressing layer material, and the aftertaste layer material are sequentially coated on the outside of the core layer material in a mass ratio of 1:30:20:10" is replaced with "the core layer material, the throat-protecting layer material, and the flavor-suppressing layer material are sequentially coated on the outside of the aftertaste layer material in a mass ratio of 1:30:20:10", while the other raw materials and steps remain unchanged.

[0192] Comparative Example 4

[0193] This comparative example provides a commercially available nicotine oral cigarette.

[0194] Test Example 1

[0195] Artificial saliva (formulation shown in Table 1, pH=6.7) was used to simulate the oral cavity environment. A drug dissolution analyzer was used to test the release of nicotine lozenges provided in Examples 1-3 or Comparative Examples 1-3, and the commercially available nicotine lozenge provided in Comparative Example 4 in the oral cavity. The temperature was set to 37℃ and the rotation speed to 100 rpm. Artificial saliva was added to a 1000 mL dissolution vessel. The nicotine lozenge was placed in the dissolution vessel, and the rotation was started; this point was recorded as 0 min. At 5 min, 10 min, 15 min, 20 min, 30 min, 40 min, and 60 min, 10 mL samples were taken for HPLC analysis, and 10 mL of artificial saliva was added after each sample.

[0196] The test results are shown in Table 2. Commercially available nicotine products release too little nicotine in the initial stage of nicotine absorption, failing to meet immediate needs, while releasing too much nicotine in the later stages. This abrupt release provides low comfort and the explosive release of nicotine in the later stages is highly irritating, causing dizziness, vomiting, and other reactions. The nicotine lozenge provided by this invention has a four-layer sustained-release structure, synergistically controlling the nicotine release within a reasonable range, balancing immediate relief in the initial stage with stable maintenance during absorption.

[0197] Table 1

[0198] composition Concentration (mM) Sodium chloride 10 Sodium hydrogen phosphate 2.4 Potassium dihydrogen phosphate 2.5 Citric acid 0.15 Potassium bicarbonate 15 Magnesium chloride 1.5 Calcium chloride 1.5

[0199] Table 2

[0200]

[0201]

[0202] Test Example 2

[0203] The main cause of abnormal breath is the increased content of volatile sulfur compounds (VSCs) in the oral cavity. A breath analyzer and an OralChroma™ portable gas chromatograph (ABILIT, Japan) were used to detect changes in the total concentration of VSCs in breath before and after using the nicotine lozenges provided in Examples 1-7 or Comparative Examples 1-3, and the commercially available nicotine lozenge provided in Comparative Example 4. Subjects used test samples. One hour later, the sampler was inserted approximately 3 cm into the subject's oral cavity. The sampler was pushed and pulled three times with the mouth closed. The sampler was then removed from the oral cavity, and the gas was pushed to the 1 mL mark. The sampler was then inserted into the instrument's inlet and the gas was pushed in for detection. This was repeated three times, and the average value was taken. The change in VSCs was calculated as: VSCs change = VSCs content after use - VSCs content before use.

[0204] The test results are shown in Table 3. The nicotine lozenge provided by this invention has a four-layer sustained-release structure, which synergistically releases each component, providing both breath freshening and throat-soothing effects, reducing the total concentration of volatile sulfur compounds in breath, and maintaining oral health. Eucalyptus oil, patchouli oil, bergamot oil, and carrot seed oil have a synergistic effect, complementing the four-layer sustained-release structure system and exhibiting excellent breath-freshening effects during the dissolving process.

[0205] Table 3

[0206]

[0207]

[0208] Test Example 3

[0209] Referring to the "Sensory Evaluation Method for Bagged Cigarettes QYNZY.J07.053_2017", 18 tobacco evaluation experts were organized to score the nicotine oral products provided in Examples 1-7 or Comparative Examples 1-3, and the commercially available nicotine oral cigarettes provided in Comparative Example 4.

[0210] The test results are shown in Table 4. This invention features a four-layer sustained-release structure that synergistically controls the release of nicotine within a reasonable range, exhibiting low oral irritation and high taste characteristics. It satisfies both immediate and maintenance nicotine needs, while also freshening breath and soothing the throat, reducing the total concentration of volatile sulfur compounds in breath, and maintaining oral health. It is suitable for people with sensitive mouths and for use in social situations. Eucalyptus oil, patchouli oil, bergamot oil, and carrot seed oil have a synergistic effect, complementing the four-layer sustained-release structure and providing excellent breath-freshening effects during the dissolving process.

[0211] Table 4

[0212]

[0213] This invention illustrates, through the above embodiments, a nicotine lozenge that rapidly suppresses taste and soothes the throat, and its preparation method. However, this invention is not limited to the above embodiments, meaning that this invention does not necessarily rely on the above embodiments for implementation. Those skilled in the art should understand that any improvements to this invention, equivalent substitutions of the raw materials, additions of auxiliary components, and selection of specific methods, etc., all fall within the protection and disclosure scope of this invention.

[0214] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solution of the present invention, and these simple modifications all fall within the protection scope of the present invention.

[0215] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, the present invention will not describe the various possible combinations separately.

Claims

1. A nicotine lozenge that quickly suppresses taste and soothes the throat, characterized in that, The nicotine lozenge includes a core layer and, from the inside out, a throat-protecting layer, a taste-suppressing layer, and a sweet aftertaste layer. The core layer consists of nicotine salts and silica nanoparticles. The throat protection layer comprises polylactic acid-glycolic acid copolymer microspheres loaded with nicotine salts, dipotassium glycyrrhizate cyclodextrin inclusion complexes, and hyaluronic acid; The components of the flavor-suppressing layer include nicotine salts, cyclodextrin microcapsules loaded with a cooling agent, and zinc zeolite particles loaded with plant essential oils. The components of the aftertaste layer include nicotine salts, hydrophilic polymers, sweeteners, and acidulants.

2. The nicotine lozenge according to claim 1, characterized in that, The core layer comprises, by weight, 1-10 parts of nicotine salt and 15-30 parts of silica nanoparticles; The components of the throat protection layer, by weight, include 20-40 parts of polylactic acid-glycolic acid copolymer microspheres loaded with nicotine salt, 0.1-5 parts of dipotassium glycyrrhizate cyclodextrin inclusion complex, and 0.1-5 parts of hyaluronic acid; The components of the flavor-suppressing layer, by weight, include 15-25 parts of nicotine salt, 0.1-3 parts of cyclodextrin microcapsules loaded with a cooling agent, and 0.1-2 parts of zinc zeolite particles loaded with plant essential oils. The components of the aftertaste layer, by weight, include 15-30 parts of nicotine salt, 20-60 parts of hydrophilic polymer material, 1-10 parts of sweetener and 1-10 parts of acidulant; The mass ratio of the core layer, throat-protecting layer, flavor-suppressing layer, and aftertaste layer is (1-10):(20-40):(15-30):(5-20).

3. The nicotine lozenge according to claim 1 or 2, characterized in that, The nicotine salt-loaded polylactic acid-glycolic acid copolymer microspheres were prepared by a method comprising the following steps: Polylactic acid-glycolic acid copolymer and organic solvent were mixed to obtain a mixture; nicotine salt aqueous solution was mixed with the mixture, ultrasonically emulsified, and then mixed with polyvinyl alcohol aqueous solution, stirred, the organic solvent was evaporated, solid-liquid separation was performed, microspheres were collected, and freeze-dried to obtain the nicotine salt-loaded polylactic acid-glycolic acid copolymer microspheres.

4. The nicotine lozenge according to claim 3, characterized in that, The polylactic acid-glycolic acid copolymer has a mass percentage content of 3-6% in the mixture; Preferably, the organic solvent includes any one or a combination of at least two of dichloromethane, ethyl acetate, chloroform, or isopropanol; Preferably, the mass ratio of the polylactic acid-glycolic acid copolymer to the nicotine salt is (2-5):1; Preferably, the power of the ultrasound is 200-500W, and the duration is 3-8 minutes; Preferably, the stirring speed is 2000-3000 rpm, and the stirring time is 2-5 hours; Preferably, the solvent is evaporated by vacuum distillation; Preferably, the process of collecting the microspheres further includes a washing step with water.

5. The nicotine lozenge according to any one of claims 1-4, characterized in that, The dipotassium glycyrrhizate cyclodextrin inclusion complex was prepared by a method comprising the following steps: Dipotassium glycyrrhizate, cyclodextrin, and water were mixed, stirred, and spray-dried to obtain the cyclodextrin inclusion complex of dipotassium glycyrrhizate. Preferably, the mass ratio of dipotassium glycyrrhizate, cyclodextrin, and water is (1-3):(1-3):(3-6); Preferably, the stirring speed is 1000-3000 rpm and the stirring time is 0.5-2 hours; Preferably, the stirring temperature is 50-70℃; Preferably, the inlet air temperature for the spray drying is 80-140°C.

6. The nicotine oral product according to any one of claims 1-5, characterized in that, The cyclodextrin microcapsules loaded with the cooling agent were prepared by a method comprising the following steps: The cooling agent and organic solvent were mixed, then mixed with an aqueous solution of cyclodextrin, stirred, and spray-dried to obtain the cyclodextrin microcapsules loaded with the cooling agent. Preferably, the cooling agent comprises any one or a combination of at least two of menthol, menthone, ethyl menthane formamide, or menthyl acetate; Preferably, the organic solvent includes any one or a combination of at least two of ethanol, acetone, or diethyl ether; Preferably, the mass ratio of the cooling agent to the organic solvent is (2-20):(98-80); Preferably, the mass ratio of the cooling agent to cyclodextrin is (1-2):(2-5); Preferably, the stirring speed is 1000-3000 rpm and the stirring time is 0.5-3 hours; Preferably, the inlet air temperature for the spray drying is 80-160°C.

7. The nicotine oral product according to any one of claims 1-6, characterized in that, The zinc zeolite particles loaded with plant essential oils were prepared by a method comprising the following steps: Plant essential oils are mixed with organic solvents, then mixed with zinc zeolite, stirred, and spray-dried to obtain the zinc zeolite particles loaded with plant essential oils. Preferably, the plant essential oil includes any one or a combination of at least two of eucalyptus essential oil, patchouli essential oil, bergamot essential oil, or carrot seed essential oil; Preferably, the plant essential oils include eucalyptus leaf essential oil, patchouli essential oil, bergamot essential oil, and carrot seed essential oil; Preferably, the organic solvent is ethanol; Preferably, the mass ratio of the plant essential oil to zinc zeolite is (4-5):1; Preferably, the stirring temperature is 35-45℃ and the stirring time is 22-26 hours; Preferably, the inlet air temperature for the spray drying is 140-170°C.

8. The nicotine lozenge according to any one of claims 1-7, characterized in that, The nicotine salt includes any one or a combination of at least two of nicotine malate, nicotine tartrate, nicotine citrate, nicotine lactate, nicotine benzoate, or nicotine levulinate; Preferably, the hydrophilic polymer material includes any one or a combination of at least two of sodium alginate, hyaluronic acid, chitosan, or gelatin; Preferably, the sweetener comprises any one or a combination of at least two of the following: mogroside, stevia, erythritol, xylitol, sorbitol, sucralose, isomaltitol, aspartame, acesulfame potassium, neotame, saccharin, sucrose, glucose, maltose, or fructose. Preferably, the acidulant comprises any one or a combination of at least two of malic acid, citric acid, tartaric acid, acetic acid, benzoic acid, butyric acid, lactic acid, fumaric acid, succinic acid, ascorbic acid, adipic acid, or phosphoric acid.

9. The method for preparing a nicotine lozenge according to any one of claims 1-8, characterized in that, The method includes: Nicotine salt and silica nanoparticles were mixed in water, sonicated, and dried to obtain the core layer material; nicotine salt-loaded polylactic acid-glycolic acid copolymer microspheres, dipotassium glycyrrhizate cyclodextrin inclusion complexes, and hyaluronic acid were mixed to obtain the throat-protecting layer material; nicotine salt, cyclodextrin microcapsules loaded with cooling agents, and zinc zeolite particles loaded with plant essential oils were mixed to obtain the flavor-suppressing layer material; and nicotine salt, hydrophilic polymer materials, sweeteners, and acidulants were mixed to obtain the aftertaste layer material. The core layer material is sequentially coated with a throat-protecting layer material, a taste-suppressing layer material, and a sweet aftertaste layer material, and then compressed into tablets to obtain the nicotine lozenge.

10. The method according to claim 9, characterized in that, The power of the ultrasound is 100-300W, and the duration is 10-30 minutes; Preferably, the drying temperature is 40-80℃ and the time is 0.5-3h.

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