A refreshing lozenge and its preparation method

Abstract

This invention belongs to the field of pharmaceutical formulation technology, specifically relating to a lozenge for refreshing the mind and freshening the breath, and its preparation method. The lozenge comprises a plain tablet and a shell. The plain tablet includes inner phase particles, an inner phase particle coating layer, and excipients: the inner phase particles use sodium carboxymethyl cellulose and crospovidone to construct an immediate-release framework, with immediate-release and sustained-release caffeine and theanine as stimulating ingredients, supplemented by poloxamer to enhance penetration, achieving rapid absorption and sustained release of caffeine, and the theanine alleviates the nerve stimulation caused by caffeine; the inner phase particle coating layer uses hydroxypropyl methylcellulose and hydroxypropyl cellulose to construct a sustained-release framework, with polyethylene glycol forming microporous channels to promote the sustained release of fermented ginsenosides, enhancing anti-fatigue ability to prolong the stimulating effect, and releasing eucalyptol and limonene to produce a cooling sensation and mask odor, supplemented by Lactobacillus rhamnosus to inhibit the growth of harmful bacteria in the mouth to reduce odor, thereby achieving the effects of rapid stimulating, long-lasting mental alertness, and fresh breath.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical preparation technology, and in particular to a lozenge for refreshing the mind and clearing the mouth, and its preparation method. Background Technology

[0002] In today's fast-paced lifestyle and work environment, mental alertness and fresh breath have become universal needs. Existing products on the market, such as traditional lozenges, chewing gum, or functional beverages, often have significant limitations in terms of comprehensive efficacy, duration of effect, and overall user experience. Specifically, most energizing products rely on the rapid release of single ingredients like caffeine, which, while effective quickly, has a short duration and can easily cause discomfort such as palpitations and anxiety due to rapid rises and falls in blood drug concentration. Simultaneously, their breath-freshening function is often limited to providing a temporary cooling sensation through ingredients like menthol or masking odors with fragrances, failing to regulate the oral flora at its root, resulting in a superficial and easily recurring freshening effect. Furthermore, dosage form designs that simply combine energizing and breath-freshening functions often neglect the optimal release kinetics of different ingredients. For example, energizing ingredients need to achieve a balance between rapid onset and stable maintenance, while breath-freshening ingredients need to balance immediate sensation and long-lasting effect. This technological deficiency makes it difficult for existing products to simultaneously meet the comprehensive expectations of rapid onset, long-lasting effect, gentle comfort, and fundamental breath freshness. Summary of the Invention

[0003] To address the shortcomings of existing technologies, the present invention aims to provide a lozenge for refreshing the mind and freshening the breath, along with its preparation method and application. The lozenge comprises inner phase particles, an inner phase particle coating layer, and a shell. The inner phase particles utilize a fast-release framework constructed from low-viscosity sodium carboxymethyl cellulose and cross-linked povidone, with fast-release and slow-release caffeine and theanine as the core stimulating ingredients. Poloxamer is added to enhance penetration, achieving rapid absorption and sustained release of caffeine, while theanine alleviates potential nerve stimulation caused by caffeine. The inner phase particle coating layer utilizes a slow-release framework constructed from hydroxypropyl methylcellulose and low-substituted hydroxypropyl cellulose. Polyethylene glycol regulates gel permeability, and the released fermented ginsenosides enhance anti-fatigue capabilities to prolong the stimulating effect. Eucalyptol and limonene are released to activate TRPM8 channels, producing a cooling sensation and masking odor. Lactobacillus rhamnosus is added to inhibit the growth of harmful oral bacteria, reducing odor. Thus, the lozenge achieves rapid stimulating effect, long-lasting mental alertness, and fresh breath.

[0004] To achieve the above objectives, the present invention employs the following technical solution:

[0005] In a first aspect, the present invention provides a lozenge for refreshing the mind and clearing the mouth, the lozenge comprising a plain tablet and a shell; the plain tablet comprising inner phase particles, an inner phase particle coating layer, and excipients; the shell comprising a film-forming agent; the inner phase particles comprising immediate-release caffeine, sustained-release caffeine, theanine, and excipients; the immediate-release caffeine is prepared by air-jet milling of caffeine under a milling pressure of 0.7-0.9 MPa and a feed rate of 10-15 kg / h, with a particle size ≤5 μm; the sustained-release caffeine has a particle size of 80-120 μm; the inner phase particle coating layer comprises a fat-soluble inclusion complex, a probiotic inclusion complex, and additives; the excipients comprise anhydrous erythritol and magnesium stearate; the excipients comprise... The composition includes sodium carboxymethyl cellulose, crospovidone, poloxamer 188, micronized silica gel, povidone, and anhydrous erythritol; the lipid-soluble inclusion complex includes eucalyptol, limonene, fermented ginsenosides, and HP-β-cyclodextrin (hydroxypropyl-β-cyclodextrin); the probiotic inclusion complex includes *Lactobacillus rhamnosus* freeze-dried bacterial powder, maltodextrin, gum arabic, and vitamin E, obtained by mixing *Lactobacillus rhamnosus* freeze-dried bacterial powder, maltodextrin, gum arabic, vitamin E, and second deionized water, followed by spray drying; the additives include hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyethylene glycol, citric acid, micronized silica gel, and hydroxypropyl cellulose; the degree of substitution of hydroxypropyl cellulose in the additives is 7%-12%.

[0006] Further, the mass ratio of the uncoated tablet to the outer shell is (101.45-118.26):(9-11); the mass ratio of the inner phase particles, the inner phase particle coating layer, and the excipients in the uncoated tablet is (45.8-52.6):(50.45-59.26):(5.2-6.4); the mass ratio of immediate-release caffeine, sustained-release caffeine, theanine, and excipients in the inner phase particles is (0.43-0.53):(1.0-1.24):(1.6-2.0):(42.77-48.83); and the mass ratio of fat-soluble inclusion complexes, probiotic inclusion complexes, and additives in the inner phase particle coating layer is (22.7-27.7). (9-11): (18.54-20.46), the mass ratio of sodium carboxymethyl cellulose, crospovidone, poloxamer 188, micronized silica gel, povidone and anhydrous erythritol in the excipients is (6.8-8.2): (1.8-2.2): (0.45-0.55): (0.27-0.33): (0.45-0.55): (33-37); the mass ratio of eucalyptol, limonene, fermented ginsenosides and HP-β-cyclodextrin in the fat-soluble inclusion complex is (1.8-2.2): (0.9-1.1): (5.4-6.6): (14.6-17.8); the probiotic inclusion complex contains Lactobacillus rhamnosus ( Lactobacillus rhamnosusThe mass ratio of freeze-dried bacterial powder, maltodextrin, gum arabic, and vitamin E is (1.8-2.2):(4.5-5.5):(2.7-3.3):(0.27-0.33); the mass ratio of hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyethylene glycol, citric acid, micronized silica gel, and sodium alginate in the additives is (12.6-15.4):(2.7-3.3):(0.45-0.55):(0.09-0.11):(0.63-0.77):(2.0-2.3); the mass ratio of anhydrous erythritol and magnesium stearate in the auxiliary agents is (4.5-5.5):(0.7-0.9); the film-forming agent is hydroxypropyl methylcellulose, and the viscosity of a 2% aqueous solution of hydroxypropyl methylcellulose at 25°C is 3.6-5.4 mPa·s.

[0007] Further, the viscosity of a 2% aqueous solution of sodium carboxymethyl cellulose in the excipients is 5-20 mPa·s at 25°C; the K value of povidone in the excipients is 27-32; the average degree of substitution of HP-β-cyclodextrin in the fat-soluble inclusion complex is 0.6-0.8; the viscosity of a 2% aqueous solution of hydroxypropyl methylcellulose in the additives is 3500-4500 mPa·s at 25°C; the molecular weight of polyethylene glycol in the additives is 5000-7000; and the viscosity of a 2% aqueous solution of sodium alginate in the additives is 30-80 mPa·s at 25°C.

[0008] Secondly, the present invention provides a method for preparing a lozenge that refreshes the mind and cleanses the mouth, comprising the following steps:

[0009] S1. Sodium carboxymethyl cellulose, crospovidone, immediate-release caffeine, sustained-release caffeine, theanine, poloxamer 188, micronized silica gel, povidone, anhydrous erythritol and ethanol solution are mixed, spray-dried and dried to obtain internal phase particles.

[0010] S2. Eucalyptol, limonene, fermented ginsenosides, HP-β-cyclodextrin and first deionized water are mixed, stirred, homogenized under high pressure, freeze-dried, and sieved to obtain a fat-soluble inclusion complex; Lactobacillus rhamnosus freeze-dried powder, maltodextrin, gum arabic, vitamin E and second deionized water are mixed and spray-dried to obtain a probiotic inclusion complex.

[0011] S3. Mix hydroxypropyl methylcellulose K4M, hydroxypropyl cellulose, polyethylene glycol, citric acid, and micronized silica gel. Add a fat-soluble inclusion complex and a probiotic inclusion complex while stirring to obtain an external phase mixture. Mix the external phase mixture, sodium alginate, and deionized water, and shear to obtain an external phase suspension.

[0012] S4. Spray the external phase suspension onto the surface of the internal phase particles and dry to obtain coated internal phase particles; mix the coated internal phase particles, anhydrous erythritol and magnesium stearate, compress into tablets to obtain uncoated tablets; mix hydroxypropyl methylcellulose and ethanol solution to obtain coating solution; spray the coating solution onto the surface of the uncoated tablets, cure and dry at the spraying temperature, and sieve to obtain a lozenge for refreshing the mind and clearing the mouth.

[0013] A 2% aqueous solution of sodium carboxymethyl cellulose has a viscosity of 5-20 mPa·s at 25°C. Due to its short molecular chain and strong hydrophilicity, it rapidly absorbs water, swells, and disintegrates upon contact with saliva. Crosslinked polyvinylpyrrolidone (PVPP), with its crosslinked network structure, generates strong capillary forces during swelling, accelerating the disintegration of the skeletal framework. Together, they form a transient dispersion channel, providing a physical basis for the release of functional components. By introducing poloxamer 188 as a nonionic surfactant, its hydrophilic segments can interact with phospholipid molecules on the oral mucosal cell membrane, temporarily increasing membrane permeability and promoting the absorption of subsequent components.

[0014] Micronized, immediate-release caffeine has a significantly increased specific surface area, allowing it to dissolve rapidly into free molecules in saliva. With the help of poloxamer, it penetrates mucosal epithelial cells, quickly enters the bloodstream, and reaches the central nervous system. Through competitive binding to adenosine receptors, it blocks adenosine-mediated sedative signals, rapidly reviving the nervous system. In contrast, sustained-release caffeine retains its original particle size. Its larger particle size makes it difficult to dissolve rapidly in the initial stages of skeletal disintegration. Instead, it is released gradually as the residual internal structure disperses, continuously replenishing caffeine concentration and avoiding palpitations and anxiety caused by a sudden increase in blood concentration, or fatigue rebound caused by a sudden decrease. Theanine crosses the blood-brain barrier to enter the central nervous system, promoting the synthesis of inhibitory neurotransmitters such as γ-aminobutyric acid (GABA) while reducing the excessive release of excitatory neurotransmitters such as norepinephrine, balancing the stimulating effect of caffeine. Furthermore, the alpha brain waves it induces can keep a person relaxed in a conscious state, achieving a mild, non-stimulating effect. In addition, povidone with a K value of 27-32 binds the powders of the internal phase into stable particles through intermolecular hydrogen bonding, avoiding excessive fine powder during granulation; micronized silica reduces the friction between particles through adsorption, ensuring uniform flowability during tableting; and anhydrous erythritol, as a low-calorie sweetener, provides a refreshing taste while its crystal structure enhances the mechanical strength of the particles, preventing breakage during transportation.

[0015] In one feasible implementation, in S1, the mass-to-volume ratio of the immediate-release caffeine to the ethanol solution is (0.43-0.53) kg:(32-38) L, and the mass fraction of the ethanol solution is 30 wt.%; the parameters of the spray drying are: inlet air temperature 115-125℃, outlet air temperature 55-65℃, and atomization pressure 0.3-0.5 MPa; the drying step is: drying for 8-12 min at a temperature of 60℃ and a wind speed of 1.5-2.0 m / s; and the particle size of the internal phase particles is 120-150 μm.

[0016] Spray drying granulation is crucial for the formation of the functional structure of internal phase particles. In an environment with a temperature difference between the inlet and outlet air, the ethanol on the droplet surface evaporates rapidly due to the high temperature, forming a hard outer shell, while the internal solvent slowly diffuses to the surface, ultimately forming porous particles. The inlet air temperature ensures instantaneous solidification of the droplets, preventing the small-sized micronized caffeine particles from agglomerating due to prolonged heating. The outlet air temperature protects the activity of theanine and povidone. The resulting porous structure provides channels for saliva penetration, preserving the rapid disintegration potential of low-viscosity sodium carboxymethyl cellulose and PVPP. Furthermore, the difference in pore size between the large surface pores and the small internal pores allows for a gradient release of components. That is, immediate-release caffeine can dissolve rapidly through the large surface pores, while slow-release caffeine needs to gradually penetrate the small internal pores, working with the residual structure of the framework material to delay its release. The subsequent drying process uses airflow to bring the particles to a boiling state, ensuring uniform contact with the drying medium. This guarantees the fluidity, framework stability, and subsequent disintegration performance of the internal phase particles, laying the foundation for their stable and rapid energizing function.

[0017] In one feasible implementation, in step S2, the mass-to-volume ratio of eucalyptol to the first deionized water is (1.8-2.2) kg: (72-88) L; the stirring temperature is 48-52℃, the stirring speed is 450-550 r / min, and the stirring time is 20-30 min; the high-pressure homogenization pressure is 27-33 MPa, and the high-pressure homogenization time is 8-12 min; the freeze-drying temperature is -40℃, and the freeze-drying time is 24-30 h; the sieve mesh size is 80 mesh.

[0018] Inclusion complexes of fat-soluble components are key carriers for achieving long-lasting freshness and synergistic energizing effects. The core of this lies in the molecular inclusion properties of HP-β-cyclodextrin, which protects and controls the release of fat-soluble components. HP-β-cyclodextrin is a cyclic molecule formed by seven glucose units linked by glycosidic bonds. It has a hydrophobic cavity inside and a hydrophilic exterior due to the dense distribution of hydroxyl groups. This internally hydrophobic and externally hydrophilic structure allows it to form stable inclusion complexes with eucalyptol, limonene, and fermented ginsenosides through van der Waals forces and hydrophobic interactions. This inclusion effect significantly reduces the volatility of eucalyptol and limonene, while improving the water solubility of fermented ginsenosides, enabling them to be uniformly dispersed in the external matrix and avoiding uneven release caused by hydrophobic aggregation.

[0019] In the oral cavity, as saliva gradually penetrates, the external hydroxyl groups of HP-β-cyclodextrin combine with water molecules, causing the inclusion complex structure to gradually disintegrate and release the encapsulated components: when eucalyptol and limonene come into contact with the oral mucosa, they can specifically activate the transient receptor potential cation channel M8. Once activated, this channel triggers an influx of calcium ions, generating a cooling signal that is transmitted to the central nervous system, creating a cooling sensation. Simultaneously, the natural citrus and eucalyptus aromas of both can directly mask odor components such as volatile sulfur compounds in the mouth, achieving immediate freshness. Fermented ginsenosides are absorbed into the body through the mucosa. Their active ingredients can promote the synthesis and release of neurotransmitters such as dopamine and serotonin in the brain, enhancing the central nervous system's tolerance to fatigue signals. This complements the sustained excitatory effect of endogenous sustained-release caffeine. Caffeine focuses on blocking inhibitory signals, while fermented ginsenosides focus on enhancing excitatory signal transmission; the two synergistically prolong the energizing effect.

[0020] In one feasible implementation, in S2, the viable count of the Lactobacillus rhamnosus freeze-dried powder is ≥1×10¹. 0 CFU / g; the mass-to-volume ratio of the Lactobacillus rhamnosus freeze-dried bacterial powder to the second deionized water is (1.8-2.2) kg: (45-55) L; the parameters of the spray drying are: inlet air temperature 75-85℃, outlet air temperature 42-48℃, and atomization pressure 0.2-0.4 MPa.

[0021] The probiotic inclusion complex achieves long-lasting oral freshness through a live bacteria protection-microbiota regulation mechanism. Its core lies in the protection and controlled release of *Lactobacillus rhamnosus* by the composite wall material. Maltodextrin, as the main wall material, forms a network structure through hydrogen bonds using its glucose units, encapsulating the bacterial powder and rapidly solidifying during spray drying to form a dense outer shell. The high molecular weight polysaccharide chains of gum arabic cross-link with maltodextrin, enhancing the mechanical strength of the wall material and resisting the high-temperature impact during drying. Vitamin E, as an antioxidant, scavenge free radicals generated during spray drying and storage, preventing oxidative damage to bacterial cell membrane lipids and significantly improving the survival rate of the freeze-dried *Lactobacillus rhamnosus* powder.

[0022] Upon entering the oral cavity, the moisture in saliva gradually dissolves the composite wall material. Maltodextrin, due to its high water solubility, dissolves first, releasing some live bacteria, while the slow dissolution of gum arabic continues to release the remaining bacteria. Lactobacillus rhamnosus, as a beneficial oral bacterium, regulates the balance of the oral flora in the following ways: first, it competes with acid-producing harmful bacteria such as Streptococcus mutans and Porphyromonas gingivalis for carbohydrate nutrients in the oral cavity, inhibiting their proliferation; second, it metabolizes to produce acidic substances such as lactic acid, lowering the local pH of the oral cavity to below 5.5, creating an environment unfavorable to the survival of harmful bacteria; and third, it secretes antibacterial substances such as bacteriocins, directly killing some harmful bacteria. This mechanism of reducing odor at its source complements the immediate odor masking effect of the fat-soluble inclusion complex, continuously producing a freshening effect, thus solving the problem of traditional lozenges relying on fragrance masking and recurring odor.

[0023] In one feasible implementation, in step S3, the stirring speed is 13-17 r / min, and the stirring time is 16-24 min; the mass-to-volume ratio of sodium alginate to deionized water is (2.0-2.3) kg:(70-90) L; the shearing speed is 1800-2200 rpm, and the shearing time is 25-35 min; the viscosity of the external phase suspension is 2000-3000 mPa·s.

[0024] Hydroxypropyl methylcellulose (HPC), a high-molecular-weight cellulose ether, has a viscosity of 3500-4500 mPa·s in a 2% aqueous solution at 25°C. Upon contact with water, its molecular chains swell slowly due to hydroxyl hydration, forming a viscoelastic gel matrix. This matrix provides continuous structural support for the external phase, preventing rapid disintegration of the tablets during sublingual administration. Low-substituted hydroxypropyl cellulose (L-HPC), with a degree of substitution of 7%-12%, contains a small number of hydroxypropyl substituents in its molecules. It has weak hydrophilicity but extremely strong water absorption and swelling capacity. Its particles expand several times in volume upon absorbing water in the gel matrix, tearing out numerous microporous channels within the matrix. By introducing polyethylene glycol as a water-soluble porogen, it can be uniformly dispersed in the gel matrix and forms additional pores after dissolving with saliva. This synergistic effect with the micropores of L-HPC regulates the permeability of the gel network. By adjusting the ratio of these three components, the release cycle of the external phase components can be adjusted to meet the requirements of long-acting function.

[0025] The external phase mixture ensures consistent functional ingredient content in each tablet by uniformly mixing fat-soluble inclusion complexes, probiotic inclusion complexes, and other excipients. For taste adjustment, citric acid stimulates acid receptors on the taste buds in the mouth, neutralizing the sweetness of anhydrous erythritol to create a refreshing, balanced sweet and sour taste. In terms of tablet structure, the crystalline structure of anhydrous erythritol increases the fluidity of the external phase mixture, ensuring uniform filling during compression; micronized silica gel reduces interparticle adhesion through physical adsorption, further improving the fluidity of the external phase and preventing tablet weight variations during compression; vitamin E protects the active ingredients of the fat-soluble inclusion complexes in the external phase through its antioxidant properties, preventing oxidative deterioration during storage.

[0026] In one feasible implementation, in step S4, the spraying step is as follows: under the conditions of an inlet air temperature of 55-60℃ and an atomization pressure of 0.08-0.12MPa, the external phase suspension is sprayed onto the surface of the internal phase particles at a rate of 4-6mL / min; the drying temperature is 55-60℃ and the drying time is 8-12min.

[0027] The inner phase particles remain suspended and tumbling in a fluidized state, ensuring that the outer phase suspension is sprayed onto its surface at a uniform rate. This dynamic contact mode avoids localized liquid accumulation or excessively thick coatings, allowing the outer phase material to form a functional layer of uniform thickness on the surface of each inner phase particle. The fluidized drying process after spraying removes moisture from the outer phase suspension through continuous airflow circulation, promoting the solidification of gel materials such as hydroxypropyl methylcellulose and low-substituted hydroxypropyl cellulose in the outer phase functional layer. Hydroxypropyl methylcellulose forms a continuous supporting gel matrix, while low-substituted hydroxypropyl cellulose retains microporous channels within the matrix. Together with the porosigenic effect of polyethylene glycol, they create a sustained-release structure with precisely regulated release rates. The solidified outer phase functional layer is tightly bonded to the inner phase particles, neither hindering the rapid dispersion of the inner phase fast-release framework upon contact with saliva, nor hindering the slow release of lipid-soluble inclusion complexes and probiotic inclusion complexes through its own gel network. This forms a functional system with a rapidly responding core and a continuously acting outer layer.

[0028] Adding anhydrous erythritol and magnesium stearate to the inner phase particles of the coating and mixing them is a crucial step in ensuring the quality and functional stability of the uncoated tablets. Anhydrous erythritol, as a filler, with its rigid particles, can fill the gaps between particles, reducing the risk of particle agglomeration caused by the viscosity of the outer functional layer, and significantly improving the flowability of the mixed particles. This ensures that the particles can uniformly fill the die holes during tableting, avoiding tablet weight differences due to uneven material distribution and ensuring the consistency of the active ingredient content in each tablet. Simultaneously, anhydrous erythritol has good compressibility, easily undergoing plastic deformation under pressure, and can tightly bind with the particles, compensating for the elastic defects of the outer phase gel material and preventing tablet cracking or loosening. Magnesium stearate, as a lubricant, forms a lubricating film on the particle surface by adsorption, reducing the frictional resistance between the mixed particles and the tableting die and die holes, preventing sticking and reducing energy loss during tableting, ensuring complete tablet formation and a smooth surface, providing a stable base for subsequent film coating.

[0029] In one feasible implementation, in step S4, the mass-to-volume ratio of hydroxypropyl methylcellulose to ethanol solution is (9-11) kg: (52-78) L; the mass fraction of the ethanol solution is 80 wt.%; the spraying step is as follows: spraying at a rate of 4.5-5.5 mL / min under conditions of inlet air temperature of 58-62℃ and outlet air temperature of 33-37℃; the curing and drying time is 15-25 min; and the sieve mesh size is 2-3 mesh.

[0030] Film coating achieves dual protection and optimized taste by forming a continuous film on the surface of the tablet. The coating solution, formed by dissolving hydroxypropyl methylcellulose in ethanol, rapidly forms a film during spraying as the solvent evaporates. Its low viscosity ensures uniform coverage of the tablet surface, eliminating pinholes and exposed areas. The resulting film has a dense network structure that effectively isolates the tablet from humidity and oxygen: on one hand, it prevents caffeine and theanine in the internal phase from clumping or degrading due to moisture absorption, ensuring the stability of the stimulating components; on the other hand, it reduces the contact between the probiotic inclusion complex and oxygen in the external phase, delaying bacterial oxidative inactivation and extending the product's shelf life. Simultaneously, the smooth texture of the film masks the slight roughness caused by particle compression on the tablet surface, reducing friction and irritation to the oral mucosa during sublingual administration and improving comfort. More importantly, the film dissolves slowly in saliva, neither hindering the gradual disintegration of the tablet during sublingual administration nor hindering its physical protection during storage and transportation, ultimately resulting in a functionally stable and high-quality sublingual tablet product.

[0031] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0032] This solution develops a lozenge that simultaneously provides rapid alertness, sustained mental clarity, and fresh breath. The internal phase particles, acting as the rapid-response stimulant, utilize a fast-release framework constructed from low-viscosity sodium carboxymethyl cellulose and crospovidone. This framework rapidly disperses upon contact with saliva. The fast-release caffeine, with its small particle size and high solubility, is quickly absorbed through the oral mucosa with the aid of the excipient poloxamer 188, rapidly relieving fatigue by blocking adenosine receptors in the central nervous system. Simultaneously, the sustained-release caffeine dissolves slowly due to the moderate blockage of the framework, ensuring continuous replenishment and preventing sudden increases or decreases in effectiveness. Furthermore, theanine promotes alpha brain wave generation and regulates neurotransmitter balance, synergistically mitigating potential caffeine-induced stimuli and ensuring a gentle and stable stimulant process.

[0033] The inner phase particle coating layer serves as a long-lasting and refreshing functional unit. It utilizes a sustained-release framework constructed from hydroxypropyl methylcellulose and low-substituted hydroxypropyl cellulose. The hydroxypropyl methylcellulose in this framework swells moderately upon contact with water, forming a supportive gel matrix. Meanwhile, the low-substituted hydroxypropyl cellulose, through its strong water absorption and swelling effect, generates numerous microporous channels within the matrix. Simultaneously, the additive polyethylene glycol further modulates the permeability of the gel network through the pores formed by dissolution, thereby promoting the continuous release of fermented ginsenosides, enhancing the central nervous system's anti-fatigue ability, and synergistically prolonging the energizing effect with the sustained-release caffeine in the inner phase particles. Furthermore, the released eucalyptol and limonene activate the M8 type transient receptor potential cation channel, producing a cooling sensation and masking oral odors with natural fragrance, achieving immediate odor removal. In addition, Lactobacillus rhamnosus, upon entering the oral cavity, inhibits the growth of harmful bacteria, reducing odor production at its source. This solution addresses the problems of traditional lozenges—strong stimulation, short duration of effect, and recurring refreshing effects—achieving a comprehensive advantage of rapid energization, long-lasting alertness, and fresh breath. Attached Figure Description

[0034] Figure 1 This is a schematic diagram illustrating the composition of a mouthwash for refreshing the mind and clearing the breath according to the present invention.

[0035] Figure 2 This is a cumulative dissolution curve of caffeine in a lozenge for refreshing the mind and clearing the mouth, as described in this invention. Detailed Implementation

[0036] To make the technical problems, technical solutions, and beneficial effects to be solved by this application clearer, the application will be further described in detail below with reference to embodiments. However, this should not be construed as limiting the scope of this application to the following examples. All other embodiments obtained by those skilled in the art without creative effort without departing from the above-described methodological spirit of this application are within the scope of protection of this application.

[0037] The singular forms “for,” “or,” “a,” “any,” and “described” used in this application are intended to include the plural forms unless the context clearly indicates otherwise. Furthermore, the terms “first” and “second” are used for descriptive purposes only and should not be construed as indicating or implying relative importance. Example

[0038] like Figure 1 As shown, a method for preparing a lozenge for refreshing the mind and clearing the mouth includes the following steps:

[0039] S1. Take 1.6 kg of caffeine, of which 0.48 kg of caffeine is subjected to air jet milling under a milling pressure of 0.8 MPa and a feeding rate of 12 kg / h, and milled to a particle size of ≤5 μm, which is used as immediate-release caffeine. The remaining 1.12 kg of caffeine retains its original particle size and is used as slow-release caffeine. 0.48 kg of immediate-release caffeine, 1.12 kg of sustained-release caffeine, 1.8 kg of theanine, 7.5 kg of sodium carboxymethyl cellulose (2% aqueous solution with a viscosity of 20 mPa·s at 25℃), 2 kg of crospovidone, 0.5 kg of poloxamer 188, 0.3 kg of micronized silica powder, 0.5 kg of povidone K30 and 35 kg of anhydrous erythritol were mixed and 35 L of 30% ethanol solution was added. Spray drying was carried out under the conditions of inlet air temperature of 120℃, outlet air temperature of 60℃ and atomization pressure of 0.4 MPa. Then, the mixture was dried in a fluidized bed at 60℃ and air velocity of 1.7 m / s for 10 min to obtain internal phase particles.

[0040] S2. Mix 2 kg of eucalyptol, 1 kg of limonene, and 6 kg of fermented ginsenosides, add 16.2 kg of HP-β-cyclodextrin with a degree of substitution of 0.6, dissolve in 80 L of deionized water, stir in a water bath at 50℃ and 500 r / min for 15 min, and simultaneously apply ultrasonic treatment at 300 W for 15 min. Then homogenize under high pressure at 30 MPa for 10 min, freeze dry at -40℃ for 27 h, and pass through an 80 mesh sieve to obtain the lipid-soluble component inclusion complex. Mix 2 kg of freeze-dried Lactobacillus rhamnosus (Sichuan Provincial Microbial Resource Platform Strain Preservation Center, strain number: SICC1.1515), 5 kg of maltodextrin, 3 kg of gum arabic, and 0.3 kg of vitamin E, dissolve in 50 L of deionized water, and spray dry and granulate under the conditions of inlet air temperature of 80℃, outlet air temperature of 45℃, and atomization pressure of 0.2 MPa to obtain the probiotic inclusion complex.

[0041] S3. Add 14 kg of hydroxypropyl methylcellulose K4M, 3 kg of hydroxypropyl cellulose with a degree of substitution of 10%, 0.5 kg of polyethylene glycol 6000, 0.1 kg of citric acid, and 0.7 kg of micronized silica powder to a three-dimensional motion mixer and mix at 15 r / min for 10 minutes. Then add 25.2 kg of lipid-soluble inclusion complex and 10 kg of probiotic inclusion complex and continue mixing at 15 r / min for 10 minutes to obtain an external phase mixture. Dissolve 2.1 kg of sodium alginate (2% aqueous solution with a viscosity of 30 mPa·s at 25°C) in 10 L of deionized water to obtain a sodium alginate solution. Add the external phase mixture and 70 L of deionized water and shear at 2000 rpm for 30 minutes to form an external phase suspension with a viscosity of 2500 mPa·s.

[0042] S4. Under the conditions of inlet air temperature of 58℃ and atomization pressure of 0.1MPa, the external phase suspension is sprayed onto the surface of the fluidized internal phase particles at a constant rate of 5mL / min. After spraying, the particles are dried for 10min in a fluidized state at 58℃ to obtain coated internal phase particles. The coated internal phase particles are transferred to a V-type mixer, 5kg of anhydrous erythritol and 0.8kg of magnesium stearate are added, and the mixture is mixed at a speed of 15r / min for 10min to obtain mixed particles. Then, a rotary tablet press is used to compress the mixed particles into tablets. 10 kg of hydroxypropyl methylcellulose E5 was dissolved in 65 L of 80% ethanol solution to obtain a coating solution. The coating solution was then evenly sprayed onto the surface of the uncoated tablets at a spraying speed of 5 mL / min under the conditions of an inlet air temperature of 60℃, an outlet air temperature of 36℃, and a rotation speed of 10 rpm. After spraying, the tablets were cured and dried at the spraying temperature for 20 min. The tablets were then screened through a 2.5 mesh sieve to obtain a lozenge that refreshes the mind and cleanses the mouth. Example

[0043] like Figure 1 As shown, a method for preparing a lozenge for refreshing the mind and clearing the mouth includes the following steps:

[0044] S1. Take 1.43 kg of caffeine, of which 0.43 kg of caffeine is subjected to air jet milling under a milling pressure of 0.7 MPa and a feeding rate of 10 kg / h, and milled to a particle size of ≤5 μm, which is used as immediate-release caffeine. The remaining 1.0 kg of caffeine retains its original particle size and is used as slow-release caffeine. 0.43 kg of immediate-release caffeine, 1.0 kg of sustained-release caffeine, 1.6 kg of theanine, 6.8 kg of sodium carboxymethyl cellulose (2% aqueous solution with a viscosity of 5 mPa·s at 25℃), 1.8 kg of crospovidone, 0.45 kg of poloxamer 188, 0.27 kg of micronized silica powder, 0.45 kg of povidone K30 and 33 kg of anhydrous erythritol were mixed and 33 L of 30% ethanol solution was added. Spray drying was carried out under the conditions of inlet air temperature of 115℃, outlet air temperature of 55℃ and atomization pressure of 0.3 MPa. Then, the mixture was dried in a fluidized bed at 60℃ and air velocity of 1.5 m / s for 8 min to obtain internal phase particles.

[0045] S2. Mix 1.8 kg of eucalyptol, 0.9 kg of limonene, and 5.4 kg of fermented ginsenosides, add 14.6 kg of HP-β-cyclodextrin with a degree of substitution of 0.7, dissolve in 72 L of deionized water, and stir in a water bath at 48 °C and 450 r / min for 20 min, while simultaneously subjecting to ultrasonic treatment at 300 W for 15 min. Then, homogenize under high pressure at 27 MPa for 8 min, freeze-dry at -40 °C for 24 h, and pass through an 80-mesh sieve to obtain the lipid-soluble component inclusion complex. Mix 1.8 kg of freeze-dried Lactobacillus rhamnosus (Sichuan Provincial Microbial Resource Platform Strain Preservation Center, strain number: SICC1.1515), 4.5 kg of maltodextrin, 2.7 kg of gum arabic, and 0.27 kg of vitamin E, dissolve in 45 L of deionized water, and spray dry and granulate under conditions of inlet air temperature of 75 °C, outlet air temperature of 42 °C, and atomization pressure of 0.2 MPa to obtain the probiotic inclusion complex.

[0046] S3. Add 12.6 kg of hydroxypropyl methylcellulose K4M, 2.7 kg of hydroxypropyl cellulose with a degree of substitution of 7%, 0.45 kg of polyethylene glycol 6000, 0.09 kg of citric acid, and 0.63 kg of micronized silica powder to a three-dimensional motion mixer and mix at 15 r / min for 10 min. Then add 22.7 kg of lipid-soluble inclusion complex and 9 kg of probiotic inclusion complex and continue mixing at 15 r / min for 10 min to obtain an external phase mixture. Dissolve 2.0 kg of sodium alginate (2% aqueous solution with a viscosity of 80 mPa·s at 25°C) in 10 L of deionized water to obtain a sodium alginate solution. Add the external phase mixture and 70 L of deionized water and shear at 2000 rpm for 30 min to form an external phase suspension with a viscosity of 2000 mPa·s.

[0047] S4. Under the conditions of inlet air temperature of 55℃ and atomization pressure of 0.08MPa, the external phase suspension is sprayed onto the surface of the fluidized internal phase particles at a constant rate of 4mL / min. After spraying, the particles are dried for 8 minutes in a fluidized state at 55℃ to obtain coated internal phase particles. The coated internal phase particles are transferred to a V-type mixer, and 4.5kg of anhydrous erythritol and 0.7kg of magnesium stearate are added. The mixture is stirred at a speed of 15r / min for 10 minutes to obtain mixed particles. Then, a rotary tablet press is used to compress the mixed particles into tablets. 9 kg of hydroxypropyl methylcellulose E5 was dissolved in 52 L of 80% ethanol solution to obtain a coating solution. The coating solution was then sprayed evenly onto the surface of the uncoated tablets at a spraying speed of 4.5 mL / min under the conditions of an inlet air temperature of 58℃, an outlet air temperature of 33℃, and a rotation speed of 8 rpm. After spraying, the tablets were cured and dried at the spraying temperature for 15 min. The tablets were then screened through a 2-mesh sieve to obtain a refreshing and invigorating lozenge. Example

[0048] like Figure 1 As shown, a method for preparing a lozenge for refreshing the mind and clearing the mouth includes the following steps:

[0049] S1. Take 1.77 kg of caffeine, of which 0.53 kg of caffeine is subjected to air jet milling under a milling pressure of 0.9 MPa and a feeding rate of 15 kg / h until the particle size is ≤5 μm, which is used as immediate-release caffeine. The remaining 1.24 kg of caffeine retains its original particle size and is used as slow-release caffeine. 0.53 kg of immediate-release caffeine, 1.24 kg of sustained-release caffeine, 2.0 kg of theanine, 8.2 kg of sodium carboxymethyl cellulose (2% aqueous solution with a viscosity of 10 mPa·s at 25℃), 2.2 kg of crospovidone, 0.55 kg of poloxamer 188, 0.33 kg of micronized silica, 0.55 kg of povidone K30 and 37 kg of anhydrous erythritol were mixed and 38 L of 30% ethanol solution was added. Spray drying was carried out under the conditions of inlet air temperature of 125℃, outlet air temperature of 65℃ and atomization pressure of 0.5 MPa. Then, the mixture was dried in a fluidized bed at 60℃ and air velocity of 2.0 m / s for 12 min to obtain internal phase particles.

[0050] S2. Mix 2.2 kg of eucalyptol, 1.1 kg of limonene, and 6.6 kg of fermented ginsenosides, add 17.8 kg of HP-β-cyclodextrin with a degree of substitution of 0.8, dissolve in 88 L of deionized water, stir in a water bath at 52 °C and 550 r / min for 30 min, and simultaneously apply ultrasonic treatment at 300 W for 15 min. Then homogenize under high pressure at 33 MPa for 12 min, freeze dry at -40 °C for 30 h, and pass through an 80 mesh sieve to obtain the lipid-soluble component inclusion complex. Mix 2.2 kg of freeze-dried Lactobacillus rhamnosus (Sichuan Provincial Microbial Resource Platform Strain Preservation Center, strain number: SICC1.1515), 5.5 kg of maltodextrin, 3.3 kg of gum arabic, and 0.33 kg of vitamin E, dissolve in 55 L of deionized water, and spray dry and granulate under the conditions of inlet air temperature of 85 °C, outlet air temperature of 48 °C, and atomization pressure of 0.4 MPa to obtain the probiotic inclusion complex.

[0051] S3. Add 15.4 kg of hydroxypropyl methylcellulose K4M, 3.3 kg of hydroxypropyl cellulose with a degree of substitution of 12%, 0.55 kg of polyethylene glycol 6000, 0.11 kg of citric acid, and 0.77 kg of micronized silica powder to a three-dimensional motion mixer and mix at 15 r / min for 10 min. Then add 27.7 kg of lipid-soluble inclusion complex and 11 kg of probiotic inclusion complex and continue mixing at 15 r / min for 10 min to obtain an external phase mixture. Dissolve 2.0-2.3 kg of sodium alginate (2% aqueous solution with a viscosity of 50 mPa·s at 25℃) in 10 L of deionized water to obtain a sodium alginate solution. Add the external phase mixture and 70 L of deionized water and shear at 2200 rpm for 35 min to form an external phase suspension with a viscosity of 3000 mPa·s.

[0052] S4. Under the conditions of inlet air temperature of 60℃ and atomization pressure of 0.12MPa, the external phase suspension is sprayed onto the surface of the fluidized internal phase particles at a constant rate of 6mL / min. After spraying, the particles are dried for 12min in a fluidized state at 60℃ to obtain coated internal phase particles. The coated internal phase particles are transferred to a V-type mixer, and 5.5kg of anhydrous erythritol and 0.9kg of magnesium stearate are added. The mixture is stirred at a speed of 15r / min for 10min to obtain mixed particles. Then, a rotary tablet press is used to compress the mixed particles into tablets. 11 kg of hydroxypropyl methylcellulose E5 was dissolved in 78 L of 80% ethanol solution to obtain a coating solution. The coating solution was then sprayed evenly onto the surface of the uncoated tablets at a spraying speed of 5.5 mL / min under the conditions of an inlet air temperature of 62℃, an outlet air temperature of 37℃, and a rotation speed of 12 rpm. After spraying, the tablets were cured and dried at the spraying temperature for 25 min. The tablets were then screened through a 3-mesh sieve to obtain a refreshing and invigorating lozenge.

[0053] Comparative Example 1

[0054] A method for preparing a lozenge that refreshes the mind and cleanses the mouth differs from Example 1 in that it does not contain instant-release caffeine; all caffeine is in its original particle size and is not micronized. The remaining steps and parameters are the same.

[0055] Comparative Example 2

[0056] A method for preparing a lozenge that refreshes the mind and cleanses the mouth differs from Example 1 in that the external phase does not contain low-substituted hydroxypropyl cellulose, but only hydroxypropyl methylcellulose K4M is used; the remaining steps and parameters are the same.

[0057] Comparative Example 3

[0058] A method for preparing a lozenge that refreshes the mind and cleanses the mouth differs from that in Example 1 in that the fat-soluble inclusion complex is not encapsulated with HP-β-cyclodextrin, but rather directly with eucalyptol, limonene, and fermented ginsenosides. The remaining steps and parameters are the same.

[0059] Comparative Example 4

[0060] A method for preparing a lozenge that refreshes the mind and cleanses the mouth differs from Example 1 in that the internal phase does not contain cross-linked polyvinyl ketone, but only low-viscosity sodium carboxymethyl cellulose; the remaining steps and parameters are the same.

[0061] Performance testing:

[0062] In vitro dissolution test: The refreshing and invigorating lozenges prepared in Examples 1-3 and Comparative Examples 1-4 were placed directly into the dissolution vessel of the dissolution apparatus. Simulating saliva, 6.80 g of potassium dihydrogen phosphate and 1.79 g of disodium hydrogen phosphate were dissolved in 1000 mL of purified water. After filtration through a 0.22 μm filter to remove impurities, dissolved air was removed by ultrasonic degassing to prepare a pH 6.8 phosphate buffer medium. The temperature was maintained at 37℃ and the rotation speed at 50 r / min. Samples were taken at the following time points: caffeine detection at 0.5 min, 1 min, 2 min, 5 min, 10 min, 15 min, 20 min, 25 min, and 30 min. At each time point, a 5 mL sample was taken from halfway down the liquid surface, and an equal volume of fresh buffer medium was added simultaneously. After filtration through a 0.45 μm filter membrane, the sample was analyzed by HPLC, and the cumulative dissolution rate was calculated using the formula: Cumulative dissolution rate (%) = (Cumulative dissolution amount of caffeine tablets / Initial total amount of caffeine tablets) × 100%. Test data are as follows... Figure 2 As shown.

[0063] In vitro release test of refreshing ingredients: Take the refreshing and invigorating oral lozenges prepared in Examples 1-3 and Comparative Examples 1-4, add 500 mL of pH 6.8 phosphate buffer prepared for the dissolution test, and place in a 37℃ constant temperature water bath. Simulate saliva flow with magnetic stirring at 50 r / min. Samples were taken at 0.5 min, 1 min, 2 min, 5 min, 10 min, 15 min, 20 min, 25 min, and 30 min, with 5 mL of sample taken at each time point. An equal amount of medium was added simultaneously. After filtration through a 0.45 μm filter membrane, the samples were extracted with ether and detected by GC-MS. The cumulative release rate of eucalyptol and limonene was calculated by the characteristic peak area. The calculation formula is: Cumulative release rate (%) = (Cumulative release amount of eucalyptol and limonene from the lozenges / Initial total amount of eucalyptol and limonene from the lozenges) × 100%.

[0064] Stability Test: The refreshing and invigorating oral remedies prepared in Examples 1-3 and Comparative Examples 1-4 were divided into an initial group and an accelerated group. The initial group was tested immediately. The accelerated group was packaged in aluminum-plastic blister packs to simulate commercially available packaging and placed in an accelerated testing chamber at a set temperature of 40°C and relative humidity of 75% for 3 months. During this period, the appearance was observed weekly for signs of deliquescence, discoloration, and cracking. After 3 months, the retention rates of key components in both the accelerated and initial groups were tested simultaneously.

[0065] Caffeine retention rate: Take 3 tablets each from the initial group and the accelerated group, grind them into powder, weigh 0.5g, add 50mL of methanol, and extract ultrasonically for 30min. After filtration, take the filtrate for HPLC analysis and calculate the content. Retention rate = (average content of accelerated group / average content of initial group) × 100%; Lactobacillus rhamnosus viable bacteria retention rate: Take 3 tablets each from the initial group and the accelerated group, grind them into powder, weigh 1g, add 9mL of sterile physiological saline, and serially dilute to 10⁻ 6 ~10⁻ 8 Take 100 μL of the diluted solution and spread it on MRS agar medium. Incubate anaerobically at 37℃ for 48 h. Count the number of colonies. Viable cell retention rate = (average viable cell count in accelerated group / average viable cell count in initial group) × 100%. Eucalyptol retention rate: Take 3 tablets each from the initial group and accelerated group, treat them in the same way as caffeine, and use GC detection to calculate the content and retention rate.

[0066] Table 1. Performance test results of the invigorating and mouth-freshening lozenges prepared in Examples 1-3 and Comparative Examples 1-4

[0067]

[0068] From Table 1 and Figure 2It can be seen that the cumulative dissolution rate of caffeine and the cumulative release rate of eucalyptol and limonene of the lozenges in Examples 1-3 are higher than those in Comparative Examples 1-4, and the stability of the lozenges within three months is higher than that in Comparative Examples 1-4. This indicates that the lozenges prepared in Examples 1-3 have better rapid onset of action, long-term controlled release effect and component stability than those in Comparative Examples 1-4.

[0069] Comparative Example 1, lacking micronization of some caffeine and retaining only caffeine of the original particle size, resulted in a loss of immediate caffeine release performance. Micronization increases the specific surface area, allowing for rapid dissolution upon contact with saliva. Combined with the rapidly disintegrating internal phase framework, this enables early, rapid release, providing a foundation for immediate energization. Without this immediate-release caffeine design, even with normal internal phase framework disintegration, the dissolution rate of large-particle caffeine is far lower than that of small-particle caffeine, leading to insufficient early release efficiency and failing to achieve a rapid energizing effect. However, the controlled-release structure of the external phase and the inclusion design of the refreshing components remained unaffected. Therefore, the long-lasting release and the basic release of the refreshing components did not change significantly. This further illustrates that micronization of immediate-release caffeine is key to ensuring an early energizing effect, and its function is specific, not interfering with the effects of other systems.

[0070] Comparative Example 2, lacking the addition of L-HPC to the external phase, disrupted the balance between the gel skeleton and the pore-forming agent in synergistic controlled release. As a highly expansive component, L-HPC can construct microporous channels within the hydroxypropyl methylcellulose gel skeleton, providing a pathway for the sustained release of caffeine and refreshing components, while also regulating the humidity of the internal microenvironment, creating stable survival conditions for probiotics. Without L-HPC, the external phase gel skeleton becomes dense due to the absence of pores, hindering the release of subsequent components and interrupting the long-lasting effect. Furthermore, the high internal humidity disrupts the anaerobic drying environment for probiotics, reducing their viable bacterial stability. This result confirms the dual role of L-HPC in external phase controlled release and probiotic protection; its synergy with the gel skeleton is crucial for ensuring the multifunctionality of the external phase.

[0071] Comparative Example 3 did not prepare inclusion complexes for fat-soluble components such as eucalyptol and limonene, which were directly added to the external phase, disrupting the release balance and stability. The hydrophobic cavities of the inclusion complexes encapsulate the fat-soluble components, slowing their dissolution rate upon contact with saliva, preventing an excessively strong cooling sensation due to early release, while ensuring sustained release for long-lasting freshness. Furthermore, they isolate the components from oxygen and humidity, preventing oxidation and volatilization during storage, thus ensuring stability. Without inclusion treatment, the fat-soluble components, lacking a protective structure, are released rapidly upon contact with saliva, leading to an excessively strong early effect followed by a supply shortage. They are also easily oxidized during storage, resulting in a significant decrease in stability. This demonstrates that the inclusion process is crucial for balancing the release rhythm and stability of fat-soluble components, directly affecting the sustainability and reliability of the refreshing effect.

[0072] Comparative Example 4 lacked the addition of PVPP to the internal phase, resulting in weakened disintegration capacity. As a highly efficient disintegrant, PVPP rapidly absorbs water and swells upon contact with saliva, generating strong disintegration force and quickly disrupting the internal phase framework. This allows the micronized immediate-release caffeine to disperse and dissolve promptly, providing a structural basis for early rapid release. Without PVPP, the disintegration capacity of the low-viscosity binder alone is insufficient to quickly disperse the internal phase particles. Consequently, the micronized immediate-release caffeine is encapsulated by the framework, making it difficult to contact saliva, thus reducing early release efficiency and delaying the rapid energizing effect. However, the controlled-release structure of the external phase and the inclusion design of the refreshing components remained unaffected. This further demonstrates that PVPP is crucial for ensuring rapid disintegration of the internal phase and the release of the immediate-release components, directly determining the efficiency of achieving the early energizing effect.

[0073] Comparative Examples 1-4, due to the lack of micronization treatment in the inclusion process of fast-release caffeine, L-HPC, PVPP, and fat-soluble components, resulted in a sharp drop in early dissolution efficiency of caffeine, stagnation of long-term release, slowdown in the disintegration rate of the internal phase skeleton, and reduced component stability. These combined to show significant shortcomings in rapid onset of action, long-term controlled release effect, component stability, and structural disintegration efficiency.

[0074] The above results demonstrate and describe the basic principles and main features of this application, as well as its advantages.

[0075] The embodiments of the present invention have been described above with reference to the accompanying drawings. However, the present invention is not limited to the specific embodiments described above. The specific embodiments described above are merely illustrative and not restrictive. Those skilled in the art can make many other forms under the guidance of the present invention without departing from the spirit and scope of the claims. All of these forms are within the protection scope of the present invention.

Claims

1. A lozenge for refreshing the mind and clearing the mouth, characterized in that, The lozenge comprises a plain tablet and a shell; the plain tablet comprises inner phase particles, an inner phase particle coating layer, and excipients; the shell comprises a film-forming agent; the inner phase particles comprise immediate-release caffeine, sustained-release caffeine, theanine, and excipients; the immediate-release caffeine is produced by air-jet milling of caffeine under a milling pressure of 0.7-0.9 MPa and a feed rate of 10-15 kg / h, with a particle size ≤5 μm; the sustained-release caffeine has a particle size of 80-120 μm; the inner phase particle coating layer comprises a fat-soluble inclusion complex, a probiotic inclusion complex, and additives; the excipients comprise anhydrous erythritol and magnesium stearate; the excipients comprise carboxymethyl cellulose. The ingredients include sodium, crospovidone, poloxamer 188, micronized silica gel, povidone, and anhydrous erythritol; the lipid-soluble inclusion complex includes eucalyptol, limonene, fermented ginsenosides, and HP-β-cyclodextrin; the probiotic inclusion complex includes *Lactobacillus rhamnosus* freeze-dried bacterial powder, maltodextrin, gum arabic, and vitamin E, which are mixed with *Lactobacillus rhamnosus* freeze-dried bacterial powder, maltodextrin, gum arabic, vitamin E, and second deionized water, and then spray-dried to obtain the probiotic inclusion complex; the additives include hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyethylene glycol, citric acid, micronized silica gel, and sodium alginate; the degree of substitution of hydroxypropyl cellulose in the additives is 7%-12%.

2. The lozenge for refreshing the mind and clearing the mouth according to claim 1, characterized in that, The mass ratio of the uncoated tablet to the outer shell is (101.45-118.26):(9-11); the mass ratio of the inner phase particles, the inner phase particle coating layer, and the excipients in the uncoated tablet is (45.8-52.6):(50.45-59.26):(5.2-6.4); the mass ratio of immediate-release caffeine, sustained-release caffeine, theanine, and excipients in the inner phase particles is (0.43-0.53):(1.0-1.24):(1.6-2.0):(42.77-48.83). The mass ratio of the lipid-soluble inclusion complex, probiotic inclusion complex, and additives in the inner phase particle coating layer is (22.7-27.7):(9-11):(18.54-20.46). The mass ratio of sodium carboxymethyl cellulose, crospovidone, poloxamer 188, micronized silica gel, povidone, and anhydrous erythritol in the excipients is (6.8-8.2):(1.8-2.2):(0.45-0.55):(0.27-0.33):(0.45-0.55):(33-37). The mass ratio of eucalyptol, limonene, fermented ginsenosides, and HP-β-cyclodextrin in the inclusion complex is (1.8-2.2):(0.9-1.1):(5.4-6.6):(14.6-17.8); the mass ratio of *Lactobacillus rhamnosus* freeze-dried bacterial powder, maltodextrin, gum arabic, and vitamin E in the probiotic inclusion complex is (1.8-2.2):(4.5-5.5):(2.7-3.3):(0.27-0.33); the additives include hydroxypropyl methylcellulose, hydroxypropyl cellulose, and polyethylene glycol. The mass ratio of glycol, citric acid, micronized silica gel, and sodium alginate is (12.6-15.4):(2.7-3.3):(0.45-0.55):(0.09-0.11):(0.63-0.77):(2.0-2.3); the mass ratio of anhydrous erythritol and magnesium stearate in the additives is (4.5-5.5):(0.7-0.9); the film-forming agent is hydroxypropyl methylcellulose, and the viscosity of a 2% aqueous solution of hydroxypropyl methylcellulose at 25°C is 3.6-5.4 mPa·s.

3. The lozenge for refreshing the mind and clearing the mouth according to claim 2, characterized in that, The viscosity of a 2% aqueous solution of sodium carboxymethyl cellulose in the excipients is 5-20 mPa·s at 25°C; the K value of povidone in the excipients is 27-32; the average degree of substitution of HP-β-cyclodextrin in the fat-soluble inclusion complex is 0.6-0.8; the viscosity of a 2% aqueous solution of hydroxypropyl methylcellulose in the additives is 3500-4500 mPa·s at 25°C; the molecular weight of polyethylene glycol in the additives is 5000-7000; and the viscosity of a 2% aqueous solution of sodium alginate in the additives is 30-80 mPa·s at 25°C.

4. A method for preparing a lozenge for refreshing the mind and clearing the mouth as described in any one of claims 1-3, characterized in that, Includes the following steps: S1. Sodium carboxymethyl cellulose, crospovidone, immediate-release caffeine, sustained-release caffeine, theanine, poloxamer 188, micronized silica gel, povidone, anhydrous erythritol and ethanol solution are mixed, spray-dried and dried to obtain internal phase particles. S2. Eucalyptol, limonene, fermented ginsenosides, HP-β-cyclodextrin and first deionized water are mixed, stirred, homogenized under high pressure, freeze-dried, and sieved to obtain a fat-soluble inclusion complex; Lactobacillus rhamnosus freeze-dried powder, maltodextrin, gum arabic, vitamin E and second deionized water are mixed and spray-dried to obtain a probiotic inclusion complex. S3. Hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyethylene glycol, citric acid, and micronized silica gel are mixed, and a fat-soluble inclusion complex and a probiotic inclusion complex are added while stirring to obtain an external phase mixture; the external phase mixture, sodium alginate, and deionized water are mixed and sheared to obtain an external phase suspension; S4. Spray the external phase suspension onto the surface of the internal phase particles and dry to obtain coated internal phase particles; mix the coated internal phase particles, anhydrous erythritol and magnesium stearate, compress into tablets to obtain uncoated tablets; mix hydroxypropyl methylcellulose and ethanol solution to obtain coating solution; spray the coating solution onto the surface of the uncoated tablets, cure and dry at the spraying temperature, and sieve to obtain a lozenge for refreshing the mind and clearing the mouth.

5. The method for preparing a lozenge for refreshing the mind and clearing the mouth according to claim 4, characterized in that, In step S1, the mass-to-volume ratio of the immediate-release caffeine to the ethanol solution is (0.43-0.53) kg:(32-38) L, and the mass fraction of the ethanol solution is 30 wt.%; the spray drying parameters are: inlet air temperature 115-125℃, outlet air temperature 55-65℃, and atomization pressure 0.3-0.5 MPa; the drying step is: drying for 8-12 min at a temperature of 60℃ and a wind speed of 1.5-2.0 m / s; the particle size of the internal phase particles is 120-150 μm.

6. The method for preparing a lozenge for refreshing the mind and clearing the mouth according to claim 4, characterized in that, In step S2, the mass-to-volume ratio of eucalyptol to the first deionized water is (1.8-2.2) kg: (72-88) L; the stirring temperature is 48-52℃, the stirring speed is 450-550 r / min, and the stirring time is 20-30 min; the high-pressure homogenization pressure is 27-33 MPa, and the high-pressure homogenization time is 8-12 min; the freeze-drying temperature is -40℃, and the freeze-drying time is 24-30 h; the sieve mesh size is 80 mesh.

7. The method for preparing a lozenge for refreshing the mind and clearing the mouth according to claim 4, characterized in that, In step S2, the viable count of the Lactobacillus rhamnosus freeze-dried powder is ≥1×10¹. 0 CFU / g; the mass-to-volume ratio of the Lactobacillus rhamnosus freeze-dried bacterial powder to the second deionized water is (1.8-2.2) kg: (45-55) L; the parameters of the spray drying are: inlet air temperature 75-85℃, outlet air temperature 42-48℃, and atomization pressure 0.2-0.4 MPa.

8. The method for preparing a lozenge for refreshing the mind and clearing the mouth according to claim 4, characterized in that, In step S3, the stirring speed is 13-17 r / min, and the stirring time is 16-24 min; the mass-to-volume ratio of sodium alginate to deionized water is (2.0-2.3) kg:(70-90) L; the shearing speed is 1800-2200 rpm, and the shearing time is 25-35 min; the viscosity of the external phase suspension is 2000-3000 mPa·s.

9. The method for preparing a lozenge for refreshing the mind and clearing the mouth according to claim 4, characterized in that, In step S4, the spraying step is as follows: under the conditions of an air inlet temperature of 55-60℃ and an atomization pressure of 0.08-0.12MPa, the external phase suspension is sprayed onto the surface of the internal phase particles at a rate of 4-6mL / min; the drying temperature is 55-60℃ and the drying time is 8-12min.

10. The method for preparing a lozenge for refreshing the mind and clearing the mouth according to claim 4, characterized in that, In step S4, the mass-to-volume ratio of hydroxypropyl methylcellulose to ethanol solution is (9-11) kg: (52-78) L; the mass fraction of ethanol solution is 80 wt.%; the spraying step is as follows: spraying at a rate of 4.5-5.5 mL / min under the conditions of inlet air temperature of 58-62℃, outlet air temperature of 33-37℃, and rotation speed of 8-12 rpm; the curing and drying time is 15-25 min; and the sieve mesh size is 2-3 mesh.

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