Lucid ganoderma-derived protein oral film and preparation method thereof

Abstract

The invention relates to a ganoderma lucidum-derived protein oral cavity film and a preparation method thereof, the ganoderma lucidum-derived protein oral cavity film comprises: a drug-containing layer: 0.2%-30% of a core active component, 30%-60% of a water-soluble film-forming material, 5%-15% of a plasticizer, 5%-30% of a mucous membrane adhesive, 1%-20% of a penetration enhancer, 1%-10% of a flavoring agent, 0.1%-5% of an opacifying agent, and 0.5%-5% of an acidity regulator, freeze-dried powder or nano-particles are added into the formula; and the backing layer comprises the following components in percentage by weight: 20-50% of a water-soluble film-forming material, 30-70% of a water-insoluble film-forming material, 3-15% of a plasticizer, 5-20% of an adhesive, 1-10% of a flavoring agent, 0.1-5% of an opacifying agent and 0.1-5% of a According to the oral cavity pasting film composed of the formula, accurate controlled release of core active ingredients in the oral cavity can be achieved, a double-layer structure is used, the medicine-containing layer can be continuously and stably released, and the back lining layer can prevent saliva from diluting the medicine-containing layer. The oral cavity film has strong adhesive force, can be attached for a long time, and has the effect of prolonging the action time of the core active component.

Description

Technical Field

[0001] The present invention relates to the field of biotechnology, and in particular to a ganoderma-derived protein oral film and a preparation method thereof. Background Art

[0002] Oral ulcers are a common oral disease, usually manifesting as superficial ulcers in the mouth, accompanied by pain, burning sensation and discomfort, which can affect eating and speaking in severe cases. The causes of oral ulcers are varied, including immune system disorders, local trauma, mental stress, etc. About 20%-40% of adults have experienced oral ulcers. Existing treatments, such as oral ointments, sprays, gels, etc., although they can relieve symptoms, most of them have shortcomings such as short-term drug release, unstable treatment effects, and poor patient compliance. Therefore, it is of great significance to develop a new formulation that can act continuously and precisely on the lesion area.

[0003] As an innovative topical drug delivery system, oral patches are an ideal choice for treating oral ulcers due to their excellent adhesion and sustained-release properties. Through oral patches, active ingredients can be applied directly to the affected area, providing long-lasting therapeutic and relief effects while preventing them from being washed away by saliva and improving their bioavailability. Furthermore, oral patches do not require swallowing, making them suitable for the elderly, children, and those with dysphagia. With minimal side effects, they are considered to have broad application prospects in the treatment of oral ulcers.

[0004] The English expression of Ganoderma microsporum immunomodulatory protein is: Ganoderma microsporum immunomodulatory protein, hereinafter referred to as the English abbreviation GMI. Ganoderma microsporum immunomodulatory protein is derived from Ganoderma microsporum and is a protein with biological activities such as immunomodulation, anti-inflammatory, and antioxidant. Studies have shown that it has significant effects in the local treatment of oral ulcers. GMI can relieve local inflammation, promote the healing of oral ulcers, reduce pain, enhance local immune function, and prevent secondary infection by regulating immune responses. By combining GMI with oral patches, the precise release and efficient action of active ingredients can be achieved. It has great application potential in improving the symptoms of inflammatory diseases such as oral ulcers.

[0005] Currently, the application of macromolecular ingredients such as proteins and peptides in oral patches faces challenges. Due to their large molecular weight and complex structure, they have a poor ability to penetrate the oral mucosa and are susceptible to protease degradation, which limits their local absorption efficiency. Therefore, the development of oral patches that can stabilize macromolecular ingredients and optimize their release and permeability is crucial. Therefore, innovative preparation processes are needed to improve the solubility, stability, and permeability of active proteins, providing new solutions for the application and industrialization of macromolecular ingredients in pharmaceuticals, foods, and health supplements. Summary of the Invention

[0006] The purpose of the present invention is to provide a protein oral film derived from Ganoderma lucidum and a preparation method thereof, so as to solve the problems existing in the above-mentioned prior art.

[0007] The above technical objectives of the present invention are achieved through the following technical solutions: A protein oral film derived from Ganoderma lucidum, comprising: Drug-containing layer: core active ingredient 0.2% to 30%, the core active ingredient is microsporous Ganoderma lucidum immunomodulatory protein, the core active ingredient is microsporous Ganoderma lucidum immunomodulatory protein, which is added to the formula in the form of freeze-dried powder or nanoparticles, water-soluble film-forming material 30% to 60%, plasticizer 5% to 15%, mucosal adhesive 5% to 30%, penetration enhancer 1% to 20%, flavoring agent 1% to 10%, sunscreen 0.1% to 5%, acidity regulator 0.5% to 5%; Backing layer: water-soluble film-forming material 20% to 50%, water-insoluble film-forming material 30% to 70%, plasticizer 3% to 15%, adhesive 5% to 20%, flavoring agent 1% to 10%, sunscreen 0.1% to 5%, colorant 0.1% to 5%.

[0008] In a further embodiment, the water-soluble film-forming material of the drug-containing layer is used to form a uniform and stable core active ingredient carrier film to uniformly disperse the core active ingredient, and the film-forming material is any one or a mixture of hydroxypropyl methylcellulose, polyvinyl pyrrolidone, sodium carboxymethyl cellulose, sodium alginate, hydroxypropyl cellulose, and chitosan; The plasticizer of the drug-containing layer is used to improve the flexibility of the film, prevent brittle cracking, and enhance adhesion to ensure stable release of the core active ingredient in the oral cavity. The plasticizer used is any one or a mixture of glycerol, propylene glycol, polyethylene glycol, sorbitol and poloxamer. The mucoadhesive of the drug-containing layer is used to enhance the adhesion of the oral film to the oral mucosa, thereby prolonging the residence time of the core active ingredient and improving the absorption efficiency; the mucoadhesive used is any one or a mixture of polyvinyl pyrrolidone, sodium alginate, chitosan, sodium carboxymethyl cellulose, carbomer, xanthan gum and gelatin; The penetration enhancer of the drug-containing layer is used to increase the permeability of the core active ingredient through the oral mucosa, thereby promoting the absorption of the core active ingredient; the penetration enhancer used is any one or a mixture of sodium lauryl sulfate, sodium deoxycholate, sodium glycocholate, menthol, Tween surfactants, glycerol fatty acid esters, and sodium 8-(2-hydroxybenzamido)octanoate; The flavoring agent in the drug-containing layer is used to improve the taste of the oral film and enhance the compliance of use; the flavoring agent used is any one or a mixture of xylitol, stevioside, sucralose, aspartame, mint essence, lemon essence, and mannitol; The sunscreen of the drug-containing layer is used to improve light stability and prevent light degradation, thereby extending the shelf life of the product; the sunscreen used is any one of titanium dioxide, zinc oxide, and talc, or a mixture of several thereof; The acidity regulator of the drug-containing layer is used to adjust the pH value of the oral film. The acidity regulator used is any one of citric acid, sodium citrate, tartaric acid, and lactic acid, or a mixture of several of them.

[0009] In a further embodiment, the water-soluble film-forming material of the backing layer is used to improve the solubility of the backing layer so that the backing layer dissolves promptly in the oral cavity; the water-soluble film-forming material is any one of polyvinyl alcohol, hydroxypropyl methylcellulose, polyethylene oxide, water-soluble acrylic resin, gelatin, or a mixture thereof; The water-insoluble film-forming material of the backing layer is used to improve the strength of the film, ensure the stability of the film layer, and play a barrier role in the oral environment; the water-insoluble film-forming material is any one or a mixture of cellulose acetate, ethyl cellulose, chitin, polylactic acid-glycolic acid copolymer, polyvinylidene chloride; The plasticizer of the backing layer is used to enhance the flexibility of the film, improve the mechanical strength, reduce the brittle cracking and shedding of the film layer, and increase the moisture resistance and wear resistance of the film. The plasticizer is any one or a mixture of glycerol, polyethylene glycol, glyceryl monostearate, triethyl citrate, and sorbitol; The adhesive of the backing layer is used to enhance the bonding force between the backing layer and the drug-containing layer, ensuring the stability of the double-layer structure composed of the drug-containing layer and the backing layer; the adhesive is any one of polyvinyl pyrrolidone, sodium alginate, sodium carboxymethyl cellulose, carbomer, and chitosan, or a mixture of several thereof; The flavoring agent of the backing layer is any one or a mixture of xylitol, steviol glycoside, sucralose, aspartame, mint essence, lemon essence, and mannitol; The sunscreen of the backing layer is any one of titanium dioxide, zinc oxide, and talc, or a mixture of several thereof; The colorant of the backing layer is any one of lemon yellow, allura red, sunset yellow and brilliant blue, or a mixture of several of them.

[0010] By adopting the above technical solution, the present invention has the following beneficial effects: the oral film composed of the above formula can achieve precise and controlled release of the core active ingredient in the oral cavity. The dual-layer design allows for sustained and stable release of the drug-containing layer, while the backing layer prevents dilution of the drug-containing layer by saliva. The oral film has strong adhesion and can adhere for a long time, thereby increasing the duration of action of the core active ingredient.

[0011] The present invention also discloses a method for preparing a protein oral film derived from Ganoderma lucidum, comprising the following steps: Step S1, preparing the core active ingredient, including preparing microspore Ganoderma lucidum immunomodulatory protein nanoparticles; Step S2, slurry preparation: Drug-containing layer: According to the proportions of the components of the drug-containing layer, weigh the core active ingredient, flavoring agent, and acidity regulator into 19 times the amount of water and stir evenly; then, mix the water-soluble film-forming material, plasticizer, penetration enhancer, mucoadhesive, and sunscreen with the slurry and stir to prepare a uniform drug-containing layer slurry; Backing layer: According to the proportions of the backing layer components, weigh the water-insoluble film-forming material and plasticizer, add 8 times the amount of 80% ethanol solution, and grind until clear; then add the water-soluble film-forming material and adhesive in sequence and continue to stir until uniform; finally, add the flavoring agent, colorant, and opacifier and continue to stir until uniform to prepare the backing layer slurry; Step S3, degassing treatment: placing the slurry in a vacuum degassing device to remove mixed bubbles; Step S4, coating and drying: The backing layer slurry is coated on a substrate (such as a polyester film), dried at 40°C to 60°C, and then the drug-containing layer slurry is coated on the backing layer and dried at 40°C. After drying, the film is peeled off from the substrate. The film thickness is controlled to be 50μm to 200μm to obtain a double-layer oral film; Step S5, cutting and packaging: cutting the film into sheet products and packaging the individual sheets in aluminum foil bags.

[0012] In a further embodiment, step S1 further comprises preparing microspore Ganoderma lucidum immunomodulatory protein nanoparticles, and the preparation method of the core active ingredient comprises the following steps: Step S11, solution preparation: dissolving the microsporic Ganoderma lucidum immunomodulatory protein freeze-dried powder in deionized water or a buffer solution, stirring evenly, filtering to remove insoluble matter, and forming a microsporic Ganoderma lucidum immunomodulatory protein solution with a concentration of 1-10 mg / ml; adding a surfactant at 0.1% to 1% of the protein mass, mixing thoroughly, and using the surfactant as the aqueous phase. The pH value of the buffer solution is 5-6, and the surfactant is one of Tween 80, poloxamer F68, and polyvinyl pyrrolidone; Step S12, antisolvent precipitation: using anhydrous ethanol or acetone as an antisolvent, slowly dripping the aqueous phase into the antisolvent at a volume ratio of 1:2 to 1:6 (preferably 1:4) at a rate of 0.5-2 ml / min under stirring, utilizing the difference in solvent polarity to induce rapid precipitation of the protein to form nanoparticles; Step S13, nanoparticle separation: After the reaction solution is allowed to stand for 5 to 10 minutes, the microspore Ganoderma lucidum immunomodulatory protein nanoparticles are separated by high-speed centrifugation at 10,000-15,000 rpm for 10 to 30 minutes, and the precipitate is washed 2 to 3 times with deionized water or a buffer solution to remove the residual antisolvent on the surface. The pH value of the buffer solution is 6.5-7.5; Step S14, freeze drying: the collected microspore Ganoderma lucidum immunomodulatory protein nanoparticles are dispersed in a solution containing 1% to 10% cryoprotectant, and after quick freezing, vacuum freeze drying is performed to obtain stable microspore Ganoderma lucidum immunomodulatory protein nanoparticle freeze-dried powder, wherein the cryoprotectant is one of mannitol, trehalose, and dextran.

[0013] By adopting the above technical solution, protein nanoparticles can be prepared by the anti-solvent precipitation method. The prepared particles have uniform particle size distribution, controlled within the range of 50-200nm, and good dispersibility. They can significantly improve the stability of the microspore Ganoderma lucidum immunomodulatory protein and meet the subsequent formulation process requirements.

[0014] The optimized oral film preparation process is simple, the mild conditions effectively protect the active ingredients, and it has the capacity for large-scale production. DETAILED DESCRIPTION

[0015] The present invention is further described in detail below with reference to specific embodiments.

[0016] The following examples are not intended to limit the present invention but are merely intended to illustrate the present invention. The experimental methods used in the following examples are generally based on conventional conditions unless otherwise specified. Materials and reagents used in the following examples are all commercially available unless otherwise specified.

[0017] The present invention includes the preparation of GMI protein nanoparticles (GMI-NPs) Lyophilized GMI protein powder was dissolved in phosphate buffer (pH 5.0) to prepare a 5 mg / ml GMI protein solution. 0.5% (w / w) Tween 80 was added, mixed thoroughly, and filtered through a 0.22 μm filter to prepare the aqueous phase. Under stirring, the aqueous phase solution was slowly added dropwise to anhydrous ethanol at a volume ratio of 1:4 at a rate of 1 ml / min. Stirring was continued for 15 minutes after the addition was complete. The mixture was allowed to stand at 4°C for 10 minutes, then centrifuged at 12,000 rpm for 20 minutes to collect the precipitate. The precipitate was washed three times with deionized water to remove residual ethanol and free protein. The purified GMI protein nanoparticles were re-dispersed in a solution containing 5% mannitol, pre-frozen at -80°C, and lyophilized to obtain lyophilized GMI protein nanoparticle powder for subsequent use.

[0018] The present invention is to prepare an oral film whose core active ingredient is GMI.

[0019] The formulation compositions of the oral patches prepared in the Examples and Comparative Examples, wherein the core active ingredient is GMI freeze-dried powder, are shown in Tables 1 to 4:

[0020] Table 2 also discloses three comparative examples for comparison with Examples 1 to 4, as shown in Table 2:

[0021] Table 3 also discloses the proportions of the components of Examples 5 to 7, which are shown below:

[0022] Table 4 also discloses four comparative examples for comparison with Examples 5 to 7, as shown below.

[0023]

[0024] The preparation methods of the oral films of Examples 1-7 and Comparative Examples 1-7 are as follows: Step 1: Mixing the slurry Drug-containing layer: According to the formula ratios in Tables 1, 2, 3, and 4, weigh the GMI protein lyophilized powder, flavoring agent, and acidity regulator into 19 times the amount of water and stir evenly; then mix the water-soluble film-forming material, plasticizer, penetration enhancer, mucoadhesive agent, and sunscreen with the above slurry and stir to prepare a uniform drug-containing layer slurry. Backing layer: According to the formula ratios in Tables 1, 2, 3, and 4, weigh the water-insoluble film-forming material and plasticizer, add them to 8 times the amount of 80% ethanol solution, and grind until clear; then add the water-soluble film-forming material and adhesive in sequence and continue to stir evenly; finally, add the flavoring agent, colorant, and sunscreen and continue to stir evenly to prepare the backing layer slurry.

[0025] The second step is degassing: the slurry is placed in a vacuum degassing device to remove the mixed bubbles to ensure the uniformity of film formation.

[0026] Step 3: Coating and Drying: The backing layer slurry is applied to a polyester film substrate at a coating speed of 20-40 mm / s and a drying temperature of 60°C, maintaining a film thickness of approximately 0.8 mm. The drug-containing layer slurry is then applied to the backing layer at a drying temperature of 40°C, maintaining a film thickness of approximately 1.1 mm. After drying, the film is peeled from the substrate. The thickness of each layer is controlled to be 50-200 μm, resulting in a double-layer oral film.

[0027] Step 4: Peeling and cutting: Peel off the dried film, cut it into tablets of uniform specifications, and package them individually.

[0028] Comprehensive performance test results of Examples 1-7 and Comparative Examples 1-7: The performance test results of the samples of Examples 1-4 and Comparative Examples 1-3 with changed drug-containing layer formulations are shown in Table 5:

[0029] In summary, in Examples 1 to 4: All embodiments meet the ratio range of each excipient specified in the present invention. The drug-containing layer forms a uniform and stable carrier of the core active ingredient, the backing layer provides effective protection, and the whole exhibits excellent mechanical strength, sustained drug release ability and good adhesion effect.

[0030] Film formation uniformity: smooth surface, no bubbles, coating uniformity>98%.

[0031] Mechanical strength: tensile strength>18MPa, ensuring the integrity and stability of the membrane in the oral environment.

[0032] Adhesion time: The oral film with optimized formula can stably adhere to the oral mucosa for 40-70 minutes, avoiding premature shedding that affects the user experience.

[0033] The proportion of water-soluble film-forming material in Comparative Example 1 is too low: A low proportion of water-soluble film-forming materials (sodium alginate + HPMC) will result in insufficient film formation of the drug-containing layer, reduced mechanical strength, and easy breakage of the film.

[0034] The proportion of plasticizer in Comparative Example 2 is too high: The proportion of plasticizer glycerol is too high, while the total amount of water-soluble film-forming materials is low, which will cause the film to be too soft, reduce mechanical strength and stability, accelerate the drug release rate and make it difficult to adhere to the oral mucosa for a long time, affecting the user experience.

[0035] In Comparative Example 3, the adhesive ratio is too high and the carbomer ratio is high: If the adhesive (PVP + carbomer) ratio is too high, the film will be too viscous. A high carbomer content will cause the slurry to gel, making it difficult to apply and prone to bubbles forming when the film dries. Therefore, the carbomer content should not exceed 15%.

[0036] The performance test results of the samples of Examples 1, 5, 6, 7 and Comparative Examples 4, 5, 6, 7 with different backing layer formulations are shown in Table 6.

[0037]

[0038] According to the test results and sample usage effects in Table 6: The EC of the water-insoluble film-forming material of the backing layer in Comparative Example 4 is too low: The ratio of the water-soluble film-forming material to the water-insoluble film-forming material in the backing layer is 1:3-2:1, more preferably 1.25:1, 1:1, 1:1.2, or 1:2. A reduction in EC to 20% reduces the hydrophobicity of the membrane, resulting in insufficient support from the backing layer and the membrane being prone to rupture or shedding.

[0039] The backing layer plasticizer in Comparative Example 5 is low: The proportion of plasticizer in the backing layer is relatively low, which leads to reduced flexibility and ductility of the film, making it prone to brittle cracking and affecting its stability in use.

[0040] In Comparative Example 6, no water-soluble acrylic resin was added: Without water-soluble acrylic resin added to the backing layer, HPMC, the primary film-forming material, dissolves slowly, resulting in a hard film and poor film uniformity. This results in poor adhesion in the mouth and affects user comfort. The addition of water-soluble acrylic resin optimizes the flexibility and film-forming properties of the HPMC film, making it smoother and more conformable, enhancing the user experience.

[0041] The adhesive of Comparative Example 7 is too low: When the proportion of adhesive in the backing layer is too low, the membrane's ductility and flexibility decrease, making it difficult to effectively adhere. At the same time, the adhesion is weakened, and the bonding strength between the backing layer and the drug-containing layer is reduced, making it easy for the layers to separate, affecting the overall stability and performance of the membrane.

[0042] The present invention also includes Comparative Example 8 (coating the drug-containing layer first and then the backing layer) to investigate the coating sequence. The coating sequence in Example 1 was changed, that is, the drug-containing layer was coated first, and then the backing layer was coated on the drug-containing layer, while the other formulations and processes remained unchanged.

[0043] Analysis of phenomenon results: The phenomenon is: Bubble formation: The bubble rate after the backing layer is coated during the drying process is 40%.

[0044] Oral adhesion time: shortened to 30±8 minutes (uneven structure leads to shedding).

[0045] And by comparing different coating methods, we can see that: Regarding applying the drug-containing layer first and then the backing layer: Due to the high viscosity of the drug-containing layer and the presence of carbomer, small bubbles are easily generated during the drying process, affecting the coating of the backing layer. On the other hand, applying the backing layer first and then the drug-containing layer: After coating, the backing layer is smooth and free of bubbles, which does not affect the coating of the drug-containing layer. Therefore, the method of applying the backing layer first and then the drug-containing layer is selected.

[0046] Preparation and analysis of oral film with GMI protein nanoparticles as the core active ingredient: The formula compositions of various examples of oral patches prepared with GMI protein nanoparticles as the core active ingredient are shown in Table 7:

[0047] The screening and combination of various excipients are analyzed through the examples in Table 7 to explore their effects on film formation, stability, and performance.

[0048] In the mucoadhesive selection experiments in Examples 8-11, the oral film containing CMC-Na (sodium carboxymethylcellulose) exhibited superior mucosal adhesion compared to Example 8, enhancing its adhesion to the oral mucosa and making it more stable and long-lasting. In contrast, the addition of xanthan gum and sodium alginate did not significantly improve mucosal adhesion, indicating that these two excipients have limited viscosity-increasing effects in this formulation system.

[0049] In Example 12, HPC exhibits excellent flexibility, and under certain circumstances, a stable film can be formed without the need for additional plasticizers. However, this experiment revealed that high-molecular-weight HPC (such as HPC-GF and HPC-MF) takes a long time to swell in 80% ethanol. If insufficient swelling occurs, the slurry tends to gel, resulting in uneven coating and poor film quality. Therefore, when using high-molecular-weight HPC, it is necessary to optimize swelling conditions or combine it with other film-forming materials to improve the controllability of the preparation process.

[0050] Example 13 optimized the combination of penetration enhancers, using 2% SNAC + 9% Tween 80, which worked synergistically with GMI protein nanoparticles to significantly improve the permeability of the protein on the oral mucosa, thereby increasing the local retention time and permeation efficiency of GMI.

[0051] In Example 14, compared with the formulation with mannitol added, the flatness of the backing layer film decreased, indicating that glycerol + mannitol can improve the softness and user experience of the film.

[0052] The content of the core active ingredient in this invention is adjustable and can be set between 0.2% and 30% (w / w) depending on specific usage requirements and application scenarios, providing good adaptability and application flexibility. The 3% content shown in the examples is a typical value and is not intended to be limiting. The proportion of the core active ingredient can also be determined based on practical scenarios and applications.

[0053] During actual use, the sunscreen needs to be adjusted according to actual needs.

[0054] This specific embodiment is merely an explanation of the present invention and is not intended to limit the present invention. After reading this specification, those skilled in the art may make non-creative modifications to this embodiment as needed. However, as long as such modifications are within the scope of the claims of the present invention, they are protected by patent law.

Claims

1. A protein oral patch derived from Ganoderma lucidum, characterized in that: include: Drug-containing layer: core active ingredient 0.2%-30%, water-soluble film-forming material 30%-60%, plasticizer 5%-15%, mucoadhesive 5%-30%, penetration enhancer 1%-20%, flavoring agent 1%-10%, opacifier 0.1%-5%, acidity regulator 0.5%-5%; Backing layer: water-soluble film-forming material 20% to 50%, water-insoluble film-forming material 30% to 70%, plasticizer 3% to 15%, adhesive 5% to 20%, flavoring agent 1% to 10%, sunscreen 0.1% to 5%, colorant 0.1% to 5%.

2. The oral protein film derived from Ganoderma lucidum according to claim 1, characterized in that: The core active ingredient is microspore Ganoderma lucidum immunomodulatory protein, which is added to the formula in the form of freeze-dried powder or nanoparticles.

3. The oral protein film derived from Ganoderma lucidum according to claim 1, characterized in that: The water-soluble film-forming material of the drug-containing layer is used to form a uniform and stable core active ingredient carrier film to uniformly disperse the core active ingredient. The film-forming material is any one of hydroxypropyl methylcellulose, polyvinyl pyrrolidone, sodium carboxymethyl cellulose, sodium alginate, hydroxypropyl cellulose, and chitosan, or a mixture of several thereof. The plasticizer of the drug-containing layer is used to improve the flexibility of the film, prevent brittle cracking, and enhance adhesion to ensure stable release of the core active ingredient in the oral cavity. The plasticizer used is any one or a mixture of glycerol, propylene glycol, polyethylene glycol, sorbitol and poloxamer. The mucoadhesive of the drug-containing layer is used to enhance the adhesion of the oral film to the oral mucosa, thereby prolonging the residence time of the core active ingredient and improving the absorption efficiency; the mucoadhesive used is any one or a mixture of polyvinyl pyrrolidone, sodium alginate, chitosan, sodium carboxymethyl cellulose, carbomer, xanthan gum and gelatin; The penetration enhancer of the drug-containing layer is used to increase the permeability of the core active ingredient through the oral mucosa, thereby promoting the absorption of the core active ingredient; the penetration enhancer used is any one or a mixture of sodium lauryl sulfate, sodium deoxycholate, sodium glycocholate, menthol, Tween surfactants, glycerol fatty acid esters, and sodium 8-(2-hydroxybenzamido)octanoate; The flavoring agent in the drug-containing layer is used to improve the taste of the oral film and enhance the compliance of use; the flavoring agent used is any one or a mixture of xylitol, stevioside, sucralose, aspartame, mint essence, lemon essence, and mannitol; The sunscreen of the drug-containing layer is used to improve light stability and prevent light degradation, thereby extending the shelf life of the product; the sunscreen used is any one of titanium dioxide, zinc oxide, and talc, or a mixture of several thereof; The acidity regulator of the drug-containing layer is used to adjust the pH value of the oral film. The acidity regulator used is any one of citric acid, sodium citrate, tartaric acid, and lactic acid, or a mixture of several of them.

4. The oral protein film derived from Ganoderma lucidum according to claim 1, characterized in that: The water-soluble film-forming material of the backing layer is used to improve the solubility of the backing layer so that the backing layer dissolves promptly in the oral cavity; the water-soluble film-forming material is any one of polyvinyl alcohol, hydroxypropyl methylcellulose, polyethylene oxide, water-soluble acrylic resin, gelatin, or a mixture of several thereof; The water-insoluble film-forming material of the backing layer is used to improve the strength of the film, ensure the stability of the film layer, and play a barrier role in the oral environment; the water-insoluble film-forming material is any one or a mixture of cellulose acetate, ethyl cellulose, chitin, polylactic acid-glycolic acid copolymer, polyvinylidene chloride; The plasticizer of the backing layer is used to enhance the flexibility of the film, improve the mechanical strength, reduce the brittle cracking and shedding of the film layer, and increase the moisture resistance and wear resistance of the film. The plasticizer is any one or a mixture of glycerol, polyethylene glycol, glyceryl monostearate, triethyl citrate, and sorbitol; The adhesive of the backing layer is used to enhance the bonding force between the backing layer and the drug-containing layer, ensuring the stability of the double-layer structure composed of the drug-containing layer and the backing layer; the adhesive is any one of polyvinyl pyrrolidone, sodium alginate, sodium carboxymethyl cellulose, carbomer, and chitosan, or a mixture of several thereof; The flavoring agent of the backing layer is any one or a mixture of xylitol, steviol glycoside, sucralose, aspartame, mint essence, lemon essence, and mannitol; The sunscreen of the backing layer is any one of titanium dioxide, zinc oxide, and talc, or a mixture of several thereof; The colorant of the backing layer is any one of lemon yellow, allura red, sunset yellow and brilliant blue, or a mixture of several of them.

5. A method for preparing the oral protein film derived from Ganoderma lucidum according to any one of claims 1 to 4, characterized in that: The following steps are involved: Step S1, preparing the core active ingredient, including preparing microspore Ganoderma lucidum immunomodulatory protein nanoparticles; Step S2, slurry preparation: Drug-containing layer: According to the proportions of the components of the drug-containing layer, weigh the core active ingredient, flavoring agent, and acidity regulator into 19 times the amount of water and stir evenly; then, mix the water-soluble film-forming material, plasticizer, penetration enhancer, mucoadhesive, and sunscreen with the slurry and stir to prepare a uniform drug-containing layer slurry; Backing layer: According to the proportions of the backing layer components, weigh the water-insoluble film-forming material and plasticizer, add 8 times the amount of 80% ethanol solution, and grind until clear; then add the water-soluble film-forming material and adhesive in sequence and continue to stir until uniform; finally, add the flavoring agent, colorant, and opacifier and continue to stir until uniform to prepare the backing layer slurry; Step S3, degassing treatment: placing the slurry in a vacuum degassing device to remove mixed bubbles; Step S4, coating and drying: The backing layer slurry is coated on the substrate and dried at 40°C to 60°C. Then, the drug-containing layer slurry is coated on the backing layer and dried at 40°C. After drying, the film is peeled off from the substrate. The film thickness is controlled to be 50μm to 200μm to obtain a double-layer oral film; Step S5, cutting and packaging: cutting the film into sheet products and packaging the individual sheets in aluminum foil bags.

6. The method for preparing a protein oral film derived from Ganoderma lucidum according to claim 5, characterized in that: Step S1 further includes preparing microspore Ganoderma lucidum immunomodulatory protein nanoparticles, and the preparation method of the core active ingredient comprises the following steps: Step S11, solution preparation: dissolving the microsporic Ganoderma lucidum immunomodulatory protein freeze-dried powder in deionized water or a buffer solution, stirring evenly, filtering to remove insoluble matter, and forming a microsporic Ganoderma lucidum immunomodulatory protein solution with a concentration of 1-10 mg / ml; adding a surfactant at 0.1% to 1% of the protein mass, mixing thoroughly, and using the surfactant as the aqueous phase. The pH value of the buffer solution is 5-6, and the surfactant is one of Tween 80, poloxamer F68, and polyvinyl pyrrolidone; Step S12, antisolvent precipitation: using anhydrous ethanol or acetone as an antisolvent, slowly dripping the aqueous phase into the antisolvent at a rate of 0.5-2 ml / min at a volume ratio of 1:2 to 1:6 under stirring conditions, utilizing the difference in solvent polarity to induce rapid protein precipitation to form nanoparticles; Step S13, nanoparticle separation: After the reaction solution is allowed to stand for 5 to 10 minutes, the microspore Ganoderma lucidum immunomodulatory protein nanoparticles are separated by high-speed centrifugation at 10,000 to 15,000 rpm for 10 to 30 minutes, and the precipitate is washed 2 to 3 times with deionized water or a buffer solution to remove the residual antisolvent on the surface. The pH value of the buffer solution is 6.5 to 7.5; Step S14, freeze drying: the collected microspore Ganoderma lucidum immunomodulatory protein nanoparticles are dispersed in a solution containing 1% to 10% cryoprotectant, and after quick freezing, vacuum freeze drying is performed to obtain stable microspore Ganoderma lucidum immunomodulatory protein nanoparticle freeze-dried powder, wherein the cryoprotectant is one of mannitol, trehalose, and dextran.

Images