A mouthpiece and method of making the same

Abstract

The application discloses a kind of oral preparation and its preparation method.Oral preparation includes by weight fraction: dissolvable substance 70-90 parts, nicotine salt 0.01-10 parts, pH regulator 0.01-5 parts, composite sustained-release substance 0.5-3 parts, solid essence 0.1-2 parts;Composite sustained-release substance is composed of sodium carboxymethyl cellulose, sodium alginate and chitosan, and the weight ratio is 50-80:10-20:0.5-20.The technical scheme of the application forms dense dynamic gel film in situ in oral saliva Polyelectrolyte complexation reaction, changes the burst rapid release of nicotine into smooth and lasting uniform speed release, not only significantly reduces the initial pungent irritation in mouth, but also breaks through the technical bottleneck that existing dry method oral preparation cannot safely load high concentration nicotine;At the same time, water-soluble substrate guarantees rapid onset, cooperates dry process and solid essence to completely avoid the volatile aroma caused by traditional wet drying, and comprehensively realizes the improvement effect of mild taste, lasting satisfaction and excellent flavor retention.

Description

Technical Field

[0001] This application relates to the field of tobacco substitute technology, and in particular to a mouth-held product and its preparation method. Background Technology

[0002] With increasing public awareness of health, traditional cigarettes are highly controversial due to the tar and thousands of harmful substances produced during combustion, while new electronic cigarettes with heated liquids may also produce harmful byproducts such as formaldehyde. Oral-feed products, as a tobacco alternative that requires no combustion or heating and can be used in smoke-free environments, have received widespread attention. Among them, dry-process oral-feed products, due to their low moisture content (approximately 3%), have advantages such as long shelf life and resistance to mold, and have become a key focus of current market research and development.

[0003] However, currently available oral products still have the following significant technical defects: Pure water-soluble bases release nicotine too quickly, causing strong irritation and making it impossible to achieve high concentrations: Currently, most oral products on the market use pure water-soluble bases. These bases disintegrate instantly in saliva, with nicotine dissolution rates exceeding 90% within 5 minutes. This explosive, rapid release causes the oral mucosa to be instantly subjected to high concentrations of nicotine, producing a strong spicy, stinging, or excessively harsh throat hit, resulting in a very poor taste experience. More seriously, due to the excessively high release rate per unit time, increasing the total amount of nicotine per packet (e.g., above 10mg) can easily lead to users ingesting excessive amounts of nicotine in a short period, causing adverse reactions such as dizziness and nausea. Current technology is limited to low-concentration products such as 3mg and 6mg, which cannot meet the needs of heavy smokers.

[0004] Therefore, there is an urgent need for a mouthwash that can release nicotine smoothly and stably in the oral cavity, significantly reducing the initial irritation. Summary of the Invention

[0005] This application provides a mouth-held product and its preparation method, aiming to solve the problem in the prior art that the rapid release of nicotine in dry mouth-held products leads to strong irritation and makes it impossible to achieve high concentration loading.

[0006] To achieve the above objectives, this application proposes a mouth-held product, which, by weight, comprises: 70-90 parts of soluble substance, 0.01-10 parts of nicotine salt, 0.01-5 parts of pH adjuster, 0.5-3 parts of compound sustained-release substance, and 0.1-2 parts of solid flavoring. The composite sustained-release substance is composed of sodium carboxymethyl cellulose, sodium alginate and chitosan, and the weight ratio of sodium carboxymethyl cellulose, sodium alginate and chitosan is 50-80:10-20:0.5-20.

[0007] In some embodiments, the weight ratio of sodium carboxymethyl cellulose, sodium alginate, and chitosan in the composite sustained-release substance is 60-70:12-18:5-15.

[0008] In some embodiments, the soluble substance is at least one of mannitol, xylitol, maltitol, and sorbitol; and the nicotine salt is at least one of nicotine tartrate, nicotine malate, and nicotine citrate.

[0009] In some embodiments, the pH adjuster is sodium carbonate and / or sodium bicarbonate, and the pH value of the oral product system is 9.0-9.9.

[0010] In some embodiments, the ingredients of the oral product further include 0.01-2 parts of sweetener, 0-10 parts of filler, and 0.1-10 parts of food additive; The sweetener is at least one of glucose, fructose, sucrose, aspartame, mogroside, chamomile glycoside, and acesulfame potassium; the filler is microcrystalline cellulose and / or starch; and the food additive is at least one of sodium chloride, glycerol, lipoic acid, potassium sorbate, sodium benzoate, WS-3, WS-23, and citric acid.

[0011] This application also provides a method for preparing an oral article, the method comprising the following steps: In a moisture-proof environment, the soluble substances are mixed with nicotine salts and pH adjusters, and premixed at the first rotation speed; A composite slow-release substance and a solid fragrance are added to the premix and mixed at a second rotation speed, so that the composite slow-release substance adheres to the surface of the soluble substance to obtain a mixed powder; the second rotation speed is less than the first rotation speed. The mixed powder is subjected to dry roller pressing granulation, followed by crushing and sieving to obtain oral product granules.

[0012] In some embodiments, the moisture-proof environment is a relative humidity ≤30% and a temperature of 20-25°C; and, The soluble substances are pulverized to 80-100 mesh before mixing.

[0013] In some embodiments, the first rotational speed is 15-20 rpm, the second rotational speed is 8-12 rpm, the mixing time at the first rotational speed is 10-20 min, and the mixing time at the second rotational speed is 8-10 min.

[0014] In some embodiments, the roller pressure of the dry roll granulation is 5-8 MPa; the sieving process collects oral product particles with a particle size of 20-40 mesh.

[0015] In some embodiments, the process after sieving further includes: filling the resulting oral product particles with nitrogen gas of ≥99.9% purity and then heat-sealing them for packaging. This application proposes a lozenge and its preparation method. The lozenge, by weight, comprises: 70-90 parts of soluble substance, 0.01-10 parts of nicotine salt, 0.01-5 parts of pH adjuster, 0.5-3 parts of compound sustained-release substance, and 0.1-2 parts of solid flavoring. The compound sustained-release substance is composed of sodium carboxymethyl cellulose, sodium alginate, and chitosan, with a weight ratio of 50-80:10-20:0.5-20. This application's technical solution has the following technical effects: By utilizing the polyelectrolyte complexation reaction of sodium carboxymethyl cellulose (anionic) and sodium alginate (anionic) with chitosan (cationic) in saliva, a dense and selectively permeable dynamic gel membrane is formed to encapsulate nicotine. This transforms the explosive release of nicotine in traditional methods into a long-term, uniform release, eliminating the initial pungent and stinging sensation. Furthermore, because the sustained-release network controls the release amount per unit time, even if the nicotine content per sachet is increased to 10mg or even 15mg or more, it will not lead to excessive intake and dizziness in a short period of time, thus meeting the needs of heavy smokers. Attached Figure Description

[0016] To more clearly illustrate the technical solutions in the embodiments of this application or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort, wherein: Figure 1 This is a schematic flowchart of a method for preparing an oral article according to an embodiment of this application; Figure 2 This is a graph showing the cumulative nicotine dissolution rate of each embodiment and comparative example in this application. Detailed Implementation

[0017] The technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of this application, and not all of the embodiments. Based on the embodiments of this application, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of this application.

[0018] It should be noted that, unless otherwise stated or limited, all directional indications (such as up, down, left, right, front, back, etc.) in the embodiments of this application are only used to explain the relative positional relationship and movement of each component in a certain specific posture (as shown in the figure). If the specific posture changes, the directional indication will also change accordingly.

[0019] It should also be noted that, unless otherwise stated or limited, when an element is referred to as "fixed to" or "set on" another element, it may be directly on the other element or there may be an intervening element present. When an element is referred to as "connected to" another element, it may be directly connected to the other element or there may be an intervening element present.

[0020] Furthermore, unless otherwise stated or limited, the descriptions involving "first," "second," etc., in this application are for descriptive purposes only and should not be construed as indicating or implying their relative importance or implicitly specifying the number of technical features indicated. Therefore, a feature defined as "first" or "second" may explicitly or implicitly include at least one of that feature. Additionally, the technical solutions of the various embodiments can be combined with each other, but only on the basis of being achievable by those skilled in the art. When the combination of technical solutions is contradictory or impossible to implement, such a combination of technical solutions should be considered non-existent and not within the scope of protection claimed in this application.

[0021] This application provides a mouth-held product comprising, by weight: 70-90 parts of soluble substance, 0.01-10 parts of nicotine salt, 0.01-5 parts of pH adjuster, 0.5-3 parts of compound sustained-release substance, and 0.1-2 parts of solid flavoring.

[0022] In this application, the composite sustained-release substance is composed of sodium carboxymethyl cellulose, sodium alginate, and chitosan, with a weight ratio of 50-80:10-20:0.5-20. It is understood that sodium carboxymethyl cellulose and sodium alginate are both anionic polymers with negatively charged carboxyl groups; chitosan is a cationic polymer, whose amino groups are partially protonated and positively charged at the neutral pH (approximately 6.8) in the oral cavity. In the dry powder state, they are uniformly mixed; upon contact with saliva, the anionic polymer rapidly hydrates to form a primary gel network, increasing viscosity and hindering diffusion; simultaneously, chitosan and the anionic polymer encounter each other, immediately undergoing a polyelectrolyte complexation reaction to form a denser and more stable secondary complex network. This network forms a selectively permeable dynamic gel membrane surrounding the sugar alcohol and nicotine salt, significantly reducing the diffusion coefficient and achieving uniform sustained release.

[0023] When the chitosan ratio is below 0.5 (e.g., 50:10:0.1), the complexation network is incomplete, resulting in a very weak sustained-release effect. When the chitosan ratio is above 20 (e.g., 65:15:25), excessive complexation occurs, forming stubborn, difficult-to-dissolve clumps in the mouth, causing a severe foreign body sensation and a very slow onset of symptoms. Therefore, a ratio of 50-80:10-20:0.5-20 achieves long-lasting sustained release while maintaining excellent palatability.

[0024] Furthermore, the weight ratio of sodium carboxymethyl cellulose, sodium alginate, and chitosan in the composite sustained-release substance is 60-70:12-18:5-15. This is a relatively preferred range. Under this ratio, the polyelectrolyte complex network is the most dense and stable, the initial dissolution rate can be controlled at around 20% within 1 minute, and there is no foreign body sensation from the micelles.

[0025] The soluble substance is at least one of mannitol, xylitol, maltitol, and sorbitol. The soluble substance provides the basic framework and sweet base color of the oral product. Mannitol is preferred because its cooling sensation harmonizes with the stimulating effect of nicotine, and its moderate solubility provides sufficient time for the in-situ formation of the sustained-release layer. Its dosage is 70-90 parts; too low a dosage will prevent granulation, while too high a dosage will crowd out the space for the sustained-release substance.

[0026] Nicotine salts are at least one of nicotine tartrate, nicotine malate, and nicotine citrate. Nicotine tartrate is preferred because it releases free nicotine more steadily in a weakly alkaline system, making it optimal for use with sustained-release systems. Dosage of 0.01-10 parts can cover the needs of smokers from light to heavy. Even at a dosage of 10 parts (approximately 15mg / packet), the sustained-release system maintains a mild taste and does not cause dizziness.

[0027] The pH adjuster is sodium carbonate and / or sodium bicarbonate. Its function is to adjust the pH of the oral product system to 9.0-9.9. In this slightly alkaline environment, it can promote the dissociation of nicotine salts into free nicotine for absorption by the mucous membrane. However, due to the presence of the slow-release network, the release rate of free nicotine is controlled, avoiding direct and strong irritation caused by excessively high pH.

[0028] Solid flavorings, preferably microcapsule powder flavorings. In the dry process, microcapsules can retain aroma components to the greatest extent and prevent volatilization. When squeezed during use, they provide a popping sensation, solving the problems of flavor loss and bland taste caused by traditional wet drying.

[0029] Furthermore, the raw materials of the oral product, by weight, also include 0.01-2 parts of sweetener, 0-10 parts of filler, and 0.1-10 parts of food additives. Among them: The sweetener is at least one of glucose, fructose, sucrose, aspartame, mogroside, chamomile glycoside, and acesulfame potassium, used to adjust the taste; the filler is microcrystalline cellulose and / or starch, used to adjust the particle density and formability; the food additive is at least one of sodium chloride, glycerin, lipoic acid, potassium sorbate, sodium benzoate, WS-3, WS-23, and citric acid, used to adjust the saltiness, moisturize, preserve, or provide a cooling sensation.

[0030] This application also provides a method for preparing the above-mentioned oral product, which is prepared by controlling a water-sensitive dry powder system, including the following steps: Step S1: Under a moisture-proof environment, mix the soluble substance with nicotine salt and pH adjuster, and premix at the first rotation speed.

[0031] In this step, the moisture-proof environment is provided by a temperature and humidity controlled workshop, with relative humidity ≤30% and temperature 20-25℃. Because sodium carboxymethyl cellulose and sodium alginate are highly hygroscopic, strict environmental control prevents the materials from absorbing moisture and clumping. Simultaneously, soluble substances are pulverized to 80-100 mesh before mixing.

[0032] In practice, the weighed soluble substances, nicotine salts, pH adjusters, and other raw materials are added to a three-dimensional mixer (V-type), and the initial speed and mixing time are set. The V-shaped structure of the three-dimensional mixer enables the powder to tumble in three-dimensional space at low speeds, ensuring uniform dispersion of materials with different specific gravities. The added raw materials may also include sweeteners and fillers.

[0033] Furthermore, the first rotation speed is 15-20 rpm, and the mixing time is 10-20 min, preferably 15-20 min.

[0034] In practice, without stopping the three-dimensional mixer, the pre-mixed, uniformly dissolved compound, microcapsule flavoring, and food additives are added. The speed is then reduced to the second speed setting, and the mixture is slowly mixed for a predetermined time. The second speed setting is 8-12 rpm, and the slow mixing lasts for 8-10 minutes.

[0035] The purpose of this step is not further dispersion, but rather to form a coating. By reducing the rotation speed (second rotation speed < first rotation speed), under low shear force, the microparticles of sodium carboxymethyl cellulose, sodium alginate, and chitosan can gently adhere to the surface of the soluble host particles, pre-forming a physical coating structure for the sustained-release layer. If the rotation speed is too high, it will destroy this adhesion structure, causing the sustained-release substances to become free and affecting the subsequent complexed sustained-release effect in saliva.

[0036] Step S3: The mixed powder is dry-rolled and granulated, then crushed and screened to obtain oral product granules.

[0037] In practice, the mixed powder is fed into a dry roller granulator, and the roller pressure is set to 5-8 MPa, preferably 6.5 MPa, to press the powder into dense flakes. Subsequently, the flakes are crushed by a granulator and then sieved through standard inspection sieves (20 mesh, 40 mesh) to collect oral product particles between 20-40 mesh.

[0038] Dry rolling under anhydrous conditions increases particle density and flowability. Simultaneously, due to the moderate pressure (5-8 MPa), it does not disrupt the pre-formed sustained-release material encapsulation structure in step S2; instead, it makes the material adhere more tightly. A particle size of 20-40 mesh ensures both oral comfort and provides a suitable specific surface area for saliva to wet and activate the sustained-release network.

[0039] Meanwhile, this dry roller pressing granulation process not only eliminates the need for water addition but also removes the high-temperature drying step, completely isolating the flavoring from heat and water damage during processing. The solid flavoring used in conjunction (microcapsule powder flavoring) retains its wall material intact under the low shear force of the dry process, firmly locking the aroma molecules inside the capsule, thus maximizing the preservation of the product's fragrance. When consumers place the product between their lips and teeth, the chewing, slight pressure from the teeth, and the wetting effect of saliva cause the wall material of these microcapsules to rupture, instantly releasing the high concentration of flavoring oils sealed inside, providing a bursting mouthfeel and greatly enriching the layers of enjoyment and pleasure of use.

[0040] Step S4, after sieving, further includes: filling the obtained oral product granules with nitrogen gas of ≥99.9% purity and then heat-sealing them. Nitrogen protection can prevent the oxidation of polyphenols and the deterioration of flavorings, ensuring the long-term stability of low-moisture products (<3%).

[0041] This application further proposes several embodiments, each containing different oral product components and corresponding preparation processes; including: Example 1 Formula: By weight, 88.3 parts soluble substances (all mannitol); 1 part sweetener (all acesulfame potassium); 2 parts nicotine salts (all nicotine tartrate); 5 parts fillers (all microcrystalline cellulose); 5 parts pH adjuster (all sodium carbonate); 1.2 parts food additives (including 1 part sodium chloride and 0.2 parts WS-3); 2 parts solid flavoring (microcapsule powder flavoring); 0.5 parts compound sustained-release substance. Among these, the compound sustained-release substance contains 0.325 parts sodium carboxymethyl cellulose, 0.075 parts sodium alginate, and 0.1 parts chitosan, i.e., sodium carboxymethyl cellulose: sodium alginate: chitosan = 65:15:20.

[0042] Preparation process: (1) Environmental control: All operations are carried out in a constant temperature and humidity workshop with relative humidity ≤30% and temperature 20-25℃ to prevent raw materials from absorbing moisture.

[0043] (2) Premixing: Crush the soluble substances to 80-100 mesh, and put them into a three-dimensional mixer along with nicotine salt, pH adjuster, sweetener and filler. Mix at 15-20 rpm for 15-20 min to ensure uniformity.

[0044] (3) Core steps: Add the pre-mixed compound slow-release substance, solid flavor and food additives, reduce the speed of the three-dimensional mixer to 12 rpm, mix slowly for 10 minutes to ensure that the slow-release microparticles adhere to the surface of the main particles.

[0045] (4) The mixed powder is fed into a dry roller press granulator, and the roller pressure is set to 6.5 MPa to press it into thin sheets.

[0046] (5) The thin film is crushed by a granulator and sieved with 20-mesh and 40-mesh standard sieves to collect oral product particles between 20-40 mesh.

[0047] (6) The oral product granules are filled with nitrogen and sealed in bags, each bag containing 0.5g.

[0048] Example 2 Formulation: The amount of compound sustained-release substance added in Example 1 was increased to 1.0 part (0.65 parts sodium carboxymethyl cellulose, 0.15 parts sodium alginate, 0.2 parts chitosan, sodium carboxymethyl cellulose: sodium alginate: chitosan = 65:15:20), while the other components and amounts remained unchanged.

[0049] The preparation process is the same as in Example 1.

[0050] Example 3 Formula: The amount of compound sustained-release substance added in Example 1 was increased to 2.0 parts (sodium carboxymethyl cellulose 1.3 parts, sodium alginate 0.3 parts, chitosan 0.4 parts, sodium carboxymethyl cellulose: sodium alginate: chitosan = 65:15:20), while the other components and amounts remained unchanged.

[0051] The preparation process is the same as in Example 1.

[0052] Example 4 Formula: The amount of compound sustained-release substance added in Example 1 was increased to 3.0 parts (sodium carboxymethyl cellulose 1.95 parts, sodium alginate 0.45 parts, chitosan 0.6 parts, sodium carboxymethyl cellulose: sodium alginate: chitosan = 65:15:20), while the other components and amounts remained unchanged.

[0053] The preparation process is the same as in Example 1.

[0054] Example 5 Formula: The soluble substance in Example 3 is replaced with xylitol instead of mannitol, and the weight parts remain 88.3 parts; other components and amounts remain unchanged.

[0055] The preparation process is the same as in Example 3.

[0056] Example 6 Formula: Increase the amount of nicotine tartrate salt in Example 3 from 2 parts to 10 parts (to simulate a high-concentration product), while keeping the other components and amounts unchanged.

[0057] The preparation process is the same as in Example 3.

[0058] Example 7 Formulation: The internal proportions of the 0.5 parts of the compound sustained-release substance in Example 1 were adjusted as follows: sodium carboxymethyl cellulose 0.4 parts, sodium alginate 0.08 parts, chitosan 0.02 parts, i.e., sodium carboxymethyl cellulose: sodium alginate: chitosan = 50:10:2.5 The preparation process is the same as in Example 1.

[0059] Example 8 Formula: The internal ratio of the 3 parts of the compound sustained-release substance in Example 4 was adjusted: 2 parts sodium carboxymethyl cellulose, 0.5 parts sodium alginate, and 0.5 parts chitosan, i.e., sodium carboxymethyl cellulose: sodium alginate: chitosan = 80:20:20; other components and amounts remained unchanged.

[0060] The preparation process is the same as in Example 4.

[0061] Example 9 Formulation: The internal ratio of the 3 parts of the compound sustained-release substance in Example 4 was adjusted as follows: sodium carboxymethyl cellulose 2.31 parts, sodium alginate 0.65 parts, chitosan 0.04 parts; sodium carboxymethyl cellulose: sodium alginate: chitosan = 69.3:19.5:1.2; other components and amounts remained unchanged.

[0062] Example 10 Formula: By weight, take 80.3 parts of soluble substances (70.3 parts mannitol, 8 parts xylitol, 1 part maltitol, 1 part sorbitol); 1.96 parts sweetener (1 part acesulfame potassium, 0.5 parts glucose, 0.05 parts fructose, 0.1 parts sucrose, 0.2 parts aspartame, 0.03 parts mogroside, 0.08 parts chamomile glycoside); 2 parts nicotine salt (1 part nicotine tartrate, 0.5 parts nicotine malate, 0.5 parts nicotine citrate); 5 parts filler (all microcrystalline cellulose); 5 parts pH adjuster (4 parts sodium carbonate, 1 part sodium bicarbonate); 2 parts solid flavor (microencapsulated powder flavor); 8.5 parts food additives (1.2 parts glycerin, 6.62 parts lipoic acid, 0.05 parts potassium sorbate, WS-23). 0.06 parts, 0.07 parts, 0.5 parts); 0.5 parts of compound sustained-release substance, of which sodium carboxymethyl cellulose 0.325 parts, sodium alginate 0.075 parts, and chitosan 0.1 parts, i.e., sodium carboxymethyl cellulose: sodium alginate: chitosan = 65:15:20.

[0063] The preparation process is the same as in Example 1.

[0064] Example 11 Formula: By weight, take 71.3 parts of soluble substances (70.3 parts of mannitol and 1 part of maltitol); 0.18 parts of sweetener (0.1 parts of acesulfame potassium, 0.05 parts of fructose, and 0.03 parts of mogroside); 0.15 parts of nicotine salt (0.1 parts of nicotine tartrate and 0.05 parts of nicotine malate); 9 parts of filler (6 parts of microcrystalline cellulose and 3 parts of starch); 0.1 parts of pH adjuster (all sodium bicarbonate); and 0.3 parts of food additives (0.01 parts of glycerin, 0.2 parts of lipoic acid, 0.03 parts of potassium sorbate, and WS-23). 0.06 parts); solid flavor 0.3 parts (microcapsule powder flavor); compound sustained-release substance 1 part, of which sodium carboxymethyl cellulose 0.65 parts, sodium alginate 0.15 parts, and chitosan 0.2 parts; i.e., sodium carboxymethyl cellulose: sodium alginate: chitosan = 65:15:20.

[0065] The preparation process is the same as in Example 1.

[0066] Example 12 Formula: By weight, take 80.3 parts of soluble substances (all mannitol), 0.65 parts of sweetener (0.5 parts glucose, 0.05 parts fructose, and 0.1 parts sucrose), 2 parts of nicotine salt (all nicotine tartrate), 5 parts of filler (all microcrystalline cellulose), 2 parts of pH adjuster (1 part sodium carbonate and 1 part sodium bicarbonate), 4.4 parts of food additives (4 parts sodium chloride, 0.2 parts lipoic acid, and 0.2 parts WS-3), 1 part of solid flavor (microcapsule powder flavor), and 2 parts of compound sustained-release substance, of which 1.3 parts sodium carboxymethyl cellulose, 0.3 parts sodium alginate, and 0.4 parts chitosan, i.e., sodium carboxymethyl cellulose: sodium alginate: chitosan = 65:15:20.

[0067] The preparation process is the same as in Example 1.

[0068] Example 13 Formula: By weight, take 78.3 parts of soluble substances (70.3 parts of mannitol and 8 parts of xylitol); 1.58 parts of sweetener (1 part of acesulfame potassium, 0.5 parts of glucose, and 0.08 parts of chamomile glycosides); 5.5 parts of nicotine salt (3 parts of nicotine tartrate and 2.5 parts of nicotine citrate); 0 parts of filler; 4.8 parts of pH adjuster (all sodium carbonate); 1.28 parts of food additives (1 part of sodium chloride, 0.01 parts of glycerin, 0.07 parts of citric acid, and 0.2 parts of WS-3); 2 parts of solid flavor (microcapsule powder flavor); 3.0 parts of compound sustained-release substance, which contains 1.95 parts of sodium carboxymethyl cellulose, 0.45 parts of sodium alginate, and 0.6 parts of chitosan, i.e., sodium carboxymethyl cellulose: sodium alginate: chitosan = 65:15:20.

[0069] The preparation process is the same as in Example 1.

[0070] This application is a one-to-one proportion, specifically: Comparative Example 1 Formula: By weight, 88.3 parts soluble substances (all mannitol); 1 part sweetener (all acesulfame potassium); 2 parts nicotine salts (all nicotine tartrate); 5 parts fillers (all microcrystalline cellulose); 5 parts pH adjuster (all sodium carbonate); 1.2 parts food additives (including 1 part sodium chloride and 0.2 parts WS-3); 2 parts solid flavoring (microcapsule powder flavoring); no added compound sustained-release substances.

[0071] Preparation process: (1) Under an environment of 25% relative humidity and 22℃, weigh mannitol, acesulfame potassium, nicotine tartrate salt, sodium carbonate and sodium chloride, put them into a three-dimensional mixer and mix at 18 rpm for 20 min.

[0072] (2) Add microcapsule citrus flavoring and ws-3, and continue mixing at 15 rpm for 10 min.

[0073] (3) The mixed powder is fed into a dry roller press granulator, and the roller pressure is set to 6.5 MPa to press it into thin sheets.

[0074] (4) The thin film is crushed by a granulator and screened with 20-mesh and 40-mesh standard sieves to collect oral product particles between 20-40 mesh.

[0075] (5) The oral product granules are filled with nitrogen and sealed in bags, each bag containing 0.5g.

[0076] This application also proposes a comparative test against a commercially available well-known brand. Specifically, it provides Comparison Example 2.

[0077] Comparative Example 2 The competing product's label indicates a nicotine content of 3mg, and actual testing shows that the nicotine content is indeed 3mg per bag.

[0078] The technical solution of this application further tests the oral articles prepared in each embodiment and comparative example to verify the performance of the oral articles prepared in this application. The test types include: (a) Moisture and pH value determination 1. Moisture test The moisture content was determined using a Karl Fischer moisture analyzer. A 1g sample of the oral product was weighed and placed in the titration cell of the Karl Fischer moisture analyzer. The instrument directly reads and records the percentage of moisture content in the sample by using Karl Fischer reagent to conduct a quantitative chemical reaction with the water in the sample.

[0079] 2. pH test of the system pH was measured using a pH meter. 0.5 g of the oral sample was accurately weighed and added to 50 mL of deionized water. The mixture was stirred on a magnetic stirrer for 5 min to ensure complete dissolution and release of alkaline salts. The calibrated pH meter electrode was then inserted into the solution, and the pH value was recorded after the reading stabilized.

[0080] (ii) Cumulative nicotine dissolution rate test The method adopted was the third method (paddle method) of General Chapter 0931 of the Chinese Pharmacopoeia. The main method used was to provide a simulated oral environment using a constant temperature dissolution apparatus and to quantitatively detect the nicotine concentration using high performance liquid chromatography (HPLC).

[0081] Test Procedure: 500 mL of artificial saliva (simulating the oral saliva environment, pH adjusted to 6.8) was injected into a dissolution vessel; the constant temperature dissolution apparatus was turned on, and the temperature of the dissolution medium was maintained at 37±0.5℃ (simulating the temperature of the human oral cavity), with the paddle rotation speed set to 50 rpm (simulating the slight shearing force during oral peristalsis); a sample of the oral product (approximately 0.5 g) was added to the dissolution vessel, and timing was started. At time points of 1, 2, 5, 10, 15, and 20 minutes, 2 mL of dissolution solution was precisely drawn from the dissolution vessel using a syringe; each 2 mL of dissolution solution was immediately filtered through a 0.45 μm microporous membrane to remove undissolved particles and large molecular gels, obtaining a clear filtrate. The filtrate was injected into a high-performance liquid chromatograph (HPLC), and the nicotine concentration in the filtrate at each time point was quantitatively determined by the chromatographic peak area.

[0082] The cumulative nicotine dissolution at that time point is calculated based on the measured concentration, and then divided by the total amount of nicotine in the sample to obtain the cumulative nicotine dissolution rate (%) at that time point.

[0083] (III) Sensory evaluation test The artificial oral feeding evaluation method was used.

[0084] Testing Process: A panel of 10 evaluators trained in professional sensory evaluation was formed. Each evaluator placed a sample of the oral product between their upper lip and gums to simulate real-world consumer use. During and after use, the evaluators scored the following three core dimensions (on a scale of 1-10) according to pre-set scoring criteria: Oral / throat irritation (1-10 points): Evaluate the initial spiciness, stinging or throat hit during the initial ingestion and the early stages of holding the food in the mouth. The lower the score, the stronger the irritation.

[0085] Speed ​​of onset (1-10 points): Evaluate the speed at which the nicotine satisfaction (onset) appears, combined with a textual description (very fast, fast, moderate, slow).

[0086] Duration of the feeling of satisfaction (1-10 points): This measures how long the satisfaction can be maintained.

[0087] Overall evaluation: The average score is taken from the scores given by 10 evaluators, and a comprehensive written evaluation is given (such as "moderate onset, long duration, mild taste" or "intensely spicy taste, hard to tolerate").

[0088] The obtained test data are summarized in Tables 1 to 3. Table 1 shows the cumulative nicotine dissolution rate test results of the oral product samples in each example and comparative example; Table 2 is a summary table of key dissolution indicators and sensory evaluation of the oral product samples in each example and comparative example; and Table 3 is a summary of the moisture content, pH value, and nicotine dissolution of the oral product samples in each example and comparative example, specifically including: Table 1. Results of Nicotine Cumulative Dissolution Rate Test (Unit: %)

[0089]

[0090] Table 2 Summary of Key Dissolution Indicators and Sensory Evaluation (Nicole content was measured using high performance liquid chromatography).

[0091] Table 3 Summary of Moisture Content, pH Value, and Nicotine Dissolution

[0092] As can be seen from Table 3, the moisture content of the oral products prepared in each embodiment of this application is basically controlled at around 3%, and the pH value is between 9.0 and 9.9, which meets the technical requirements of the oral products of this application.

[0093] As can be seen from Table 1 above, the actual dissolution time of the oral products samples using the composite sustained-release substance of this application is no less than 30 min, and some can reach 45 min or even 50 min; while the actual dissolution time of Comparative Example 2 is 10 min; and that of Comparative Example 1 is 15 min. Therefore, it can be determined that, under the synergistic effect of the composite sustained-release substance, the prepared nicotine bag can stably release nicotine. Among them: A comparison between Examples 1-4 shows that as the weight fraction of the compound sustained-release substance gradually increases within a set range, the nicotine release time becomes longer.

[0094] A comparison between Examples 3 and 5 shows that the composite sustained-release system of this application is effective against different soluble sugar alcohols.

[0095] A comparison between Examples 3 and 6 shows that the composite sustained-release system of this application can also achieve stable release of oral products with high concentrations of nicotine.

[0096] A comparison between Example 7, Comparative Example 2, and Comparative Example 1 shows that due to the extremely small total amount of the sustained-release substance (only 0.5 parts), the resulting polyelectrolyte network is relatively sparse. Its 1-minute dissolution rate is 32%, higher than Examples 2-3, but significantly lower than Comparative Example 2 (44%) and Comparative Example 1 without sustained release (43.67%). This demonstrates that even at the most extreme lower limit of addition, the system can still produce a certain sustained-release effect of nicotine through a small amount of complexation reaction.

[0097] A comparison between Examples 4 and 8 shows that in Example 8, the chitosan content in the composite sustained-release material was set to the upper limit, resulting in an extremely high chitosan content. At this point, the nicotine dissolution time exceeded 50 minutes, indicating that when the chitosan proportion was significantly increased, the polyelectrolyte complexation became excessive, forming an extremely dense and difficult-to-disintegrate gel barrier. Furthermore, based on the key dissolution indicators and sensory evaluation summary table in Table 2, the 1-minute dissolution rate dropped to an extremely low 8%, and less than 20% of the nicotine was released after 30 minutes. Sensory evaluation showed that although the irritation was extremely low, the "headache was slow (2 points)." Meanwhile, a comparison between Examples 4 and 9 shows that the chitosan content in the composite sustained-release material was low. Due to the lack of sufficient cationic chitosan for deep complexation, it mainly relied on the high-viscosity sodium carboxymethyl cellulose hydration layer for physical inhibition. Its 1-minute dissolution rate was 21%, which, while showing some nicotine sustained-release effect, was not as good as Example 3 (18.67%) with anion-cation balance. This proves that the anions and cations in the compound sustained-release substance must reach a relatively balanced range in order to achieve the best balance between nicotine sustained-release effect and taste.

[0098] In addition, a cumulative nicotine dissolution rate curve was plotted based on the examples in Table 1 and the cumulative nicotine dissolution rate test data, as shown in the figure. Figure 2 As shown in the figure, this graph visually compares the nicotine release kinetics of 13 representative products. Comparative Examples 1 and 2 both exhibit steep "J-shaped" curves, completing the full release within a very short time (5-15 min), representing a typical rapid release mode. In contrast, Examples 3 and 6 (high concentration) of this application exhibit gently rising "S-shaped" or approximately linear curves, achieving continuous and uniform release over a period of up to 45 min. Particularly noteworthy is that although Example 6 contains more than three times the total nicotine of its competitors, its dissolution amounts at 1 min and 5 min are only 2.25 mg and 4.5 mg, respectively, achieving high concentration and low irritation by controlling the release rate.

[0099] Furthermore, as shown in Table 1, the changes in the mass fraction of soluble substances and / or the mass fraction of sweeteners and / or the mass fraction of nicotine salts in Examples 10 to 13 had little effect on the nicotine release effect of the oral products containing the compound sustained-release substances, thus proving that the oral products containing the compound sustained-release substances have a positive effect on nicotine release.

[0100] The above description is only a part or preferred embodiment of this application. Neither the text nor the drawings should limit the scope of protection of this application. All equivalent structural transformations made using the content of this application's specification and drawings under the overall concept of this application, or direct / indirect applications in other related technical fields, are included within the scope of protection of this application.

Claims

1. A mouth-held product, characterized in that, By weight, it includes: 70-90 parts soluble substances, 0.01-10 parts nicotine salt, 0.01-5 parts pH adjuster, 0.5-3 parts compound sustained-release substances, and 0.1-2 parts solid flavoring; The composite sustained-release substance is composed of sodium carboxymethyl cellulose, sodium alginate and chitosan, and the weight ratio of sodium carboxymethyl cellulose, sodium alginate and chitosan is 50-80:10-20:0.5-20.

2. The oral article according to claim 1, characterized in that, The weight ratio of sodium carboxymethyl cellulose, sodium alginate, and chitosan in the composite sustained-release substance is 60-70:12-18:5-15.

3. The oral article according to claim 1, characterized in that, The soluble substance is at least one of mannitol, xylitol, maltitol, and sorbitol; the nicotine salt is at least one of nicotine tartrate, nicotine malate, and nicotine citrate.

4. The oral article according to claim 1, characterized in that, The pH adjuster is sodium carbonate and / or sodium bicarbonate, and the pH value of the oral product system is 9.0-9.

9.

5. The oral article according to claim 1, characterized in that, The ingredients of the oral product also include 0.01-2 parts of sweetener, 0-10 parts of filler, and 0.1-10 parts of food additives; The sweetener is at least one of glucose, fructose, sucrose, aspartame, mogroside, chamomile glycoside, and acesulfame potassium; the filler is microcrystalline cellulose and / or starch; and the food additive is at least one of sodium chloride, glycerol, lipoic acid, potassium sorbate, sodium benzoate, WS-3, WS-23, and citric acid.

6. A method for preparing an oral article as described in any one of claims 1-5, characterized in that, Including the following steps: In a moisture-proof environment, the soluble substances are mixed with nicotine salts and pH adjusters, and premixed at the first rotation speed; Add a composite slow-release substance and a solid fragrance to the premix and mix at a second rotation speed to allow the composite slow-release substance to adhere to the surface of the soluble substance, thereby obtaining a mixed powder. The second rotational speed is less than the first rotational speed; The mixed powder is subjected to dry roller pressing granulation, followed by crushing and sieving to obtain oral product granules.

7. The preparation method according to claim 6, characterized in that, The moisture-proof environment is defined as relative humidity ≤30% and temperature 20-25℃; and, The soluble substances are pulverized to 80-100 mesh before mixing.

8. The preparation method according to claim 6, characterized in that, The first rotational speed is 15-20 rpm, the second rotational speed is 8-12 rpm, the mixing time at the first rotational speed is 10-20 min, and the mixing time at the second rotational speed is 8-10 min.

9. The preparation method according to claim 6, characterized in that, The roller pressure of the dry roller granulation is 5-8 MPa; the sieving process collects oral product granules with a particle size of 20-40 mesh.

10. The preparation method according to claim 6, characterized in that, The process after sieving also includes: filling the resulting oral product granules with nitrogen gas with a purity of ≥99.9% and then heat-sealing and packaging them.

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