Oral dissolving film-type propolis food composition and method for manufacturing the same

Abstract

The present invention relates to an oral dissolving film-type propolis food composition and a method for preparing the same, characterized by having excellent effects of inhibiting harmful bacteria in the oral cavity and reducing bad breath, comprising a propolis complex extracted and nano-sized with high yield, specific postbiotics, and plant-based lysozyme. Specifically, the manufacturing method of the present invention combines 10-HDA and a high-pressure cavitation process to extract high-purity propolis in high yield without chemical additives and maximize the water-dispersible stability of the formulation. Furthermore, by nano-powdering the obtained extract and encapsulating it in a porous carrier, the aggregation between particles and the blocking phenomenon of film adhesion can be fundamentally prevented. In addition, the present invention applies a plasticizer comprising a mixture of maltitol and erythritol in an optimal ratio to prevent crystallization of the formulation even under harsh conditions and secure excellent mechanical flexibility. Moreover, by combining bee-derived postbiotics and rice-derived lysozyme, which have excellent compatibility with propolis, the invention provides an excellent effect that exhibits powerful oral antibacterial and bad breath reduction synergies while maintaining film transparency without inducing allergies.

Description

Technology Field

[0001] The present invention relates to an oral dissolving film-type propolis food composition and a method for preparing the same, characterized by having excellent effects of inhibiting harmful bacteria in the oral cavity and reducing bad breath, comprising a propolis complex extracted and nano-sized with high yield, specific postbiotics, and plant-based lysozyme. Background Technology

[0003] With the recent rise in interest in oral health and immunity enhancement, propolis, possessing powerful natural antibacterial and antioxidant properties, is gaining attention as an ingredient in health functional foods. However, propolis has a critical drawback: its solubility in aqueous solvents is extremely low because it is a highly hydrophobic substance containing large amounts of the wax and resin components that naturally constitute beehives. Conventional extraction methods struggle to completely remove insoluble wax components, and there are limitations in that active ingredients immediately precipitate or aggregate upon contact with aqueous solutions or saliva, significantly reducing the transparency of the formulation and lowering its absorption rate and solubilization.

[0004] Meanwhile, oral dissolving film (ODF) formulations, which allow for rapid absorption of active ingredients through the oral mucosa, are attracting attention for their convenience of intake and high absorption rate; however, there are high technical barriers to applying propolis, which has the aforementioned limitations, to films at high concentrations. Due to the unique sticky, non-specific adhesiveness of propolis, blocking phenomena, where films stick together during storage, are prone to occur. Furthermore, if general sugar alcohol-based plasticizers (such as sorbitol) are simply applied to ensure the flexibility of the film, there is a chronic problem in which mechanical properties and long-term storage stability are significantly compromised, such as when surface adhesion increases excessively under harsh storage conditions or spontaneous crystallization (whitening) is induced, causing the film to crumble easily.

[0005] Furthermore, research is underway to mix propolis with antimicrobial enzymes such as lactic acid bacteria (probiotics) or lysozyme to maximize the effects of inhibiting harmful oral bacteria and reducing bad breath, but this approach also has clear limitations. The powerful antimicrobial substances unique to propolis can actually denature or interfere with the physiologically active substances of beneficial human bacteria, hindering the expression of biological synergy, and can also impair the transparency of the formulation due to protein clumping. In addition, commonly used egg-derived enzyme components pose a risk of causing allergies, which limits their application in safe food products.

[0006] Therefore, under these circumstances, there is an urgent need to develop advanced ingredient blending and formulation technologies that can dramatically improve the water dispersibility and transparency of propolis without chemical additives, prevent stickiness and crystallization of the film to ensure structural stability of the formulation, and safely maximize the synergy of regulating the oral microbiome and reducing bad breath without conflicting with the propolis ingredients. The problem to be solved

[0008] One aspect provides a method for manufacturing an oral dissolving film-type propolis food composition.

[0009] Specifically, one aspect provides a method for preparing an orally dissolving film-type propolis food composition, comprising: (a) a step of preparing nano-propolis powder having an average particle size in the range of 100 to 800 nm by treating a propolis extract with a nano-spray drying process; (b) a step of forming a propolis nano-composite by adsorbing or encapsulating the nano-propolis powder inside one or more carriers selected from the group consisting of porous silica and cyclodextrin; (c) a step of preparing a film-base slurry with inhibited crystallization by mixing maltitol and erythritol in a polymer solution comprising a water-soluble polymer substrate and purified water; (d) a step of introducing the propolis nano-composite of step (b), postbiotics, and lysozyme into the film-base slurry and homogenizing; and (e) a step of casting the homogenized slurry onto a substrate and drying to form a film.

[0011] Another aspect provides an orally dissolving film-type propolis food composition characterized by being manufactured by the above-described manufacturing method.

[0013] Another aspect provides a health functional food composition for oral antibacterial and bad breath removal comprising the above composition.

[0015] Another aspect provides a quasi-drug composition for preventing or improving stomatitis having oral mucosal adhesion ability comprising the above composition. means of solving the problem

[0017] One aspect provides a method for manufacturing an orally dissolving film-type propolis food composition.

[0018] Specifically, one aspect provides a method for preparing an orally dissolving film-type propolis food composition, comprising: (a) a step of preparing nano-propolis powder having an average particle size in the range of 100 to 800 nm by treating a propolis extract with a nano-spray drying process; (b) a step of forming a propolis nano-composite by adsorbing or encapsulating the nano-propolis powder inside one or more carriers selected from the group consisting of porous silica and cyclodextrin; (c) a step of preparing a film-base slurry with inhibited crystallization by mixing maltitol and erythritol in a polymer solution comprising a water-soluble polymer substrate and purified water; (d) a step of introducing the propolis nano-composite of step (b), postbiotics, and lysozyme into the film-base slurry and homogenizing; and (e) a step of casting the homogenized slurry onto a substrate and drying to form a film.

[0020] In the step of producing nano propolis powder having an average particle size in the range of 100 to 800 nm by treating the above (a) propolis extract with a nano spray drying process, the “propolis” refers to a substance made by honeybees by mixing resin collected from plants with saliva, beeswax, etc., and in the present invention, it refers to a key active ingredient that inhibits harmful bacteria in the oral cavity through powerful natural antibacterial and antioxidant effects.

[0021] While conventional propolis has the fatal disadvantage of extremely low solubility in aqueous solvents and aggregation due to insoluble wax and resin components, the present invention has technical significance in utilizing propolis extracted with high purity and high yield without chemical additives by combining chemical compatibility using 10-HDA (10-hydroxy-2-decenoic acid) with a high-pressure cavitation process.

[0022] In this specification, “propolis extract” refers to a substance obtained by isolating flavonoids, which are active ingredients, from propolis with high purity. It may include various forms such as crude extract, fraction, concentrate, liquid, dried product, or powder after the extraction process, and preferably may be in powder form, but is not particularly limited thereto.

[0023] Specifically, this may be prepared through the following steps: (a-1) preparing a preliminary mixture by mixing raw propolis with an aqueous ethanol solution in which 10-HDA (10-hydroxy-2-decenoic acid) is dissolved at a concentration of 0.1 to 2.0 weight%; (a-2) destroying the propolis resin matrix and simultaneously forming a micelle structure in which 10-HDA surrounds flavonoid particles through a high-pressure cavitation process in which the preliminary mixture is passed through a nozzle under a pressure of 800 to 1,200 bar; (a-3) allowing the extract obtained from the above process to stand at a low temperature of -15 to -5°C to separate the soluble components and the insoluble wax components; (a-4) taking the supernatant and passing it through a filter membrane of 0.2 to 1.0 μm to precisely remove fine impurities; and (a-5) freeze-drying the filtered concentrate to obtain a propolis extract powder stabilized by 10-HDA.

[0024] In this specification, “acid” refers to a natural fatty acid compound that is a key indicator component determining the quality of royal jelly, and in this invention, it can perform a unique role as a natural surfactant (solubilizer) that dissolves the rigid resin component of propolis and encapsulates the hydrophobic active ingredient (flavonoid).

[0025] In one experimental example, the characteristics of propolis extraction and dispersion stability were evaluated according to 10-HDA concentration and high-pressure cavitation pressure conditions. In the example where the 10-HDA concentration was adjusted to 1.0 wt% and a pressure of 1,000 bar was applied, the water dispersion transparency was recorded at 94.8%, confirming that the hydrophobic propolis extract was almost perfectly solubilized in an aqueous solution. This was determined to be because 10-HDA effectively encapsulated the active ingredients of propolis into the micelle structure under high pressure, thereby forming an excellent synergy that fundamentally blocked the aggregation phenomenon that occurs when mixed with an oral dissolving film slurry, which is an aqueous matrix.

[0026] On the other hand, when the 10-HDA concentration was less than 0.1 wt%, there was a lack of surfactant molecules to encapsulate hydrophobic flavonoids, resulting in immediate precipitation upon water dispersion and a decrease in transparency; when it exceeded 2.0 wt%, the excessive fatty acid component itself increased the turbidity of the extract and induced redissolution of the wax component, leading to a result that simultaneously impairs purity and transparency.

[0027] In this specification, the “high-pressure cavitation” process refers to a technique that physically breaks down the structure of a material using the rapid pressure drop and shear force generated when a fluid passes through a fine (100 to 500 μm) orifice nozzle. In this invention, the process can be performed under pressure conditions of 800 to 1,200 bar to maximize the extraction efficiency of flavonoids by destroying the resin matrix of propolis in a short time without chemical solvents or prolonged heating.

[0028] In one experimental example, it was confirmed that when the cavitation pressure was less than 800 bar, there was insufficient physical energy to break down the rigid resin structure of propolis, resulting in a significant decrease in the elution of indicator components and wax separation efficiency. Conversely, when the pressure exceeded 1,200 bar, thermal denaturation of active ingredients was induced by excessive shear friction heat, and at the same time, forced emulsification of wax components occurred, which significantly reduced the purity and water dispersion stability of the extract.

[0029] In this specification, the term “micelle structure” may refer to a spherical thermodynamically stable structure formed by the powerful physical energy of the high-pressure cavitation process, in which 10-HDA, an amphiphilic substance, encapsulates hydrophobic propolis active ingredients (flavonoids) in the center and arranges hydrophilic groups outwardly. In the present invention, the micelle structure has the key technical significance of fundamentally blocking the aggregation phenomenon characteristic of propolis during water dispersion and maintaining a perfectly solubilized state within a film-based slurry.

[0030] Furthermore, the aforementioned “phase separation” and “low-temperature standing” refer to a process of physically separating soluble flavonoid components (supernatant) and insoluble wax components (precipitate) mixed within the extract by storing the extract, which has undergone a high-pressure process, in a low-temperature environment of -15 to -5°C for a certain period of time. This corresponds to an essential purification process intended to preemptively exclude wax components that cause stickiness and turbidity in the formulation by coagulating them.

[0031] In this specification, “filtration membrane” refers to a physical filter that precisely filters out fine impurities or unsettled fine wax particles that may remain in the phase-separated supernatant. Specifically, in the present invention, a precision filtration membrane with a pore size of 0.2 to 1.0 μm is used to safely allow the 10-HDA micelle structure to pass through while selectively removing only impurities, thereby maximizing the purity and light transmittance of the extract.

[0032] The “freeze-drying” described above is a process of rapidly freezing a filtered concentrate at a sub-zero temperature and then drying it by sublimating the moisture under a vacuum. In the present invention, this process may be performed to prevent thermal denaturation of flavonoids and destruction of the 10-HDA micelle structure that may occur during high-temperature drying, and to obtain a high-purity “propolis extract powder” in a form that is easy for the subsequent nano spray drying process.

[0033] In this specification, “Oral Dissolving Film (ODF)” is a general term for a thin film formulation that dissolves rapidly in the oral cavity by saliva without water, and in the present invention, it may refer to a means for enhancing convenience of intake and for directly and rapidly absorbing the active ingredients of propolis through the oral mucosa.

[0034] In this specification, the “nano spray drying” process refers to a nano-process in which the prepared propolis extract is finely sprayed in liquid form and dried instantaneously. The nano propolis powder obtained through this process in the present invention, having an average particle size in the range of 100 to 800 nm, has the characteristic of maximizing the surface area of ​​the propolis active ingredient to increase the absorption rate in the body, while simultaneously preventing the aggregation of particles that may occur when mixing film-based slurries.

[0036] (b) In the step of forming a propolis nanocomposite by adsorbing or encapsulating the above nano propolis powder within one or more carriers selected from the group consisting of porous silica and cyclodextrin, the “porous silica” and “cyclodextrin” refer to materials having a plurality of micropores or cavities within them, and in the present invention, they serve as porous carriers that structurally stabilize the nano propolis powder by adsorbing or encapsulating it.

[0037] Specifically, by trapping propolis nanoparticles inside these carriers, a nanocomposite is formed that is homogeneously dispersed within a water-soluble polymer matrix, and the blocking phenomenon in which films stick together during long-term storage due to the non-specific stickiness characteristic of propolis can be fundamentally prevented.

[0039] (c) In the step of preparing a film base slurry with inhibited crystallization by mixing maltitol and erythritol into a polymer solution comprising a water-soluble polymer substrate and purified water, the “water-soluble polymer substrate” is a polymer material that forms a structural framework (matrix) of a film that can be dissolved in the oral cavity, and specifically, hydroxypropylmethylcellulose (HPMC) and pullulan, etc. may be used, but are not particularly limited thereto. At this time, in this specification, “water-soluble polymer matrix” may refer to the overall framework structure of a film formed by drying and molding the water-soluble polymer substrate, and may be understood to refer to substantially the same object as the water-soluble polymer substrate in the context.

[0040] In this specification, “maltitol” and “erythritol” are sugar alcohol compounds, and in the present invention, they can serve as plasticizers that impart flexibility to the water-soluble polymer substrate.

[0041] The manufacturing method according to the present invention may be characterized by using maltitol and erythritol not alone, but mixed in a weight ratio of 1:0.2 to 1:1, specifically 1:0.5.

[0042] In one experimental example, it was confirmed that in an example where the weight ratio of maltitol to erythritol was 1:0.5, the degree of crystallinity was lowest at 1.5%, forming a matrix close to an amorphous state and maintaining excellent mechanical flexibility.

[0043] Meanwhile, it was confirmed that when highly hygroscopic sorbitol is applied, surface adhesion increases rapidly, causing a blocking phenomenon, and when erythritol exceeds the upper limit, the degree of crystallization increases rapidly due to spontaneous crystal nucleation, and the tensile strength of the film is significantly reduced, resulting in brittleness that causes crumbling. From this, it was confirmed that the optimal ratio combination of maltitol and erythritol of the present invention is a unique composition that provides triple synergy of preventing crystallization of the formulation, controlling adhesion, and ensuring flexibility even under harsh storage conditions.

[0044] In this specification, “film base slurry” refers to a viscous mixture in which the above-mentioned water-soluble polymer substrate, purified water, and a mixed plasticizer of maltitol and erythritol are dissolved, and can function as a medium in which active ingredients can be homogeneously mixed immediately before formulation.

[0046] (d) In the step of adding the propolis nanocomposite, postbiotics, and lysozyme of step (b) to the film base slurry and homogenizing, “postbiotics” refers to powder or culture dried material of probiotics such as lactic acid bacteria that have been treated to be inactivated, and can be applied in the present invention to suppress harmful bacteria in the oral cavity and fundamentally reduce bad breath.

[0047] Specifically, the postbiotic of the present invention is Lactobacillus kuncei ( L. kunkeei It may be a postbiotic derived from ) and may be included in an amount of 0.5 to 5 parts by weight, more specifically 2.5 parts by weight, per 100 parts by weight of the slurry.

[0048] In one experimental example, in an example where Lactobacillus kunkei, a bee-derived fructose-affinity lactic acid bacterium, was applied, a general human-derived oral lactic acid bacterium ( L. reuteriIt was confirmed that the antibacterial activity against harmful oral bacteria improved by more than 22% compared to when applied. This was determined to be because bee-derived lactic acid bacteria, which have adapted to the high concentration of phenolic compounds in propolis, formed a synergy that selectively attacked the cell membranes of harmful bacteria while maintaining high chemical compatibility with the propolis components without denaturation or interference.

[0049] On the other hand, if the postbiotic content is less than 0.5 parts by weight, the concentration of active ingredients derived from lactic acid bacteria, such as bacteriocins, may not reach the minimum threshold required to inhibit the metabolism of harmful bacteria, resulting in insufficient expression of significant antibacterial synergy with propolis ingredients. Additionally, if the postbiotic content exceeds 5 parts by weight, excessive dead cell powder may cause uneven aggregation within the film matrix and lead to a 'trapping phenomenon' that physically traps propolis nanoparticles during the drying process, which may impede the elution and release efficiency of active ingredients from the oral mucosa.

[0050] In this specification, “Lysozyme” refers to an antimicrobial enzyme that hydrolyzes peptidoglycan bonds in bacterial cell walls to form microcracks. In the present invention, to maximize pre-treatment synergy that helps propolis nanoparticles easily penetrate into harmful bacteria, it may be included in an amount of 0.2 to 2 parts by weight, more specifically 1.0 part by weight, per 100 parts by weight of slurry.

[0051] In addition, the rice-derived lysozyme according to one embodiment of the present invention is characterized by being able to maintain excellent transparency within an acidic film formulation based on high hydrophilicity and thermodynamic stability, while fundamentally blocking the allergy-inducing risk of conventional egg-derived enzymes.

[0052] In one experimental example, it was confirmed that when rice-derived lysozyme is included at 1.0 part by weight per 100 parts by weight of slurry, a 'pretreatment synergy' is maximized by hydrolyzing the peptidoglycan bonds of the bacterial cell wall to form microcracks, thereby helping the nanoflavonoid components of propolis to easily penetrate into the cell.

[0053] On the other hand, it was confirmed that when the lysozyme content is less than 0.2 parts by weight, the absolute concentration of the enzyme and the probability of substrate contact to physically weaken the bacterial cell wall fall below the critical threshold, and conversely, when the lysozyme content exceeds 2 parts by weight, the transparency of the formulation decreases rapidly due to excessive aggregation of enzyme proteins, and the antibacterial synergy decreases due to the loss of substrate binding activity caused by the denaturation of the enzyme's three-dimensional structure due to protein aggregation.

[0054] In this specification, “homogenization” refers to a process of evenly mixing the introduced propolis nanocomposite, postbiotics, and lysozyme within the slurry without bias, and is preferably performed at a rotational speed of 3,000 to 5,000 rpm. Additionally, a vacuum degassing process may be further included for 30 to 60 minutes under a vacuum of 0.5 to 1.0 atm to remove incorporated bubbles and improve the structural density and appearance quality of the film.

[0056] (e) In the step of forming a film by casting the homogenized slurry onto a substrate and drying, the mixed slurry undergoes a casting process to apply the mixture to a certain thickness on a certain substrate, such as a PET release film, and then undergoes a drying process to evaporate the applied moisture to obtain a final thin film-type composition.

[0057] The above description refers to a release support that supports the lower part so that a slurry can be applied and formed into a film of a certain thickness. For example, it may be a polymer film such as PET (Polyethylene Terephthalate), PE (Polyethylene), PP (Polypropylene), or PC (Polycarbonate), a Teflon sheet, or a release paper with a release treatment on the surface, but it is not particularly limited to this as long as it is a material that does not deform at the drying temperature of the film and has no chemical reactivity with the slurry.

[0058] In particular, the drying process of the present invention may be characterized by being performed for 10 to 30 minutes at a temperature range of 35 to 50°C, and by being performed as a variable-temperature drying process in which the temperature is gradually increased to prevent destruction of the biological activity of lysozyme and postbiotics contained in the slurry.

[0059] Specifically, the above variable temperature drying process can be performed by first drying at a temperature of 35°C for 10 minutes inside a drying oven, and then raising the temperature to 45°C and second drying for 20 minutes.

[0060] This stepwise variable temperature drying method is intended to prevent surface hardening, which prevents the release of internal moisture, by rapidly hardening the film surface when high temperatures are applied from the beginning. By stabilizing the structure by slowly evaporating surface moisture of the formulation at an initial relatively low temperature (35℃) and then raising the temperature to a slightly higher temperature (45℃) within a safe range to effectively remove even the remaining internal moisture, the final moisture content can be precisely controlled to an optimal range of 5 to 7% without destroying biological activity.

[0061] The “film” produced by the above manufacturing method has a structure in which propolis nanocomposites and functional enzymes are homogeneously dispersed within a water-soluble polymer matrix, and can be characterized by maintaining excellent mechanical properties, appearance transparency, and long-term storage stability even under harsh storage conditions.

[0062] Specifically, according to one embodiment, the film may be precisely controlled to have a final moisture content of 5 to 7%, preferably 6%, by casting a film base slurry to a thickness of 200 μm and then undergoing a variable temperature drying process, which provides optimal structural density that allows the film to disintegrate quickly by saliva while ensuring flexibility so that the film does not crumble.

[0064] Another aspect provides an orally dissolving film-type propolis food composition characterized by being manufactured by the above-described manufacturing method. The same details as those described above regarding the manufacturing method of the orally dissolving film-type propolis food composition apply equally to the said composition.

[0065] In this specification, “food” may encompass compositions in a form suitable for daily consumption based on naturally derived substances that are not harmful to the human body and plasticizers, polymers, etc., whose safety has been proven. Food in the ordinary sense may include meat, sausage, bread, chocolate, candies, snacks, confectionery, pizza, ramen, other noodles, chewing gum, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages, and vitamin complexes.

[0066] Specifically, the food according to the present invention may refer to a health-oriented food consumed to achieve the purpose of inhibiting harmful bacteria in the oral cavity and reducing bad breath. While it is most preferable for the composition to be provided in the form of an oral dissolving film (ODF) in the form of a thin film so that the active ingredient can be rapidly and directly absorbed through the oral mucosa, it may also be flexibly modified and manufactured into various formulations such as candies, jellies, gums, chewable tablets that can increase the retention time in the oral cavity, oral sprays capable of rapid spraying, gargle-type liquid beverages, or concentrates, depending on the intention or application purpose of those skilled in the art.

[0067] In addition, the food composition of the present invention may further include various food additives commonly accepted in the art to improve the physical stability, moldability, and palatability of the formulation, in addition to the active ingredients (propolis nanocomplex, postbiotics, lysozyme) and base ingredients (water-soluble polymer, maltitol, erythritol) described above.

[0068] Specifically, it may further include one or more selected from the group comprising: excipients such as binders, disintegrants, and diluents that maintain the shape of the formulation and form volume; thickeners that appropriately adjust the viscosity of the slurry to improve the workability of the casting process; acidity regulators that stabilize the pH of the formulation; antioxidants and preservatives to improve shelf life; and natural or synthetic flavors, sweeteners, and coloring agents to enhance palatability for livestock or humans. However, these additives must be appropriately selected within a range that does not impair the water dispersion stability of the propolis micelle structure or the antibacterial synergistic effect, which is a core feature of the present invention.

[0069] In addition, the above composition may include a structure in which a nanocomposite, in which nano propolis is encapsulated on a porous carrier, is homogeneously dispersed within a water-soluble polymer matrix, and may be characterized in that the blocking phenomenon caused by the non-specific adhesiveness characteristic of propolis is suppressed by the nanocomposite.

[0070] Specifically, in the present invention, the propolis is finely powdered to a nano size, and then an advanced formulation technology is applied to physically encapsulate (enclose or adsorb) it within a carrier such as porous silica or cyclodextrin having a plurality of micropores. This fundamentally prevents the hydrophobic propolis component, which causes stickiness, from being directly exposed to the film surface, while simultaneously allowing it to be uniformly and stably dispersed within a water-soluble polymer matrix. Through this, the stickiness of the film surface is perfectly controlled even under harsh long-term storage and high-temperature, high-humidity distribution environments, thereby preventing physical damage to the formulation. Furthermore, this invention has technical significance in providing excellent structural stability and handling convenience, allowing the consumer to easily separate the film in its original form without tearing when consuming it.

[0072] Another aspect is to provide a health functional food composition for oral antibacterial and bad breath removal comprising the above composition. The same details as described above apply equally to the health functional food composition.

[0073] In this specification, “oral antimicrobial” may refer to the action of inhibiting or killing the growth and proliferation of pathogenic harmful bacteria that inhabit the oral cavity and cause various oral diseases such as dental caries and periodontitis, and “bad breath removal” may refer to the action of reducing or inhibiting odor-causing substances, such as volatile sulfur compounds (VSC), which are generated by the decomposition of proteins during the metabolic process of microorganisms in the oral cavity.

[0074] In one experimental example, the film according to one embodiment is a major harmful bacterium in the oral cavity, Streptococcus mutans ( S. mutans ) and Porphyromonas gingivalis ( P. gingivalis It was confirmed that it recorded an excellent antibacterial activity of 96.2% against ), and that it dramatically reduced the concentrations of hydrogen sulfide (H2S) and methyl mercaptan (CH3SH), which are the main causative substances of bad breath.

[0075] In this specification, “health functional food” refers to a food manufactured and processed using raw materials or ingredients having functional properties useful to the human body, and may collectively refer to compositions that can be consumed daily for the purposes of regulating biological functions, preventing diseases, and promoting health. The formulation of the health functional food is not particularly limited, but an orally dissolving film (ODF) form that maximizes absorption rate through the oral mucosa and convenience of consumption may be most preferable.

[0077] Another aspect is to provide a quasi-drug composition for preventing or improving stomatitis having oral mucosal adhesion ability comprising the above composition. The same as described above applies equally to the above quasi-drug composition.

[0078] The above “oral mucosal adhesion ability (Bio-adhesion)” may refer to a physical characteristic in which, when the film formulation according to the present invention comes into contact with saliva (moisture) in the oral cavity, the water-soluble polymer matrix forming the framework of the formulation immediately hydrates and gels, thereby strongly adhering to the surface of the oral mucosa.

[0079] As described above, the composition according to the present invention is individually packaged and stored in a dry state, so that the non-specific adhesiveness characteristic of propolis is thoroughly suppressed through the action of the nano-composite inclusion structure and the optimal plasticizer, thereby completely preventing the blocking phenomenon where the films stick together and tear. At the moment when the consumer ingests it into the mouth for actual use and reacts with moisture, the inherent viscosity of the water-soluble polymer matrix is ​​expressed, thereby exhibiting a strong mucosal adhesion ability that adheres to the mucosal area.

[0080] In this specification, “stomatitis” is a general term for all inflammatory diseases that occur on the oral mucosa, such as the lips, inside of the cheeks, gums around the teeth, and tongue, caused by various factors including bacterial and viral infections, weakened immunity, and stress. In this invention, propolis nanocomposites with strong antibacterial and antioxidant properties and functional enzymes are delivered directly and rapidly to the lesion site through the mucosal adhesion ability of an oral dissolving film, thereby suppressing harmful bacteria that cause inflammation.

[0081] In this specification, “prevention” may mean any act of preventing or delaying the onset of stomatitis by administering a composition according to the present invention to preemptively inhibit the proliferation of pathogenic microorganisms in the oral cavity, and “improvement” may mean any act of administering the composition in a state where stomatitis has already occurred to improve or beneficially change symptoms such as inflammation, ulcers, and pain.

[0082] In this specification, “quasi-drug” refers to a group of products used for the purpose of treating, alleviating, managing, or preventing diseases in humans or animals, wherein the effect on the disease is milder than that of pharmaceuticals and there is less concern regarding direct side effects on the human body. The quasi-drug composition according to the present invention is manufactured based on natural base ingredients that have been proven safe in food science, and can be used daily without side effects, while also providing local and continuous antibacterial / anti-inflammatory action on stomatitis lesions through excellent oral mucosal adhesion ability.

[0083] The above-described quasi-drug composition may be most preferably provided in the form of the oral dissolving film (ODF) described above in terms of forming a physical protective film on the lesion site and intensive release of the active ingredient. However, depending on the intent or purpose of application of a person skilled in the art, it may be flexibly modified and processed into various quasi-drug formulations commonly manufactured in the industry for application to oral mucosa, such as oral cleansing wipes, toothpastes, mouthwashes, oral sprays, oral ointments, and gel formulations.

[0084] In addition, the quasi-drug composition of the present invention may further include additives that are conventionally accepted in the field of quasi-drugs to improve the physical properties, cleaning power, and feel of use of the formulation, in addition to the core active ingredients described above.

[0085] Specifically, it may further include one or more selected from the group comprising: moisturizers and humectants that alleviate mucosal irritation; surfactants and foaming agents that remove contaminants; binders and thickeners that maintain the shape of the formulation; pH adjusters that regulate acidity in the oral cavity; natural flavorings and sweeteners such as menthol and peppermint oil to enhance the sensation of use; and coloring agents and preservatives. However, these additives must be appropriately selected within a range that does not impair the propolis micelle structure and multi-antimicrobial synergistic effect of the present invention. Effects of the invention

[0087] The manufacturing method of the present invention combines 10-HDA and a high-pressure cavitation process to extract high-purity propolis in high yield without chemical additives and maximize the water-dispersible stability of the formulation. Furthermore, by nano-powdering the obtained extract and encapsulating it in a porous carrier, the aggregation between particles and the blocking phenomenon of film adhesion can be fundamentally prevented. In addition, the present invention applies a plasticizer comprising a mixture of maltitol and erythritol in an optimal ratio to prevent crystallization of the formulation even under harsh conditions and ensure excellent mechanical flexibility. Moreover, by combining bee-derived postbiotics and rice-derived lysozyme, which have excellent compatibility with propolis, the invention provides an excellent effect that exhibits powerful oral antibacterial and bad breath reduction synergies while maintaining film transparency without inducing allergies. Specific details for implementing the invention

[0089] The following examples will be explained in more detail. However, these examples are for illustrative purposes only and the scope of the present invention is not limited to these examples.

[0091] Preparation Example. Preparation of an orally dissolving film-type propolis food composition according to the present invention

[0092] To prepare an orally dissolving film-type propolis food composition according to the present invention, the following step-by-step process was performed.

[0094] 1-1. Preparation of High-Purity Propolis Extract

[0095] An 85% (v / v) ethanol aqueous solution in which 10-HDA (10-hydroxy-2-decenoic acid) was dissolved at a concentration of 1.0 wt% was prepared, and a Brazilian propolis raw material was mixed into this solution in a weight ratio of 1:10 to prepare a preliminary mixture. The preliminary mixture was introduced into a high-pressure cavitation apparatus and passed through an orifice nozzle three times under a pressure of 1,000 bar to destroy the resin matrix and extract the active ingredient. The obtained extract was left to stand at a low temperature of -10°C for 24 hours to separate the insoluble wax components, after which the supernatant was taken, finely filtered through a 0.45 μm filter membrane, and freeze-dried to obtain high-purity propolis extract powder stabilized by 10-HDA.

[0096] 1-2. Formation of Propolis Nanocomposite

[0097] After redissolving the propolis extract powder obtained in 1-1 above in ethanol, nano-sized propolis powder was prepared using a nano spray dryer to have an average particle size of about 400 nm (within the range of 100 to 800 nm). To control the adhesiveness of the obtained nano-propolis powder, a propolis nano-composite was formed by mixing it with a porous silica carrier in a weight ratio of 1:1 and adsorbing the nano-particles into the pores of the carrier.

[0098] 1-3. Preparation of Film-Based Slurry

[0099] A water-soluble polymer base mixed with hydroxypropylmethylcellulose (HPMC) and pullulan was stirred and dissolved in purified water at 70°C, and then maltitol and erythritol were mixed and added as plasticizers in a weight ratio of 1:0.5 to prepare a film base slurry with inhibited crystallization.

[0100] 1-4. Final Formulation and Drying

[0101] To the film base slurry of 1-3 above, 5.0 parts by weight of the propolis nanocomplex of 1-2 and Lactobacillus kuunkei ( L. kunkeei 2.5 parts by weight of postbiotics derived from ) and 1.0 parts by weight of rice-derived lysozyme were added. Afterward, the mixture was homogenized at a rotational speed of 3,000 rpm, and then vacuum degassing was performed for 40 minutes under a vacuum of 0.8 atm to remove bubbles. The homogenized slurry was cast onto a PET release film to a thickness of 200 μm, and an orally dissolving film-type propolis food composition with a final moisture content of 6% was obtained through a variable temperature drying process in which the temperature was gradually increased in a drying oven at 35°C for 10 minutes and then at 45°C for 20 minutes.

[0103] Experimental Example 1. Evaluation of Propolis Extraction Characteristics and Dispersion Stability According to 10-HDA Concentration and High-Pressure Cavitation Pressure Conditions

[0104] In order to determine the optimal conditions for the propolis extraction process according to the present invention, the effects of changes in the addition concentration of 10-HDA (10-hydroxy-2-decenoic acid) and high-pressure cavitation pressure on the yield of the extract, the concentration of indicator components, and the wax removal efficiency were analyzed.

[0105] Specifically, raw propolis was mixed with an 85% (v / v) aqueous ethanol solution in a weight ratio of 1:10, and a preliminary mixture was prepared by pre-dissolving 10-HDA in the aqueous ethanol solution at a concentration of 0.05 to 3.0 wt%. In the subsequent high-pressure process, the mixture was passed through the orifice nozzle of a high-pressure cavitation device three times at a pressure of 500 to 1,500 bar each to induce the elution of active ingredients from the propolis resin matrix. Subsequently, the extract obtained from the above process was left to stand in a low-temperature chamber at -10°C for 24 hours to completely precipitate insoluble wax components, after which only the supernatant was separated. The obtained supernatant was passed through a filter membrane with 0.45 μm pores to precisely remove fine impurities. Finally, the filtered concentrate was freeze-dried at -50°C for 48 hours to obtain a final propolis extract powder surface-stabilized by 10-HDA.

[0106] The flavonoid yield of the obtained extract powder was calculated as the total sum of the content of the indicator components, quercetin and galangin, analyzed using HPLC after redissolving 1 g of the obtained powder in methanol. The wax content (weight%) was determined by analyzing the ratio of residual impurities after redissolving the extract powder with n-hexane, and the water dispersion transparency (%) was evaluated by measuring the light transmittance at 600 nm using a spectrophotometer after dispersing the obtained extract powder in purified water at a concentration of 1% (w / v), thereby assessing the degree of hydrophilicity imparted and solubilization by 10-HDA.

[0107] [Table 1]

[0108]

[0110] As a result, Examples 1-1 to 1-3 of the present invention showed higher content of indicator components and lower wax content compared to comparative examples, and in particular, showed dramatically improved water dispersion transparency. In particular, Example 1-2, to which 1.0 wt% of 10-HDA and a pressure of 1,000 bar were applied, recorded a transparency of 94.8%, confirming that the hydrophobic propolis extract was almost perfectly solubilized in an aqueous solution. This suggests that 10-HDA effectively captures the active ingredients of propolis into the micelle structure under high pressure, thereby fundamentally blocking aggregation phenomena when mixed with an oral dissolving film slurry, which is an aqueous matrix.

[0111] On the other hand, when the 10-HDA concentration was below the lower limit (Comparative Examples 1-1 to 1-3), it was determined that there was a lack of surfactant molecules to encapsulate hydrophobic flavonoids, resulting in immediate precipitation upon water dispersion and a rapid decrease in transparency. Conversely, when the 10-HDA concentration exceeded the upper limit (Comparative Examples 1-10 to 1-12), it was determined that the excessive fatty acid component itself increased the turbidity of the extract and induced the redissolution of wax components, thereby causing a result that simultaneously inhibited purity and transparency.

[0112] Meanwhile, when the cavitation pressure was low (Comparative Examples 1-4, 1-6, 1-8, 1-10), it was determined that there was insufficient physical energy to break down the rigid resin structure of propolis, resulting in a significant decrease in the elution of indicator components and wax separation efficiency. When the cavitation pressure exceeded the upper limit (Comparative Examples 1-3, 1-5, 1-7, 1-9, 1-12), it was determined that excessive shear frictional heat induced thermal denaturation of the active ingredients and simultaneously caused forced emulsification of the wax components, resulting in a significant decrease in the purity and water dispersion stability of the extract.

[0113] From this, it was confirmed that the combination of the 10-HDA concentration (0.1 to 2.0 wt%) and high-pressure cavitation pressure (800 to 1,200 bar) range of the present invention is an essential technical element for achieving a high-quality oral dissolving film formulation with homogeneous properties by ensuring high-purity extraction of the propolis active ingredient and optimal water dispersion transparency.

[0115] Experimental Example 2. Evaluation of film properties and long-term storage stability according to the mixing ratio of maltitol and erythritol

[0116] In preparing a film base slurry according to the present invention, we intended to determine the effect of the mixing ratio of maltitol and erythritol, used as plasticizers, on the flexibility, crystallization inhibition, and surface properties of the final film.

[0117] Specifically, a water-soluble polymer base mixed with hydroxypropylmethylcellulose (HPMC) and pullulan in purified water was completely dissolved by stirring at 500 rpm at a temperature of 70°C, and then a plasticizer mixture was added to the mixture, with the weight ratio of maltitol and erythritol adjusted to a range of 1:0.1 to 1:2.0 or substituted with other sugar alcohols (sorbitol, xylitol) to prepare a film base slurry.

[0118] At this time, the solid content of the slurry was fixed at 25% (w / w), and the homogeneity of the film was ensured by removing microbubbles from the prepared slurry through a vacuum degassing process for 40 minutes under a vacuum of 0.8 atm. In the subsequent formulation process, the slurry was uniformly cast onto a PET release film substrate to a thickness of 200 μm using an applicator, and variable temperature drying was performed in a drying oven by gradually increasing the temperature from 35°C for 10 minutes to 45°C for 20 minutes to control the final moisture content to be in the range of 5 to 7%. The obtained film was stabilized for 48 hours in a constant temperature and humidity chamber under conditions of 25°C and 60% relative humidity, and then cut into pieces of 10 mm × 30 mm to be used as samples.

[0119] The tensile strength (MPa) of the obtained film was calculated by measuring the maximum load at which the film broke at a speed of 10 mm / min using a universal testing machine (UTM), the crystallinity (%) was calculated as the ratio of the crystalline region to the amorphous region by quantifying the peak intensity at the erythritol-specific diffraction angle (2θ = 20°~25°) using an X-ray diffraction analyzer (XRD), and the surface tackiness (N) was evaluated by measuring the maximum peel force generated when the film surface was separated after being compressed for 10 seconds with a load of 100 g / cm² using a probe tack tester.

[0120] [Table 2]

[0121]

[0123] As a result, it was confirmed that Examples 2-1 to 2-3 of the present invention demonstrated excellent crystallization inhibition capabilities compared to comparative examples while simultaneously maintaining superior mechanical properties. In particular, Example 2-2, in which the ratio of maltitol to erythritol was 1:0.5, showed the lowest degree of crystallization among all treatment groups at 1.5%, forming a polymer matrix close to a completely amorphous state. It was confirmed that this served as a critical basis for providing optimal flexibility without whitening or crumbling of the film even under harsh storage conditions.

[0124] On the other hand, Comparative Example 2-1, in which the erythritol content was below the lower limit, exhibited a brittle problem in which cracks easily occurred even under small bending impacts, as although the tensile strength was high due to a lack of plasticizing effect, it lacked flexibility. In Comparative Example 2-2, in which the erythritol content exceeded the upper limit, it was confirmed that the excess erythritol acted as a spontaneous crystal nucleus, causing the degree of crystallization to rise rapidly to 25.4%, which resulted in a breakdown of the density of the film's internal structure and a significant decrease in tensile strength.

[0125] Meanwhile, Comparative Example 2-3, in which maltitol was substituted with sorbitol, was effective in inhibiting crystallization, but due to the high hygroscopicity characteristic of sorbitol, the surface adhesion increased to 2.45 N, exhibiting a fatal defect that caused severe blocking between films; and Comparative Example 2-4, in which erythritol was substituted with xylitol, resulted in a rough film surface and unstable mechanical stability because irregular crystal growth during the drying process was not controlled.

[0126] From this, it was confirmed that a 1:0.2 to 1:1 combination of maltitol and erythritol is a unique technical composition that provides triple synergy of preventing crystallization, controlling adhesion, and securing flexibility, which is impossible to achieve with other plasticizer combinations.

[0128] Experimental Example 3. Evaluation of antibacterial synergy and bad breath reduction effects according to the type and content of postbiotics and lysozyme

[0130] 3-1. Analysis of Inhibitory Activity Against Harmful Oral Bacteria According to Type and Content of Postbiotics

[0131] To maximize the functionality of the oral dissolving film according to the present invention, major harmful bacteria in the oral cavity according to the type and input content of postbiotics S. mutans and P. gingivalis The antibacterial activity and bad breath reduction efficacy were analyzed.

[0132] Specifically, first, Lactobacillus reuteri, a common human-derived oral lactic acid bacterium ( L. reuteri ) and bee-derived Lactobacillus kunkei, which is a component of the present invention ( L. kunkeeiEach strain was cultured in MRS liquid medium at 37°C for 24 hours. After the culture was complete, each strain was centrifuged at 10,000 rpm for 15 minutes to recover the cells. These cells were washed three times with purified water and then inactivated by heating at 100°C for 30 minutes. The inactivated cells were freeze-dried at -50°C for 48 hours to produce the final postbiotic powder form (crude extract). Subsequently, the content of each type of postbiotic was subdivided into 0.1, 0.5, 2.5, 5.0, and 7.0 parts by weight relative to 100 parts by weight of the film-based slurry with the optimal plasticizer ratio derived in Experimental Example 2, and the mixture was homogenized at 3,000 rpm for 20 minutes. Each prepared film was cut into discs measuring 10 mm × 10 mm and used in the experiment.

[0133] The antimicrobial activity (%) of each manufactured film was calculated as the growth inhibition rate relative to the control group by measuring the diameter of the inhibition zone formed on a culture medium coated with harmful bacteria via agar well diffusion. For the bad breath reduction index, subjects (n=10) with confirmed bad breath were prohibited from using mouthwash for 12 hours prior to the experiment, and oral gases were collected before film application and 4 hours after application and analyzed by gas chromatography (GC-FPD). The final evaluation was based on the combined reduction rate of hydrogen sulfide (H2S) and methyl mercaptan (CH3SH), the main causes of bad breath, by assigning a score from 1 to 5 (80% or more reduction) in 20% increments of reduction rate.

[0134] [Table 3]

[0135]

[0137] As a result, Examples 3-1 to 3-3 of the present invention simultaneously achieved the most outstanding antibacterial activity and bad breath reduction efficacy among all treatment groups. In particular, Example 3-2, in which 2.5 parts by weight of L. kunkeei, a bee-derived lactic acid bacterium, was added, recorded an antibacterial activity of 96.2% and a bad breath reduction index of 4.9, confirming an unrivaled synergy. This corresponds to a significant effect in which activity was improved by more than 22% compared to Comparative Example 3-3, which applied the same amount of human-derived lactic acid bacteria. This is due to the propolis nanocomposite and L. kunkeei It was determined that this was because the synergy of the derived ingredients effectively blocked the metabolic pathways of bad breath-causing bacteria, thereby fundamentally inhibiting the production of sulfur compounds.

[0138] Specifically, bee-derived lactic acid bacteria L. kunkeei It is a 'Fructophilic Lactic Acid Bacteria' that has adapted to the harsh environment inside beehives, where high concentrations of phenolic compounds—the main components of propolis—are present. It was determined that the structural stability of the antimicrobial peptide derived from dead cells is maintained even when mixed with highly acidic propolis extract, and that it forms a synergy that selectively attacks the cell membranes of harmful bacteria through high chemical compatibility with propolis nanoparticles. On the other hand, L. reuteri In the case of propolis, it was confirmed that the unique physiologically active substances were partially denatured or interfered with by the strong antibacterial components of propolis, resulting in a relatively low synergy.

[0139] Meanwhile, when the postbiotic content fell below the lower limit, it was determined that the concentration of active ingredients derived from lactic acid bacteria, such as bacteriocins, did not reach the minimum threshold required to inhibit the metabolism of harmful bacteria, resulting in insufficient expression of significant antibacterial synergy with the propolis component. On the other hand, when the postbiotic content exceeded the upper limit, a reversal phenomenon was observed in which the antibacterial activity decreased sharply to 64.8% despite the increase in content. This was determined to be because the excessive amount of dead cell powder caused uneven aggregation within the film matrix and triggered an 'entrapment effect' that physically trapped propolis nanoparticles during the drying process, thereby hindering the elution and release efficiency of the active ingredients from the oral mucosa.

[0140] From this, it was confirmed that applying bee-derived Lactobacillus kunkei postbiotics in a specific content range (0.5 to 5.0 parts by weight) is an essential technical means to complement the antibacterial mechanism of the propolis of the present invention and to secure sustained bad breath reduction.

[0142] 3-2. Evaluation of Pretreatment Effects and Formulation Stability According to Rice-Derived Lysozyme Content

[0143] In order to maximize the antibacterial synergy of the oral dissolving film according to the present invention and maintain the transparency of the formulation, the effect of changes in the content of plant-derived lysozyme extracted from rice (Oryza sativa) on the penetration efficiency of the propolis nanocomposite and the characteristics of the final film was evaluated.

[0144] Specifically, a high-purity enzyme powder was prepared by separating and purifying a rice-derived lysozyme fraction from rice bran using ion exchange chromatography and gel filtration. In the subsequent composition preparation step, the content of the rice-derived lysozyme was adjusted to a range of 0.1 to 3.0 parts by weight and added to the optimal composition slurry of Example 3-2. After homogenization at 3,000 rpm, a film base slurry was prepared by undergoing a degassing process for 40 minutes under a vacuum of 0.8 atm. The prepared slurry was cast onto a PET release film to a thickness of 200 μm using an applicator, and stepwise variable-temperature drying was performed in a drying oven at 35°C for 10 minutes and at 45°C for 20 minutes to obtain a film sample with a final moisture content of 5 to 7%.

[0145] For the obtained film samples, enzyme stability (%) is the activity of the remaining lysozyme after standing in a slurry containing propolis extract at 40°C for 24 hours. Micrococcus lysodeikticus It was calculated as a ratio relative to the initial value by measuring substrate degradation ability, formulation transparency (%) was evaluated for the occurrence of opacity due to protein denaturation by measuring light transmittance at 600 nm using a spectrophotometer, and complex antimicrobial synergy (%) was the causative bacteria of bad breath P. gingivalis The change in minimum inhibitory concentration (MIC) when a propolis nanocomposite was added after lysozyme pretreatment was calculated as a percentage relative to the control group.

[0146] [Table 4]

[0147]

[0149] As a result, Examples 3-4 to 3-6, which applied rice-derived lysozyme, showed excellent results in terms of antibacterial synergy as well as the appearance stability of the formulation. In particular, Example 3-5, in which 1.0 weight part of lysozyme was added, recorded the highest complex antibacterial synergy of 97.2%, which was determined to be the result of maximizing the 'pretreatment synergy' in which rice-derived lysozyme hydrolyzes the peptidoglycan bonds of the bacterial cell wall to form microcracks, thereby helping the nanoflavonoid components of propolis to easily penetrate into the bacterial cell.

[0150] Meanwhile, it was confirmed that when the lysozyme content falls below the lower limit, the absolute concentration of the enzyme and the probability of substrate contact required to physically weaken the bacterial cell wall drop below the critical threshold, preventing the stepwise antimicrobial mechanism with the propolis component from functioning smoothly. Conversely, when the lysozyme content exceeds the upper limit, the transparency of the formulation drops sharply to 54.1% due to excessive aggregation of enzyme proteins, leading to a lack of marketability as a food product. Furthermore, the denaturation of the enzyme's three-dimensional structure due to protein aggregation resulted in the loss of substrate binding activity, which in turn led to a decrease in antimicrobial synergy.

[0151] In particular, it was confirmed that the rice-derived lysozyme of the present invention maintains a high transparency of over 89% up to 2.0 parts by weight. This supports the fact that the excellent thermodynamic stability and hydrophilicity of the grain-derived enzyme protein are technical means optimized for the acidic film formulation of the present invention, and suggests that safety as a food for human consumption has been secured by fundamentally blocking the possibility of allergy-inducing egg-derived ingredients.

[0153] The foregoing description of the present invention is for illustrative purposes only, and those skilled in the art will understand that other specific forms can be easily modified without altering the technical spirit or essential features of the present invention. Therefore, the embodiments described above should be understood as illustrative in all respects and not restrictive.

Claims

Claim 1 A method for preparing an orally dissolving film-type propolis food composition, comprising: (a) a step of preparing nano-propolis powder having an average particle size in the range of 100 to 800 nm by treating a propolis extract with a nano-spray drying process; (b) a step of forming a propolis nano-composite by adsorbing or encapsulating the nano-propolis powder inside one or more carriers selected from the group consisting of porous silica and cyclodextrin; (c) a step of preparing a film-base slurry with inhibited crystallization by mixing maltitol and erythritol in a polymer solution comprising a water-soluble polymer substrate and purified water; (d) a step of introducing the propolis nano-composite of step (b), postbiotics, and lysozyme into the film-base slurry and homogenizing; and (e) a step of casting the homogenized slurry onto a substrate and drying to form a film, wherein the maltitol and erythritol are mixed in a weight ratio of 1:0.2 to 1:

1. Claim 2 In claim 1, the propolis extract comprises: (a-1) a step of preparing a preliminary mixture by mixing raw propolis with an aqueous ethanol solution in which 10-HDA (10-hydroxy-2-decenoic acid) is dissolved at a concentration of 0.1 to 2.0 weight%; (a-2) a step of destroying the propolis resin matrix and simultaneously forming a micelle structure in which 10-HDA surrounds flavonoid particles through a high-pressure cavitation process in which the preliminary mixture is passed through a nozzle under a pressure of 800 to 1,200 bar; (a-3) a step of allowing the extract obtained from the above process to stand at a low temperature of -15 to -5℃ to separate the soluble components and the insoluble wax components; (a-4) a step of taking the supernatant and passing it through a filtration membrane of 0.2 to 1.0 μm to precisely remove fine impurities; A method for preparing an orally dissolving film-type propolis food composition, characterized by the step of (a-5) freeze-drying the filtered concentrate to obtain a propolis extract powder stabilized by 10-HDA. Claim 3 delete Claim 4 A method for preparing an orally dissolving film-type propolis food composition, characterized in that, in step (d), the postbiotic is included in an amount of 0.5 to 5 parts by weight per 100 parts by weight of the film base slurry, and the lysozyme is included in an amount of 0.2 to 2 parts by weight. Claim 5 In claim 1, in step (d), the postbiotic is Lactobacillus kuncei ( Lactobacillus kunkeei A method for preparing an orally dissolving film-type propolis food composition, characterized in that the lysozyme is a dead cell derived from ) or a culture thereof, and the lysozyme is a plant-derived lysozyme derived from rice. Claim 6 A method for preparing an orally dissolving film-type propolis food composition, wherein, in claim 1, the homogenization of step (d) is performed at a rotational speed of 3,000 to 5,000 rpm, and further includes a vacuum degassing process for 30 to 60 minutes under a vacuum of 0.5 to 1.0 atm to remove bubbles incorporated during the preparation of the slurry. Claim 7 A method for preparing an orally dissolving film-type propolis food composition, wherein, in claim 1, the drying in step (e) is performed for 10 to 30 minutes at a temperature range of 35 to 50°C, and is performed as a variable-temperature drying process in which the temperature is gradually increased to prevent destruction of the biological activity of lysozyme and postbiotics contained in the slurry. Claim 8 An orally dissolving film-type propolis food composition characterized by being manufactured by any one of the manufacturing methods of claims 1, 2, 4 to 7. Claim 9 An orally dissolving film-type propolis food composition according to claim 8, wherein the composition comprises a structure in which a nanocomposite, in which nano-propolis is encapsulated on a porous carrier, is homogeneously dispersed within a water-soluble polymer matrix, and the blocking phenomenon caused by the non-specific adhesiveness characteristic of propolis is suppressed by the nanocomposite. Claim 10 A health functional food composition for oral antibacterial and bad breath removal comprising the composition of claim 8. Claim 11 A quasi-drug composition for preventing or improving stomatitis having oral mucosal adhesion ability, comprising the composition of claim 8.

Images