Adhesive bandage for oral cavity and preparation method thereof

Abstract

The invention discloses an adhesive bandage for an oral cavity and a preparation method thereof, relates to the technical field of medical products, and provides the convenient adhesive bandage for the oral cavity and the preparation method thereof, carboxymethyl chitosan, recombinant I-type humanized collagen and ethyl cellulose are added, so that the adhesive bandage has the functions of resisting bacteria, easing pain and accelerating wound healing; the prepared adhesive bandage has good biocompatibility and biodegradability, and the problem of bacterial infection in the implanting process is effectively solved. The carboxymethyl chitosan coating in the adhesive bandage for the oral cavity has high viscosity after being infiltrated, can be tightly attached to a planting area, and does not affect actions such as chewing and swallowing. The ethyl cellulose coating can effectively isolate the influence of the external environment on the wound in the using process, and the effect of enhancing protection is achieved. In addition, by introducing recombinant I-type humanized collagen, biocompatibility is effectively improved, and wound recovery is promoted.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medical products, in particular to a mouth wound plaster and a preparation method thereof. BACKGROUND

[0002] In addition to common oral wounds caused by factors such as ulceration and external force, various surgical treatments in the oral cavity, such as periodontal surgery, implant surgery, orthodontics, etc., can also cause oral wounds. Therefore, a mouth wound dressing is needed to play the role of a "wound plaster". The wound plaster should protect the wound surface, isolate bacteria, prevent infection, relieve pain, and accelerate wound healing, etc. Considering the use environment in the oral cavity, the wound dressing needs to be soft and comfortable, easy to operate, have strong adhesion, and be able to withstand frequent eating, swallowing, and pronunciation movements in the mouth.

[0003] However, the existing oral wound plaster products still have some problems, such as a complicated preparation process, poor antibacterial effect, and weak adhesion, etc.

[0004] To solve the above problems and improve the antibacterial property and adhesion, the present application provides a mouth wound plaster and a preparation method thereof. SUMMARY

[0005] The present application aims to provide a mouth wound plaster and a preparation method thereof to solve the problems in the prior art.

[0006] To achieve the above-mentioned purpose, the present application provides the following technical solutions: A preparation method of a mouth wound plaster, comprising the following steps: Step 1: adding ethyl cellulose into anhydrous ethanol, stirring uniformly to obtain an ethyl cellulose solution; Step 2: adding carboxymethyl chitosan into deionized water, stirring uniformly to obtain a carboxymethyl chitosan solution; Step 3: adding recombinant humanized collagen type I into the carboxymethyl chitosan solution, stirring uniformly to obtain a chitosan solution containing recombinant humanized collagen type I; Step 4: uniformly coating the ethyl cellulose solution on a flat dish, drying to obtain an ethyl cellulose film; Step 5: uniformly coating the chitosan solution containing recombinant humanized collagen type I on the ethyl cellulose film, freeze-drying to obtain a mouth wound plaster.

[0007] More preferably, in step 1, the concentration of the ethyl cellulose solution is 1wt%-5wt%, the stirring temperature is 30-50℃, and the time is 1-4h; In step 2, the concentration of the carboxymethyl chitosan solution is 1wt%-5wt%, the stirring temperature is 40-80℃, and the time is 1-7h; In step 3, the recombinant humanized collagen type I accounts for 1-50% of the mass percentage of the carboxymethyl chitosan, the stirring temperature is 30-50℃, and the stirring time is 0.5-1h.

[0008] More preferably, in step 4, the coating amount of the ethyl cellulose solution is 0.05-0.5g / cm 2 , the drying temperature is 40-80℃, and the drying time is 0.5-4h.

[0009] More preferably, the degree of substitution of the carboxymethyl chitosan is 70-90%, and the molecular weight is 50000-100000.

[0010] More preferably, the ethyl cellulose solution is a modified ethyl cellulose solution, and the preparation method comprises the following steps: S1: Take sodium alginate and deionized water, stir uniformly, add mercaptoacetic acid and hydrochloric acid, heat to 80-82℃, react for 3-3.5h, precipitate, freeze, and dry to obtain mercapto sodium alginate; S2: Take gallic acid and ethanol, stir uniformly to obtain a gallic acid solution; take mercapto sodium alginate and deionized water, stir uniformly, add the gallic acid solution, and stir for 10-12h to obtain modified mercapto sodium alginate; S3: Add ethyl cellulose to anhydrous ethanol, stir, add modified mercapto sodium alginate, heat and stir at 40℃ for 1-2h to obtain a modified ethyl cellulose solution.

[0011] More preferably, the carboxymethyl chitosan is nano-silver modified chitosan, and the preparation method of the nano-silver modified chitosan comprises the following steps: (1): Take ethanol and deionized water, stir uniformly, add orobanchol, stir uniformly to obtain an orobanchol solution, and add an aqueous silver nitrate solution; stir uniformly, heat to 60-65℃, react for 30-40min, cool, filter, and dry to obtain nano-silver particles; (2): Take glacial acetic acid and deionized water, stir uniformly, add double-bonded carboxymethyl chitosan, stir for 10-12h, centrifuge, take the supernatant, add nano-silver particles, and stir for 30-40min to obtain nano-silver modified chitosan.

[0012] More preferably, the preparation method of the double-bonded carboxymethyl chitosan comprises the following steps: take carboxymethyl chitosan and deionized water, heat to 48-50℃, stir uniformly, add triethylamine, tetrabutylammonium bromide, and glycidyl methacrylate, react for 70-74h, then pour the solution into ethanol to precipitate, dialyze, and freeze-dry to obtain double-bonded carboxymethyl chitosan.

[0013] More preferably, in step 3, a photoinitiator is further added to the chitosan solution of the recombinant humanized collagen type I.

[0014] More preferably, the oral wound plaster needs to be irradiated by ultraviolet light, and the preparation method is as follows: the chitosan solution containing the recombinant humanized collagen type I is uniformly coated on an ethyl cellulose film, and then the film is irradiated by ultraviolet light at 365 nm for 10 min, the light intensity is 10 mW / cm 2 , and then the film is freeze-dried at-20~-5℃ for 24-48 h to obtain the oral wound plaster.

[0015] Compared with the prior art, the oral wound plaster has the following beneficial effects: 1. The oral wound plaster and the preparation method thereof are convenient, and the carboxymethyl chitosan, the recombinant humanized collagen type I and the ethyl cellulose are added, so that the wound plaster has the functions of antibiosis, analgesia, acceleration of wound healing and the like, the wound plaster prepared by the method has good biocompatibility and biodegradability, and the problem of bacterial infection in the implantation process is also effectively solved.

[0016] 2. The carboxymethyl chitosan coating layer of the oral wound plaster has strong adhesion after infiltration, can be closely attached to the implantation area, and does not affect the actions such as chewing and swallowing. The ethyl cellulose coating layer can effectively isolate the influence of the external environment on the wound during use, and plays a role in strengthening protection. The biocompatibility is effectively improved by introducing the recombinant humanized collagen type I, and the wound recovery is promoted.

[0017] 3. The nano-silver particles are prepared by using salicylic acid, the antibacterial performance of the nano-silver is improved, and then the nano-silver is loaded on the double-bonded carboxymethyl chitosan, so that the carboxymethyl chitosan is improved, the double bond is introduced, and the adhesion of the chitosan solution is improved.

[0018] 4. The sodium alginate is modified by using gallic acid, the coagulation-promoting ability of the wound plaster is improved, and the hemostatic ability is enhanced. The mercapto is introduced into the modified ethyl cellulose, and under the action of photoinitiation, the ethyl cellulose film is covalently crosslinked with the chitosan solution containing the recombinant humanized collagen type I having a double bond, so that the adhesion of the oral wound plaster is improved. DETAILED DESCRIPTION

[0019] Figure 1 The scanning electron microscope image of the oral wound plaster prepared in the present application comparative example 1; Figure 2 The scanning electron microscope image of the oral wound plaster prepared in the present application example 1; Figure 3 The biocompatibility diagram of the oral wound plaster prepared in the present application comparative example 1; Figure 4Biocompatibility chart of the oral wound patch prepared for the present embodiment 1; Figure 5 Biocompatibility chart of the oral wound patch prepared for the present embodiment 2. DETAILED DESCRIPTION

[0020] The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application.

[0021] The source and model of the substances mentioned in the present application are not specially limited, and exemplarily include: recombinant humanized collagen type I provided by Jiangsu Chuojian Medical Technology Co., Ltd., the amino acid sequence and gene expression sequence of the recombinant humanized collagen type I are shown in SEQ ID NO. 1 and SEQ ID NO. 2 in patent number CN110964099A); the degree of substitution of the carboxymethyl chitosan is 70-90%, and the molecular weight is 50000-100000; the nano silver particles are 5nm-200nm, which can be purchased from Beijing Zhongke Keyou Technology Co., Ltd.

[0022] Embodiment 1: A preparation method of an oral wound patch, comprising the following steps: Step one: S1: 3g of ethyl cellulose is added to 100mL of anhydrous ethanol, heated and stirred at 40℃ for 2h to obtain an ethyl cellulose solution; S2: 3g of carboxymethyl chitosan is added to 100mL of deionized water, heated and stirred at 60℃ for 5h to obtain a carboxymethyl chitosan solution; S3: 0.1g of recombinant humanized collagen type I is added to the carboxymethyl chitosan solution, heated and stirred at 40℃ for 1h to obtain a chitosan solution containing recombinant humanized collagen type I; Step two: Preparation of ethyl cellulose film: The ethyl cellulose solution is uniformly coated on a plastic dish, and the coating amount is 0.1g / cm 2 , dried, the drying temperature is 50℃, and the drying time is 2h to obtain an ethyl cellulose film; Step three: Preparation of the oral wound patch: The chitosan solution containing recombinant humanized collagen type I is uniformly coated on the ethyl cellulose film, and the coating amount is 1g / cm 2 , and freeze-dried at-20℃ for 24h to obtain an oral wound patch.

[0023] Example 2: A preparation method of the oral wound plaster, comprising the following steps: Step one: S1: 3g of ethyl cellulose is added to 100mL of anhydrous ethanol, heated and stirred at 40℃ for 2h to obtain an ethyl cellulose solution; S2: 3g of carboxymethyl chitosan is added to 100mL of deionized water, heated and stirred at 60℃ for 4h to obtain a carboxymethyl chitosan solution; S3: 0.1g of recombinant humanized collagen type I is added to the carboxymethyl chitosan solution, heated and stirred at 40℃ for 1h to obtain a chitosan solution containing recombinant humanized collagen type I; Step two: Preparation of ethyl cellulose film: The ethyl cellulose solution is uniformly coated on a plastic dish, and the coating amount is 0.3g / cm 2 , dried, the drying temperature is 50℃, and the drying time is 2h to obtain an ethyl cellulose film; Step three: Preparation of the oral wound plaster: The chitosan solution containing recombinant humanized collagen type I is uniformly coated on the ethyl cellulose film, and the coating amount is 1.5g / cm 2 , freeze-dried at -10℃ for 36h to obtain the oral wound plaster.

[0024] Example 3: A preparation method of the oral wound plaster, comprising the following steps: Step one: S1: 3g of ethyl cellulose is added to 100mL of anhydrous ethanol, heated and stirred at 40℃ for 2h to obtain an ethyl cellulose solution; S2: 3g of carboxymethyl chitosan is added to 100mL of deionized water, heated and stirred at 65℃ for 7h to obtain a carboxymethyl chitosan solution; S3: 0.1g of recombinant humanized collagen type I is added to the carboxymethyl chitosan solution, heated and stirred at 40℃ for 1h to obtain a chitosan solution containing recombinant humanized collagen type I; Step two: Preparation of ethyl cellulose film: The ethyl cellulose solution is uniformly coated on a plastic dish, and the coating amount is 0.1g / cm 2 , dried, the drying temperature is 50℃, and the drying time is 2h to obtain an ethyl cellulose film; Step three: Preparation of the oral wound plaster: The chitosan solution containing recombinant humanized collagen type I is uniformly coated on the ethyl cellulose film, and the coating amount is 1g / cm 2Freeze-drying at -20℃ for 36h to obtain the oral wound dressing.

[0025] Example 4: A preparation method of an oral wound dressing, comprising the following steps: Step one: S1: 3g of ethyl cellulose was added to 100mL of anhydrous ethanol, heated and stirred at 40℃ for 1h to obtain an ethyl cellulose solution; S2: 3g of carboxymethyl chitosan was added to 100mL of deionized water, heated and stirred at 70℃ for 3h to obtain a carboxymethyl chitosan solution; S3: 0.1g of recombinant humanized collagen type I was added to the carboxymethyl chitosan solution, heated and stirred at 40℃ for 1h to obtain a chitosan solution containing recombinant humanized collagen type I; Step two: Preparation of ethyl cellulose film: The ethyl cellulose solution was uniformly coated on a plastic dish, and the coating amount was 0.3g / cm 2 , and dried at 50℃ for 2h to obtain an ethyl cellulose film; Step three: Preparation of the oral wound dressing: The chitosan solution containing recombinant humanized collagen type I was uniformly coated on the ethyl cellulose film, and the coating amount was 2g / cm 2 , and freeze-dried at -5℃ for 48h to obtain the oral wound dressing.

[0026] Example 5: Add nano-silver modified chitosan, modified thiolated sodium alginate, etc., and the rest is the same as example 1: Step one: Nano-silver modified chitosan: S1: Take 2g of carboxymethyl chitosan, 200mL of deionized water, heat to 50℃, stir evenly, add 8mL of triethylamine, 8.5g of tetrabutylammonium bromide, 30mL of glycidyl methacrylate, react for 72h, then pour the solution into 1000mL of ethanol to precipitate, dialysis, freeze-drying to obtain double-bonded carboxymethyl chitosan; S2: Preparation of nano-silver particles: Take 95mL of ethanol, 5mL of deionized water, stir evenly, add 0.6g of rosmarinic acid, stir evenly to obtain a rosmarinic acid solution, add 100mL of 0.05mol / L silver nitrate aqueous solution; stir evenly, heat to 62℃, react for 35min, cool, filter, dry to obtain nano-silver particles; S3: Take 1mL of glacial acetic acid, 75mL of deionized water, stir evenly, add 1g of double-bonded carboxymethyl chitosan, stir for 11h, centrifuge, take the supernatant, add 2.4g of nano-silver particles, stir for 35min to obtain nano-silver modified chitosan; Step two: preparation of modified thiolated sodium alginate S1: take 2g sodium alginate, 80mL deionized water, stir evenly, add 2.5mL mercaptoacetic acid, 2mL, 7M hydrochloric acid, heat to 81℃, react for 3.2h, precipitate, freeze, dry, get thiolated sodium alginate; S2: take 3g gallic acid, 300mL ethanol, stir evenly, get gallic acid solution; take 0.5g thiolated sodium alginate, 500mL deionized water, stir evenly, add gallic acid solution, stir for 12h, get modified thiolated sodium alginate; Step three: S1: add 3g ethyl cellulose to 100mL anhydrous ethanol, stir, add 1g modified thiolated sodium alginate, heat and stir at 40℃ for 2h, get modified ethyl cellulose solution; S2: add 3g nano silver modified chitosan to 100mL deionized water, heat and stir at 60℃ for 5h, get nano silver modified chitosan solution; S3: add 0.1g recombinant humanized collagen type I, 0.1g photoinitiator I2959, nano silver modified chitosan, heat and stir at 40℃ for 1h, get chitosan solution containing recombinant humanized collagen type I; Step four: preparation of ethyl cellulose film Uniformly coat the modified ethyl cellulose solution on a plastic dish, the coating amount is 0.1g / cm 2 , dry, the drying temperature is 50℃, the drying time is 2h, get ethyl cellulose film; Step five: preparation of oral wound plaster Uniformly coat the chitosan solution containing recombinant humanized collagen type I on the ethyl cellulose film, the coating amount is 1g / cm 2 , irradiate under 365nm ultraviolet light for 10min, the light intensity is 10mW / cm 2 , freeze at-20℃ for 24h, get oral wound plaster.

[0027] Example 6: use 5nm-200nm nano silver particles purchased from Beijing Zhongke Keyou Technology Co., Ltd., the rest is the same as example 5.

[0028] Example 7: no double bond carboxymethyl chitosan is added, the rest is the same as example 5: Step one: nano silver modified chitosan S1: take 95 mL of ethanol, 5 mL of deionized water, stir evenly, add 0.6 g of cannabisc acid, stir evenly, get cannabisc acid solution, add 100 mL of silver nitrate aqueous solution with a concentration of 0.05 mol / L; stir evenly, warm up to 62℃, react for 35 min, cool, filter, dry, get nano silver particles; S2: take 1 mL of glacial acetic acid, 75 mL of deionized water, stir evenly, add 1 g of carboxymethyl chitosan, stir for 11 h, centrifuge, take supernatant, add 2.4 g of nano silver particles, stir for 35 min, get nano silver modified chitosan; Step two: preparation of modified mercapto sodium alginate: S1: take 2 g of sodium alginate, 80 mL of deionized water, stir evenly, add 2.5 mL of mercapto acetic acid, 2 mL of 7M hydrochloric acid, warm up to 81℃, react for 3.2 h, precipitate, freeze, dry, get mercapto sodium alginate; S2: take 3 g of gallic acid, 300 mL of ethanol, stir evenly, get gallic acid solution; take 0.5 g of mercapto sodium alginate, 500 mL of deionized water, stir evenly, add gallic acid solution, stir for 12 h, get modified mercapto sodium alginate; Step three: S1: add 3 g of ethyl cellulose to 100 mL of anhydrous ethanol, stir, add 1 g of modified mercapto sodium alginate, heat and stir at 40℃ for 2 h, get modified ethyl cellulose solution; S2: add 3 g of nano silver modified chitosan to 100 mL of deionized water, heat and stir at 60℃ for 5 h, get nano silver modified chitosan solution; S3: add 0.1 g of recombinant humanized collagen type I, 0.1 g of photoinitiator I2959, nano silver modified chitosan, heat and stir at 40℃ for 1 h, get chitosan solution containing recombinant humanized collagen type I; Step four: preparation of ethyl cellulose film: Uniformly coat the modified ethyl cellulose solution on a plastic dish, the coating amount is 0.1 g / cm 2 , dry, the drying temperature is 50℃, the drying time is 2 h, get ethyl cellulose film; Step five: preparation of oral wound plaster: Uniformly coat the chitosan solution containing recombinant humanized collagen type I on the ethyl cellulose film, the coating amount is 1 g / cm 2 , irradiate under 365 nm ultraviolet light for 10 min, the light intensity is 10 mW / cm 2 , freeze dry at-20℃ for 24 h, get oral wound plaster.

[0029] Example 8: no thiol group is introduced into the modified ethyl cellulose, and the rest is the same as example 5: Step one: nano-silver modified chitosan: S1: take 2g carboxymethyl chitosan, 200mL deionized water, heat to 50℃, stir evenly, add 8mL triethylamine, 8.5g tetrabutylammonium bromide, 30mL glycidyl methacrylate, react for 72h, then pour the solution into 1000mL ethanol for precipitation, dialysis, freeze-drying to obtain double bond carboxymethyl chitosan; S2: preparation of nano-silver particles: Take 95mL ethanol, 5mL deionized water, stir evenly, add 0.6g mouse tail acid, stir evenly, get mouse tail acid solution, add 100mL 0.05mol / L silver nitrate aqueous solution; Stir evenly, heat to 62℃, react for 35min, cool, filter, dry to get nano-silver particles; S3: take 1mL glacial acetic acid, 75mL deionized water, stir evenly, add 1g double bond carboxymethyl chitosan, stir for 11h, centrifuge, take the supernatant, add 2.4g nano-silver particles, stir for 35min, get nano-silver modified chitosan; Step two: preparation of modified sodium alginate: Take 3g gallic acid, 300mL ethanol, stir evenly, get gallic acid solution; Take 0.5g sodium alginate, 500mL deionized water, stir evenly, add gallic acid solution, stir for 12h, get modified sodium alginate; Step three: S1: add 3g ethyl cellulose to 100mL anhydrous ethanol, stir, add 1g modified sodium alginate, heat and stir at 40℃ for 2h, get modified ethyl cellulose solution; S2: add 3g nano-silver modified chitosan to 100mL deionized water, heat and stir at 60℃ for 5h, get nano-silver modified chitosan solution; S3: add 0.1g recombinant type I humanized collagen, 0.1g photoinitiator I2959, nano-silver modified chitosan, heat and stir at 40℃ for 1h, get chitosan solution containing recombinant type I humanized collagen; Step four: preparation of ethyl cellulose film: Uniformly coat the modified ethyl cellulose solution on the plastic dish, the coating amount is 0.1g / cm 2 , dry, the drying temperature is 50℃, the drying time is 2h, get ethyl cellulose film; Step five: preparation of oral wound plaster: Uniformly coat the chitosan solution containing recombinant type I humanized collagen on the ethyl cellulose film, the coating amount is 1g / cm2 Under 365 nm ultraviolet light for 10 min, the light intensity is 10 mW / cm 2 Freeze-drying at -20℃ for 24 h to obtain the oral wound dressing.

[0030] Preparation method of an oral wound dressing, comprising the following steps: Step one: S1: 3 g of ethyl cellulose is added to 100 mL of anhydrous ethanol, heated and stirred at 40℃ for 2 h to obtain an ethyl cellulose solution; S2: 3 g of carboxymethyl chitosan is added to 100 mL of deionized water, heated and stirred at 60℃ for 5 h to obtain a carboxymethyl chitosan solution; Step two: preparation of ethyl cellulose film: The ethyl cellulose solution is uniformly coated on a plastic dish, and the coating amount is 0.1 g / cm 2 , and dried at 50℃ for 2 h to obtain an ethyl cellulose film; Step three: preparation of an oral wound dressing: The carboxymethyl chitosan solution is uniformly coated on the ethyl cellulose film, and the coating amount is 1 g / cm 2 , and freeze-dried at -20℃ for 24 h to obtain an oral wound dressing.

[0031] The oral wound dressings prepared in Example 1 and Comparative Example 1 are subjected to scanning electron microscope experiment, and the obtained picture is shown in Figures 1-2 ; Conclusion: From the scanning electron microscope images of Figures 1-2 , it can be shown that: from the comparison of Example 1 and Comparative Example 1, it can be seen that Comparative Example 1 does not add I-type recombinant humanized collagen, and the surface microstructure of Comparative Example 1 is loose and has large pore size, which leads to poor antibacterial property of the wound dressing and decreased viscosity.

[0032] The wound dressings prepared in Examples 1-8 and Comparative Example 1 are subjected to antibacterial experiment, 15 μL of Staphylococcus aureus bacterial solution (1×10 6 CFU•mL -1 ) is added to the central area of the wound dressing; then a 1 cm×1 cm polyethylene film is covered on the bacterial solution, and then PBS is added to the holes around the sample, and the 12-hole plate is placed in a 37℃ incubator, and after 24 hours of culture, 2 mL of PBS buffer is added to each hole, and the hole plate is subjected to 5 minutes of ultrasonic treatment to release the bacteria adhered to the wound dressing, and then the PBS is continuously diluted and coated on an agar plate for 24 hours of incubation, and then colony counting is performed, and the obtained results are shown in Table 1: Table 1

[0033] Conclusion: From the above Table 1, Examples 1-4, it can be seen that the higher the carboxymethyl chitosan coating amount of the adhesive plaster has a better sterilization rate. Example 4 is 2 g / cm 2 , Example 1 is 1 g / cm 2 , Example 2 is 1.5 g / cm 2, , and Example 4 has a better sterilization rate. Example 5 adds nano-silver modified chitosan, modified thiolated sodium alginate and other substances for modification, although the coating amount is 1 g / cm 2 , but the sterilization rate can reach 100%. Example 6 does not add saligenin, and the sterilization rate decreases slightly.

[0034] Experiment 3: The oral wound dressings prepared in Examples 1-2 and Comparative Example 1 were subjected to biocompatibility experiments; first, L929 (mouse fibroblasts) were cultured in DMEM medium containing 10% fetal bovine serum, and the oral wound dressings were soaked in the above-mentioned medium for 24 hours (6 cm 2 / mL), and the cells were inoculated into a 96-well plate at a concentration of 1×10 4 per well, and cultured in a humidified atmosphere at 37°C, 5% CO2 for 24 hours; then the dressing extract was serially diluted to 100%, 75%, 50%, 25%, and added to the 96-well plate for incubation with the cells for 24 hours; then MTT reagent (40 μL) was added, and incubated at 37°C for 4 hours, then the MTT reagent was removed, and the purple crystals were dissolved with 100% dimethyl sulfoxide (DMSO, 100 μL), and the absorbance of the samples was measured using a multifunctional enzyme label instrument (λ = 570 nm), and the results are shown in Figures 3-4 ; wherein the significant differences are all compared with the negative control, “*” represents P < 0.05, “**” represents P < 0.01, “***” represents P < 0.001, and “****” represents P < 0.0001.

[0035] Conclusion: From the Figures 3-5 biocompatibility graph, it can be seen that the I-type recombinant humanized collagen can improve the biocompatibility of the material, and Examples 1-2 have better biocompatibility, meeting the requirements of oral wound dressings.

[0036] Experiment 4: The viscosity of Examples 1-8 and Comparative Example 1 was tested, and the data is shown in Table 2 below: Table 2

[0037] Conclusion: From the data comparison in the above table, it can be seen that the higher the carboxymethyl chitosan coating amount of the adhesive plaster in Examples 1-4, the better the viscosity. Example 5 modifies the adhesive plaster, and the peeling force is higher. The thiol group is introduced into the modified ethyl cellulose, and under the action of light initiation, the ethyl cellulose film is covalently crosslinked with the chitosan solution containing recombinant type I humanized collagen with double bonds, thereby improving the viscosity of the oral adhesive plaster. Example 7 does not add double-bonded carboxymethyl chitosan, and Example 8 does not introduce thiol groups into the modified ethyl cellulose, and the peeling force is slightly lower than that of Example 5.

[0038] It will be obvious to a person skilled in the art that the application is not limited to the details of the above-described exemplary embodiments, but that the application can be implemented in other concrete forms without departing from the spirit or the essential characteristics of the application. The embodiments are therefore to be considered in all respects as illustrative and not restrictive, the scope of the application being defined by the appended claims rather than by the above description, and it is therefore intended that all changes and modifications that fall within the meaning and range of equivalency of the elements of the claims are to be embraced by the application. Any reference signs in the claims should not be construed as limiting the claims to the figures in which the reference signs are used.

Claims

1. A method of preparing an oral patch, characterized by: The method comprises the following steps: Step 1: ethyl cellulose is added to anhydrous ethanol and stirred to obtain an ethyl cellulose solution; Step 2: carboxymethyl chitosan is added to deionized water and stirred to obtain a carboxymethyl chitosan solution; Step 3: the recombinant humanized collagen type I is added to the carboxymethyl chitosan solution and stirred to obtain a chitosan solution containing the recombinant humanized collagen type I; Step 4: the ethyl cellulose solution is uniformly coated on a flat dish and dried to obtain an ethyl cellulose film; Step 5: the chitosan solution containing the recombinant humanized collagen type I is uniformly coated on the ethyl cellulose film and freeze-dried to obtain the oral wound plaster.

2. A process for the preparation of a mouth patch according to claim 1, characterized in that: In step 1, the concentration of the ethyl cellulose solution is 1wt%-5wt%, the stirring temperature is 30-50 DEG C, and the stirring time is 1-4h; In step 2, the concentration of the carboxymethyl chitosan solution is 1wt%-5wt%, the stirring temperature is 40-80 DEG C, and the stirring time is 1-7h; In step 3, the recombinant humanized collagen type I accounts for 1%-50% of the mass percentage of the carboxymethyl chitosan, the stirring temperature is 30-50 DEG C, and the stirring time is 0.5-1h.

3. A process for the preparation of a mouth patch as claimed in claim 1, wherein: In Step 4, the coating amount of the ethyl cellulose solution is 0.05 to 0.5 g / cm 2 The drying temperature is 40 to 80°C, and the drying time is 0.5 to 4 hours.

4. A process for the preparation of a mouth patch as claimed in claim 1, wherein: The degree of substitution of the carboxymethyl chitosan is 70%-90%, and the molecular weight is 50000-100000.

5. A process for the preparation of an oral patch according to claim 1, characterized in that: The ethyl cellulose solution is a modified ethyl cellulose solution, and the preparation method is as follows: The method comprises the following steps: S1: sodium alginate and deionized water are taken and stirred to obtain a mixture, then mercaptoacetic acid and hydrochloric acid are added, the mixture is heated to 80-82 DEG C and reacted for 3-3.5h, and then the mixture is precipitated, frozen and dried to obtain mercapto sodium alginate; S2: gallic acid and ethanol are taken and stirred to obtain a gallic acid solution; mercapto sodium alginate and deionized water are taken and stirred to obtain a mixture, and then the gallic acid solution is added and stirred for 10-12h to obtain modified mercapto sodium alginate; S3: ethyl cellulose is added to anhydrous ethanol and stirred, and then the modified mercapto sodium alginate is added and stirred at 40 DEG C for 1-2h to obtain a modified ethyl cellulose solution.

6. A process for the preparation of an oral patch according to claim 1, characterized in that: The carboxymethyl chitosan is nano-silver modified chitosan, and the preparation method of the nano-silver modified chitosan is as follows: (1) ethanol and deionized water are taken and stirred to obtain a mixture, then mouse tail acid is added and stirred to obtain a mouse tail acid solution, and then silver nitrate aqueous solution is added; the mixture is stirred, heated to 60-65 DEG C and reacted for 30-40min, and then the mixture is cooled, filtered and dried to obtain nano-silver particles; (2) glacial acetic acid and deionized water are taken and stirred to obtain a mixture, then double-bond carboxymethyl chitosan is added and stirred for 10-12h, and then the mixture is centrifuged, and the supernatant is taken and added with nano-silver particles and stirred for 30-40min to obtain nano-silver modified chitosan.

7. A process for the preparation of a mouth patch according to claim 6, characterized in that: The preparation method of the double-bond carboxymethyl chitosan is as follows: carboxymethyl chitosan and deionized water are heated to 48-50 DEG C and stirred to obtain a mixture, then triethylamine, tetrabutylammonium bromide and glycidyl methacrylate are added, and the mixture is reacted for 70-74h, and then the solution is poured into ethanol to precipitate, and then the mixture is dialyzed and freeze-dried to obtain double-bond carboxymethyl chitosan.

8. A process for the preparation of an oral patch according to claim 1, characterized in that: In step 3, a photoinitiator is further added to the chitosan solution of the recombinant humanized collagen type I.

9. A method of making an oral patch according to claim 8, characterized in that: The oral wound plaster needs to be irradiated by ultraviolet light, and the preparation method is as follows: uniformly applying a chitosan solution containing recombinant humanized collagen I on an ethyl cellulose film, irradiating under 365nm ultraviolet light for 10min, the light intensity is 10mW / cm 2 , and freeze-drying at-20~-5℃ for 24-48h to obtain the oral wound plaster.

10. An oral adhesive bandage prepared according to the method of any one of claims 1 to 9.

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