Nicotine buccal tablet and preparation method thereof

Abstract

The invention discloses a nicotine buccal tablet and a preparation method thereof. The nicotine buccal tablet comprises a nicotine source and a microbubble generating component, the microbubble-causing component is a gas generated by a neutralization reaction under the condition of water or saliva, the microbubble-causing component comprises an acid source and an alkali source, the acid source and the alkali source are both solid, and the acid source is mixed with the alkali source after being embedded with a filling agent through an adhesive. The nicotine buccal tablet provided by the invention can be gradually disintegrated and melted after being put in the mouth, and under the action of saliva in the oral cavity, the acid source and the alkali source are subjected to a neutralization reaction to generate a gas microbubble component, so that rapid onset and continuous release of nicotine in the nicotine buccal product are promoted, the requirement of consumers on rapid intake of nicotine is met, and meanwhile, the nicotine buccal tablet has the advantages of being safe and reliable. The mouth feel problems such as mouth irritation and throat discomfort are reduced, the interestingness is enhanced, the preparation process is simplified, the production cost is reduced, and the consumption experience is improved.

Description

TECHNICAL FIELD

[0001] The patent belongs to the technical field of oral tobacco products, and particularly relates to a nicotine oral tablet and a preparation method thereof. BACKGROUND

[0002] The development of nicotine oral tablets is derived from the continuous evolution of nicotine replacement therapy and the continuous refinement of market demand. As an important category of smoking cessation aids, its research and development background can be traced back to the research on nicotine replacement therapy in the 1960s, which aims to help smokers get rid of tobacco dependence by providing a safe and controllable dose of nicotine, while avoiding harmful substances produced by tobacco burning. With the deepening of market awareness and the diversification of consumer demand, nicotine oral tablets are increasingly accepted by consumers as an alternative way to ingest nicotine, and the product form has gradually expanded from the initial chewing gum, patch to the more convenient oral tablet dosage form, forming a complete product matrix.

[0003] Currently, nicotine oral tablets have formed a considerable market system worldwide, and their value has been recognized by an increasing number of consumers. Such products have clear advantages: on the one hand, they can provide a standardized dose of nicotine, avoiding harmful components such as tar in tobacco, significantly improving safety; on the other hand, their use is flexible and convenient, not limited by location, providing higher privacy protection for users. These characteristics make them an important choice in tobacco replacement options. However, existing nicotine oral tablets still have obvious limitations. For example, the patent document with publication number CN116585279A discloses a nicotine oral tablet product with controlled release of nicotine and a preparation method thereof, which is obtained by compounding different release rates of nicotine salts formed by nicotine and different organic acids during the oral process. However, the physiological satisfaction of this nicotine oral tablet product has poor onset, and common local adverse reactions such as oral irritation and throat discomfort affect user acceptance, while complex usage requirements (such as specific oral techniques) further reduce use compliance.

[0004] In addition, the patent document with publication number CN120391718A discloses a nicotine oral product and a preparation method thereof, which includes at least one effervescent granule and a substrate. Through the cooperation of the two, the release amount and onset experience of the first active agent are rapidly increased after entry, and the subsequent slow-release function of the second active agent is also considered. However, this nicotine oral product is in the form of a bag, and the release effect of the effervescent granule wrapped by non-woven fabric in the oral cavity is greatly reduced. At the same time, the preparation process of the effervescent granule is complex, and the cost is high.

[0005] Therefore, there is an urgent need to develop a nicotine lozenge in order to solve the problems of the existing nicotine lozenge, such as slow effect in the oral cavity, easy to produce oral cavity irritation and throat discomfort, and other taste problems, so as to meet the needs of consumers for rapid intake of nicotine, simplify the preparation process, reduce production costs, and increase consumer experience. SUMMARY

[0006] The purpose of the patent is to provide a nicotine lozenge and a preparation method thereof, in order to solve the problems of the existing nicotine lozenge, such as slow effect in the oral cavity, easy to produce oral cavity irritation and throat discomfort, and other taste problems, meet the needs of consumers for rapid intake of nicotine, simplify the preparation process, reduce production costs, and increase consumer experience.

[0007] To solve the above technical problems, the patent uses the following technical solutions:

[0008] A nicotine lozenge, the nicotine lozenge comprising a nicotine source and a microbubble-forming component; the microbubble-forming component is a component that generates gas under neutralization reaction in water or saliva, the microbubble-forming component comprises an acid source and a base source, both the acid source and the base source are in solid state, and the acid source is embedded by a binder and a filler and then mixed with the base source.

[0009] Further, the nicotine source is added in an amount of 1.0-2.0%, 2.0-3.0% or 3.0-4.0% of the mass of the nicotine lozenge, and the nicotine source comprises one or more combinations of free nicotine salt or nicotine element.

[0010] Further, the free nicotine salt comprises one or more combinations of nicotine hydrochloride, nicotine dihydrochloride, nicotine citrate, nicotine monotartrate, nicotine hydrogen tartrate, nicotine hydrogen tartrate dihydrate, nicotine sulfate, nicotine resin acid salt or nicotine salicylate.

[0011] Further, the acid source is added in an amount of 13-15%, 15-18%, 18-25%, 25-35% or 35-45% of the mass of the nicotine lozenge.

[0012] Further, the acid source comprises an organic acid, and the organic acid comprises one or more combinations of citric acid, malic acid, lactic acid, tartaric acid, adipic acid, gluconic acid or fumaric acid.

[0013] Further, the base source is added in an amount of 15-18%, 18-25%, 25-30%, 30-355 or 35-40% of the mass of the nicotine lozenge.

[0014] Further, the base source comprises one or more combinations of sodium bicarbonate, sodium carbonate, potassium bicarbonate, potassium carbonate, calcium bicarbonate, calcium carbonate, sodium phosphate, monosodium phosphate and disodium phosphate.

[0015] Further, the filling agent is added in an amount of 25-35%, 35-50% or 50-60% by weight of the nicotine lozenge; the filling agent includes one or more combinations of plant fiber, cellulose derivative, glucose, lactose, mannitol, maltodextrin, starch, and β-cyclodextrin.

[0016] Further, the adhesive is added in an amount of 1.0-1.5%, 1.5-2.2% or 2.2-3.0% by weight of the nicotine lozenge; the adhesive includes one or more combinations of polyvinylpyrrolidone, carrageenan, gelatin, pectin, guar gum, gum arabic, xanthan gum, sodium alginate, sodium caseinate, enzymatically treated starch, and propylene glycol alginate.

[0017] Further, the nicotine lozenge further includes a lubricant, a sweetener, and a flavoring agent.

[0018] Further, the lubricant is added in an amount of 1.5-2.0%, 2.0-3.5% or 3.5-5.0% by weight of the nicotine lozenge; the lubricant includes one or more combinations of polyethylene glycol, magnesium stearate, sodium stearyl fumarate, sodium lauryl sulfate, or lecithin.

[0019] Further, the sweetener is added in an amount of 1.0-2.0%, 2.0-4.0% or 4.0-7.0% by weight of the nicotine lozenge.

[0020] Further, the flavoring agent is added in an amount of 3.0-5.0%, 5.0-8.0% or 8.0-10.0% by weight of the nicotine lozenge.

[0021] Further, the nicotine lozenge has a weight of 0.5-2.0 g, a size of (0.8-1.5) cm x (0.8-2.5) cm, and a nicotine content of 0.1-1.0 mg, 1.0-2.0 mg, 2.0-5.0 mg, 5.0-10.0 mg, or 10.0-15.0 mg.

[0022] Another aspect of the present patent provides a preparation method of a nicotine lozenge, including the following steps:

[0023] Step A: pre-mixing a nicotine source and an acid source to obtain a pre-mixture; embedding the pre-mixture with a first filling agent and a first adhesive to obtain embedded particles;

[0024] Step B: mixing the embedded particles obtained in Step A with a second filling agent, an alkali source, a sweetener, and a lubricant for the first time to obtain a raw powder;

[0025] Step C: The raw material powder obtained in step B is mixed with the second binder and flavoring for the second time. After granulation, sieving, tableting and ultraviolet sterilization, nicotine lozenges are obtained.

[0026] Furthermore, in step A, the mass ratio of nicotine source to acid source is 1:(5.0~30.0), the premixing condition is stirring and mixing for 20~40 min; the encapsulation condition is stirring and encapsulating at 55~80℃.

[0027] Furthermore, in step A, the first filler includes one or more combinations of plant fibers, cellulose derivatives, glucose, lactose, mannitol, maltodextrin, starch, and β-cyclodextrin; wherein the plant fibers include wheat fiber, corn fiber, sunflower fiber, or rice fiber; the cellulose derivatives include one or more combinations of hydrolyzed cellulose, cellulose ethers, cellulose esters, or cellulose ether esters; hydrolyzed cellulose includes microcrystalline cellulose; cellulose esters include cellulose nitrates, cellulose acetates, cellulose acetate butyrate, or cellulose xanthates; and cellulose ethers include methylcellulose, carboxymethylcellulose, ethylcellulose, hydroxyethylcellulose, cyanoethylcellulose, hydroxypropylcellulose, or hydroxypropyl methylcellulose. The particle size D of the cellulose derivative powder... 50 The size is 15~200 μm, and the water content is ≤6.0~9.0%.

[0028] Furthermore, the first adhesive includes one or more combinations of polyvinylpyrrolidone, carrageenan, gelatin, pectin, guar gum, gum arabic, xanthan gum, sodium alginate, sodium caseinate, sodium alginate, enzymatically hydrolyzed starch, and sodium propylene glycol alginate.

[0029] Furthermore, in step B, the first mixing is carried out by stirring under ice-water bath conditions.

[0030] Furthermore, in step B, the second filler includes one or more combinations of plant fibers, cellulose derivatives, glucose, lactose, mannitol, maltodextrin, starch, and β-cyclodextrin; wherein the plant fibers include wheat fiber, corn fiber, sunflower fiber, or rice fiber; the cellulose derivatives include one or more combinations of hydrolyzed cellulose, cellulose ethers, cellulose esters, or cellulose ether esters; hydrolyzed cellulose includes microcrystalline cellulose; cellulose esters include cellulose nitrates, cellulose acetates, cellulose acetate butyrate, or cellulose xanthates; and cellulose ethers include methylcellulose, carboxymethylcellulose, ethylcellulose, hydroxyethylcellulose, cyanoethylcellulose, hydroxypropylcellulose, or hydroxypropyl methylcellulose. The powder particle size D of the cellulose derivatives... 50 The size is 15~200 μm, and the water content is ≤6.0~9.0%.

[0031] Furthermore, in step C, the second mixing is carried out under stirring conditions for 20-40 minutes.

[0032] Furthermore, in step C, the second adhesive comprises one or more combinations of polyvinylpyrrolidone, carrageenan, gelatin, pectin, guar gum, gum arabic, xanthan gum, sodium alginate, sodium caseinate, sodium alginate, enzymatically hydrolyzed starch, and sodium propylene glycol alginate.

[0033] Furthermore, the cumulative nicotine release rate of nicotine lozenges in the oral cavity from 0 to 5 minutes is ≥60%; the cumulative nicotine release rate of nicotine lozenges in the oral cavity from 0 to 35 minutes is ≥85%.

[0034] Furthermore, non-limiting examples of sweeteners include aspartame, acesulfame potassium, cyclamate, saccharin, sodium saccharin, sucralose, neotame, sodium cyclohexylsulfamate, stevia, licorice, disodium glycyrrhizate, tripotassium and trisodium glycyrrhizate, glucose, fructose, sucrose, maltose, corn syrup, starch sugars and lactose, sorbitol, maltitol, isomaltitol, palaginitol, xylitol, lactitol, mannitol, erythritol and dextran.

[0035] Furthermore, the flavorings and fragrances are non-exhaustive examples, including coconut, coffee, chocolate, vanilla, citrus fruits (e.g., grapefruit, orange, lime, bergamot, or lemon), mint, licorice, caramel, honey, peanut, walnut, cashew, hazelnut, almond, pineapple, strawberry, raspberry, tropical fruits, cherry, cinnamon, cumin, peppermint, deer antler, spearmint, eucalyptus, mint, and fruit flavorings (e.g., from green apple, blueberry, mango, watermelon, pear, peach, strawberry, apricot, raspberry, cherry, pineapple, lemongrass, lime, chili (capsaicin), citrus, tobacco flavor, bergamot, and plum). Preferably, the flavorings and fragrances also contain essential oils, including any one or more combinations of peppermint, spearmint, menthol, eucalyptus, clove oil, laurel oil, fennel, thyme, cedarwood oil, nutmeg, and oils from the aforementioned fruits.

[0036] Furthermore, nicotine lozenges also include preservatives, including one or more of potassium sorbate, benzoic acid, sodium benzoate, and sorbic acid.

[0037] As used in this patent, "nicotine lozenges" generally refers to compressed oral smokeless tobacco products that are placed in the mouth or between the lips and gums and release some of the soluble substances through saliva.

[0038] As used in this patent, "nicotine" (also known as nicotine alkaloid) has the chemical formula C. 10 H 14N2 is a pyridine alkaloid. In this text, the terms "nicotine" and "nicotine alkaloid" are used interchangeably.

[0039] This patent provides a nicotine lozenge and its preparation method. The method involves encapsulating an acid source and an alkali source with fillers and binders, respectively, followed by physical mixing and sieving to form a uniform powder. This powder is then granulated and compressed using traditional processes to form the nicotine lozenge. The nicotine lozenge prepared in this application gradually disintegrates and melts upon ingestion. In the mouth, under the influence of saliva, the acid and alkali sources react to generate microbubbles, promoting the rapid onset and sustained release of nicotine in the lozenge, thus meeting consumers' nicotine intake needs. Simultaneously, it reduces oral irritation and throat discomfort, enhances enjoyment, simplifies the preparation process, reduces production costs, and improves the consumer experience. Attached Figure Description

[0040] The above content of this patent and the following detailed embodiments will be better understood when read in conjunction with the accompanying drawings. It should be noted that the drawings are merely examples of the claimed technical solution.

[0041] Figure 1 This is a flowchart illustrating the preparation process of the nicotine lozenges in this patent embodiment. Detailed Implementation

[0042] The following detailed description of the features and advantages of this application is sufficient to enable any person skilled in the art to understand the technical content of this application and implement it accordingly. Based on the specification, claims and drawings disclosed in this specification, those skilled in the art can easily understand the related objectives and advantages of this application.

[0043] In this specification and claims, several terms will be used, and unless otherwise indicated, these terms will be defined to have the following meanings:

[0044] All figures used to represent component amounts, properties (e.g., weight-average molecular weight), reaction conditions, etc., should be considered to be modified in all cases by the terms "within the unavoidable margin of error" or "approximately". Therefore, the numerical values ​​presented herein are approximate and may vary depending on the desired properties sought to be obtained by this patent. The principle of equivalents, which is applied to a minimum and not intended to limit the scope of the claims, should be applied, for example, each value should be interpreted at least according to the reported significant digits and by applying conventional rounding techniques.

[0045] All other terms used herein for special definition are intended to have the general meaning understood by one of ordinary skill in the art, and in particular, meaning that one of ordinary skill in the art, upon reading the claims, specification and drawings of this patent, can directly and without doubt determine how the technical solution of this patent can be implemented.

[0046] Even if there are incomplete descriptions, omissions, or ambiguities in the grammar, words, punctuation, graphics, symbols, etc. of the claims, specification, and drawings of this patent, a person skilled in the art can still arrive at the only correct understanding by reading the claims, specification, and drawings as a whole without extensive reasoning or experimentation, and effectively exclude various incorrect interpretations that are not aimed at achieving the purpose of this patent.

[0047] The "range" disclosed herein is defined by a lower limit and an upper limit. A given range is defined by selecting a lower limit and an upper limit, which define the boundaries of a particular range. Ranges defined in this way can include or exclude endpoints and can be arbitrarily combined; that is, any lower limit can be combined with any upper limit to form a range. For example, if ranges of 60-120 and 80-110 are listed for a specific parameter, it is expected that ranges of 60-110 and 80-120 are also expected. Furthermore, if minimum range values ​​of 1 and 2 are listed, and if maximum range values ​​of 3, 4, and 5 are listed, then the following ranges are all expected: 1-3, 1-4, 1-5, 2-3, 2-4, and 2-5. In this application, unless otherwise stated, the numerical range "ab" represents a shortened representation of any combination of real numbers between a and b, where a and b are real numbers. For example, the numerical range "0-5" indicates that all real numbers between "0-5" have been listed in this article; "0-5" is simply a shortened representation of these numerical combinations. Furthermore, when a parameter is stated as an integer ≥2, it is equivalent to disclosing that the parameter is, for example, an integer such as 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, etc.

[0048] Unless otherwise specified, all embodiments and preferred embodiments mentioned herein can be combined to form new technical solutions.

[0049] Unless otherwise specified, all the technical features and preferred features mentioned herein can be combined to form new technical solutions.

[0050] Unless otherwise specified, all steps mentioned herein may be performed sequentially or randomly, but are preferably performed sequentially. For example, the method includes steps (a) and (b), indicating that the method may include steps (a) and (b) performed sequentially, or it may include steps (b) and (a) performed sequentially. For example, the mention that the method may also include step (c) indicates that step (c) may be added to the method in any order; for example, the method may include steps (a), (b), and (c), or it may include steps (a), (c), and (b), or it may include steps (c), (a), and (b), etc.

[0051] Unless otherwise specified, the terms "comprising" and "including" as used herein can be open-ended or closed-ended. For example, "comprising" and "including" may mean that other components not listed may also be included, or that only the listed components may be included.

[0052] In the description of this article, it should be noted that, unless otherwise stated, "above" and "below" include the number itself, and "several" in "one or more" means two or more.

[0053] In this description, unless otherwise stated, the term "or" is inclusive. For example, the phrase "A or B" means "A, B, or both A and B". More specifically, the condition "A or B" is satisfied by any of the following conditions: A is true (or exists) and B is false (or does not exist); A is false (or does not exist) and B is true (or exists); or both A and B are true (or exist).

[0054] Unless otherwise specified, percentages (%) in this document refer to percentages by mass relative to the composition.

[0055] Unless otherwise stated herein, the sum of the contents of the components in the composition is 100%.

[0056] In this document, unless otherwise stated, “combination of” means a multi-component mixture of the elements, such as two, three, four, and up to the maximum possible multi-component mixture.

[0057] Unless otherwise specified, the term "a" as used in this specification means "at least one".

[0058] The terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include at least one of that feature. In the description of this invention, "a plurality of" means at least two, such as two, three, etc., unless otherwise explicitly specified.

[0059] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.

[0060] To make the objectives, technical solutions, and advantages of the present invention clearer, the embodiments of the present invention will be further described in detail below with reference to the accompanying drawings. Unless otherwise specified, the experimental methods described in the embodiments of the present invention are conventional methods, and the materials and reagents used in the following embodiments are commercially available unless otherwise specified.

[0061] like Figure 1 As shown, this patent provides a nicotine lozenge and its preparation method, including the following steps:

[0062] (1) Add the nicotine source and acid source to a 1 kg planetary three-dimensional mixer (commercially available) for premixing. After uniform premixing, the first mixture is obtained.

[0063] The nicotine source and acid source are premixed at a mass ratio of 1:(5.0~30.0) for 20~40 min.

[0064] Nicotine sources include one or a combination of free nicotine salts or elemental nicotine. Free nicotine salts include one or a combination of nicotine hydrochloride, nicotine dihydrochloride, nicotine citrate, nicotine monotartrate, nicotine hydrogen tartrate, nicotine hydrogen tartrate dihydrate, nicotine sulfate, nicotine resinate, or nicotine salicylate. Nicotine sources are soluble in water or in organic solvents, including one or a combination of glycerol, ethyl acetate, alcohols, triglycerides, diglycerides, and monoglycerides.

[0065] The acid source includes organic acids, including one or more combinations of citric acid, malic acid, lactic acid, tartaric acid, adipic acid, gluconic acid, or fumaric acid.

[0066] (2) Add the first filler and the first binder to the first mixture prepared in step (1) above, and mix and embed at 55~80°C to obtain the second mixture;

[0067] The first filler and the first mixture are mixed in a mass ratio of 1:(0.5~2.5), and the first adhesive and the first mixture are mixed in a mass ratio of 1:(12.0~40.0).

[0068] The first filler includes one or more combinations of plant fibers, cellulose derivatives, glucose, lactose, mannitol, maltodextrin, starch, and β-cyclodextrin; wherein, plant fibers include wheat fiber, corn fiber, sunflower fiber, or rice fiber; cellulose derivatives include one or more combinations of hydrolyzed cellulose, cellulose ethers, cellulose esters, or cellulose ether esters; hydrolyzed cellulose includes microcrystalline cellulose; cellulose esters include cellulose nitrates, cellulose acetates, cellulose acetate butyrate, or cellulose xanthates; cellulose ethers include methylcellulose, carboxymethylcellulose, ethylcellulose, hydroxyethylcellulose, cyanoethylcellulose, hydroxypropylcellulose, or hydroxypropyl methylcellulose. The powder particle size D of the cellulose derivative is... 50 The size is 15~200 μm, and the water content is ≤6.0~9.0%.

[0069] The first adhesive includes one or more combinations of polyvinylpyrrolidone, carrageenan, gelatin, pectin, guar gum, gum arabic, xanthan gum, sodium alginate, sodium caseinate, sodium alginate, enzymatically hydrolyzed starch, and sodium propylene glycol alginate.

[0070] (3) Transfer the second mixture obtained in step (2) above to a stirring container (commercially available), add the second filler and alkali source to the stirring container, and mix evenly under ice-water bath conditions to obtain the third mixture;

[0071] The second filler and the second mixture are mixed in a mass ratio of 1:(3.0~13.0), and the alkali source and the second mixture are mixed in a mass ratio of 1:(1.0~4.0).

[0072] The second filler includes one or more combinations of plant fibers, cellulose derivatives, glucose, lactose, mannitol, maltodextrin, starch, and β-cyclodextrin; wherein, plant fibers include wheat fiber, corn fiber, sunflower fiber, or rice fiber; cellulose derivatives include one or more combinations of hydrolyzed cellulose, cellulose ethers, cellulose esters, or cellulose ether esters; hydrolyzed cellulose includes microcrystalline cellulose; cellulose esters include cellulose nitrates, cellulose acetates, cellulose acetate butyrate, or cellulose xanthates; cellulose ethers include methylcellulose, carboxymethylcellulose, ethylcellulose, hydroxyethylcellulose, cyanoethylcellulose, hydroxypropylcellulose, or hydroxypropyl methylcellulose. The powder particle size D of the cellulose derivative is... 50 The size is 15~200 μm, and the water content is ≤6.0~9.0%.

[0073] The alkali source includes one or more combinations of sodium bicarbonate, sodium carbonate, potassium bicarbonate, potassium carbonate, calcium bicarbonate, calcium carbonate, sodium phosphate, sodium monohydrogen phosphate, and sodium dihydrogen phosphate.

[0074] (4) Add sweetener and lubricant to the third mixture prepared in step (3) above, and mix evenly under ice water bath conditions to obtain the fourth mixture, which is the raw material powder;

[0075] The sweetener and the third mixture are mixed in a mass ratio of 1:(15.0~30.0), the lubricant and the third mixture are mixed in a mass ratio of 1:(15.0~30.0), and the mass ratio of sweetener to lubricant is (0.6~1.5):1.

[0076] Sweeteners include one or more combinations of sucrose, saccharin, sucralose, glucose, maltose, corn syrup, cyclamate, aspartame, acesulfame potassium, xylitol, mannose, salts of acesulfame (e.g., potassium acesulfame), alitame, cyclohexanesulfonic acid and its salts, glycyrrhizin, dihydrochalcone, kiwifruit protein, indigofera protein, or steviol glycosides.

[0077] Lubricants include one or more combinations of polyethylene glycol, magnesium stearate, sodium stearate fumarate, sodium lauryl sulfate, or lecithin.

[0078] (5) Add the second binder and fragrance to the fourth mixture prepared in step (4) above, and stir in a mixer for 20-40 min to obtain the fifth mixture;

[0079] The second binder accounts for 0.5 to 1.5% of the total mass of the fourth mixture; the fragrance and flavoring account for 3.0 to 6.0% of the total mass of the fourth mixture.

[0080] The second adhesive includes one or more combinations of polyvinylpyrrolidone, carrageenan, gelatin, pectin, guar gum, gum arabic, xanthan gum, sodium alginate, sodium caseinate, sodium alginate, enzymatically hydrolyzed starch, and sodium propylene glycol alginate.

[0081] Flavorings and fragrances are a non-exhaustive list, including coconut, coffee, chocolate, vanilla, citrus fruits (e.g., grapefruit, orange, lime, bergamot, or lemon), mint, licorice, caramel, honey, peanut, walnut, cashew, hazelnut, almond, pineapple, strawberry, raspberry, tropical fruit, cherry, cinnamon, cumin, peppermint, deer antler, spearmint, eucalyptus, mint, and fruit flavorings (e.g., from green apple, blueberry, mango, watermelon, pear, peach, strawberry, apricot, raspberry, cherry, pineapple, lemongrass, lime, chili (capsaicin), citrus, tobacco flavor, bergamot, and plum). Preferably, the flavorings and fragrances also comprise essential oils, including any one or more combinations of peppermint, spearmint, menthol, eucalyptus, clove oil, laurel oil, fennel, thyme, cedarwood oil, nutmeg, and oils from the aforementioned fruits.

[0082] The fifth mixture obtained in step (5) above is post-processed according to the traditional process, that is, the fifth mixture is granulated in a granulator (commercially available), then sieved to remove excess powder, and then compressed into tablets. After ultraviolet sterilization, nicotine lozenges are obtained. The weight of the nicotine lozenges is 0.5~2.0 g, the overall size of the nicotine lozenges is (0.8~1.5) cm×(0.8~2.5) cm, and the nicotine content in the nicotine lozenges is 0.1~15.0 mg.

[0083] Meanwhile, by placing the nicotine lozenge in their mouths, consumers can stimulate the release of nicotine by reacting the alkaline and acidic sources in the lozenge with saliva, thereby reducing oral irritation and increasing enjoyment.

[0084] Example 1

[0085] (1) Weigh 21 g of nicotine tartrate and 230 g of citric acid and place them in a 1 kg planetary three-dimensional mixer for premixing. The premixing time is 30 min. After the premixing is uniform, the first mixture is obtained.

[0086] (2) Add 250 g of microcrystalline cellulose and 10 g of pectin to the first mixture prepared in step (1) above, and mix and embed at 75°C to obtain the second mixture;

[0087] (3) Transfer the second mixture obtained in step (2) above to a stirring container, add 86 g of microcrystalline cellulose, 210 g of sodium bicarbonate and 60 g of sodium carbonate to the stirring container, and mix evenly under ice-water bath conditions to obtain the third mixture;

[0088] (4) Add 45 g of aspartame and 31 g of polyethylene glycol to the third mixture prepared in step (3) above, and mix them evenly under ice-water bath conditions to obtain the fourth mixture, which is the raw material powder;

[0089] (5) Add 7 g of pectin and 50 g of mango flavoring to the fourth mixture prepared in step (4) above, and stir in a mixer for 30 min to obtain the fifth mixture;

[0090] (6) The fifth mixture prepared in step (5) above is post-processed. The fifth mixture is placed in a granulator for granulation, and then the excess powder is removed by sieving. The mixture is then compressed into tablets. After ultraviolet sterilization, nicotine lozenges are obtained. The weight of the nicotine lozenges is 1.0 g, the overall size of the nicotine lozenges is 0.8 cm x 1.5 cm, the thickness is 1.0 mm, the nicotine content in the nicotine lozenges is 2 mg, and it is labeled as P1.

[0091] Example 2

[0092] (1) Weigh 6 g of nicotine citrate and 160 g of citric acid and place them in a 1 kg planetary three-dimensional mixer for premixing. The premixing time is 30 min. After the premixing is uniform, the first mixture is obtained.

[0093] (2) Add 400 g of microcrystalline cellulose and 6 g of gelatin to the first mixture prepared in step (1) above, and mix and embed at 75°C to obtain the second mixture;

[0094] (3) Transfer the second mixture prepared in step (2) above to a stirring container, add 127 g microcrystalline cellulose, 150 g calcium bicarbonate and 30 g calcium carbonate to the stirring container, and mix evenly under ice water bath conditions to obtain the third mixture.

[0095] (4) Add 36 g of sucralose and 45 g of magnesium stearate to the third mixture prepared in step (3) above, and mix evenly under ice-water bath conditions to obtain the fourth mixture, which is the raw material powder;

[0096] (5) Add 5 g of gelatin and 35 g of peppermint flavoring to the fourth mixture prepared in step (4) above, and stir in a stirrer for 30 min to obtain the fifth mixture;

[0097] (6) The fifth mixture prepared in step (5) above is post-processed. The fifth mixture is placed in a granulator for granulation, and then the excess powder is removed by sieving. The mixture is then compressed into tablets. After ultraviolet sterilization, nicotine lozenges are obtained. The weight of the nicotine lozenges is 1.5 g, the overall size of the nicotine lozenges is 0.8 cm x 1.5 cm, the thickness is 1.5 mm, the nicotine content in the nicotine lozenges is 5 mg, and it is labeled as P2.

[0098] Example 3

[0099] (1) Weigh 42 g of nicotine salicylate and 320 g of malic acid and place them in a 1 kg planetary three-dimensional mixer for premixing. The premixing time is 30 min. After the premixing is uniform, the first mixture is obtained.

[0100] (2) Add 110 g of microcrystalline cellulose and 14 g of carrageenan to the first mixture prepared in step (1) above, and mix and embed at 75°C to obtain the second mixture;

[0101] (3) Transfer the second mixture obtained in step (2) above to a stirring container, add 43 g microcrystalline cellulose, 315 g potassium bicarbonate and 73 g potassium carbonate to the stirring container, and mix evenly under ice water bath conditions to obtain the third mixture.

[0102] (4) Add 50 g of aspartame and 49 g of polyethylene glycol to the third mixture prepared in step (3) above, and mix them evenly under ice-water bath conditions to obtain the fourth mixture, which is the raw material powder;

[0103] (5) Add 12 g of carrageenan and 45 g of green apple flavoring to the fourth mixture prepared in step (4) above, and stir in a stirrer for 30 min to obtain the fifth mixture;

[0104] (6) The fifth mixture prepared in step (5) above is post-processed. The fifth mixture is placed in a granulator for granulation, and then the excess powder is removed by sieving. The mixture is then compressed into tablets. After ultraviolet sterilization, nicotine lozenges are obtained. The weight of the nicotine lozenges is 1.5 g, the overall size of the nicotine lozenges is 0.8 cm x 1.5 cm, the thickness is 1.5 mm, the nicotine content in the nicotine lozenges is 5 mg, and it is labeled as P3.

[0105] Comparative Example 1

[0106] Nicotine lozenges were prepared using the method disclosed in Chinese patent document CN116585279A. The nicotine content of the product was 2 mg / tablet, and it was marked as A1.

[0107] Comparative Example 2

[0108] The method for preparing nicotine oral products using the method disclosed in Chinese patent document CN120391718A is marked as A2.

[0109] Comparative Example 3

[0110] The difference between this comparative example and Example 2 is that this comparative example uses nicotine benzoate, aspartame, dextrin, sodium carbonate, lecithin, magnesium stearate and flavoring as the formulation ingredients, and does not contain microbubble ingredients that conform to the principle. The nicotine content of the product is 2 mg / tablet, and it is labeled as A3.

[0111] Test Example 1: Cumulative Nicotine Release and Release Rate Test

[0112] Nicotine lozenges prepared in Example 2 (with a weight of 1.0 g / lozenge and a nicotine content of 2 mg / lozenge) were selected and compared with nicotine lozenges A1 and A3 prepared in Comparative Examples 1 and 3 with the same nicotine content as in Example 2, and nicotine pouch product A2 in Comparative Example 2 with the same nicotine content and specifications for in vitro nicotine release experiments.

[0113] The specific method is as follows: 100 mL of simulated artificial saliva with a pH of 6.8 is placed in each beaker and maintained at 37.0 ± 0.1℃. Nicotine oral products with the same nicotine content are placed in each beaker, and the mixture is stirred at 100 rpm. A precise sample of 2 mL is taken every minute until 10 minutes have elapsed. After 10 minutes, a sample is taken every 10 minutes, with 2 mL of simulated artificial saliva added after each sample (to simulate the cumulative nicotine release in the oral cavity, artificial saliva needs to be added after each sample as saliva is continuously secreted). The 2 mL solution is then diluted to 10 mL with simulated artificial saliva. The nicotine content is detected using HPLC, and the relative cumulative nicotine release is calculated.

[0114] Table 1 shows the cumulative nicotine release over time for the nicotine lozenge P2 prepared in Example 2 and the nicotine oral products A1-A3 prepared in Comparative Examples 1-3. The nicotine lozenge P2 prepared in Example 2 of this application achieved a cumulative nicotine release rate of over 85% at 2100 s, while the cumulative nicotine release rate of the nicotine oral products prepared in the comparative examples was significantly lower than that of Example 2. Specifically, P2 achieved a cumulative nicotine release of 62.55% at 5 min (300 s), while the cumulative nicotine release of A1-A3 at 5 min (300 s) was only about 40%, and the highest cumulative nicotine release at 35 min (2100 s) was only 80.35%, which is significantly lower than the cumulative nicotine release of the nicotine lozenge P2 prepared in Example 2 of this application. This indicates that the reaction of acid and alkali sources under salivary conditions to generate gaseous microbubbles significantly stimulates nicotine release. In contrast, although Comparative Example 2 also involves the reaction of acid and alkali sources under salivary conditions to generate gaseous microbubbles, the effervescent particles prepared by combining encapsulation and coating are placed in non-woven fabric to form a nicotine pouch that blocks the rapid reaction of acid and alkali sources, thereby reducing the stimulation of nicotine by the gaseous microbubbles and resulting in a lower nicotine release rate.

[0115] Table 1. Statistical table of cumulative nicotine release and release rate in different nicotine oral products.

[0116] Test Example 2: Taste Test

[0117] The taste test method is as follows: a professional evaluation team (n=5) will conduct the evaluation, and the above P2, A1, A2 and A3 will be placed directly between the upper lip and the upper teeth, with a standard consumption time of 30 minutes.

[0118] The evaluation was conducted based on visual characteristics, olfactory characteristics, gustatory characteristics, and overall experience. The evaluation grading is shown in Table 2. Table 2 Taste Test Evaluation Grading Table

[0119] (1) The taste test scores of nicotine lozenge P2 and nicotine oral products A1~A3 were conducted, and the results are shown in Table 3. The overall score of nicotine lozenge P2 was higher than that of A1~A3. Among them, the scores of flavor intensity, flavor persistence, aftertaste, physiological satisfaction persistence and taste comfort of P2 were all higher than those of A1~A3, indicating that P2 is much less irritating in the oral cavity than A1~A3 and has a higher taste comfort.

[0120] Table 3. Taste Test Scoring Table for Different Nicotine Oral Products

[0121] Therefore, it can be concluded that this patent provides a nicotine lozenge and its preparation method. The method involves encapsulating an acid source and an alkali source with an adhesive and filler, respectively, followed by physical mixing and sieving to form a uniform powder. This powder is then granulated and compressed using traditional processes to form the nicotine lozenge. The nicotine lozenge provided by this patent gradually disintegrates and melts upon ingestion. In the mouth, under the influence of saliva, the acid and alkali sources undergo a neutralization reaction to generate gaseous microbubbles, promoting the rapid onset and sustained release of nicotine in the lozenge, meeting consumers' demand for rapid nicotine intake. Simultaneously, it reduces oral irritation and throat discomfort, enhances enjoyment, simplifies the preparation process, reduces production costs, and improves the consumer experience.

[0122] In the foregoing description of exemplary embodiments / specific implementations of this patent, various features of this patent are sometimes combined in a single embodiment / specific implementation or its figures and description, with the aim of simplifying the disclosure and aiding in the understanding of one or more of the various aspects of the invention. However, unless expressly stated otherwise or in obvious technical contradiction or exclusion, the descriptive method of this patent should not be construed as reflecting an intention that the claimed features of the invention are more than expressly stated in each claim. Rather, the inventive aspect reflected in the claims lies in not all the features of a single foregoing disclosed embodiment / specific implementation. Therefore, the claims following the detailed description are hereby expressly incorporated into this detailed description, each claim existing independently as a separate embodiment / specific implementation of this patent.

[0123] The terms and expressions used in this specification are for illustrative purposes and not for limitation. Their use is not intended to exclude any equivalents of the shown and described features or portions thereof, but rather to facilitate the understanding that various modifications may be possible within the scope of this patent claim. Therefore, it should be understood that while this patent has been specifically disclosed through preferred embodiments, exemplary embodiments, and optional features, variations or modifications of the concepts disclosed herein may be adopted by those skilled in the art, and such variations and modifications are therefore considered to be within the scope of this patent as defined by the appended claims. The specific embodiments given in this specification are examples of useful embodiments of this patent, and it will be apparent to those skilled in the art that this patent can be implemented using many variations of the devices, device components, and method steps disclosed herein.

[0124] The foregoing description of specific embodiments fully discloses the general features of this patent, enabling others to easily modify and / or adapt such embodiments for various applications by applying knowledge within the scope of the art, without excessive experimentation or deviation from the general concept of this patent. Therefore, based on the teachings and guidance provided herein, it is intended that such modifications and alterations be included within the meaning and scope of equivalents of the disclosed embodiments. It should be understood that the wording or terminology used herein is for descriptive purposes and not intended to be limiting; thus, the wording or terminology in this specification will be interpreted by those skilled in the art based on the foregoing teachings and guidance.

[0125] Furthermore, the scope of this patent should not be limited to any of the exemplary embodiments described above, but only to the appended claims and their equivalents.

Claims

1. A nicotine lozenge, characterized in that, The nicotine lozenge comprises a nicotine source and a microbubble-generating component; The microbubble-generating component is a component that generates gas through a neutralization reaction under water or saliva conditions, the microbubble-generating component comprises an acid source and a base source, both the acid source and the base source are in solid state, the acid source is mixed with the base source after being embedded with a binder and a filler.

2. The nicotine oral patch of claim 1, wherein, The nicotine source is added in an amount of 1.0-2.0%, 2.0-3.0% or 3.0-4.0% of the mass of the nicotine lozenge, and the nicotine source comprises one or more combinations of free nicotine salt or nicotine element; The free nicotine salt comprises one or more combinations of nicotine hydrochloride, nicotine dihydrochloride, nicotine citrate, nicotine monotartrate, nicotine bitartrate, nicotine bitartrate dihydrate, nicotine sulfate, nicotine resin acid or nicotine salicylate.

3. The nicotine oral patch of claim 1, wherein, The acid source is added in an amount of 13-15%, 15-18%, 18-25%, 25-35% or 35-45% of the mass of the nicotine lozenge; The acid source comprises an organic acid, and the organic acid comprises one or more combinations of citric acid, malic acid, lactic acid, tartaric acid, adipic acid, gluconic acid or fumaric acid.

4. The nicotine oral patch of claim 3, wherein, The base source is added in an amount of 15-18%, 18-25%, 25-30%, 30-355 or 35-40% of the mass of the nicotine lozenge; The base source comprises one or more combinations of sodium bicarbonate, sodium carbonate, potassium bicarbonate, potassium carbonate, calcium bicarbonate, calcium carbonate, sodium phosphate, monosodium hydrogen phosphate and disodium hydrogen phosphate.

5. The nicotine lozenge according to claim 1, wherein The filler is added in an amount of 25-35%, 35-50% or 50-60% of the mass of the nicotine lozenge; and the filler comprises one or more combinations of plant fiber, cellulose derivative, glucose, lactose, mannitol, maltodextrin, starch and β-cyclodextrin. The binder is added in an amount of 1.0-1.5%, 1.5-2.2% or 2.2-3.0% of the mass of the nicotine lozenge; and the binder comprises one or more combinations of polyvinylpyrrolidone, carrageenan, gelatin, pectin, guar gum, gum arabic, xanthan gum, sodium alginate, sodium caseinate, sodium alginate, enzymatically treated starch and propylene glycol alginate sodium ester.

6. The nicotine oral patch of claim 5, wherein, The nicotine lozenge further comprises a lubricant, a sweetener and a flavoring agent; The lubricant is added in an amount of 1.5-2.0%, 2.0-3.5% or 3.5-5.0% of the mass of the nicotine lozenge; and the lubricant comprises one or more combinations of polyethylene glycol, magnesium stearate, sodium stearate fumarate, sodium lauryl sulfate and lecithin. The sweetener is added in an amount of 1.0-2.0%, 2.0-4.0% or 4.0-7.0% of the mass of the nicotine lozenge. The flavoring agent is added in an amount of 3.0-5.0%, 5.0-8.0% or 8.0-10.0% of the mass of the nicotine lozenge.

7. The nicotine oral patch of any one of claims 1 to 6, wherein, The nicotine lozenge has a weight of 0.5-2.0 g, a size of (0.8-1.5) cm x (0.8-2.5) cm, and a nicotine content of 0.1-1.0 mg, 1.0-2.0 mg, 2.0-5.0 mg, 5.0-10.0 mg, or 10.0-15.0 mg.

8. A process for the preparation of a nicotine lozenge according to claim 7, characterized in that, The method comprises the following steps: Step A: premixing the nicotine source and the acid source to obtain a premix; embedding the premix with a first filler and a first binder to obtain embedded particles; Step B: first mixing the embedded particles obtained in Step A with a second filler, the base source, a sweetener, and a lubricant to obtain a raw powder; Step C: second mixing the raw powder obtained in Step B with a second binder and a flavoring agent, granulating, sieving, tabletting, and ultraviolet sterilization to obtain the nicotine lozenge.

9. The method of claim 8, wherein In Step A, the mass ratio of the nicotine source to the acid source is 1:(5.0-30.0), and the premixing is performed by stirring for 20-40 min; the embedding is performed by stirring at 55-80°C; In Step B, the first mixing is performed by stirring in an ice water bath; In Step C, the second mixing is performed by stirring for 20-40 min.

10. The method of preparing a nicotine oral tablet according to claim 9, characterized by, The nicotine lozenge has a cumulative nicotine release rate of ≥60% in the oral cavity at 0-5 min, and a cumulative nicotine release rate of ≥85% in the oral cavity at 0-35 min.

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