Mouthwash products and methods of making the same

Abstract

The application discloses a mouthwash product and a preparation method thereof, and relates to the field of food or medicine. The mouthwash product comprises a mouthwash composition, the mouthwash composition is in a solid state at room temperature and is at least partially soluble or dispersible in water; the mouthwash composition comprises an active substance inclusion compound and a solid substrate, the active substance inclusion compound is dispersed in the solid substrate, and the active substance inclusion compound comprises an active substance and an inclusion carrier. In the application, when the mouthwash composition is in contact with water, the water gradually infiltrates the solid substrate, triggers a disintegration and erosion process of the solid substrate, realizes the contact and continuous infiltration of the water to the active substance inclusion compound, slowly and continuously releases the active substance, avoids the release impact peak formed by the instantaneous mass dissolution of the active substance, maintains the concentration of the active substance in the oral cavity in a relatively stable range, helps to prolong the effect duration of a single use, and meets the physiological needs of consumers for the active substance.

Description

Technical Field

[0001] This application belongs to the field of daily necessities or pharmaceutical technology, specifically relating to a mouthwash product and its preparation method. Background Technology

[0002] Oral products include various dosage forms such as lozenges, oral films, and mouthwashes. Among them, mouthwashes have the functions of cleaning the oral cavity and delivering active substances.

[0003] In related technologies, mouthwash is made by dissolving active substances in an aqueous medium containing water, solubilizers, flavoring agents, and buffer salts. When using it, an appropriate amount of mouthwash is placed in the mouth and gargled for a certain period of time. The active substances are absorbed through the mucous membranes, meeting the user's physiological needs for these substances.

[0004] However, the active ingredients are released in large quantities and come into contact with the mucous membranes immediately upon rinsing, which is too irritating to the oral cavity and causes discomfort to the user. Summary of the Invention

[0005] The purpose of this application is to provide a mouthwash product and its preparation method, which at least solves the problems of active substances being released in large quantities and coming into contact with the mucous membrane at the moment of rinsing, causing excessive irritation to the oral cavity and discomfort to the user.

[0006] In a first aspect, embodiments of this application provide a mouthwash product, including a mouthwash composition, wherein the mouthwash composition is solid at room temperature and is at least partially soluble in or dispersed in water; The mouthwash composition includes an active substance inclusion complex and a solid substrate, wherein the active substance inclusion complex is dispersed in the solid substrate, and the active substance inclusion complex includes an active substance and an inclusion carrier.

[0007] In some embodiments, the active substance includes at least one of nicotine and its derivatives; And / or, the inclusion carrier includes at least one of cyclodextrin, cucurbitacin, cucurbituril, and modified starch; And / or, the solid substrate is selected from water-soluble substrates.

[0008] In some embodiments, the water-soluble substrate includes at least one of water-soluble dextrin, polyethylene glycol, povidone, hydroxypropyl methylcellulose, mannitol, and erythritol; The water-soluble dextrin includes at least one of maltodextrin, cyclodextrin, corn dextrin, potato dextrin, and hydroxymethyl dextrin. The molecular weight of the polyethylene glycol is 2000 Da to 8000 Da; The polyvinylpyrrolidone includes at least one of polyvinylpyrrolidone K30 and polyvinylpyrrolidone K90, wherein the molecular weight of polyvinylpyrrolidone K30 is 40,000 Da to 50,000 Da, and the molecular weight of polyvinylpyrrolidone K90 is 800,000 Da to 1,300,000 Da. The viscosity of the hydroxypropyl methylcellulose is 5 mPa·s to 15 mPa·s.

[0009] In some embodiments, the mouthwash composition further includes at least one of an antibacterial agent, a mucosal adhesive, a pH adjuster, a flavoring agent, an antioxidant, a cooling agent, and a flavoring.

[0010] In some embodiments, the antibacterial agent includes at least one selected from reed rhizome extract, honeysuckle extract, indigo naturalis extract, chlorhexidine and its derivatives, cetirizine, benzalkonium chloride, domiphen, and oteninidine; and / or, The mucosal adhesive comprises at least one of hydroxypropyl methylcellulose, sodium carboxymethyl cellulose, sodium alginate, xanthan gum, guar gum, sodium hyaluronate, polycarbofi, carbomer, and polyvinyl alcohol; and / or, The pH adjuster includes a single-salt pH adjuster, a buffer pair pH adjuster, or an organic biological buffer; wherein the single-salt pH adjuster includes at least one of disodium hydrogen phosphate, sodium citrate, citric acid, sodium tartrate, sodium lactate, sodium bicarbonate, and sodium carbonate; the buffer pair pH adjuster includes a pH adjuster composed of sodium dihydrogen phosphate and dipotassium hydrogen phosphate; and the organic biological buffer includes tris(hydroxymethyl)aminomethane or histidine; and / or, The flavoring agent comprises at least one of sucralose, neotame, aspartame, acesulfame potassium, steviol glycosides, xylitol, iodine, mannitol, sorbitol, erythritol, maltitol, lactitol, sodium saccharin, mongosaccharin, sucram, agarose, maple syrup, fructose, alitane, cyclamate, mogroside, and ammonium glycyrrhizate; and / or, The antioxidant includes at least one of vitamin E, ascorbic acid, and tea polyphenols; and / or, The cooling agent includes at least one of WS-3, WS-5, WS-12, WS-23, WS-27, menthol, and isomenthol; and / or, The fragrances include naturally extracted fragrances, synthetic fragrances, or compound fragrances.

[0011] In some embodiments, the mouthwash composition comprises, by weight parts: 0.5 to 2.5 parts of the inclusion compound, 40 to 100 parts of the solid substrate, 0.1 to 1.5 parts of the antibacterial agent, 1.5 to 3 parts of the mucosal adhesive, 3 to 6 parts of the pH adjuster, 1.8 to 7 parts of the flavoring agent, 0.2 to 1 part of the antioxidant, 0.1 to 1 part of the cooling agent, and 0.1 to 2 parts of the flavoring.

[0012] In some embodiments, the mouthwash product further includes a packaging bag for loading and sealing the mouthwash composition.

[0013] Secondly, embodiments of this application also provide a method for preparing a mouthwash product, comprising the following steps: The active substance, inclusion carrier, and water are mixed to prepare an inclusion complex solution; The inclusion complex solution was dried to obtain the active substance inclusion complex; The active substance inclusion complex is mixed with a solid substrate to form a mouthwash composition, thereby obtaining a mouthwash product.

[0014] In some embodiments, the active substance inclusion complex is mixed with a solid substrate to form a mouthwash composition comprising: After the active substance inclusion complex is mixed with the solid substrate, an extruded strip is obtained by an extrusion molding process. The conditions of the extrusion molding process include: temperature 55℃~75℃ and screw speed 30r / min~80r / min. The extruded strip is subjected to cooling and shaping treatment and stabilization treatment in sequence to prepare the mouthwash composition. The temperature during the cooling and shaping treatment is 15℃~25℃, and the conditions for the stabilization treatment include: temperature 23℃~27℃, relative humidity 40%~50%, and time 12h~24h.

[0015] In some embodiments, the active substance inclusion complex is mixed with the solid substrate to form a mouthwash composition: The mouthwash composition is prepared by mixing at least one of an antibacterial agent, a mucosal adhesive, a pH adjuster, a flavoring agent, an antioxidant, a cooling agent, and a flavoring, along with the active substance inclusion complex and the solid substrate, and by extrusion molding.

[0016] This application provides a mouthwash product and its preparation method. The mouthwash product includes a mouthwash composition, which is solid at room temperature and at least partially soluble in or dispersed in water. The mouthwash composition includes an active substance inclusion complex and a solid substrate. The active substance inclusion complex is dispersed in the solid substrate and includes an active substance and an inclusion carrier. In this application, the inclusion carrier encapsulates the active substance molecules, forming a structurally stable active substance inclusion complex. When the mouthwash composition comes into contact with water, the water gradually wets the solid substrate, triggering the disintegration and dissolution process of the solid substrate. This achieves continuous contact and wetting of the active substance inclusion complex by water, resulting in a slow and continuous release of the active substance. This avoids the release shock peak formed by the instantaneous large-scale dissolution of the active substance, maintaining the concentration of the active substance in the oral cavity within a relatively stable range. This helps to prolong the duration of the effect after a single use and meets the physiological needs of consumers for active substances. Detailed Implementation

[0017] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, the present invention will be further described in detail below with reference to specific embodiments.

[0018] The terms "first" and "second" in the specification and claims of this application may explicitly or implicitly include one or more of the features. In the description of this application, unless otherwise stated, "multiple" means two or more. Furthermore, "and / or" in the specification and claims indicates at least one of the connected objects, and the character " / " generally indicates that the preceding and following objects are in an "or" relationship.

[0019] This application provides a mouthwash product, including a mouthwash composition. The mouthwash composition is solid at room temperature and is at least partially soluble in or dispersed in water. The mouthwash composition includes an active substance inclusion complex and a solid substrate. The active substance inclusion complex is dispersed in the solid substrate. The active substance inclusion complex includes an active substance and an inclusion carrier.

[0020] In this embodiment, the inclusion carrier encapsulates the active substance molecules, forming a structurally stable active substance inclusion complex. When the mouthwash composition comes into contact with water, the water gradually wets the solid substrate, triggering the disintegration and dissolution process of the solid substrate. This allows water to contact and continuously wet the active substance inclusion complex, resulting in a slow and continuous release of the active substance. This avoids the release shock peak caused by the instantaneous dissolution of a large amount of active substance, maintaining the concentration of the active substance in the oral cavity within a relatively stable range. This helps to prolong the duration of the effect after a single use and meets the physiological needs of consumers for active substances.

[0021] In some embodiments, the inclusion carrier includes at least one of cyclodextrin, cucurbitacin, cucurbituril, and modified starch, wherein the cyclodextrin includes natural cyclodextrin and cyclodextrin derivatives, the natural cyclodextrin includes at least one of α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin, and the cyclodextrin derivative includes at least one of methyl-β-cyclodextrin and hydroxypropyl-β-cyclodextrin; the modified starch includes at least one of carboxymethyl starch and hydroxypropyl starch.

[0022] These inclusion carriers have a cavity structure that is hydrophobic inside and hydrophilic outside. They can embed active substance molecules into their cavity structure through non-covalent bonding such as van der Waals forces and hydrophobic interactions, achieving effective encapsulation at the molecular level and forming an active substance inclusion complex with a complete structure and good stability. The active substance inclusion complex is then dispersed in a solid substrate to form an instant-soluble, solid mouthwash composition.

[0023] When used, the mouthwash composition mixes with water, triggering the disintegration of the solid substrate. The active substance inclusion complex is then exposed to the water. Due to the hydrophilic nature of the inclusion carrier, the active substance inclusion complex can be uniformly dispersed in the water without aggregation or precipitation. As water continues to act on the active substance inclusion complex, the active substance molecules within the cavity structure of the inclusion carrier are slowly and continuously released. This avoids the release shock peak caused by the instantaneous dissolution of a large amount of active substance, thus maintaining the concentration of active substance in the oral cavity within a relatively stable range. This helps to prolong the duration of the effect after a single use and meets the physiological needs of consumers for active substances.

[0024] The mouthwash composition of this embodiment can be flexibly designed into various solid dosage forms, such as mouthwash strips and mouthwash tablets, depending on the usage scenario. When the mouthwash composition is designed as a mouthwash strip, the strip disintegrates into a mouthwash liquid upon contact with water, and the active substance inclusion complex is uniformly dispersed in the mouthwash liquid. During rinsing, the active substance is continuously released, providing both mouthwash cleaning and mucosal absorption functions. Regardless of the dosage form used, the synergistic effect of the active substance inclusion complex and the solid substrate achieves the regulation of the release rate of the active substance and the improvement of oral irritation.

[0025] In some embodiments, the active substance includes at least one of nicotine and its derivatives for satisfying a user's nicotine experience. Nicotine includes at least one of synthetic nicotine and natural nicotine. Nicotine derivatives include nicotine salts, nicotine in a matrix such as a glycobase or an organometallic complex, and nicotine... The nicotine derivative comprises one or more of the following: resin compounds, nicotine inclusion complexes, and non-covalently bonded nicotine. Non-covalently bonded nicotine includes nicotine lactate, nicotine malate, nicotine salicylate, nicotine hydrochloride, nicotine dihydrochloride, nicotine tartrate, nicotine tartrate dihydrate, nicotine sulfate, nicotine zinc chloride, and nicotine benzoate. Nicotine derivatives also include nicotine containing substituents, such as 6-methylnicotine, 6-methylnicotine lactate, 6-methylnicotine malate, 6-methylnicotine salicylate, 6-methylnicotine cyclodextrin-encapsulated complexes, 6-methylnicotine hydrochloride, 6-methylnicotine dihydrochloride, 6-methylnicotine tartrate, 6-methylnicotine tartrate dihydrate, 6-methylnicotine sulfate, 6-methylnicotine zinc chloride, and one or more mixtures of 6-methylnicotine benzoate.

[0026] In some embodiments, the mass ratio of the active substance to the inclusion carrier is 1:(3.5~5.5). This ratio range ensures that the inclusion carrier provides sufficient cavity structure to achieve full and effective inclusion of the active substance molecules, forming an active substance inclusion complex with complete structure, good stability, and appropriate sustained release time. At the same time, it avoids problems such as active substance release, oxidative degradation, and oral irritation caused by insufficient inclusion carrier, as well as avoids increased viscosity, decreased dissolution rate, and raw material waste caused by excessive inclusion carrier.

[0027] In some embodiments, the mass ratio of the active substance to the inclusion carrier is 1:3.5, 1:4, 1:4.5, 1:5, or 1:5.5.

[0028] In some embodiments, the solid substrate is selected as a water-soluble substrate, which can absorb water and dissolve, promoting the continuous interaction between the active substance inclusion complex and water, thereby achieving the sustained release of the active substance.

[0029] The water-soluble base material includes at least one of water-soluble dextrin, polyethylene glycol, povidone, hydroxypropyl methylcellulose, mannitol, and erythritol.

[0030] It should be noted that water-soluble dextrins include at least one of maltodextrin, cyclodextrin, corn dextrin, potato dextrin, and hydroxymethyl dextrin. These water-soluble dextrins have a large number of hydrophilic hydroxyl groups distributed on their molecular chains, have good water solubility, and can dissolve rapidly in the moist environment of the oral cavity.

[0031] The molecular weight of polyethylene glycol is 2000 Da to 8000 Da, and polyethylene glycol includes at least one of polyethylene glycol 2000, polyethylene glycol 3350, polyethylene glycol 4000, polyethylene glycol 6000 and polyethylene glycol 8000.

[0032] In this embodiment, polyethylene glycol is a hydrophilic polymer carrier that has solubilizing, lubricating and plasticizing functions. Polyethylene glycol with a molecular weight in the range of 2000 Da to 8000 Da is solid at room temperature and has a moderate melting temperature. In the extrusion molding process, it can reduce the melt viscosity of the material and improve its fluidity, which is convenient for continuous extrusion molding. At the same time, when it comes into contact with water, polyethylene glycol can dissolve rapidly and generate an osmotic pressure effect, which promotes the penetration of water into the mouthwash composition and accelerates its disintegration.

[0033] Povidone includes at least one of povidone K30 and povidone K90. Among them, povidone K30 has a molecular weight of 40,000 Da to 50,000 Da, a short molecular chain, and low steric hindrance. It dissolves faster in polar solvents such as water and ethanol, and usually dissolves completely in 3 to 5 minutes.

[0034] Povidone K90 has a molecular weight of 800,000 Da to 1,300,000 Da. Its long molecular chains are easy to entangle, requiring a longer wetting time to dissolve. Complete dissolution often takes 10 to 15 minutes, which prolongs the disintegration time of the solid substrate and allows the active substances to be released gradually at a controllable rate.

[0035] Hydroxypropyl methylcellulose has a viscosity of 5 mPa·s to 15 mPa·s (this viscosity was measured in a 2% aqueous solution at 20°C). It can rapidly hydrate in the moist environment of the oral cavity to form a uniform gel layer, allowing the solid mouthwash composition to disintegrate and release active substances within a suitable time. This avoids both the burst release of active substances caused by rapid disintegration and the release delay caused by slow dissolution.

[0036] In some embodiments, the solid substrate comprises a combination of maltodextrin and polyethylene glycol 6000, or a combination of mannitol and povidone K30.

[0037] In some embodiments, the mouthwash composition further includes an antibacterial agent, which includes at least one of reed rhizome extract, honeysuckle extract, indigo naturalis extract, chlorhexidine and its derivatives, cetirizine, benzalkonium chloride, domiphen, and oteninidine.

[0038] Reed rhizome extract, honeysuckle extract, and indigo extract are derived from plant materials. Their main antibacterial activities come from flavonoids, alkaloids, organic acids, and phenolic compounds contained in the plants. For example, reed rhizome extract, derived from the rhizome of reeds, contains active ingredients such as flavonoids, polysaccharides, and organic acids. It has the effects of clearing heat and promoting body fluid production, anti-inflammatory and analgesic properties. Furthermore, reed rhizome extract has low irritation to the oral mucosa and can relieve dry mouth discomfort that may be caused by active substances such as nicotine, while also possessing mild antibacterial activity.

[0039] At least one of chlorhexidine and its derivatives, cetylpyridinium chloride, benzalkonium chloride, domiphen and otetinidin belongs to the cationic quaternary ammonium salt or biguanide antibacterial agents. They can inhibit or kill common oral pathogens by electrostatically adsorbing onto the surface of bacterial cell membranes, thereby disrupting the integrity of the membrane and the function of the permeation barrier.

[0040] For example, chlorhexidine and its derivatives have inhibitory effects on common oral pathogens such as Streptococcus mutans and Porphyromonas gingivalis, and can form an antibacterial film on the oral mucosa and tooth surface, maintaining oral hygiene for a long time. Chlorhexidine derivatives include chlorhexidine gluconate. Cetylpyridinium chloride is a quaternary ammonium salt cationic surfactant with good inhibitory effects on Gram-positive bacteria and fungi. Compared with chlorhexidine, it has a milder taste and less bitterness, making it suitable for formulation in mouthwash compositions that require a good taste.

[0041] The above-mentioned antibacterial agents can be used alone or in combination. For example, chlorhexidine or its derivatives can be combined with honeysuckle extract, benzalkonium chloride with indigo extract, and cetirizine chloride with reed rhizome extract. These antibacterial agents are evenly dispersed in the oral environment during rinsing, which can inhibit bacterial growth and reduce plaque formation. At the same time, they work synergistically with other functional ingredients in the mouthwash composition to maintain oral health while meeting the needs of nicotine replacement.

[0042] In some embodiments, the mouthwash composition further includes a mucosal adhesive, which includes at least one of hydroxypropyl methylcellulose, sodium carboxymethyl cellulose, sodium alginate, xanthan gum, guar gum, sodium hyaluronate, polycarbofil, carbomer, and polyvinyl alcohol. When used alone or in combination, the mucosal adhesive can form an adhesive hydration layer on the surface of the oral mucosa, effectively prolonging the release and absorption window of the active substance and improving bioavailability.

[0043] In some embodiments, the mouthwash composition further includes a pH adjuster, which includes a single-salt pH adjuster, a buffer pair pH adjuster, or an organic biological buffer. The single-salt pH adjuster includes at least one of disodium hydrogen phosphate, sodium citrate, citric acid, sodium tartrate, sodium lactate, sodium bicarbonate, and sodium carbonate. The buffer pair pH adjuster includes a pH adjuster composed of sodium dihydrogen phosphate and dipotassium hydrogen phosphate. The organic biological buffer includes tris(hydroxymethyl)aminomethane or histidine. The pH adjuster stabilizes the pH of the solution formed after the mouthwash composition dissolves in water within a weakly alkaline range (7.2-8.0). In this weakly alkaline environment, nicotine molecules and other active substances exist in a non-protonated free base form, increasing their lipid solubility and enhancing their ability to penetrate the oral mucosa, thereby promoting the absorption efficiency of nicotine and other active substances and resulting in a faster onset of action at the same dosage.

[0044] In some embodiments, the mouthwash composition further includes a flavoring agent, which includes at least one of sucralose, neotame, aspartame, acesulfame potassium, steviol glycosides, xylitol, iodine, mannitol, sorbitol, erythritol, maltitol, lactitol, sodium saccharin, mongosaccharin, sucram, agave, maple syrup, fructose, alitane, cyclamate, mogroside, advanyl glycoside, and ammonium glycyrrhizate. The flavoring agents described above can provide a pure and pleasant sweet taste perception, effectively masking the inherent spicy and bitter taste of active substances such as nicotine, as well as the off-flavors that may be introduced by some functional excipients, thereby improving the sensory acceptance and user pleasure of the mouthwash composition during rinsing or holding in the mouth.

[0045] In some embodiments, the mouthwash composition further includes an antioxidant, including at least one of vitamin E, ascorbic acid, and tea polyphenols. The antioxidant can inhibit the generation of free radicals in the mouthwash composition during storage and use, and block the oxidation chain reaction initiated by oxygen, light, and trace metal ions, thereby protecting active substances such as nicotine from oxidative degradation and improving the stability and effectiveness of the mouthwash composition.

[0046] In some embodiments, the mouthwash composition further includes a cooling agent, which includes at least one of WS-3, WS-5, WS-12, WS-23, WS-27, menthol, and isomenthol. The cooling agent selectively activates TRPM8 cold receptors in the oral mucosa to produce a cool and refreshing physiological sensation without depending on actual temperature changes, thereby alleviating the burning and spicy discomfort of active substances such as nicotine on the oral mucosa and improving the user experience.

[0047] In some embodiments, the mouthwash composition further includes a flavoring, which may include naturally extracted flavorings, synthetic flavorings, or compound flavorings. The flavoring imparts a pleasant and distinctive flavor profile to the mouthwash composition, masks the bitter taste of active substances such as nicotine, and the chemical odor that functional excipients may introduce, thereby enhancing the user experience.

[0048] Among them, naturally extracted fragrances may include, but are not limited to, peppermint oil, lemon oil, linalool, licorice extract, tea polyphenols, clove oil, apple oil, banana oil, lychee oil, etc.; synthetic fragrances may include, but are not limited to, ethyl acetate, vanillin, vanillin, menthol, geraniol, coumarin, etc.; compound fragrances may include fragrances obtained by secondary blending of various fragrances.

[0049] In some embodiments, the mouthwash composition comprises, by weight parts, at least one of the following components: 0.5 to 2.5 parts of inclusion complex, 40 to 100 parts of solid substrate, 0.1 to 1.5 parts of antibacterial agent, 1.5 to 3 parts of mucosal adhesive, 3 to 6 parts of pH adjuster, 1.8 to 7 parts of flavoring agent, 0.2 to 1 part of antioxidant, 0.1 to 1 part of cooling agent, and 0.1 to 2 parts of flavoring.

[0050] In the mouthwash composition provided in this embodiment, the active substance inclusion complex is set to 0.5 to 2.5 parts by weight, which ensures that sufficient active substances are provided for a single use to meet physiological needs, while avoiding excessive oral irritation or discomfort.

[0051] The solid substrate of 40 to 100 parts provides sufficient skeletal support and rapid disintegration properties for the mouthwash composition. Within this range, the powder has good flowability and formability, and can be fully dissolved in water to form a palatable solution.

[0052] An antibacterial agent of 0.1 to 1.5 parts can effectively inhibit the growth of common oral pathogens and reduce plaque formation, while avoiding the risk of bitter taste or mucosal staining caused by excessive use.

[0053] A 1.5 to 3.0 part mucosal adhesive is beneficial for forming a moderately adhesive hydration layer on the oral mucosa surface, thus prolonging the retention and absorption window of active substances such as nicotine.

[0054] When the pH adjuster is 3 to 6 parts, it can ensure that the solution remains stably in a weakly alkaline range after dissolution, thus promoting the absorption of active substances such as nicotine by the oral mucosa.

[0055] The flavoring agent, at 1.8 to 7 parts, can mask the odor of active substances such as nicotine and optimize the taste of the mouthwash composition.

[0056] The antioxidant, at 0.2 to 1 part, can resist oxidation during shelf life and improve the storage stability of the mouthwash composition.

[0057] The cooling agent (0.1 to 1.0 parts) produces a cooling sensation, and the fragrance (0.1 to 2.0 parts) provides a pleasant aroma, thereby effectively relieving the burning sensation of active substances such as nicotine and giving the mouthwash composition a refreshing and pleasant user experience.

[0058] In some embodiments, the mouthwash composition may be in the form of an elongated solid and shall at least satisfy one of the following conditions: a length of 50 mm to 70 mm, a width of 8 mm to 12 mm, and a mass of 0.8 g to 1.2 g.

[0059] In this embodiment, a single strip weight of 0.8g to 1.2g ensures a sufficient loading of the active ingredient.

[0060] It should be noted that the above-mentioned size and weight ranges are only some preferred examples of this application. In actual production, adaptive adjustments can be made according to the oral characteristics, dosage requirements or product positioning of the target consumer group. For example, the size and weight of the children's version can be reduced, while the high-dose version can be appropriately enlarged. All of these are within the scope of protection of this application.

[0061] In some embodiments, the mouthwash composition has a length of 50 mm, a width of 8 mm, and a mass of 0.8 g; in other embodiments, the mouthwash composition has a length of 60 mm, a width of 10 mm, and a mass of 1.0 g; in still other embodiments, the mouthwash composition has a length of 70 mm, a width of 12 mm, and a mass of 1.2 g.

[0062] In some embodiments, the mouthwash product further includes a packaging bag for loading and sealing the mouthwash composition, the packaging bag being made of aluminum foil composite film or polyethylene film.

[0063] This packaging bag isolates the mouthwash composition from the external environment, preventing oxygen and moisture from the air during transportation and storage. This avoids deterioration due to moisture absorption and oxidation, thus ensuring the chemical stability and microbiological safety of the mouthwash product within its shelf life. Users can easily remove the mouthwash composition by tearing or cutting open the packaging bag, making it convenient for carrying and single-use.

[0064] This application also provides a method for preparing a mouthwash product, comprising the following steps: Step 1: Mix the active substance, inclusion carrier, and water to prepare an inclusion solution.

[0065] In this step, the active substance and the inclusion carrier are weighed according to the mass ratio; the inclusion carrier is added to purified water and stirred at a constant temperature of 40℃~50℃ until completely dissolved to prepare an inclusion carrier solution with a mass concentration of 10%~15%; the active substance is added to the inclusion carrier solution, and the mixture is stirred at 200r / min~400r / min in the dark for 2.0h~3.0h to obtain the inclusion complex solution.

[0066] Step 2: Dry the inclusion complex solution to obtain the active substance inclusion complex.

[0067] In this step, a low-temperature spray drying process is used to dry the inclusion complex solution. The process parameters for low-temperature spray drying include: inlet air temperature 80℃~110℃, outlet air temperature 45℃~60℃, feed rate 5mL / min~15mL / min, and atomization pressure 0.2MPa~0.4MPa.

[0068] Using the above-mentioned low-temperature spray drying process, the inlet air temperature is controlled at 80℃~110℃, which allows the water in the inclusion complex solution to evaporate rapidly, while avoiding excessive temperature that could lead to the volatilization and loss of active substances or the destruction of the active substance inclusion complex structure. The coordinated adjustment of the feeding speed and atomization pressure atomizes the liquid into uniform micro-droplets, resulting in a powder with a narrow particle size distribution, good flowability, and fast dissolution rate. The outlet air temperature is 45℃~60℃, which ensures that the powder is fully dried and does not stick to the wall or clump, making it suitable for subsequent mixing and molding processes.

[0069] After drying, the powder is collected and passed through an 80-120 mesh sieve to further remove agglomerated coarse particles, ensuring the uniformity of powder particle size, and finally obtaining the active substance inclusion complex, which is then sealed and stored away from light.

[0070] Step 3: Mix the active substance inclusion complex with a solid substrate to prepare a mouthwash composition, thereby obtaining a mouthwash product, including the following steps: S31. Raw material mixing: The active substance inclusion complex and solid substrate are added to a mixing device and mixed at a speed of 10-20 rpm for 20-40 minutes until homogeneous. Then, at least one of the following can be added: a mucosal adhesive, pH adjuster, flavoring agent, antioxidant, cooling agent, and flavoring agent. Stirring continues until all components are evenly dispersed, resulting in a homogeneous mixed powder. This mixing step can be completed in a three-dimensional motion mixer, utilizing its multi-directional tumbling motion to achieve sufficient convection and diffusion between powder particles, ensuring uniform distribution of functional components in a large amount of solid substrate.

[0071] S32, Extrusion molding: The mixed powder is formed into a solid strip structure. In this embodiment, the mixed powder is added to an extrusion molding device to obtain an extruded strip. The extrusion molding device is a single-screw extruder or a twin-screw extruder, which performs continuous extrusion molding through a flat, elongated, narrow-slit die.

[0072] The extrusion molding process conditions are controlled as follows: the barrel temperature is 55℃~75℃. Within this barrel temperature range, the solid substrate softens and melts, providing sufficient fluidity and cohesiveness for the mixed powder. This allows the mixed powder to be plasticized under the shearing action of the screw and smoothly pass through the flat, long, narrow die to form a continuous extruded strip. At the same time, the barrel temperature is lower than the thermal decomposition temperature of the active material and inclusion complex, ensuring the stability of the active ingredient during processing.

[0073] The screw speed is 30r / min~80r / min, which can ensure that the material is fully plasticized while maintaining appropriate production efficiency, and avoid material retention caused by too low speed or shear overheating caused by too high speed.

[0074] S33, Cooling and Shaping: The extruded strip is immediately conveyed to a cooling device for cooling and shaping. The cooling temperature is 15℃~25℃, and air-cooled conveyor rollers can be used to uniformly cool the upper and lower surfaces of the extruded strip simultaneously during the conveying process. This cooling condition allows the molten solid substrate to solidify rapidly, preventing deformation, uneven shrinkage, or surface stickiness of the extruded strip caused by slow cooling, and ensuring a smooth and flat surface with controllable dimensions.

[0075] S34. Fixed-length cutting, including: The cooled and shaped extruded strip is fed into a cutting device and cut to a fixed length according to preset specifications to obtain individual products. The dimensions of each cut strip are 50mm~70mm in length, 8mm~12mm in width, and 0.8g~1.2g in weight. This size and weight range is suitable for the hand-held operation habits of adult consumers, and at the same time, it forms a suitable water-to-powder ratio with the recommended water addition, ensuring instant dissolution and user experience.

[0076] S35, Stabilization treatment: The cut strips were placed in a constant temperature and humidity environment for stabilization treatment. The treatment conditions were 23℃~27℃, 40%~50% relative humidity, and 12h~24h. This gently removed trace amounts of residual moisture that might have been introduced during the thermoforming and cutting process, while simultaneously releasing internal stress in the mouthwash composition and bringing the components of the solid substrate to a balanced state. This improved the hardness, stiffness, and dimensional stability of the mouthwash strips, preventing softening and deformation or degradation of active ingredients due to moisture absorption during subsequent storage. Thus, a mouthwash composition with structural stability and suitable dimensions was obtained.

[0077] To ensure the mouthwash composition meets market standards, the qualified compositions can be fed into a fully automatic strip packaging machine for individual sealing using aluminum foil composite film. The heat-sealing temperature of the fully automatic strip packaging machine is controlled between 120℃ and 140℃, with a heat-sealing time of 0.3s to 0.8s, ensuring a tight seal while preventing heat damage to the mouthwash composition. After packaging, defective products are inspected by light to remove any that fail to seal properly, then the mouthwash is boxed and stored, yielding the final mouthwash product.

[0078] The mouthwash product obtained in this application is used as follows: dissolve and rinse with water, that is, tear open the packaging bag, mix the mouthwash composition with 15mL~20mL of drinking water or purified water, stir or shake gently to make the mouthwash composition quickly disintegrate to form a mouthwash liquid, rinse and spit it out. During rinsing, the solid matrix disintegrates, and the active substances in the active substance inclusion complex are slowly released and steadily absorbed through the oral mucosa, thus achieving oral cleaning while meeting the user's physiological needs for active substances such as nicotine.

[0079] The present application will be further described in detail below through specific embodiments and comparative examples.

[0080] The following embodiments are only some embodiments of this application and are not intended to limit this application. In the embodiments and comparative examples, unless otherwise specified, the reagents and instruments used are all commercially available, and the experimental operations are all performed in accordance with the product instructions and conventional experimental procedures.

[0081] Example 1 (1) Preparation of active substance inclusion complexes Weigh out nicotine benzoate and β-benzoate at a mass ratio of 1:3.5. Cyclodextrin; add β-cyclodextrin to purified water Cyclodextrin was stirred at 45°C until completely dissolved to prepare a 15% (w / w) β-cyclodextrin solution. Cyclodextrin solution; Nicotine benzoate is slowly added to β-cyclodextrin solution. Cyclodextrin solution was stirred at 300 r / min for 2.5 h in the dark to obtain an inclusion complex solution. The inclusion complex solution was dried by low-temperature spray drying with an inlet air temperature of 100℃, an outlet air temperature of 50℃, a feed rate of 10 mL / min, and an atomization pressure of 0.3 MPa. After drying, the powder was collected, passed through a 100-mesh sieve, and the active substance inclusion complex was obtained. It was then sealed and stored in the dark.

[0082] (2) Preparation of mixed powder Based on mass parts, 1.2 parts of the active substance inclusion complex (including 0.27 parts of nicotine benzoate and 0.95 parts of β-benzoate) were included. Cyclodextrin, 72 parts maltodextrin, 8 parts polyethylene glycol 4000, 2 parts hydroxypropyl methylcellulose, 4.5 parts disodium hydrogen phosphate-citric acid buffer, 4.8 parts erythritol, and 0.5 parts vitamin E were sieved through an 80-mesh sieve. The sieved powder was added to a three-dimensional motion mixer and mixed at 15 rpm for 30 minutes until homogeneous. Then, 0.2 parts chlorhexidine and 0.3 parts reed rhizome extract were added and mixed for another 10 minutes to obtain a homogeneous powder mixture.

[0083] (3) Hot extrusion molding and strip cutting The mixed powder is added to a twin-screw hot extruder. During extrusion, the barrel temperature is controlled at 65℃ and the screw speed is 50r / min. The extruded strip is continuously extruded through a flat, long, narrow slit die. The extruded strip is cooled and shaped by a 20℃ air-cooled conveyor roller. It is then cut into single strips of a fixed length to obtain concentrated strips with dimensions of 60mm in length, 10mm in width, and 1g in weight.

[0084] (4) Stabilization treatment The concentrated strip was placed in an environment of 25±2℃ and 40%~50% relative humidity for 20 hours to remove residual moisture, improve hardness and stability, and obtain a mouthwash composition.

[0085] Examples 2-4 The difference from Example 1 is that the ratio of nicotine benzoate to β was adjusted in step (2). The mass ratio of cyclodextrin, and the mass parts of active substance inclusion complex, maltodextrin, polyethylene glycol 4000, hydroxypropyl methylcellulose, disodium hydrogen phosphate-citrate buffer, erythritol, vitamin E, chlorhexidine and / or reed rhizome extract.

[0086] The relevant parameters of the mouthwash compositions prepared in Examples 1-4 are shown in Table 1.

[0087] Table 1

[0088] Comparative Example 1 By mass fraction, 0.27 parts of nicotine benzoate (the same mass as the nicotine benzoate contained in the 1.2 parts of active substance inclusion complex in Example 1), 72 parts of maltodextrin, 8 parts of polyethylene glycol 4000, 2 parts of hydroxypropyl methylcellulose, 4.5 parts of disodium hydrogen phosphate-citric acid buffer, 4.8 parts of erythritol, and 0.5 parts of vitamin E were all sieved through an 80-mesh sieve. The sieved powder was added to a three-dimensional motion mixer and mixed at 15 r / min for 30 min until homogeneous to obtain a mixed powder. 10 mL of purified water was added to 1 g of the mixed powder and stirred evenly to obtain a mouthwash.

[0089] Test case (1) Accelerated stability test: The sample was placed in a constant temperature and humidity chamber at 45°C and 75% relative humidity for 30 days. The nicotine content in the sample was determined by high performance liquid chromatography. The ratio of the nicotine content to the initial content was calculated to obtain the nicotine retention rate, which was used to evaluate the chemical stability of the mouthwash composition of the example and the mouthwash of the comparative example under high temperature and high humidity conditions.

[0090] (2) In vitro release test: The paddle method was used, the dissolution medium was artificial saliva, the temperature was controlled at 37℃, and the rotation speed was 50r / min. Samples were taken at 10 minutes and 30 minutes after the start of release. The cumulative release of nicotine was determined by high performance liquid chromatography and the cumulative release rate was calculated to evaluate the release behavior of the active substance of the formulation in a simulated oral environment.

[0091] (3) Dissolution time test: 1.0g of the mouthwash composition of the example was placed in purified water at 20°C, and the time required for the mouthwash composition to become completely clear and transparent after being added was recorded to evaluate the disintegration and dissolution rate of the solid mouthwash composition in the moist oral environment.

[0092] (4) Oral mucosal irritation test: The test was conducted according to the rabbit eye mucosal irritation test model. The solution of the mouthwash composition of the example and the mouthwash of the comparative example were dropped into the conjunctival sac of the rabbit eye. The irritation reaction of the cornea, iris and conjunctiva was observed and recorded at the specified time points. The reaction was graded into 0 to 3 levels (0 for no irritation, 1 for mild irritation, 2 for moderate irritation and 3 for severe irritation) to evaluate the local tolerance and safety of each mouthwash product to the oral mucosa.

[0093] Table 2

[0094] As can be seen from Table 2, the nicotine retention rates of Examples 1-4 are all higher than 90%, which is better than the 76.5% of Comparative Example 1. This indicates that the molecular encapsulation of nicotine by β-cyclodextrin encapsulation isolates oxygen and moisture from the external environment, thereby improving the chemical stability of nicotine under high temperature and high humidity conditions.

[0095] The cumulative release rates at 10 min for Examples 1-4 were 22.7%-35.1%, and at 30 min, they were 75.6%-85.6%. In contrast, the cumulative release rates at 10 min and 30 min for Comparative Example 1 were as high as 68.2% and 92.3%, respectively. This indicates that unencapsulated nicotine dissolves rapidly in artificial saliva, lacks a sustained-release effect, and is prone to causing burst release of the active substance and oral irritation. Among them, the cumulative release rate at 10 min for Example 4 (nicotine benzoate to β-cyclodextrin mass ratio of 1:5.5) was 22.7%, a significantly reduced release rate, which may lead to a delayed onset of nicotine action.

[0096] The dissolution time of Examples 1-4 was 10-14 seconds, which enabled rapid dissolution in the oral environment and facilitated use. The mucosal irritation rating of Examples 1-4 was 0, which was better than the 2 rating of Comparative Example 1. This indicates that through the inclusion and solid strip formulation design, the active substance was effectively encapsulated in the carrier, avoiding the irritation caused by the direct contact of the free active substance with the oral mucosa.

[0097] Although preferred embodiments of the present invention have been described, those skilled in the art, upon learning the basic inventive concept, can make other changes and modifications to these embodiments. Therefore, the claims are intended to be interpreted as including the preferred embodiments as well as all changes and modifications falling within the scope of the embodiments of the present invention.

Claims

1. A mouthwash product, characterized in that, The invention includes a mouthwash composition that is solid at room temperature and is at least partially soluble in or dispersed in water. The mouthwash composition includes an active substance inclusion complex and a solid substrate, wherein the active substance inclusion complex is dispersed in the solid substrate, and the active substance inclusion complex includes an active substance and an inclusion carrier.

2. The mouthwash product according to claim 1, characterized in that, The active substance includes at least one of nicotine and its derivatives; And / or, the inclusion carrier includes at least one of cyclodextrin, cucurbitacin, cucurbituril, and modified starch; And / or, the solid substrate is selected from water-soluble substrates.

3. The mouthwash product according to claim 2, characterized in that, The water-soluble substrate includes at least one of water-soluble dextrin, polyethylene glycol, povidone, hydroxypropyl methylcellulose, mannitol, and erythritol; The water-soluble dextrin includes at least one of maltodextrin, cyclodextrin, corn dextrin, potato dextrin, and hydroxymethyl dextrin. The molecular weight of the polyethylene glycol is 2000 Da to 8000 Da; The polyvinylpyrrolidone includes at least one of polyvinylpyrrolidone K30 and polyvinylpyrrolidone K90, wherein the molecular weight of polyvinylpyrrolidone K30 is 40,000 Da to 50,000 Da, and the molecular weight of polyvinylpyrrolidone K90 is 800,000 Da to 1,300,000 Da. The viscosity of the hydroxypropyl methylcellulose is 5 mPa·s to 15 mPa·s.

4. The mouthwash product according to claim 1, characterized in that, The mouthwash composition further includes at least one of the following: antibacterial agent, mucosal adhesive, pH adjuster, flavoring agent, antioxidant, cooling agent, and flavoring.

5. The mouthwash product according to claim 4, characterized in that, The antibacterial agent includes at least one selected from the following: reed rhizome extract, honeysuckle extract, indigo naturalis extract, chlorhexidine and its derivatives, cetirizine chloride, benzalkonium chloride, domiphen, and oteninidine; and / or, The mucosal adhesive comprises at least one of hydroxypropyl methylcellulose, sodium carboxymethyl cellulose, sodium alginate, xanthan gum, guar gum, sodium hyaluronate, polycarbofi, carbomer, and polyvinyl alcohol; and / or, The pH adjuster includes a single-salt pH adjuster, a buffer pair pH adjuster, or an organic biological buffer; wherein the single-salt pH adjuster includes at least one of disodium hydrogen phosphate, sodium citrate, citric acid, sodium tartrate, sodium lactate, sodium bicarbonate, and sodium carbonate; the buffer pair pH adjuster includes a pH adjuster composed of sodium dihydrogen phosphate and dipotassium hydrogen phosphate; and the organic biological buffer includes tris(hydroxymethyl)aminomethane or histidine; and / or, The flavoring agent comprises at least one of sucralose, neotame, aspartame, acesulfame potassium, steviol glycosides, xylitol, iodine, mannitol, sorbitol, erythritol, maltitol, lactitol, sodium saccharin, mongosaccharin, sucram, agarose, maple syrup, fructose, alitane, cyclamate, mogroside, and ammonium glycyrrhizate; and / or, The antioxidant includes at least one of vitamin E, ascorbic acid, and tea polyphenols; and / or, The cooling agent includes at least one of WS-3, WS-5, WS-12, WS-23, WS-27, menthol, and isomenthol; and / or, The fragrances include naturally extracted fragrances, synthetic fragrances, or compound fragrances.

6. The mouthwash product according to claim 4, characterized in that, The mouthwash composition comprises, by weight parts: 0.5 to 2.5 parts of the inclusion complex, 40 to 100 parts of the solid substrate, 0.1 to 1.5 parts of the antibacterial agent, 1.5 to 3 parts of the mucosal adhesive, 3 to 6 parts of the pH adjuster, 1.8 to 7 parts of the flavoring agent, 0.2 to 1 part of the antioxidant, 0.1 to 1 part of the cooling agent, and 0.1 to 2 parts of the flavoring.

7. The mouthwash product according to claim 1, characterized in that, The mouthwash product also includes a packaging bag for containing and sealing the mouthwash composition.

8. A method for preparing a mouthwash product, characterized in that, Includes the following steps: The active substance, inclusion carrier, and water are mixed to prepare an inclusion complex solution; The inclusion complex solution was dried to obtain the active substance inclusion complex; The active substance inclusion complex is mixed with a solid substrate to form a mouthwash composition, thereby obtaining a mouthwash product.

9. The method for preparing the mouthwash product according to claim 8, characterized in that, The active substance inclusion complex is mixed with a solid substrate to form a mouthwash composition comprising: After the active substance inclusion complex is mixed with the solid substrate, an extruded strip is obtained by an extrusion molding process. The conditions of the extrusion molding process include: temperature 55℃~75℃ and screw speed 30r / min~80r / min. The extruded strip is subjected to cooling and shaping treatment and stabilization treatment in sequence to prepare the mouthwash composition. The temperature during the cooling and shaping treatment is 15℃~25℃, and the conditions for the stabilization treatment include: temperature 23℃~27℃, relative humidity 40%~50%, and time 12h~24h.

10. The method for preparing the mouthwash product according to claim 8, characterized in that, The active substance inclusion complex is mixed with the solid substrate to prepare a mouthwash composition: The mouthwash composition is prepared by mixing at least one of an antibacterial agent, a mucosal adhesive, a pH adjuster, a flavoring agent, an antioxidant, a cooling agent, and a flavoring, along with the active substance inclusion complex and the solid substrate, and by extrusion molding.

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