Benvimod oral soluble film composition, preparation method and medical application thereof

Abstract

The invention relates to a benvimod oral-soluble film composition, a preparation method thereof and application of the benvimod oral-soluble film composition in medicine, the benvimod oral-soluble film composition comprises an active component, a film-forming material and a plasticizer, and the active component is selected from one or more of benvimod, pharmaceutically acceptable salts of benvimod, clathrate compounds of benvimod and compounds of benvimod. The invention particularly relates to application of the oral soluble film composition in preparation of medicines for treating and / or preventing oral related diseases, and the oral related diseases are preferably selected from stomatitis, dental ulcer, oral herpes, gingivitis and periodontal diseases. The oral soluble film composition provided by the invention has the advantages of being thin in thickness, good in taste, stable in property, capable of being instantly dissolved in the oral cavity and high in absorption speed.

Description

Technical Field

[0001] The present disclosure belongs to the field of medicine and relates to a bevimod orodispersible film composition, a preparation method thereof and its application in medicine. The active ingredient of the bevimod orodispersible film composition is selected from one or more of bevimod, a pharmaceutically acceptable salt of bevimod and its inclusion compound or a complex thereof; in particular, it relates to the use of the orodispersible film composition in the preparation of a medicament for treating and / or preventing oral-related diseases, wherein the oral-related diseases are preferably selected from stomatitis, oral ulcers, oral herpes, gingivitis and periodontal disease. Background Art

[0002] Benvimod is a new type of small molecule non-hormonal drug with the following structure:

[0003]

[0004] Benvimod is a world-first national Class 1 new drug with complete independent intellectual property rights, and is the result of my country's major scientific and technological special project of "Major New Drug Creation". Since its launch in China and the United States, it has been proven to have definite efficacy, extremely low systemic absorption, no treatment-related systemic adverse reactions, and high safety.

[0005] Studies have shown that Benvimod is an AhR (Aryl Hydrocarbon Receptor) agonist that can specifically bind to and regulate AhR, playing an important role in many inflammatory autoimmune skin diseases. Oral diseases such as oral ulcers are difficult to cure autoimmune diseases. Currently, there are limited treatments for oral ulcers, especially recurrent oral ulcers or oral ulcers caused by Behcet's disease, and there is a lack of effective treatments.

[0006] Oral ulcers, commonly known as "mouth sores", are a common ulcerative injury disease that occurs in the oral mucosa. They are often seen on the inner side of the lips, tongue, tongue ventral surface, buccal mucosa, vestibule groove, soft palate and other parts. The current incidence rate is relatively high. It has a great impact on the work and life of patients. Oral ulcers include recurrent oral ulcers, traumatic oral ulcers and oral ulcers associated with diseases. Among them, recurrent oral ulcers are also called recurrent aphthous ulcers or frequent oral ulcers. The "Guidelines for the Diagnosis and Treatment of Recurrent Aphthous Ulcers" issued by my country in 2012 pointed out that 10% to 25% of the population suffers from recurrent oral ulcers, with a high incidence age of 10 to 30 years old; traumatic oral ulcers include oral ulcers caused by mechanical damage (such as damage to the oral mucosa caused by hard objects such as fish bones, sand and gravel in food, toothbrushes, tartar deposited on the surface of teeth, etc.), chemical burns (such as local oral mucosal damage caused by the use of analgesic lozenges such as aspirin, silver nitrate, iodine tincture and other irritating drugs), cold and hot stimulation (such as mucosal burns caused by high water temperature, overly hot food, etc., or mucosal frostbite caused by improper low-temperature treatment); oral ulcers associated with diseases include oral ulcers associated with diseases such as Behcet's disease, Reiter's syndrome, Behcet's syndrome and tumors.

[0007] At present, the cause of oral ulcers is still unclear, and its possible inducing factors include genetic factors, dietary factors, immune factors, mental factors or traumatic factors. The drug treatment of oral ulcers gives priority to local treatment, including the use of analgesics (such as lidocaine, benzocaine, benzydamine), anti-inflammatory drugs (such as chlorhexidine, iodine), healing-promoting drugs (such as Bingpengsan, Xiguashuang, recombinant human epidermal growth factor), hormone drugs and Kangfuxin liquid. For patients with severe oral ulcers or high recurrence frequency, systemic administration can be applied, including the use of immune preparations or vitamins. Long-term use of hormones can produce some serious adverse side effects. Immune preparations can also reduce the recurrence of ulcers, such as transfer factor, thymosin, etc., but the efficacy of such drugs may be reduced after long-term use.

[0008] So far, there is no safe, effective and highly specific therapeutic drug for oral diseases such as oral ulcers. Therefore, developing new and highly effective drugs for treating oral diseases is a difficult problem that needs to be solved urgently.

[0009] Based on the above background, the present invention develops new indications for benvimod and provides a dosage form with good patient compliance, namely an orodispersible film composition or orodispersible film agent, providing a new option for the treatment of oral-related diseases. Summary of the invention

[0010] In view of this, the purpose of the present disclosure is to provide a bevimod orodispersible film composition, a preparation method thereof and its application in medicine, wherein the active ingredient of the bevimod orodispersible film composition is selected from one or more of bevimod, a pharmaceutically acceptable salt of bevimod and its inclusion compound or a complex thereof; it has been verified that the orodispersible film composition provided by the present disclosure has the advantages of thin thickness, good taste, stable properties, instant dissolution in the oral cavity and fast absorption speed. The disclosure provides a new option with better patient compliance for the treatment of oral-related diseases.

[0011] Furthermore, the present disclosure provides a bevimod orodispersible film composition, characterized in that the orodispersible film composition comprises an active ingredient, a film-forming material, a plasticizer and an optional surfactant, an optional flavoring agent, an optional colorant and an optional antioxidant; wherein the active ingredient is selected from one or more of bevimod, a pharmaceutically acceptable salt of bevimod and its inclusion compound or its complex.

[0012] In some embodiments of the present disclosure, the bevimod orodispersible film composition described in the present disclosure, wherein the active ingredient is selected from one or more of bevimod and a pharmaceutically acceptable salt of bevimod.

[0013] In some embodiments of the present disclosure, the bevimod orosoluble film composition described in the present disclosure, wherein the particle size of the active ingredient (preferably bevimod and one or more of bevimod pharmaceutically acceptable salts) is 0.1 μm to 60 μm, preferably 0.1 μm to 26 μm, more preferably 1 μm to 10 μm; examples thereof may be 5 μm, 8 μm.

[0014] In some embodiments of the present disclosure, the bevimod orodispersible film composition described in the present disclosure, wherein the active ingredient is preferably bevimod and one or more of its pharmaceutically acceptable salts, calculated on the basis of the content of the above-mentioned orodispersible film composition, and the content is 0.01% to 30%, preferably 1% to 25%, and more preferably 1% to 15%; examples thereof may be 2%, 4%, 5%, 7%, 9%, 12%, 15%, 20%, 25% or 30%.

[0015] In some embodiments of the present disclosure, the orodispersible film composition of bevimod described in the present disclosure, wherein the film-forming material is a carrier of the drug; specifically, the film-forming material is selected from one or more of water-soluble polymer film-forming materials, gelatin, xanthan gum, shellac, gum arabic, starch, dextrin, agar, sodium alginate, zein and silicone rubber; preferably, the water-soluble polymer film-forming material is preferably selected from one or more of hydroxypropyl methylcellulose, pullulan, hyaluronic acid chitosan, polyvinyl alcohol, polyoxyethylene, acrylic acid copolymer, povidone, polylactic acid hydroxypropyl starch, hydroxypropyl cellulose and polyvinyl pyrrolidone.

[0016] In some embodiments of the present disclosure, the bevimod orodispersible film composition described in the present disclosure, wherein the content of the film-forming material is 20% to 75%, preferably 30% to 70%, and more preferably 40% to 60%, based on the content of the orodispersible film composition; examples thereof may be 10%, 15%, 20%, 30%, 40%, 50%, 60%, 65% or 70%.

[0017] In some embodiments of the present disclosure, the orodispersible film composition of Bevimod described in the present disclosure, wherein the plasticizer is a component used to lower the glass transition temperature of the film, increase plasticity and toughness, and improve elongation. Specifically, the plasticizer is preferably selected from one or more of glycerol, Tween 80, propylene glycol, polyethylene glycol, phthalate, polysorbate, ethyl citrate, triethylglycerol and castor oil; preferably, the plasticizer is one or both of glycerol or polyethylene glycol.

[0018] In some embodiments of the present disclosure, the bevimod orodispersible film composition described in the present disclosure, wherein the content of the plasticizer is 5% to 30%, preferably 5% to 20%, based on the content of the orodispersible film composition; examples thereof may be 5%, 8%, 10%, 12%, 15%, 18%, 20% and 23%.

[0019] In some embodiments of the present disclosure, the bevimod orodispersible film composition described in the present disclosure further optionally includes a surfactant, and the surfactant is selected from one or more of sodium lauryl sulfate, poloxamer, and polysorbate, preferably polysorbate.

[0020] In some embodiments of the present disclosure, the bevimod orodispersible film composition described in the present disclosure, wherein the content of the surfactant is 0.1% to 15%, preferably 1% to 10%, based on the content of the orodispersible film composition; examples thereof may be 1%, 1.5%, 2%, 4%, 5%, 7%, 8% and 10%.

[0021] In some embodiments of the present disclosure, the orodispersible film composition of the present disclosure, wherein the orodispersible film composition further optionally includes a flavoring agent. The flavoring agent is a substance that acts as a flavoring agent in the film. As an example, the sweetener is preferably a human sweetener or a spice flavor; wherein the sweetener is selected from one or more of xylitol, sorbitol, ribose, glucose, mannose, galactose, sucrose, maltose, steviol glycoside, glycyrrhizic acid, saccharin sodium, sodium cyclamate, acesulfame potassium, aspartame, sucralose, alitame, and neotame; the spice flavor is selected from one or more of peppermint oil, menthol, citric acid, malic acid, and fruit flavor.

[0022] In some embodiments of the present disclosure, the brevitamod orodispersible film composition described in the present disclosure, wherein the content of the flavoring agent is 0.5% to 10%, preferably 0.7% to 5%, based on the content of the orodispersible film composition; examples thereof may be 0.5%, 0.75%, 1%, 1.5%, 2%, 4%, 5%, 7% and 8%.

[0023] In some embodiments of the present disclosure, the orodispersible film composition of the present disclosure, wherein the orodispersible film composition further optionally includes a colorant. The colorant refers to a substance that can improve the appearance color of the preparation, can be used to identify the concentration of the preparation, distinguish the application method, and reduce the patient's aversion to taking the medicine. As an example, the colorant is selected from one or more of yellow iron oxide, red iron oxide, sunset yellow, lemon yellow and FD&C approved colorants.

[0024] In some embodiments of the present disclosure, the bevimod orodispersible film composition described in the present disclosure, wherein the content of the colorant is 0.01% to 5%, preferably 0.1% to 3%, based on the content of the orodispersible film composition; examples thereof may be 0.1%, 0.2%, 0.25%, 1%, 2%, 3% and 5%.

[0025] In some embodiments of the present disclosure, the bevimod orodispersible film composition of the present disclosure further optionally comprises an antioxidant. As an example, the antioxidant is selected from one or more of butylated hydroxyanisole, butylated hydroxytoluene, propyl gallate, tert-butylhydroquinone, and disodium edetate; preferably, the antioxidant is butylated hydroxyanisole or butylated hydroxytoluene.

[0026] In some embodiments of the present disclosure, the bevimod orodispersible film composition described in the present disclosure, wherein the content of the antioxidant is 0.01% to 5%, preferably 0.01% to 2%, based on the content of the orodispersible film composition; examples thereof may be 0% and 0.1%, 2%, 3% and 5%.

[0027] In some embodiments of the present disclosure, the brevimemod orodispersible film composition described in the present disclosure further optionally includes one or more of a chelating agent, an absorption enhancer and a filler.

[0028] In some embodiments of the present disclosure, the bevimod orosoluble film composition described in the present disclosure has a thickness of 1 μm to 100 μm.

[0029] In some embodiments of the present disclosure, the bevimod orodispersible film composition described in the present disclosure, wherein the active ingredient of the orodispersible film composition is selected from one or more of bevimod, a pharmaceutically acceptable salt of bevimod, and its inclusion compound or a complex thereof; for example, the active ingredient is selected from one or more of bevimod and a pharmaceutically acceptable salt of bevimod; for example, the active ingredient is selected from one or more of an inclusion compound of bevimod and an inclusion compound of a pharmaceutically acceptable salt of bevimod; for example, the active ingredient is selected from one or more of a complex of bevimod and a complex of a pharmaceutically acceptable salt of bevimod.

[0030] In some embodiments of the present disclosure, the bevimod orodispersible film composition described in the present disclosure, wherein the active ingredient is selected from one or more of the inclusion complex of bevimod and the inclusion complex of the pharmaceutically acceptable salt of bevimod; the inclusion complex is preferably a cyclodextrin inclusion complex, preferably a mixture of one or more of α-cyclodextrin, β-cyclodextrin, hydroxypropyl-β-cyclodextrin and sulfobutyl-β-cyclodextrin. Preferably, in the inclusion complex, the molar ratio of the bevimod to the cyclodextrin is selected from (0.1 to 10):1.

[0031] In some embodiments of the present disclosure, the bevimod orosoluble film composition described in the present disclosure, wherein the active ingredient is selected from one or more of a complex of bevimod and a complex of a pharmaceutically acceptable salt of bevimod; the complex of bevimod is a complex formed by bevimod and an ion exchange resin; the complex of a pharmaceutically acceptable salt of bevimod is a complex formed by a pharmaceutically acceptable salt of bevimod and an ion exchange resin.

[0032] In some embodiments of the present disclosure, the bevimod orosoluble film composition of the present disclosure, wherein the ion exchange resin includes but is not limited to sodium polystyrene sulfonate (C100Na MR), cross-linked polyacrylate copolymer ( 335), polyclinic (C115H MR) and polacrilin potassium (C115K MR).

[0033] Furthermore, the present disclosure provides a method for preparing the benvimod orodispersible film composition, characterized in that the preparation method comprises mixing the active ingredients in the benvimod orodispersible film composition with other ingredients to obtain a slurry, applying it to form a film; drying and cutting to obtain the product.

[0034] In some embodiments of the present disclosure, the present disclosure provides a method for preparing the bevimod orodispersible film composition, which comprises the following steps:

[0035] 1) Add the active ingredient into a solvent at a certain temperature (such as 20-80% ethanol) and stir evenly;

[0036] 2) Add other auxiliary materials into step 1) and continue to stir and mix evenly;

[0037] 3) adding the film-forming material to the solution of step 2) and stirring to obtain a drug-containing gel solution;

[0038] 4) Apply, dry and cut the drug-containing glue solution.

[0039] Furthermore, the present disclosure provides a bevimod orodispersible film-forming agent, wherein the bevimod orodispersible film-forming agent comprises the bevimod orodispersible film composition described above; preferably, the bevimod orodispersible film-forming agent has a thickness of 1 μm to 100 μm.

[0040] Furthermore, the present disclosure relates to the use of the above-mentioned bevimod orodispersible film composition or the above-mentioned bevimod orodispersible film preparation in the preparation of a medicament for treating and / or preventing oral-related diseases; wherein the oral-related diseases are preferably selected from stomatitis, oral ulcers, oral herpes, gingivitis and periodontal disease, more preferably stomatitis or oral ulcers, and most preferably oral ulcers.

[0041] The present disclosure also relates to a method for treating and / or preventing oral-related diseases, which comprises administering a therapeutically effective amount of the bevimod orodispersible film composition or the bevimod orodispersible film formulation as described above to a patient in need thereof; wherein the oral-related disease is preferably selected from stomatitis, oral ulcers, oral herpes, gingivitis and periodontal disease, more preferably stomatitis or oral ulcers, and most preferably oral ulcers.

[0042] The present disclosure also relates to a bevimod orodispersible film composition or bevimod orodispersible film preparation as described above for use as a medicament.

[0043] The present disclosure also relates to a benvimod orodispersible film composition or benvimod orodispersible film agent as described above, which is used as a drug for treating and / or preventing oral-related diseases; wherein the oral-related diseases are preferably selected from stomatitis, oral ulcers, oral herpes, gingivitis and periodontal disease, more preferably stomatitis or oral ulcers, and most preferably oral ulcers.

[0044] Definitions and explanations of terms

[0045] Unless otherwise specified, the definitions of terms recorded in the specification and claims of this application, including definitions as examples, exemplary definitions, preferred definitions, definitions recorded in tables, definitions of specific components in embodiments, etc., may be arbitrarily combined and coupled with each other. Such combinations and couplings shall fall within the scope of the description of this application.

[0046] With respect to a drug or pharmacologically active agent, the term "therapeutically effective amount" refers to a sufficient amount of the drug or agent that is non-toxic but can achieve the desired effect. The determination of the effective amount varies from person to person, depending on the age and general condition of the recipient, and also on the specific active substance. The appropriate effective amount in each case can be determined by a person skilled in the art based on routine experiments.

[0047] The term "subject or patient" refers to a patient in need of prevention or treatment of a skin disease or disorder, wherein the patient is a mammal, for example selected from rodents, cows, pigs, dogs, cats and primates, particularly humans.

[0048] To avoid ambiguity, the content of a certain type of excipients, such as oily base, mentioned in this article refers to the total content. If the excipient of this type contains more than one ingredient, it refers to the sum of the contents of all ingredients, not the content of each ingredient separately. If the content is clearly stated as "each", it means the content of each ingredient separately.

[0049] As used herein, the singular form of "a," "an," and "the" include plural references and vice versa unless the context clearly dictates otherwise.

[0050] When the term "about" is applied to a parameter such as pH, concentration, temperature, etc., it indicates that the parameter can vary by ±10%, and sometimes more preferably within ±5%. As will be understood by those skilled in the art, when a parameter is not critical, numbers are generally given only for illustrative purposes and not for limitation.

[0051] In the context of the present disclosure, when the expression "one or more" is used, the "plurality" means two or more, such as 2, 3, 4, 5, 6 or more.

[0052] In the context of the present disclosure, "orodissolving film" means an oral dissolving film (ODF).

[0053] Beneficial Effects

[0054] The benvimod oral dissolving film composition provided by the present disclosure, whose active ingredient benvimod is the first AhR modulator on the market, has been verified to have extremely low systemic absorption, no relevant systemic adverse reactions, high safety, and is a non-hormonal small molecule compound. The benvimod oral dissolving film composition and benvimod oral dissolving film prepared by the present disclosure have the advantages of thin thickness, good taste, stable properties, instant dissolution in the oral cavity without drinking water, fast absorption rate, and no gritty feeling after dissolving in the oral cavity, and can improve the taste of the drug and increase patient compliance. At the same time, the film appearance of the oral thin film is uniform and flexible. In addition, no sedimentation occurs during the preparation of the film liquid of the oral thin film, and the content uniformity meets the requirements. DETAILED DESCRIPTION

[0055] The following examples are used to further describe the present disclosure, but these examples are not intended to limit the scope of the present disclosure. If no specific conditions are specified for an experimental method, it is usually carried out under conventional conditions.

[0056] Examples 1-3 investigate the film-forming properties of different active ingredient contents:

[0057] Examples 1-3

[0058]

[0059]

[0060] Preparation method:

[0061] 1. Add the active ingredient into 60% ethanol solvent at a certain temperature and stir evenly;

[0062] 2. Add plasticizer, surfactant, flavoring agent, colorant and other auxiliary materials into step 1 and continue to stir evenly;

[0063] 3. Add the film-forming material to the solution in step 2, stir and mix evenly to obtain a drug-containing glue solution;

[0064] 4. Apply the drug-containing glue solution, dry at 50°C for 1-2 hours, peel off and cut.

[0065] In the prescriptions of Examples 1-3, uniform drug-containing glue solutions were obtained, and the solutions had excellent film-forming and peeling properties, and had certain ductility.

[0066] Examples 4-7 investigate the effects of different film-forming materials on film-forming properties and stripping properties.

[0067] Embodiment 4-7

[0068]

[0069] Preparation method:

[0070] 1. Add the active ingredient into 60% ethanol solvent at a certain temperature and stir evenly;

[0071] 2. Add other auxiliary materials such as plasticizer, surfactant, flavoring agent and colorant into step 1 and continue to stir evenly;

[0072] 3. Add the film-forming material to the solution in step 2 and stir to obtain a uniform drug-containing gel solution;

[0073] 4. Apply the drug-containing glue solution, dry at 50°C for 1-2 hours, peel off and cut.

[0074] The drug-containing glues of uniform color were obtained in the prescriptions of Examples 4, 6 and 7, and had good film-forming and peeling properties, and had certain ductility. The film-forming property of Example 5 was good, but the peeling property was poor, and the plasticity was strong.

[0075] Embodiment 8-9

[0076]

[0077] Preparation method:

[0078] 1. Add the active ingredient into 60% ethanol solvent at a certain temperature and stir evenly;

[0079] 2. Add other auxiliary materials such as plasticizer, surfactant, flavoring agent and colorant into step 1 and continue to stir evenly;

[0080] 3. Add the film-forming material to the solution in step 2 and stir to obtain a uniform drug-containing gel solution;

[0081] 4. Apply the drug-containing glue solution, dry at 50°C for 1-2 hours, peel off and cut.

[0082] Evaluation of orally dissolving film performance: Evaluation is conducted based on the appearance, film-forming properties, folding resistance, peeling properties, and dissolution and dispersion speed of the orally dissolving film.

[0083] Appearance: smooth and uniform, without lumps.

[0084] Film-forming property: Spreads into a good film, can be peeled off, and has good folding resistance. The results are evaluated by excellent, good, qualified, and unqualified.

[0085] Folding resistance: Fold the paper repeatedly along a crease and record the number of folds.

[0086] Peelability: Whether it has strong adhesion to the watch glass.

[0087] The following table shows the results of the oral dissolving film performance test of Examples 1-9:

[0088]

[0089] Summary: Benvimod can be made into a new type of orodispersible film preparation with good performance. The content of Benvimod is preferably 10%-25%, and the film-forming material is preferably hydroxypropyl methylcellulose or a combination of hydroxypropyl cellulose, and more preferably a polyvinyl alcohol film-forming material, which not only has good film-forming property and good ductility, but also has strong toughness, which is conducive to later scale-up production and faster dissolution and dispersion, which is conducive to rapid absorption through the oral cavity and can improve compliance. The addition of other trace excipients does not have much effect on the performance of the orodispersible film. Preparing Benvimod into a new type of orodispersible film preparation can enable it to exert a better therapeutic effect.

Claims

1. A benvimod orodispersible film composition, characterized in that: The orodispersible film composition comprises an active ingredient, a film-forming material, a plasticizer and optionally a surfactant, optionally a flavoring agent, optionally a colorant and optionally an antioxidant; wherein the active ingredient is selected from one or more of benvimod, a pharmaceutically acceptable salt of benvimod and its inclusion compound or a complex thereof.

2. The bevimod orosoluble film composition according to claim 1, characterized in that When the active ingredient is selected from one or more of benvimod and a pharmaceutically acceptable salt of benvimod, the particle size of the active ingredient is 5 μm to 45 μm.

3. The bevimod orosoluble film composition according to claim 1 or 2, characterized in that The content of the active ingredient is 0.1% to 30% based on the content of the orodispersible film composition.

4. The bevimod orosoluble film composition according to any one of claims 1 to 3, characterized in that The film-forming material is a water-soluble polymer film-forming material, and the water-soluble polymer film-forming material is preferably selected from one or more of hydroxypropyl methylcellulose, pullulan, hyaluronic acid chitosan, polyvinyl alcohol, hydroxypropyl starch, hydroxypropyl cellulose and polyvinyl pyrrolidone; and / or the plasticizer is preferably selected from one or more of glycerol, Tween 80, propylene glycol, polyethylene glycol, phthalate, polysorbate, ethyl citrate, triethylglycerol and castor oil; more preferably, the film-forming material is hydroxypropyl methylcellulose E5, hydroxypropyl cellulose, polyvinyl alcohol.

5. The bevimod orosoluble film composition according to any one of claims 1 to 4, characterized in that Based on the content of the orodispersible film composition, the content of the film-forming material is 30% to 75%, preferably 30% to 60%; and / or the content of the plasticizer is 1% to 20%.

6. The bevimod orosoluble film composition according to any one of claims 1 to 5, characterized in that The surfactant is polysorbate, preferably polysorbate 80, with a content of 10%.

7. The bevimod orosoluble film composition according to any one of claims 1 to 6, characterized in that The flavor corrector is sucralose, peppermint oil or a combination thereof, and the content thereof is 0% to 5%.

8. The method for preparing the bevimod orosoluble film composition according to any one of claims 1 to 7, characterized in that: The preparation method comprises mixing the active ingredients in the bevimod orodispersible film composition with other ingredients to obtain a slurry, applying the slurry to form a film, and drying and cutting to obtain the product.

9. A benvimod orodispersible film-forming agent, characterized in that: The bevimod orodispersible film comprises the bevimod orodispersible film composition according to any one of claims 1 to 7; preferably, the bevimod orodispersible film has a thickness of 1 μm to 100 μm.

10. Use of the benvimod orodispersible film composition according to any one of claims 1 to 7 or the benvimod orodispersible film according to claim 9 in the preparation of a medicament for treating and / or preventing oral-related diseases, wherein the oral-related diseases are preferably selected from stomatitis, oral ulcers, oral herpes, gingivitis and periodontal disease.

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