Adhesive oral ulcer film and preparation process thereof

Abstract

The invention belongs to the field of medical instruments, and particularly relates to an adhesive oral ulcer film and a preparation process thereof. The oral ulcer film is composed of an inner layer, an outer layer and a base material layer, the inner layer comprises partially alcoholyzed polyvinyl alcohol and active ingredients, the outer layer comprises a film-forming material and a water-soluble material, and the base material layer is made of a PET (Polyethylene Terephthalate) material. In the actual use process, the prepared oral ulcer film can be effectively prevented from falling off from the ulcer surface, the protection time is remarkably prolonged, and favorable conditions are created for rapid healing of ulcer; the dental ulcer protective film is simple in structure, high in mechanical strength, not prone to breakage in the using process, capable of better protecting the dental ulcer face and more convenient to use. Moreover, the dental ulcer membrane material prepared by the invention can be completely dissolved in an oral environment, and does not cause health threat to a human body.

Description

Technical Field

[0001] The invention belongs to the field of medical devices, and particularly relates to an adhesive oral ulcer membrane and a preparation process thereof. Background Art

[0002] In the medical device field, oral ulcer membranes are a common product for treating oral ulcers, widely used in clinical applications and daily life. However, existing oral ulcer membranes on the market have exposed many problems in actual application, seriously affecting their therapeutic effects and patient experience.

[0003] From an adhesion perspective, most traditional oral ulcer films struggle to achieve stable and long-lasting adhesion within the complex oral environment. Frequent chewing, swallowing, talking, and other oral activities, as well as the constant secretion of saliva, make these films susceptible to external forces and a humid environment. Many oral ulcer films begin to lift up shortly after application, failing to adhere tightly and firmly to the ulcer surface. This makes them prone to falling off. Oral ulcer films generally have poor strength and can break during use, exposing the ulcer surface and reducing the effectiveness of treatment.

[0004] In terms of protective performance, the film easily falls off due to poor adhesion or rupture, and thus cannot effectively block saliva and bacteria from contacting the ulcer surface. Saliva contains various enzymes and microorganisms, and bacteria can multiply on the ulcer surface, prolonging the healing time of the ulcer.

[0005] Furthermore, deficiencies in preparation processes and material research have limited the performance improvement of existing oral ulcer membranes. Some products employ overly simplistic preparation processes, relying solely on traditional production methods and lacking in-depth exploration of material properties and innovative applications. Furthermore, insufficient material research fails to fully consider the material's stability in the oral environment, biocompatibility, and correlation with therapeutic efficacy. These deficiencies result in inconsistent product quality, failing to meet clinical and patient expectations for consistent and reliable product quality.

[0006] In summary, current oral ulcer membranes have shortcomings in terms of adhesion, protection, preparation technology, and material research, and innovative technical solutions are urgently needed to address these issues. Therefore, developing a water-soluble, intelligent oral ulcer membrane with good adhesion, reliable protection, and innovative preparation technology and material selection is of great practical significance for improving oral ulcer treatment and patients' quality of life. Summary of the Invention

[0007] In order to solve the problems existing in the prior art, the present invention provides an adhesive oral ulcer membrane and a preparation process thereof, aiming to comprehensively overcome the many difficulties currently faced by oral ulcer membranes in practical applications.

[0008] One of the purposes of the present invention is an adhesive oral ulcer membrane, which comprises an inner layer, an outer layer and a substrate layer.

[0009] Preferably, the inner layer serves as a layer adhering to the oral mucosa and comprises partially alcoholyzed polyvinyl alcohol and an active ingredient.

[0010] Preferably, the active ingredients include but are not limited to one or more of hyaluronic acid, carboxymethyl chitosan, propolis, and vitamin B2.

[0011] Preferably, the outer layer is a protective layer, comprising a film-forming material and a water-soluble material.

[0012] Preferably, the film-forming material is one of modified cross-linked starch and completely alcoholyzed polyvinyl alcohol, or a mixture thereof.

[0013] More preferably, the film-forming material is modified cross-linked starch.

[0014] Preferably, the preparation method of the modified cross-linked starch comprises the following steps: S11, adding starch to deionized water and stirring for 5 to 10 minutes, then adding sodium chloride and continuing to stir for 10 to 20 minutes to obtain a starch emulsion; S12, adding oleic acid and an emulsifier to deionized water and stirring for 5 to 10 minutes to obtain an oleic acid solution; S13. Add the starch emulsion and oleic acid solution into a reactor and stir for 10 to 20 minutes. Then adjust the pH of the system to 9 to 10 with sodium hydroxide solution. Keep stirring the reaction under nitrogen. After the reaction is completed, adjust the pH of the system to 6 to 6.5 with hydrochloric acid solution. After standing for 4 to 6 hours, filter, wash, dry and crush to obtain modified cross-linked starch.

[0015] Preferably, the mass fraction of starch in the starch emulsion in S11 is 10-13%, and the mass fraction of sodium chloride is 0.2-0.3%.

[0016] Preferably, the emulsifier in S12 is sodium oleate or sodium stearate, and the added amount is 0.5-2% of the mass of oleic acid.

[0017] Preferably, the mass fraction of oleic acid in the oleic acid solution in S12 is 20-30%.

[0018] Preferably, the mass ratio of the starch emulsion to the oleic acid solution in S13 is 18-22:3-5.

[0019] Preferably, the stirring reaction rate in S13 is 150-300 r / min, the stirring reaction temperature is 50-60° C., and the stirring reaction time is 1-2 h.

[0020] Preferably, the drying in S13 is carried out under nitrogen conditions, the drying temperature is 60-70° C., and the drying time is 6-8 hours; the fineness of the modified cross-linked starch is 200-300 mesh.

[0021] Preferably, the water-soluble material includes but is not limited to one or more of PVP, partially hydrolyzed polyvinyl alcohol, carboxymethyl cellulose, sodium alginate, carrageenan, and xanthan gum.

[0022] Preferably, the alcoholysis degree of the partially alcoholyzed polyvinyl alcohol is in the range of 87 to 89%; and the alcoholysis degree of the completely alcoholyzed polyvinyl alcohol is in the range of 99 to 100%.

[0023] Preferably, the substrate layer is made of PET.

[0024] The molecular chains of the partially hydrolyzed polyvinyl alcohol (PVA), the inner layer material, contain a large number of hydroxyl groups and a small number of acetate groups. Compared to completely hydrolyzed PVA, the interference of the acetate groups results in reduced crystallinity and weaker interactions between the molecular chains. This allows it to dissolve more quickly when exposed to water. This unique chemical structure endows PVA with exceptional hydrophilicity and cold-water solubility. Upon contact with saliva, it rapidly dissolves in water, while its viscosity rapidly increases, allowing it to adhere tightly to the ulcer surface. The active ingredients possess anti-inflammatory and antibacterial properties, promoting the healing of oral ulcers.

[0025] The outer layer, serving as a protective layer, is primarily constructed from film-forming and water-soluble materials. The film-forming materials are modified cross-linked starch and fully hydrolyzed polyvinyl alcohol. The modified cross-linked starch has a cross-linked structure, with the water-soluble material bound within it. The modified cross-linked starch is cross-linked with oleic acid, resulting in a cross-linked network structure and unsaturated double bonds. The modified cross-linked starch is prepared under nitrogen to prevent oxidation of the unsaturated double bonds in the oleic acid. During the subsequent post-coating drying process, the high temperature promotes further cross-linking of the unsaturated double bonds in the modified cross-linked starch with the hydroxyl and carboxyl groups in the water-soluble material and the inner layer, forming a more compact structure with improved mechanical properties and resisting separation between the inner and outer layers. Upon entering the mouth, the outer layer rapidly swells under the influence of saliva and the cross-linked structure, but does not dissolve, resulting in a plump outer layer. This characteristic gives the outer layer a plump, smooth surface, excellent mechanical strength, and barrier properties, thereby providing temporary protection for the inner layer. As saliva is continuously secreted in the mouth, the modified cross-linked starch is broken down by amylase, the cross-linking structure gradually loosens, the outer layer structure slowly decomposes, the water-soluble material contacts more water molecules, the solubility is enhanced, and the outer layer material continues to disperse and dissolve. Therefore, the oral ulcer film effectively extends the application time without posing a health threat to the human body.

[0026] When fully hydrolyzed polyvinyl alcohol is used as the outer film-forming material, it has high crystallinity and regularity. It swells but does not dissolve after entering the mouth, which allows the outer layer material to form a smooth surface. After interacting with water-soluble materials, it slowly dissolves and will not cause harm to human health if swallowed accidentally. However, although fully hydrolyzed polyvinyl alcohol has a good film-forming effect, it lacks a cross-linked structure, resulting in poor strength after contact with saliva. It is easily broken by external forces in the oral environment, affecting the overall effect of the oral ulcer film.

[0027] Due to the different materials used in the inner and outer layers, there are significant differences in their water absorption and dissolution rates. The low-temperature water solubility of the partially hydrolyzed polyvinyl alcohol in the inner layer causes it to dissolve rapidly and become sticky upon contact with saliva. However, the outer layer of the oral ulcer membrane swells after absorbing saliva, with a larger swelling area than the inner layer. This difference in swelling area causes the outer layer to generate inward stress. When the inner layer comes into contact with saliva, causing the oral ulcer membrane to warp outward, the inward stress of the outer layer counteracts this external force and, in conjunction with the adhesion between the inner layer and the ulcer surface, ensures that the oral ulcer membrane can be firmly adhered to the ulcer surface, thereby effectively functioning.

[0028] The inner and outer layers are formed through a sequential coating process. First, the inner surface of the substrate layer is pre-treated by spraying a polyethyleneimine solution to strengthen the bond between the inner layer and the substrate layer. After coating, the inner and outer layers are tightly bonded and dissolved into one piece through drying and solidification processes, with the inner layer firmly attached to the inner surface of the substrate layer. This coating-based structure greatly improves the adhesion between the layers of the oral ulcer membrane, ensuring that the product will not experience interlayer separation during subsequent cutting, storage, and use, thereby providing a solid guarantee for the product's effectiveness and safety.

[0029] A second object of the present invention is to provide a preparation process for an adhesive oral ulcer membrane, the preparation process comprising the following steps: S21, preparing inner layer coating liquid Weigh part of the alcoholyzed polyvinyl alcohol and active ingredients in proportion, add them to deionized water, turn on the stirring device, heat to 40-50°C and stir for 20-30 minutes until completely dissolved, with a stirring speed of 30-60 rpm. After stirring, cool to room temperature and degas to obtain a uniformly dispersed inner layer coating liquid.

[0030] Preferably, the alcoholysis degree of the partially alcoholyzed polyvinyl alcohol in S21 is in the range of 87 to 89%.

[0031] Preferably, the mass of the active ingredient in S21 is 1 to 23% of the mass of the partially alcoholyzed polyvinyl alcohol.

[0032] Preferably, the solid content of the inner layer coating liquid in S21 is 10 to 25 wt %.

[0033] S22, preparing outer coating liquid The film-forming material and the water-soluble material are weighed in proportion, added into deionized water, the stirring device is turned on and the temperature is increased, and the stirring is constant at a constant temperature to prepare the outer coating liquid.

[0034] Preferably, the amount of the water-soluble material added in S22 is 20-30% of the total mass of the film-forming material and the water-soluble material.

[0035] Preferably, when the film-forming material is modified cross-linked starch, the constant temperature stirring temperature is 30-40° C., and the time is 30-60 min to avoid oxidation of unsaturated double bonds in the modified cross-linked starch, and a slurry is formed after stirring.

[0036] Preferably, when the film-forming material is completely alcoholyzed polyvinyl alcohol, the constant temperature stirring temperature is 95 to 100° C. and the time is 30 to 60 minutes to promote the dissolution of the completely alcoholyzed polyvinyl alcohol.

[0037] Preferably, when the film-forming materials are modified cross-linked starch and completely hydrolyzed polyvinyl alcohol, the completely hydrolyzed polyvinyl alcohol is first added to deionized water, stirred at a constant temperature of 95-100°C for 30-40 minutes, and then cooled to 30-40°C; then the modified cross-linked starch and water-soluble material are added, and the constant temperature stirring is continued at 30-40°C for 30-50 minutes.

[0038] Completely hydrolyzed polyvinyl alcohol is dissolved in water at high temperature and then cooled. Since the hydroxyl groups on the molecular chain form hydrogen bonds with water molecules, the molecules are evenly dispersed in the water. At the same time, the flexibility of the molecular chain enables it to stretch freely in water and adapt to the distribution of water molecules. The two work together to maintain the stability of the solution. Therefore, after completely hydrolyzed polyvinyl alcohol is dissolved and then cooled and stirred, it will not solidify in water.

[0039] Preferably, the solid content of the outer coating liquid in S22 is controlled at 10-25 wt %.

[0040] S23. Pretreatment of substrate layer The polyethyleneimine solution is sprayed on the inner surface of the substrate layer to obtain a pretreated substrate layer.

[0041] Preferably, the concentration of the polyethyleneimine solution in S23 is 1-3%, and the spraying amount is 120-150 g / m 2 .

[0042] S24, coating The coating process is equipped with two independent feeding systems and coating machines to achieve precise coating of the inner and outer layer materials.

[0043] Inner layer coating, the inner layer coating liquid is delivered to the coating head through the first feeding system, and is evenly coated on the inner surface of the pretreated substrate layer using a scraper; When the inner coating liquid is still in the aqueous solution state and has not solidified, the outer coating liquid is immediately applied to the surface of the inner layer material through the second feeding system. The thickness is precisely controlled by the outer scraper to form a tightly fitting uniform inner and outer layer structure. After coating is completed, the material is sent into the oven at a uniform speed through the transmission system, heated and dried to fully evaporate the solvent, and finally rolled up to obtain the oral ulcer membrane roll.

[0044] Preferably, the thickness after drying in S24 is: inner layer 0.01-0.3 mm, outer layer 0.02-0.25 mm, substrate layer 0.01-0.3 mm; Preferably, the drying temperature in S24 is 90-110° C. and the drying time is 2-6 minutes.

[0045] S25, post-processing The oral ulcer membrane roll is cut into strips of membrane material with a length of 3 to 10 cm and a width of 2 to 6 cm, and then punched into a plurality of small round pieces or small square pieces, namely the oral ulcer membrane.

[0046] In terms of adhesion, when the oral ulcer membrane comes into contact with saliva, the partially alcoholyzed polyvinyl alcohol in the inner layer rapidly dissolves and becomes sticky due to its low-temperature water-solubility, but swelling is not obvious. After absorbing water, the outer layer mainly exhibits significant swelling but dissolves more slowly. This difference in swelling-dissolution behavior causes the outer layer to expand larger than the inner layer, generating inward stress, causing the ulcer membrane to automatically curl toward the mucosa. This self-curling effect significantly improves the fit of the membrane to the ulcer surface, enhances adhesion, prolongs adhesion time, effectively prevents shedding in the complex environment of the oral cavity, and ensures the continuity and stability of treatment.

[0047] To precisely control the duration of protection, the outer layer utilizes modified cross-linked starch or fully hydrolyzed polyvinyl alcohol (PVA) with added water-soluble materials. These materials exhibit excellent film-forming and swelling properties, slowing the dissolution of the outer layer and protecting the inner drug layer. Furthermore, the addition of water-soluble materials moderately improves the overall solubility of the outer layer, ensuring on-demand dissolution in the oral environment.

[0048] From the perspective of enhancing substrate adhesion and quality control, the weak interfacial bonding between the inner layer and the substrate due to polarity differences is addressed by spraying polyethyleneimine on the inner surface of the substrate. The abundant amino groups in the polyethyleneimine molecule form multiple intermolecular forces with the hydroxyl groups of polyvinyl alcohol and the PET substrate, significantly enhancing interfacial adhesion and preventing the substrate and inner layer from separating and contaminating the inner layer.

[0049] Due to the adoption of the above technical solution, the technical effects achieved by the present invention are: 1. The oral ulcer membrane prepared by the present invention can effectively prevent the oral ulcer from falling off from the ulcer surface during actual use, significantly prolonging the protection time and creating favorable conditions for the rapid healing of the ulcer.

[0050] 2. During the preparation of the oral ulcer membrane, the coating process was coherent and smooth, successfully overcoming the problem of poor connection between materials.

[0051] 3. The oral ulcer membrane material prepared by the present invention can be completely dissolved in the oral environment and will not pose a health threat to the human body.

[0052] 4. The oral ulcer membrane material prepared by the present invention has high mechanical strength and is not easy to break during use. It can better protect the oral ulcer surface and is more convenient to use.

[0053] 5. During the high-temperature drying process, the unsaturated double bonds in the modified cross-linked starch can not only react with the hydroxyl and carboxyl groups in the water-soluble material, but also react with the hydroxyl and carboxyl groups in the inner layer material, so that the mechanical strength of the outer layer material is high and the inner and outer layers are more tightly bonded, so that when people peel off the base material layer during use, it is not easy for the inner and outer layers to separate due to improper operation, affecting the use. DETAILED DESCRIPTION

[0054] The present invention will be further described below with reference to specific embodiments.

[0055] Example 1: An adhesive oral ulcer membrane and its preparation process The invention discloses an adhesive oral ulcer membrane, which comprises an inner layer, an outer layer and a substrate layer.

[0056] The inner layer serves as a layer adhering to the oral mucosa and comprises partially hydrolyzed polyvinyl alcohol and an active ingredient; the active ingredient is carboxymethyl chitosan.

[0057] The outer layer is a protective layer, which includes a film-forming material and a water-soluble material.

[0058] The film-forming material is modified cross-linked starch.

[0059] The preparation method of the modified cross-linked starch comprises the following steps: S11, adding starch to deionized water and stirring for 8 minutes, then adding sodium chloride and continuing to stir for 15 minutes to obtain a starch emulsion; S12, adding oleic acid and emulsifier to deionized water and stirring for 7 minutes to obtain an oleic acid solution; S13. Add the starch emulsion and oleic acid solution into the reactor and stir for 15 minutes. Then adjust the pH of the system to 9.5 with a 1 mol / L sodium hydroxide solution. Keep stirring the reaction under nitrogen. After the reaction is completed, adjust the pH of the system to 6 with a 1 mol / L hydrochloric acid solution. After standing for 5 hours, filter, wash, dry and crush to obtain modified cross-linked starch.

[0060] The mass fraction of starch in the starch emulsion in S11 is 12%, and the mass fraction of sodium chloride is 0.25%.

[0061] The emulsifier in S12 is sodium oleate, and the added amount is 1% of the mass of oleic acid.

[0062] The mass fraction of oleic acid in the oleic acid solution in S12 is 25%.

[0063] The mass ratio of the starch emulsion to the oleic acid solution in S13 is 20:4.

[0064] In the step S13, the stirring reaction rate is 200 r / min, the stirring reaction temperature is 55° C., and the stirring reaction time is 1.5 h.

[0065] The drying in S13 is carried out under nitrogen conditions, the drying temperature is 65° C., and the drying time is 7 hours; the fineness of the modified cross-linked starch is 250 mesh.

[0066] The water-soluble material is partially alcoholyzed polyvinyl alcohol, and the alcoholysis degree is 88%.

[0067] The substrate layer is made of PET.

[0068] A preparation process for an adhesive oral ulcer membrane, comprising the following steps: S21, preparing inner layer coating liquid Weigh part of the alcoholyzed polyvinyl alcohol and carboxymethyl chitosan in proportion, add them to deionized water, turn on the stirring device, heat to 45°C and stir for 25 minutes until completely dissolved, the stirring speed is 40 rpm, cool to room temperature after stirring, and degas to obtain a uniformly dispersed inner layer coating liquid.

[0069] The alcoholysis degree of the partially alcoholyzed polyvinyl alcohol in S21 is 88%.

[0070] The mass of the carboxymethyl chitosan in the S21 is 10% of the mass of the partially hydrolyzed polyvinyl alcohol.

[0071] The solid content of the inner layer coating liquid in S21 is 18 wt %.

[0072] S22, preparing outer coating liquid Modified cross-linked starch and partially hydrolyzed polyvinyl alcohol were weighed in proportion, added into deionized water, the stirring device was turned on and the temperature was raised to 35° C., and stirred at a constant temperature for 50 minutes to prepare an outer coating liquid.

[0073] The amount of partially hydrolyzed polyvinyl alcohol added in S22 is 25% of the total mass of the modified cross-linked starch and the partially hydrolyzed polyvinyl alcohol.

[0074] The solid content of the outer coating liquid in S22 is controlled at 20 wt %.

[0075] S23. Pretreatment of substrate layer The polyethyleneimine solution is sprayed on the inner surface of the substrate layer to obtain a pretreated substrate layer.

[0076] The concentration of the polyethyleneimine solution in S23 is 2%, and the spraying amount is 130g / m 2 .

[0077] S24, coating The coating process is equipped with two independent feeding systems and coating machines to achieve precise coating of the inner and outer layer materials.

[0078] Inner layer coating, the inner layer coating liquid is delivered to the coating head through the first feeding system, and is evenly coated on the inner surface of the pretreated substrate layer using a scraper; When the inner coating liquid is still in the aqueous solution state and has not solidified, the outer coating liquid is immediately applied to the surface of the inner layer material through the second feeding system. The thickness is precisely controlled by the outer scraper to form a tightly fitting uniform inner and outer layer structure. After coating is completed, the material is sent into the oven at a uniform speed through the transmission system, heated and dried to fully evaporate the solvent, and finally rolled up to obtain the oral ulcer membrane roll.

[0079] The thickness after drying in S24 is: inner layer 0.05mm, outer layer 0.12mm, base material layer 0.15mm; The drying temperature in S24 is 100° C. and the drying time is 4 minutes.

[0080] S25, post-processing The oral ulcer membrane roll is cut into strips of 8 cm in length and 3 cm in width, and then punched into several small discs, namely the oral ulcer membrane.

[0081] Example 2: An adhesive oral ulcer membrane and its preparation process The invention discloses an adhesive oral ulcer membrane, which comprises an inner layer, an outer layer and a substrate layer.

[0082] The inner layer serves as a layer adhering to the oral mucosa and comprises partially hydrolyzed polyvinyl alcohol and an active ingredient; the active ingredient is propolis.

[0083] The outer layer is a protective layer, which includes a film-forming material and a water-soluble material.

[0084] The film-forming material is modified cross-linked starch.

[0085] The preparation method of the modified cross-linked starch comprises the following steps: S11, adding starch to deionized water and stirring for 5 minutes, then adding sodium chloride and continuing to stir for 10 minutes to obtain a starch emulsion; S12, adding oleic acid and emulsifier to deionized water and stirring for 5 minutes to obtain an oleic acid solution; S13. Add the starch emulsion and oleic acid solution into the reactor and stir for 10 minutes. Then adjust the pH of the system to 9 with a 1 mol / L sodium hydroxide solution and keep stirring under nitrogen. After the reaction, adjust the pH of the system to 6.5 with a 1 mol / L hydrochloric acid solution. After standing for 4 hours, filter, wash, dry and crush to obtain modified cross-linked starch.

[0086] The mass fraction of starch in the starch emulsion in S11 is 10%, and the mass fraction of sodium chloride is 0.2%.

[0087] The emulsifier in S12 is sodium stearate, and the added amount is 0.5% of the mass of oleic acid.

[0088] The mass fraction of oleic acid in the oleic acid solution in S12 is 20%.

[0089] The mass ratio of the starch emulsion to the oleic acid solution in S13 is 18:3.

[0090] In the step S13, the stirring reaction rate is 150 r / min, the stirring reaction temperature is 50° C., and the stirring reaction time is 1 h.

[0091] The drying in S13 is carried out under nitrogen conditions, the drying temperature is 60° C., and the drying time is 8 hours; the fineness of the modified cross-linked starch is 200 mesh.

[0092] The water-soluble material is partially alcoholyzed polyvinyl alcohol, and the alcoholysis degree is 87%.

[0093] The substrate layer is made of PET.

[0094] A preparation process for an adhesive oral ulcer membrane, comprising the following steps: S21, preparing inner layer coating liquid Weigh part of the alcoholyzed polyvinyl alcohol and propolis in proportion and add them to deionized water, then turn on the stirring device, heat to 40°C and stir for 20 minutes until completely dissolved, with a stirring speed of 30 rpm. After stirring, cool to room temperature and degas to obtain a uniformly dispersed inner layer coating liquid.

[0095] The alcoholysis degree of the partially alcoholyzed polyvinyl alcohol in S21 is 87%.

[0096] The mass of the propolis in the S21 is 6% of the mass of the partially alcoholyzed polyvinyl alcohol.

[0097] The solid content of the inner layer coating liquid in S21 is 10 wt %.

[0098] S22, preparing outer coating liquid Modified cross-linked starch and partially hydrolyzed polyvinyl alcohol were weighed in proportion, added into deionized water, the stirring device was turned on and the temperature was raised to 30° C., and stirred at a constant temperature for 60 minutes to prepare an outer coating liquid.

[0099] The amount of partially hydrolyzed polyvinyl alcohol added in S22 is 20% of the total mass of the modified cross-linked starch and the partially hydrolyzed polyvinyl alcohol.

[0100] The solid content of the outer coating liquid in S22 is controlled at 10 wt %.

[0101] S23. Pretreatment of substrate layer The polyethyleneimine solution is sprayed on the inner surface of the substrate layer to obtain a pretreated substrate layer.

[0102] The concentration of the polyethyleneimine solution in S23 is 1%, and the spraying amount is 150g / m 2 .

[0103] S24, coating The coating process is equipped with two independent feeding systems and coating machines to achieve precise coating of the inner and outer layer materials.

[0104] Inner layer coating, the inner layer coating liquid is delivered to the coating head through the first feeding system, and is evenly coated on the inner surface of the pretreated substrate layer using a scraper; When the inner coating liquid is still in the aqueous solution state and has not solidified, the outer coating liquid is immediately applied to the surface of the inner layer material through the second feeding system. The thickness is precisely controlled by the outer scraper to form a tightly fitting uniform inner and outer layer structure. After coating is completed, the material is sent into the oven at a uniform speed through the transmission system, heated and dried to fully evaporate the solvent, and finally rolled up to obtain the oral ulcer membrane roll.

[0105] The thickness after drying in S24 is: inner layer 0.03mm, outer layer 0.08mm, base material layer 0.01mm; The drying temperature in S24 is 90° C. and the drying time is 2 min.

[0106] S25, post-processing The oral ulcer membrane roll is cut into strips of 3 cm in length and 6 cm in width, and then punched into several small discs, namely the oral ulcer membrane.

[0107] Example 3: An adhesive oral ulcer membrane and its preparation process The invention discloses an adhesive oral ulcer membrane, which comprises an inner layer, an outer layer and a substrate layer.

[0108] The inner layer serves as a layer adhering to the oral mucosa and comprises partially hydrolyzed polyvinyl alcohol and an active ingredient; the active ingredient is carboxymethyl chitosan.

[0109] The outer layer is a protective layer, which includes a film-forming material and a water-soluble material.

[0110] The film-forming material is modified cross-linked starch.

[0111] The preparation method of the modified cross-linked starch comprises the following steps: S11, adding starch to deionized water and stirring for 10 minutes, then adding sodium chloride and continuing to stir for 20 minutes to obtain a starch emulsion; S12, adding oleic acid and emulsifier to deionized water and stirring for 10 minutes to obtain an oleic acid solution; S13. Add the starch emulsion and oleic acid solution into the reactor and stir for 20 minutes. Then adjust the pH of the system to 10 with a 1 mol / L sodium hydroxide solution and keep stirring under nitrogen. After the reaction, adjust the pH of the system to 6.5 with a 1 mol / L hydrochloric acid solution. After standing for 6 hours, filter, wash, dry and crush to obtain modified cross-linked starch.

[0112] The mass fraction of starch in the starch emulsion in S11 is 13%, and the mass fraction of sodium chloride is 0.3%.

[0113] The emulsifier in S12 is sodium oleate or sodium stearate, and the added amount is 2% of the mass of oleic acid.

[0114] The mass fraction of oleic acid in the oleic acid solution in S12 is 30%.

[0115] The mass ratio of the starch emulsion to the oleic acid solution in S13 is 22:5.

[0116] In the step S13, the stirring reaction rate is 300 r / min, the stirring reaction temperature is 60° C., and the stirring reaction time is 2 h.

[0117] The drying in S13 is carried out under nitrogen conditions, the drying temperature is 70° C., and the drying time is 6 hours; the fineness of the modified cross-linked starch is 300 mesh.

[0118] The water-soluble material is partially alcoholyzed polyvinyl alcohol, and the alcoholysis degree is 89%.

[0119] The substrate layer is made of PET.

[0120] A preparation process for an adhesive oral ulcer membrane, comprising the following steps: S21, preparing inner layer coating liquid Weigh part of the alcoholyzed polyvinyl alcohol and carboxymethyl chitosan in proportion, add them to deionized water, turn on the stirring device, heat to 50°C and stir for 30 minutes until completely dissolved, the stirring speed is 60 rpm, cool to room temperature after stirring, and degas to obtain a uniformly dispersed inner layer coating liquid.

[0121] The alcoholysis degree of the partially alcoholyzed polyvinyl alcohol in S21 is 89%.

[0122] The mass of the carboxymethyl chitosan in the S21 is 14% of the mass of the partially alcoholyzed polyvinyl alcohol.

[0123] The solid content of the inner layer coating liquid in S21 is 25 wt %.

[0124] S22, preparing outer coating liquid Modified cross-linked starch and partially hydrolyzed polyvinyl alcohol were weighed in proportion, added into deionized water, the stirring device was turned on and the temperature was raised to 40° C., and stirred at a constant temperature for 30 minutes to prepare an outer coating liquid.

[0125] The amount of partially hydrolyzed polyvinyl alcohol added in S22 is 30% of the total mass of the modified cross-linked starch and the partially hydrolyzed polyvinyl alcohol.

[0126] The solid content of the outer coating liquid in S22 is controlled at 25 wt %.

[0127] S23. Pretreatment of substrate layer The polyethyleneimine solution is sprayed on the inner surface of the substrate layer to obtain a pretreated substrate layer.

[0128] The concentration of the polyethyleneimine solution in S23 is 3%, and the spraying amount is 120g / m 2 .

[0129] S24, coating The coating process is equipped with two independent feeding systems and coating machines to achieve precise coating of the inner and outer layer materials.

[0130] Inner layer coating, the inner layer coating liquid is delivered to the coating head through the first feeding system, and is evenly coated on the inner surface of the pretreated substrate layer using a scraper; When the inner coating liquid is still in the aqueous solution state and has not solidified, the outer coating liquid is immediately applied to the surface of the inner layer material through the second feeding system. The thickness is precisely controlled by the outer scraper to form a tightly fitting uniform inner and outer layer structure. After coating is completed, the material is sent into the oven at a uniform speed through the transmission system, heated and dried to fully evaporate the solvent, and finally rolled up to obtain the oral ulcer membrane roll.

[0131] The thickness after drying in S24 is: inner layer 0.15mm, outer layer 0.25mm, base material layer 0.15mm; The drying temperature in S24 is 110° C. and the drying time is 6 minutes.

[0132] S25, post-processing The oral ulcer membrane roll is cut into strips of 10 cm in length and 2 cm in width, and then punched into several small square pieces, namely the oral ulcer membrane.

[0133] Example 4 The difference between this embodiment and embodiment 1 is that the film-forming material is completely alcoholyzed polyvinyl alcohol with an alcoholysis degree of 99%, the temperature in S22 is set to 95° C., and the rest is consistent with embodiment 1.

[0134] Example 5 The difference between this embodiment and Example 1 is that the film-forming material is completely hydrolyzed polyvinyl alcohol with a hydrolysis degree of 99% and modified cross-linked starch in a mass ratio of 1:1. The specific steps of S22 are: first, completely hydrolyzed polyvinyl alcohol is added to deionized water, and the temperature of constant stirring is 95°C, and the stirring time is 30 minutes, and then cooled to 40°C; then, modified cross-linked starch and partially hydrolyzed polyvinyl alcohol with a hydrolysis degree of 88% are added, and constant stirring is continued at 35°C for 50 minutes to obtain an outer coating liquid.

[0135] Comparative Example 1 Representative Example 1 was selected as Comparative Example 1, in which the modified cross-linked starch was removed and replaced with partially hydrolyzed polyvinyl alcohol with a degree of alcoholysis of 88%. The rest was the same as Example 1.

[0136] Comparative Example 2 Representative Example 1 was selected as Comparative Example 2, in which the raw material oleic acid of the modified cross-linked starch was replaced with citric acid, and the rest was the same as Example 1.

[0137] The strip films of Examples 1-4 and Comparative Examples 1-2 were cut into rectangles of 80 mm × 15 mm. The substrate layer was peeled off and the samples were immersed in artificial saliva at 37°C for 10 min to obtain samples. The tensile strength was tested using an electronic universal testing machine at a test rate of 25 mm / min. Five samples were tested in each case, and the average value was calculated. The specific results are shown in Table 1.

[0138] Table 1 The oral ulcer membranes of Examples 1-4 and Comparative Examples 1-2 were placed in artificial saliva, maintained at a constant temperature of 37° C., and their complete dissolution time was tested. Five samples were tested for each case, and the average value was calculated. See Table 2 for details.

[0139] Table 2 The oral ulcer films of Examples 1-4 and Comparative Examples 1-2 were applied to clean porcine colon mucosa and then placed in an artificial saliva environment at a constant temperature of 37°C. The adhesion time was tested. Five samples were tested for each case and the average value was calculated. See Table 3 for details.

[0140] Table 3 As can be seen from Tables 1-3, the oral ulcer membranes prepared using Examples 1-3 not only have good mechanical properties, but also have excellent adhesion. They are not easy to fall off or break during use, causing the ulcer surface to be exposed, and are eventually dissolved in the human body. The raw materials are safe and will not pose a threat to human health.

[0141] At the same time, when using Examples 1-3, the inner and outer layers will not separate when peeling the substrate layer. The inner and outer layers have a strong bonding force, avoiding waste caused by improper operation.

[0142] In Example 4, the modified cross-linked starch is removed and replaced with completely hydrolyzed polyvinyl alcohol with a degree of hydrolysis of 99%. The completely hydrolyzed polyvinyl alcohol with a degree of hydrolysis of 99% has high crystallinity and swells but does not dissolve in water. However, the partially hydrolyzed polyvinyl alcohol in the outer layer material dissolves faster, so the strength is reduced and the action time is also shorter than that in Example 1.

[0143] The film-forming material of Example 5 uses modified cross-linked starch and completely alcoholyzed polyvinyl alcohol in a mass ratio of 1:1. The performance is between that of Example 1 and Example 4, but better than that of the comparative example.

[0144] In Comparative Example 1, the modified cross-linked starch was removed and replaced with partially hydrolyzed polyvinyl alcohol with a degree of hydrolysis of 88%, which has strong water solubility, so the coating time is shorter and the action time is short.

[0145] In Comparative Example 2, the raw material oleic acid of the modified cross-linked starch is replaced with citric acid. The obtained modified cross-linked starch does not contain unsaturated double bonds and cannot react with the hydroxyl and carboxyl groups in the water-soluble material and the hydroxyl and carboxyl groups of the inner layer material. The structure is also relatively loose, so all performances are lower than those in Example 1.

[0146] Unless otherwise specified, the ratios and percentages described in the present invention are all by mass; all raw materials are commercially available.

[0147] Finally, it should be noted that the above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art will be able to modify the technical solutions described in the aforementioned embodiments or substitute equivalents for some of the technical features. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention shall be included within the scope of protection of the present invention.

Claims

1. An adhesive oral ulcer membrane, characterized in that: The adhesive oral ulcer membrane comprises an inner layer, an outer layer and a substrate layer; The inner layer includes partially alcoholyzed polyvinyl alcohol and active ingredients; The outer layer includes a film-forming material and a water-soluble material; The film-forming material is one of modified cross-linked starch and completely alcoholyzed polyvinyl alcohol or a mixture thereof.

2. The adhesive oral ulcer membrane according to claim 1, characterized in that: The active ingredients include but are not limited to one or more of hyaluronic acid, carboxymethyl chitosan, propolis, and vitamin B2; The water-soluble material includes but is not limited to one or more of PVP, partially hydrolyzed polyvinyl alcohol, carboxymethyl cellulose, sodium alginate, carrageenan, and xanthan gum; the hydrolysis degree of the partially hydrolyzed polyvinyl alcohol ranges from 87 to 89%; The alcoholysis degree of the fully alcoholyzed polyvinyl alcohol is 99-100%; The substrate layer is made of PET.

3. The adhesive oral ulcer membrane according to claim 1, characterized in that: The preparation method of the modified cross-linked starch comprises the following steps: S11, adding starch to deionized water and stirring for 5 to 10 minutes, then adding sodium chloride and continuing to stir for 10 to 20 minutes to obtain a starch emulsion; S12, adding oleic acid and an emulsifier to deionized water and stirring for 5 to 10 minutes to obtain an oleic acid solution; S13. Add the starch emulsion and oleic acid solution into a reactor and stir for 10 to 20 minutes. Then adjust the pH of the system to 9 to 10 with sodium hydroxide solution. Keep stirring the reaction under nitrogen. After the reaction is completed, adjust the pH of the system to 6 to 6.5 with hydrochloric acid solution. After standing for 4 to 6 hours, filter, wash, dry and crush to obtain modified cross-linked starch.

4. The adhesive oral ulcer membrane according to claim 3, characterized in that: The mass fraction of starch in the starch emulsion in S11 is 10-13%, and the mass fraction of sodium chloride is 0.2-0.3%; The emulsifier in S12 is sodium oleate or sodium stearate, and the added amount is 0.5-2% of the mass of oleic acid; The mass fraction of oleic acid in the oleic acid solution in S12 is 20-30%; The mass ratio of the starch emulsion to the oleic acid solution in S13 is 18-22:3-5; In S13, the stirring reaction rate is 150-300 r / min, the stirring reaction temperature is 50-60° C., and the stirring reaction time is 1-2 h; The drying in S13 is carried out under nitrogen conditions, the drying temperature is 60-70° C., and the drying time is 6-8 hours; the fineness of the modified cross-linked starch is 200-300 mesh.

5. A process for preparing an adhesive oral ulcer membrane, characterized in that: The preparation process includes preparing an inner layer coating liquid, preparing an outer layer coating liquid, pre-treating a substrate layer, coating and post-treating.

6. The process for preparing an adhesive oral ulcer membrane according to claim 5, characterized in that: The inner coating liquid is prepared by weighing partially hydrolyzed polyvinyl alcohol and active ingredients in proportion, adding them to deionized water, turning on a stirring device, heating to 40-50° C. and stirring for 20-30 minutes until completely dissolved, at a stirring speed of 30-60 rpm, cooling to room temperature after stirring, and degassing to obtain a uniformly dispersed inner coating liquid; The alcoholysis degree of the partially alcoholyzed polyvinyl alcohol is in the range of 87 to 89%; The mass of the active ingredient is 1 to 23% of the mass of the partially alcoholyzed polyvinyl alcohol; The solid content of the inner layer coating liquid is 10 to 25 wt %.

7. The process for preparing an adhesive oral ulcer membrane according to claim 5, characterized in that: The outer coating liquid is prepared by weighing the film-forming material and the water-soluble material in proportion, adding them into deionized water, turning on the stirring device and heating, and stirring at a constant temperature to prepare the outer coating liquid; The amount of the water-soluble material added is 20-30% of the total mass of the film-forming material and the water-soluble material; The solid content of the outer coating liquid is controlled at 10-25 wt %.

8. The process for preparing an adhesive oral ulcer membrane according to claim 5, characterized in that: The pretreatment of the substrate layer is to spray a polyethyleneimine solution on the inner surface of the substrate layer to obtain a pretreated substrate layer; The concentration of the polyethyleneimine solution is 1-3%, and the spraying amount is 120-150g / m 2 .

9. The process for preparing an adhesive oral ulcer membrane according to claim 5, characterized in that: The coating process is equipped with two independent feeding systems and coating machines to achieve precise coating of the inner and outer layer materials; for inner layer coating, the inner layer coating liquid is delivered to the coating head through the first feeding system and evenly coated on the inner surface of the pretreated substrate layer by a scraper; for outer layer coating, while the inner layer coating liquid is still in an aqueous solution state and has not solidified, the outer layer coating liquid is immediately applied to the surface of the inner layer material by the second feeding system, and the thickness is accurately controlled by the outer layer scraper to form a tightly fitting uniform inner and outer layer structure; after coating is completed, the material is uniformly fed into the oven through the transmission system, heated and dried to fully volatilize the solvent, and finally rolled up to obtain the oral ulcer membrane roll; The thickness after drying is: inner layer 0.01-0.3mm, outer layer 0.02-0.25mm, substrate layer 0.01-0.3mm; The drying temperature is 90-110° C. and the drying time is 2-6 minutes.

10. The process for preparing an adhesive oral ulcer membrane according to claim 5, characterized in that: The post-processing is to cut the oral ulcer membrane coil into strips of 3 to 10 cm in length and 2 to 6 cm in width, and then punch them into a number of small round or square pieces, namely the oral ulcer membrane.

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