阅读说明：本技术 一种治疗口腔黏膜疾病的组合物及其制备方法 (Composition for treating oral mucosa diseases and preparation method thereof ) 是由 赵行 闫毓杰 刘江 江潞 陈谦明 于 2021-09-28 设计创作，主要内容包括：本发明提供了一种治疗口腔黏膜疾病的组合物,它是由羧甲基纤维素钠0.5-6份、聚乙烯吡咯烷酮1-10份、甘油1-10份组成的组合物与治疗口腔黏膜疾病的药物制备而成的贴剂,具有优异的口腔黏膜粘附性能。进一步在其表面覆盖玉米蛋白疏水层,能够防止药物多向释放造成损失,同时避免贴剂被唾液快速溶解,保证较长的粘附时间和优异的缓释效果,且玉米蛋白味道佳,能够提高患者顺应性,在口腔黏膜给药治疗口腔黏膜疾病的药物中具有非常好的应用前景。(The invention provides a composition for treating oral mucosa diseases, which is a patch prepared from a composition consisting of 0.5-6 parts of sodium carboxymethylcellulose, 1-10 parts of polyvinylpyrrolidone and 1-10 parts of glycerol and a medicament for treating the oral mucosa diseases, and has excellent oral mucosa adhesion performance. The zein hydrophobic layer is further covered on the surface of the zein hydrophobic layer, so that the loss caused by multidirectional release of the medicine can be prevented, the patch is prevented from being quickly dissolved by saliva, the long adhesion time and the excellent slow release effect are ensured, the zein taste is good, the patient compliance can be improved, and the zein hydrophobic layer has a good application prospect in medicines for treating oral mucosa diseases by oral mucosa administration.)

1. The drug carrier is characterized by being prepared from the following raw materials in parts by weight: 0.5-6 parts of sodium carboxymethylcellulose, 1-10 parts of polyvinylpyrrolidone and 1-10 parts of glycerol.

2. The drug carrier of claim 1, which is prepared from the following raw materials in parts by weight: 0.5-2 parts of sodium carboxymethylcellulose, 1-3 parts of polyvinylpyrrolidone and 1-3 parts of glycerol.

3. A composition for treating oral mucosa diseases, which is characterized by comprising a medicament for treating oral mucosa diseases and a medicament carrier according to claim 1 or 2, wherein the medicament and the medicament carrier have the following parts by weight: 0.01-0.3 part of medicine for treating oral mucosa diseases and 2-4 parts of medicine carrier.

4. The composition of claim 3, further comprising 0.1 to 1.3 parts by weight of a hydrophobic component, wherein the hydrophobic component is zein or ethyl cellulose.

5. The composition of claim 3 or 4, wherein the drug for treating oral mucosal disease comprises a drug for treating oral ulcer, stomatitis, cheilitis, oral leukoplakia, oral lichen planus and/or oral submucosal fibrous lesion, and the drug for treating stomatitis comprises a drug for treating herpetic stomatitis, drug allergic stomatitis and/or fungal stomatitis;

or, the medicine for treating oral mucosa diseases comprises adrenocortical hormone medicine, antibacterial medicine, antiviral medicine and/or photosensitizer;

the adrenocortical hormone medicine comprises dexamethasone or a salt thereof, and betamethasone or a salt thereof;

the antibacterial drug comprises nystatin, ketoconazole or fluconazole;

the antiviral drug comprises acyclovir;

the photosensitizer comprises aminolevulinic acid hydrochloride.

6. The composition according to claim 3 or 4, which is a preparation prepared by taking the medicament for treating the oral mucosa diseases as an active ingredient and taking the medicament carrier as an auxiliary material;

or the preparation is prepared by taking the medicine for treating the oral mucosa diseases as an active ingredient and taking the medicine carrier and the hydrophobic ingredient as auxiliary materials.

7. The composition according to claim 6, wherein the formulation is a patch, preferably a patch for oromucosal administration.

8. A method of preparing the composition of claim 7, comprising the steps of:

(1) dissolving the raw materials of the drug carrier in water, stirring uniformly, adding the drug for treating oral mucosa diseases, stirring uniformly, and removing bubbles;

(2) drying the mixture for 2 to 8 hours at the temperature of between 50 and 70 ℃ to form the adhesive layer patch.

9. The method of claim 8, further comprising the steps of:

and (3) dissolving a hydrophobic component in an organic solvent, spraying the hydrophobic component on the surface of the adhesive layer sticker obtained in the step (2), and drying to obtain the double-layer patch consisting of the adhesive layer and the hydrophobic layer, wherein the hydrophobic component is not sprayed on at least one surface of the adhesive layer sticker.

10. Use of the pharmaceutical carrier according to claims 1-2 or the composition according to any one of claims 3-7 for the preparation of a medicament for the treatment of oral mucosal diseases.

Technical Field

The invention belongs to the field of pharmaceutical preparations, and particularly relates to a composition for treating oral mucosa diseases and a preparation method thereof.

Background

Oral mucosa diseases refer to diseases in which the normal color, shape, integrity and function of the mucosa of a certain part of the oral cavity are changed. The lesions are various and complex, and comprise diseases such as vesicular stomatitis, oral ulcer, oral leukoplakia and the like. Among them, oral ulcers are characterized by recurrent attacks, including recurrent aphthous ulcers, recurrent necrotic periglandular inflammation of the mucosa, behcet's syndrome, and the like. The number of ulcers is from small to large, the ulcers are mostly on the oral mucosa, gum, upper and lower parts of the tongue body, the side surfaces and throat part from front to back, the ulcerated surface is as large as soybean and as small as rice grains, and a white ulcerated necrotic film is attached to the surface. The mild patients can take place once a few months, the intermittent period of the severe patients is gradually shortened, the severe patients get worse year by year, even the ulcer is slow to heal for years and decades, and various complications in vivo can be caused, and the physical health and the working life of the patients are directly influenced. In clinic, a 10% silver nitrate aqueous solution is mostly adopted to burn a local wound, or 0.1% potassium permanganate solution, compound boric acid solution and other gargling are adopted to relieve oral ulcer pain, or powder such as Bingpeng powder is adopted to treat the oral ulcer pain, however, the treatment methods cannot protect the ulcer wound, and a patient still rubs the ulcer wound when speaking and eating, so that pain is caused, and effective healing of the wound is also prevented.

The mucosa has the structural characteristics of abundant vascular network and strong permeability, so that compared with other administration routes, the mucosa administration has unique advantages, overcomes the first pass effect of the liver and the drug degradation under the action of various gastrointestinal enzymes and intestinal flora, and can play the purpose of quick effect. For oral mucosa diseases, the oral mucosa adhesive administration can play a treatment role of local targeting continuous administration aiming at focuses; in addition, it can be further used for local and systemic administration of many other drugs for the treatment of other diseases, especially for unconscious and poorly fitted patients.

The oral ulcer film (tablet) is used as a patch for drug delivery through mucosa adhesion, can be adhered to an oral ulcer part, protects a wound surface, and can effectively promote the healing of the oral ulcer wound surface through a mucosa adhesion drug delivery way. However, most of the existing oral ulcer patches have the following problems: 1. the adhesive is not strong and is easy to fall off; 2. the toughness is poor, the fitting performance is not good, the material is hard, and the compliance of a patient is poor; 3. some double surfaces are sticky, and are easy to stick to other parts of the oral cavity to fall off; 4. the slow release effect of the medicine is not good, or the medicine is lost due to multidirectional release, and the medicine cannot be used for the oral mucosa in a targeted and continuous way. To ameliorate these problems, researchers have made efforts to improve canker sore patches. For example, patent CN112603911A discloses a double-layer oral mucosa adhesive film, which is composed of an adhesive layer and a separation protective layer, wherein the adhesive layer is made of water-soluble derivatives of chitosan, and has the functions of adhesion and sterilization, and the separation protective layer is made of soft, inert and excellent-ductility materials such as polyurethane. However, the adhesion effect and the wound healing promoting effect of the double-layer adhesive film are not clear.

Therefore, the novel patch for oral mucosa adhesion administration, which has good adhesion, less drug loss, excellent mechanical property and sustained release property, is further developed, and has very important significance and excellent application prospect.

Disclosure of Invention

In order to solve the problems of poor adhesion, mechanical property and slow release effect of the existing oral mucosa drug delivery sticking film, the invention provides the oral mucosa drug delivery sticking film which has excellent adhesion, mechanical property and slow release effect and good biocompatibility.

The invention provides a drug carrier which is prepared from the following raw materials in parts by weight: 0.5-6 parts of sodium carboxymethylcellulose, 1-10 parts of polyvinylpyrrolidone and 1-10 parts of glycerol.

Further, the feed additive is prepared from the following raw materials in parts by weight: 0.5-2 parts of sodium carboxymethylcellulose, 1-3 parts of polyvinylpyrrolidone and 1-3 parts of glycerol, preferably 1 part of sodium carboxymethylcellulose, 1 part of polyvinylpyrrolidone and 1 part of glycerol.

The invention also provides a composition for treating oral mucosa diseases, which contains the medicine for treating oral mucosa diseases and the medicine carrier, wherein the medicine and the medicine carrier have the following parts by weight: 0.01-0.3 part of medicine for treating oral mucosa diseases and 2-4 parts of medicine carrier;

preferably, the medicine for treating oral mucosa diseases is 0.01-0.3 part, and the medicine carrier is 3 parts.

Furthermore, the composition for treating the oral mucosa diseases also contains 0.1 to 1.3 weight parts of hydrophobic ingredients, and the hydrophobic ingredients are zein or ethyl cellulose.

Further, the above-mentioned drugs for treating oral mucosal diseases include drugs for treating oral ulcer, stomatitis, cheilitis, oral leukoplakia, oral lichen planus, and/or oral submucosal fibrous lesion, and the drugs for treating stomatitis include drugs for treating herpetic stomatitis, drug allergic stomatitis, and/or fungal stomatitis;

or, the medicine for treating oral mucosa diseases comprises adrenocortical hormone medicine, antibacterial medicine, antiviral medicine and/or photosensitizer;

the adrenocortical hormone medicine comprises dexamethasone or a salt thereof, and betamethasone or a salt thereof;

the antibacterial drug comprises nystatin, ketoconazole or fluconazole;

the antiviral drug comprises acyclovir;

the photosensitizer comprises aminolevulinic acid hydrochloride.

Furthermore, the composition for treating oral mucosa diseases is a preparation prepared by taking the medicine for treating oral mucosa diseases as an active ingredient and taking the medicine carrier as an auxiliary material;

or the preparation is prepared by taking the medicine for treating the oral mucosa diseases as an active ingredient and taking the medicine carrier and the hydrophobic ingredient as auxiliary materials.

Further, the preparation is a patch, preferably a patch for oral mucosal administration.

The invention also provides a preparation method of the composition, which comprises the following steps:

(1) dissolving the raw materials of the drug carrier in water, stirring uniformly, adding the drug for treating oral mucosa diseases, stirring uniformly, and removing bubbles;

(2) drying the mixture for 2 to 8 hours at the temperature of between 50 and 70 ℃ to form the adhesive layer patch.

Further, the preparation method also comprises the following steps:

dissolving a hydrophobic component in an organic solvent, spraying the hydrophobic component on the surface of the adhesive layer sticker obtained in the step (2), and drying to obtain a double-layer patch consisting of an adhesive layer and a hydrophobic layer, wherein at least one surface of the adhesive layer sticker is not sprayed with the hydrophobic component; preferably, the organic solvent is an alcohol.

The invention also provides the application of the drug carrier or the composition in preparing drugs for treating oral mucosa diseases.

The invention has the beneficial effects that: the oral ulcer film prepared by the invention has excellent biocompatibility, very good oral mucosa adhesion performance and mechanical property, and good corn protein taste of the hydrophobic layer, can improve the compliance of patients, and simultaneously avoids the rapid dissolution of the film by saliva, thereby ensuring longer adhesion time and excellent slow release effect.

The oral ulcer film disclosed by the invention has good wrapping and slow-release effects on dexamethasone sodium phosphate, can realize slow release of the dexamethasone sodium phosphate effective component on the oral ulcer wound surface, and promotes ulcer healing.

Obviously, many modifications, substitutions, and variations are possible in light of the above teachings of the invention, without departing from the basic technical spirit of the invention, as defined by the following claims.

The present invention will be described in further detail with reference to the following examples. This should not be understood as limiting the scope of the above-described subject matter of the present invention to the following examples. All the technologies realized based on the above contents of the present invention belong to the scope of the present invention.

Drawings

FIG. 1 shows the state of different formulations of compositions with tissue adhesion as adhesive layers.

FIG. 2 is a graph showing the results of adhesion tests for different formulations of compositions having tissue adhesion properties.

FIG. 3 is the state of a hydrophobic layer prepared by spraying different hydrophobic components on the basis of the same kind of adhesive layer.

FIG. 4 is a photograph showing a comparison of the adhesion test of the patch of example 6 of the present invention with a commercially available oral film.

FIG. 5 is a graph comparing the adhesion time of the patch of example 6 of the present invention with a commercially available oral film.

Detailed Description

The raw materials used in the invention are as follows:

1. sodium carboxymethylcellulose 300-800 mPa-^.s (chemical purity CP300-800mPa.s 500g, [ C ]₆H₇O₂(OH)_X(OCH₂CO₂Na)_y]_nNational drug group chemical reagents limited, lot number: 20201109, 30036328)

2. Polyvinylpyrrolidone K30 (guaranteed reagent, (C)₆H₉NO)_nNational pharmaceutical group chemical reagents limited, batch number: 20201210,30154481)

3. Glycerol (> 99.5%, sigma-aldrich,102137984, Lot # BCCB1653)

4. Zein (from corn) (Chishiai (Shanghai) Seiki Industrial development Co., Ltd. Z0001, Lot. PSIOO-LN)

5. Ethyl cellulose (ethyl cellulose, ethoxyl, content 48%, 300cps, New Jersey, USA:1-800-ACROS-01,232705000, Lot: A0231059).

The method for testing the adhesion performance of the invention comprises the following steps:

rotary artificial saliva method: pasting a sample to be tested with the size of about 1cm x 1cm on the mucous membrane of the back of a fresh pig tongue, placing the mucous membrane of the back of the pig tongue pasted with the membrane in a beaker filled with artificial saliva, stirring the artificial saliva on a magnetic stirrer at 35 ℃ at the speed of 1000 revolutions, and recording the falling time of the membrane from the mucous membrane of the back of the pig tongue;

a titration method: pasting a sample to be tested with the size of about 1cm x 1cm on a fresh pig tongue back mucous membrane, fixing the pig tongue back mucous membrane pasted with the membrane in a groove inclined by about 30 degrees, titrating by a burette at the speed of 2mL/min, and recording the falling time of the membrane;

mouse intraoral adhesion: samples to be tested, approximately 1.5mm by 1.5mm in size, were attached to the right cheek of the mice and the time to membrane detachment was recorded.

Example 1 preparation of a composition according to the invention with adhesive Properties

Dissolving 0.2g of sodium carboxymethylcellulose, 0.2g of polyvinylpyrrolidone (PVP) and 0.2g of glycerol in triple distilled water (10mL), uniformly stirring at a low speed, and drying in a drying oven at 65 ℃ for about 5h to obtain the sodium carboxymethyl cellulose.

Example 2 preparation of a composition according to the invention with adhesive Properties

Dissolving 0.1g of sodium carboxymethylcellulose, 0.2g of polyvinylpyrrolidone (PVP) and 0.2g of glycerol in triple distilled water (10mL), uniformly stirring at a low speed, and drying in a drying oven at 65 ℃ for about 5h to obtain the sodium carboxymethyl cellulose.

Example 3 preparation of a composition according to the invention with adhesive Properties

Dissolving 0.3g of sodium carboxymethylcellulose, 0.2g of polyvinylpyrrolidone (PVP) and 0.2g of glycerol in triple distilled water (10mL), uniformly stirring at a low speed, and drying in a drying oven at 65 ℃ for about 5h to obtain the sodium carboxymethyl cellulose.

Example 4 preparation of a composition according to the invention with adhesive Properties

Dissolving 0.4g of sodium carboxymethylcellulose, 0.2g of polyvinylpyrrolidone (PVP) and 0.2g of glycerol in triple distilled water (10mL), uniformly stirring at a low speed, and drying in a drying oven at 65 ℃ for about 5h to obtain the sodium carboxymethyl cellulose.

Example 5 preparation of the composition for treating oral mucosal diseases (Single layer Patch) of the present invention

Dissolving 0.2g of sodium carboxymethylcellulose, 0.2g of polyvinylpyrrolidone (PVP) and 0.2g of glycerol in triple distilled water (9mL), stirring uniformly at a low speed, adding 1mL of dexamethasone sodium phosphate injection (with the concentration of 5mg/mL), stirring fully to form viscous semisolid fluid, uniformly spreading the viscous semisolid fluid in a culture dish with beeswax (for preventing adhesion and facilitating demoulding), removing bubbles, and drying in an oven at 65 ℃ for about 5 hours to obtain the product.

Example 6 preparation of the inventive double-layered Patch for treatment of oral mucosal disorders

The product prepared in the example 5 is used as an adhesive layer, 2g of zein is dissolved in 75% alcohol (30mL) to obtain a spraying liquid, 1-2 mL of the spraying liquid is uniformly sprayed on the surface of the adhesive layer prepared in the example 5, and at least one surface is not sprayed, so that at least one surface of the double-layer patch can be adhered to the oral mucosa under the action of the adhesive layer. Oven drying at 65 deg.C for 1h to obtain a yellowish double-layer oral ulcer film, pressing into sheet with desired thickness, cutting, and packaging.

Example 7 preparation of the inventive double-layered Patch for treatment of oral mucosal disorders

The product prepared in the example 5 is used as an adhesive layer, 4g of zein is dissolved in 75% alcohol (30mL) to obtain a spraying liquid, 1-2 mL of the spraying liquid is uniformly sprayed on the surface of the adhesive layer prepared in the example 5, and at least one surface is not sprayed, so that at least one surface of the double-layer patch can be adhered to the oral mucosa under the action of the adhesive layer. Oven drying at 65 deg.C for 1h to obtain a yellowish double-layer oral ulcer film, pressing into sheet with desired thickness, cutting, and packaging.

Example 8 preparation of the inventive double layer Patch for treatment of oral mucosal disorders

The product prepared in the example 5 is used as an adhesive layer, 2g of ethyl cellulose is dissolved in 95% alcohol (40mL) to obtain a spraying liquid, 1-2 mL of the spraying liquid is uniformly sprayed on the surface of the adhesive layer prepared in the example 5, and at least one surface is not sprayed, so that at least one surface of the double-layer patch can be adhered to the oral mucosa under the action of the adhesive layer. Oven drying at 65 deg.C for 1h to obtain a yellowish double-layer oral ulcer film, pressing into sheet with desired thickness, cutting, and packaging.

Example 9 preparation of the inventive double layer Patch for treatment of oral mucosal disorders

The product prepared in the example 5 is used as an adhesive layer, 2g of ethyl cellulose is dissolved in 75% alcohol (20mL) to obtain a spraying liquid, 1-2 mL of the spraying liquid is uniformly sprayed on the surface of the adhesive layer prepared in the example 5, and at least one surface is not sprayed, so that at least one surface of the double-layer patch can be adhered to the oral mucosa under the action of the adhesive layer. Oven drying at 65 deg.C for 1h to obtain a yellowish double-layer oral ulcer film, pressing into sheet with desired thickness, cutting, and packaging.

The beneficial effects of the present invention are demonstrated by the following experimental examples.

Experimental example 1 screening of raw material ratio of composition having adhesive Properties of the present invention

1. Effect of raw materials on film Forming and adhesion

The inventor conducts screening on raw materials of the adhesive composition in preliminary experiments, including sodium alginate, PVA, HMPC, chitosan and the like, finally discovers that sodium carboxymethylcellulose + glycerol + polyvinylpyrrolidone (PVP) has significant advantages in the aspects of film forming property, film stability, adhesion time and the like, further conducts screening on the three raw materials, discovers that the three components of the sodium carboxymethylcellulose, the polyvinylpyrrolidone and the glycerol have influences on the overall adhesion, and the raw materials cannot be formed into a film if the sodium carboxymethylcellulose is not added. Thus, the remaining adhesion layer material was selected based on sodium carboxymethyl cellulose, as shown in the formula chart 1.

Table 1, formulation compositions of examples and comparative examples

The film formation state of the above different formulations is shown in FIG. 1.

As can be seen from table 1 and fig. 1, the film made with pure sodium carboxymethylcellulose (formulation 2) is softer and not compact, and after a period of standing, the film becomes dry and hard, with a significant reduction in performance; after addition of polyvinylpyrrolidone (formula 4), the film becomes compact, while if the drying time or the standing time is longer, the film shrinks significantly and becomes a very dry and hard sheet (like hard plastic); after the glycerol is added into the sodium carboxymethylcellulose (formula 3), the shrinkage is still obvious when the sodium carboxymethylcellulose is dried to form a film, although the flexibility is increased to a certain extent, the hand feeling and the adhesion are poor; and only the adhesion layer (example 1) prepared by the three components of sodium carboxymethylcellulose, glycerol and PVP has very excellent film forming property, the adhesion is further improved along with the prolonging of the standing time, the adhesion layer does not become dry and hard, and the durability and the adhesion are obviously improved.

The different formulations were used as adhesive layer materials of the double-layered patch, and after the double-layered patch was prepared, the adhesive properties thereof were tested by the rotary artificial saliva method, and the results obtained are shown in fig. 2. It can be seen that the composition of example 1 (formulation 1) of the present invention has significantly better adhesion compared to other formulations, and is suitable for further application as an adhesive layer adjuvant of an oral mucosal patch.

2. Effect of raw material ratio on film Forming Properties

By adjusting the amount of the sodium carboxymethyl cellulose, the viscosity of the solution of the composition of preparation examples 1 to 4 increases with the content of the sodium carboxymethyl cellulose in the film forming process, the spreading difficulty increases during film forming, but better adhesion can be obtained, and when the content of the sodium carboxymethyl cellulose is lower, the viscosity of the solution is low, the formed film can be better and smoother, the form is better, but relatively, the adhesion can be slightly reduced. The results of the adhesion performance test by the rotary artificial saliva method of the two-layer patch prepared by using the compositions of examples 1 to 4 as the adhesive layer component are shown in Table 2. However, in general, the compositions with adhesiveness can be successfully prepared in examples 1 to 4, and a film structure is formed, so that the compositions can be further applied as an adhesive layer auxiliary material of an oral mucosa patch. In view of the increased film-forming and spreading difficulty of sodium carboxymethylcellulose, sodium carboxymethylcellulose is preferred: glycerol: the mass ratio of PVP 1:1:1 is a preferable embodiment of the adhesive layer of the present invention.

TABLE 2

Experimental example 2 screening of hydrophobic Components of the present invention

For the oral mucosal patch, the hydrophobic layer needs to satisfy the following condition: the biological compatibility is good, the biological film can play a certain moisture-proof role, the saliva erosion is reduced as much as possible, on one hand, the adhesive force and the integrity of the adhesive layer are maintained, and meanwhile, the slow release of the medicine can be realized. Thus, the inventors have selected zein and ethylcellulose as alternative hydrophobic components and evaluated the effect of forming a hydrophobic layer on the surface of a particular adhesive layer of the present invention. Four kinds of double-layered patches of examples 6 to 9 were prepared, in which the adhesive layers were the same (the adhesive layers were all prepared in example 5) and the hydrophobic layers were different, and the results of comparison are shown in FIG. 3.

As can be seen from FIG. 3, both zein and ethylcellulose can form a hydrophobic layer on the surface of the adhesive composition of the present invention, resulting in a successful two-layer patch. However, it takes a longer time for the ethylcellulose to dissolve compared to zein, and the hydrophobic layer is slightly less homogeneous and less excellent in taste than zein, and thus it is more preferable to prepare the hydrophobic layer of the double-layered patch using zein as the hydrophobic ingredient of the present invention.

Experimental example 3 adhesiveness of the double-layered adhesive preparation of the present invention

1. The adhesion performance of the double-layer patch of the invention is compared with that of patches of different adhesion layer raw materials

The adhesiveness of the two-layer patch prepared in example 6 of the present invention was evaluated by the rotary artificial saliva method, titration method, and intraoral adhesive adhesion of mice. The test result of the rotary artificial saliva method shows that the double-layer patch can be pasted for more than 1h and can not fall off; the result of a titration method test shows that the double-layer patch can be left on the mucous membrane of the back of the tongue of the pig for more than 12 hours and still can not fall off; the results of the adhesion in the mouth of the mouse show that the double-layer patch can be adhered in the mouth of the mouse for 1 hour without falling off.

The above results indicate that the double-layered oral ulcer film has good oral mucoadhesive properties.

2. The adhesion performance of the double-layer patch of the invention is compared with that of the commercial oral cavity membrane

The adhesion time of the double-layer oral ulcer membrane of example 6 of the present invention and a commercially available oral cavity membrane was evaluated by a rotary artificial saliva method, various oral cavity membranes were respectively adhered to the mucous membrane of the back of a fresh pig tongue, and stabilized for 10 minutes, the mucous membrane of the back of a pig tongue to which the membrane was adhered was placed in a beaker containing artificial saliva, the artificial saliva was stirred on a magnetic stirrer at 35 ℃ at 1000 rpm, and the falling time of the membrane from the mucous membrane of the back of a pig tongue was recorded, and the results are shown in fig. 4 and 5. Therefore, the double-layer patch prepared by the invention has the adhesion time as long as 1h, and the adhesion performance is far better than that of a commercially available oral cavity membrane.

In conclusion, the oral ulcer film prepared by the invention has excellent biocompatibility, very good oral mucosa adhesion performance and mechanical property, and good corn protein taste of the hydrophobic layer, can improve the compliance of patients, simultaneously avoids the rapid dissolution of the film by saliva, ensures longer adhesion time, and has good wrapping and slow release effects on drugs for treating oral mucosa diseases. For example, when dexamethasone sodium phosphate is coated, the sustained release of active ingredients on the wound surface of the oral ulcer can be realized, ulcer healing is promoted, and the sustained release preparation has a wide application prospect.