Oral mucosa injury repairing composition and repairing method thereof

Abstract

The invention discloses an oral mucosa lesion repairing composition and a repairing method thereof, and relates to the technical field of oral care, and the oral mucosa lesion repairing composition comprises methacrylated polylysine hydrogel, MnO2 nano-enzyme and cannabidiol. According to the oral mucosal lesion repairing composition and the repairing method thereof, a repairing system combining cannabidiol (CBD), MnO2 and PLMA hydrogel is adopted, the biological activity of the CBD is exerted, the excellent performance of the hydrogel is utilized, a novel medicine carrier and a novel support are formed, and repairing of mucosal defects is promoted; meanwhile, the hydrogel material has excellent biocompatibility and can be well combined with surrounding tissues, cell proliferation is promoted, and the repairing effect is improved; and the repair system has obvious effects in the aspects of promoting cell proliferation and tissue regeneration, can effectively improve the repair efficiency of hard palate mucosa defects, and is superior to the traditional repair method.

Description

Technical Field

[0001] The present invention relates to the technical field of oral care, and in particular to an oral mucosal damage repair composition and a repair method thereof. Background Art

[0002] Oral mucosal injuries are common in dentistry, often caused by a variety of factors, including external trauma, accidental injury during oral treatment, surgical resection, infectious diseases, and tumor treatment (radiotherapy, chemotherapy). These injuries not only affect patients' oral health but can also lead to problems such as difficulty eating, dysphonia, and the spread of infection, severely impacting their quality of life.

[0003] The treatment of oral mucosal injuries faces many difficulties and pain points. First, the oral environment is complex and is often exposed to external stimuli such as bacteria and food debris, which can easily lead to infection and affect the speed of wound healing. Secondly, the oral mucosal tissue structure is thin and soft, which is easily damaged by mechanical damage. At the same time, due to frequent oral activities (such as talking and chewing), it is difficult for the wound to maintain a stable healing environment. In addition, existing treatments, such as oral antibacterial drugs or topical repair materials, have limited effects and it is difficult to completely solve the problem of infection and accelerate healing. Another pain point is that individual healing ability varies depending on factors such as age and immune status. Especially for diabetic patients or people with low immunity, the healing speed is slower and more prone to complications.

[0004] Existing methods for repairing oral mucosal defects mostly rely on topical medications (such as antibacterials and anti-inflammatory drugs). However, these methods have limited effectiveness in promoting tissue regeneration, especially when dealing with large, deep injuries, which result in slow healing. Due to the specific characteristics of the oral environment (such as the continuous secretion of saliva and high bacterial diversity), the repair process is easily disturbed, resulting in prolonged treatment cycles, unstable efficacy, and increased patient suffering. Summary of the Invention

[0005] In view of the deficiencies in the prior art, the present invention provides an oral mucosal damage repair composition and a repair method thereof, which solve the problems mentioned in the above background technology.

[0006] To achieve the above objectives, the present invention is implemented through the following technical solutions: an oral mucosal damage repair composition, comprising: methacrylated polylysine hydrogel, MnO2 nanozyme and cannabidiol.

[0007] A method for preparing an oral mucosal damage repair composition uses methacrylated polylysine hydrogel as a drug carrier and repair scaffold, and carries MnO2 nanozyme and cannabidiol in the system.

[0008] Preferably, the preparation method of the methacrylated polylysine hydrogel is:

[0009] (1) At room temperature, methacrylic acid was poured into deionized water at a volume ratio of 1:(1.5-2.5), and then N-hydroxysuccinimide and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride were added;

[0010] (2) After adding ε-polylysine, adjust the pH value of the reaction system to 4-6, raise the temperature to 40-60°C, and react for 18-24 hours;

[0011] (3) After the reaction is completed, the reaction product is dialyzed and purified and freeze-dried;

[0012] (4) Pour the mixture into an aqueous solution 2-4 times the volume of ε-polylysine and containing 2%-5% photoinitiator, and mix well;

[0013] (5) Finally, ultraviolet irradiation is used for curing to obtain a hydrogel.

[0014] Preferably, in (1), the molar ratio of N-hydroxysuccinimide, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and methacrylic acid is 1:(1-1.5);

[0015] In said (2), the molecular weight of ε-polylysine is 3600-4300 Daltons, and the molar ratio of ε-polylysine to methacrylic acid is 1:(1-3);

[0016] In the above (4), the photoinitiator is 2-hydroxy-2-methyl-1-phenyl-1-propanone.

[0017] Preferably, in (5), the ultraviolet light irradiation time is 45-60s, the ultraviolet wavelength is 340-365nm, and the light energy density is 600-1000mJ / cm 2 .

[0018] Preferably, the preparation method of the MnO2 nanozyme is:

[0019] S1. dissolving manganese nitrate in deionized water to prepare a manganese nitrate solution with a concentration of 0.2-0.5 mol / L;

[0020] S2. Add the complexing agent, stir evenly, then add the solvent, and while stirring, add aqueous ammonia at a rate of 1-2 mL / min to adjust the pH value of the solution to 7.8-8, and continue stirring for 2-4 h to obtain a sol;

[0021] S3. Place the sol in a sealed container at room temperature for 12-24 hours;

[0022] S4. Place the mixture in a drying oven at 60-80°C and dry for 12-24 hours, then place it in a muffle furnace and calcine for 2-4 hours to obtain MnO2 nanozyme.

[0023] Preferably, in S2, the complexing agent is citric acid, and the molar ratio of the complexing agent to manganese nitrate is (1-2):1.

[0024] Preferably, in S2, the solvent is selected from a mixture of ethylene glycol, methyl ether and deionized water, and the volume ratio of ethylene glycol or methyl ether to deionized water is (1-3):1; the volume ratio of the solvent to manganese nitrate is (1.5-3):1.

[0025] Preferably, in S4, the temperature in the muffle furnace is raised to 300-500° C. at a heating rate of 1-5° C. / min.

[0026] Beneficial effects

[0027] The present invention provides a composition and method for repairing oral mucosal damage. Compared with the prior art, it has the following advantages:

[0028] (1) The oral mucosal injury repair composition and the repair method thereof adopt a repair system combining cannabidiol (CBD) + MnO2 with PLMA hydrogel, which not only exerts the biological activity of CBD, but also utilizes the superior performance of hydrogel to form a new type of drug carrier and scaffold, thereby promoting the repair of mucosal defects; at the same time, the hydrogel material has excellent biocompatibility and can be well combined with the surrounding tissue, thereby promoting cell proliferation and improving the repair effect; and the repair system shows significant effects in promoting cell proliferation and tissue regeneration, and can effectively improve the repair efficiency of hard palate mucosal defects, which is superior to traditional repair methods.

[0029] (2) The oral mucosal damage repair composition and repair method thereof can achieve anti-inflammatory effects without the use of antibiotics through the anti-inflammatory properties of CBD, reducing the risk of drug resistance and side effects caused by the use of antibiotics, and providing a safer treatment option.

[0030] (3) The oral mucosal injury repair composition and repair method thereof have significant cost advantages compared to growth factor-based treatment methods. Cannabidiol is widely available and stable, and the hydrogel material is easy to prepare and store, reducing the financial burden on patients.

[0031] (4) The oral mucosal injury repair composition and repair method thereof combine the antioxidant, anti-inflammatory and tissue regeneration promoting properties of CBD, enhance the overall therapeutic effect, and provide a comprehensive repair solution; MnO2 can reduce the expression of inflammatory markers by regulating the inflammatory microenvironment, thereby reducing local inflammatory response and helping to promote the mucosal repair process. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 The appearance characteristics of the SD rat hard palate mucosal defect repair provided by the present invention;

[0033] Figure 2 HE staining and Masson staining of the SD rat hard palate mucosal defect repair provided by the present invention;

[0034] Figure 3 PCNA immunohistochemical staining of the SD rat hard palate mucosal defect repair provided by the present invention;

[0035] Figure 4 IL6 immunohistochemical staining of the SD rat hard palate mucosal defect repair provided by the present invention;

[0036] Figure 5 The hydrogel system provided by the present invention. DETAILED DESCRIPTION

[0037] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. All other embodiments obtained by ordinary technicians in this field based on the embodiments of the present invention without making any creative efforts shall fall within the scope of protection of the present invention.

[0038] Example 1

[0039] (1) Preparation of methacrylated polylysine hydrogel: At room temperature, methacrylic acid was poured into deionized water at a volume ratio of 1:1.5, and then N-hydroxysuccinimide and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride were added at a molar ratio of 1:1 to methacrylic acid; after adding ε-polylysine with a molecular weight of 3600 Daltons at a molar ratio of 1:1 to methacrylic acid, the pH value of the reaction system was adjusted to 4, and the temperature was raised to 40°C and the reaction was carried out for 18 hours; after the reaction was completed, the reaction product was dialyzed and freeze-dried in turn; then poured into an aqueous solution with a volume twice that of ε-polylysine and containing 2% 2-hydroxy-2-methyl-1-phenyl-1-propanone, and mixed evenly; finally, cured by ultraviolet irradiation, wherein the ultraviolet irradiation time was 45 seconds, the ultraviolet wavelength was 340 nm, and the light energy density was 600 mJ / cm 2 , that is, the hydrogel is prepared

[0040] (2) Preparation of MnO2 nanozyme: dissolve manganese nitrate in deionized water to prepare a manganese nitrate solution with a concentration of 0.2 mol / L; add citric acid at a molar ratio of 1:1 to manganese nitrate, stir evenly, and then add a solvent at a volume ratio of 1.5:1 to manganese nitrate, wherein the solvent is a mixture of ethylene glycol and deionized water at a volume ratio of 1:1, while stirring, add ammonia water at a drop rate of 1 mL / min, adjust the pH value of the solution to 7.8, continue stirring for 2 hours, and prepare a sol; at room temperature, place the sol in a sealed container for 12 hours; then place it in a drying oven at 60°C and dry it for 12 hours, then place it in a muffle furnace, heat it to 300°C at a heating rate of 1°C / min, and calcine it for 2 hours to obtain MnO2 nanozyme;

[0041] (3) Methacryloylation of polylysine hydrogel was used as a drug carrier and repair scaffold, and MnO2 nanozymes and cannabidiol were loaded into the system.

[0042] Example 2

[0043] (1) Preparation of methacrylated polylysine hydrogel: At room temperature, methacrylic acid was poured into deionized water in a volume ratio of 1:2, and then N-hydroxysuccinimide and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride were added in a molar ratio of 1:1.2 to methacrylic acid; after adding ε-polylysine with a molecular weight of 3900 Daltons in a molar ratio of 1:2 to methacrylic acid, the pH value of the reaction system was adjusted to 5, and the temperature was raised to 50°C and the reaction was carried out for 21 hours; after the reaction was completed, the reaction product was dialyzed and freeze-dried in turn; then poured into an aqueous solution with a volume 3 times that of ε-polylysine and containing 3% 2-hydroxy-2-methyl-1-phenyl-1-propanone, and mixed evenly; finally, cured by ultraviolet irradiation, wherein the ultraviolet irradiation time was 50 seconds, the ultraviolet wavelength was 350 nm, and the light energy density was 800 mJ / cm 2 , that is, the hydrogel is prepared

[0044] (2) Preparation of MnO2 nanozyme: dissolve manganese nitrate in deionized water to prepare a manganese nitrate solution with a concentration of 0.4 mol / L; add citric acid at a molar ratio of 1.5:1 to manganese nitrate, stir evenly, and then add a solvent at a volume ratio of 2:1 to manganese nitrate, wherein the solvent is a mixture of ethylene glycol and deionized water at a volume ratio of 2:1, while stirring, add ammonia water at a drip rate of 1.5 mL / min, adjust the pH value of the solution to 7.9, continue stirring for 3 hours, and prepare a sol; at room temperature, place the sol in a sealed container and leave it for 18 hours; then place it in a drying oven at 70°C and dry it for 18 hours, then place it in a muffle furnace, heat it to 400°C at a heating rate of 3°C / min, and calcine it for 3 hours to obtain MnO2 nanozyme;

[0045] (3) Methacryloylation of polylysine hydrogel was used as a drug carrier and repair scaffold, and MnO2 nanozymes and cannabidiol were loaded into the system.

[0046] Example 3

[0047] (1) Preparation of methacrylated polylysine hydrogel: At room temperature, methacrylic acid was poured into deionized water at a volume ratio of 1:2.5, and then N-hydroxysuccinimide and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride were added at a molar ratio of 1:1.5 to methacrylic acid; after adding ε-polylysine with a molecular weight of 4300 Daltons at a molar ratio of 1:3 to methacrylic acid, the pH value of the reaction system was adjusted to 6, and the temperature was raised to 60°C and the reaction was carried out for 24 hours; after the reaction was completed, the reaction product was dialyzed and freeze-dried in turn; then poured into an aqueous solution with a volume 4 times that of ε-polylysine and containing 5% 2-hydroxy-2-methyl-1-phenyl-1-propanone, and mixed evenly; finally, cured by ultraviolet irradiation, wherein the ultraviolet irradiation time was 60 seconds, the ultraviolet wavelength was 365 nm, and the light energy density was 1000 mJ / cm 2 , that is, the hydrogel is prepared

[0048] (2) Preparation of MnO2 nanozyme: dissolve manganese nitrate in deionized water to prepare a manganese nitrate solution with a concentration of 0.5 mol / L; add citric acid at a molar ratio of 2:1 to manganese nitrate, stir evenly, and then add a solvent at a volume ratio of 3:1 to manganese nitrate, wherein the solvent is a mixture of methyl ether and deionized water at a volume ratio of 3:1, while stirring, add ammonia water at a drip rate of 2 mL / min, adjust the pH value of the solution to 8, continue stirring for 4 hours, and prepare a sol; under room temperature, place the sol in a sealed container for 24 hours; then place it in a drying oven at 80°C and dry it for 24 hours, then place it in a muffle furnace, heat it to 500°C at a heating rate of 5°C / min, and calcine it for 4 hours to obtain MnO2 nanozyme;

[0049] (3) Methacryloylation of polylysine hydrogel was used as a drug carrier and repair scaffold, and MnO2 nanozymes and cannabidiol were loaded into the system.

[0050] In an animal experiment using SD rats as experimental subjects, a full-thickness defect of the hard palate mucosa with a diameter of 2 mm was constructed and repaired using the system constructed by this method.

[0051] like Figure 1 and Figure 2 As shown: Whether observed from a macroscopic or tissue level, the system constructed using this method can significantly improve the efficiency of mucosal defect repair when repairing mucosal defects.

[0052] like Figure 3 As shown: This method can significantly increase the expression of PCNA, a cell proliferation marker, in the repair area of the hard palate mucosa defect, indicating that it can promote cell proliferation.

[0053] like Figure 4 As shown: This method can reduce the expression of IL6, an inflammatory marker, in the repair area of the hard palate mucosal defect. By adopting a repair system combining CBD with PLMA hydrogel, in which PLMA has antibacterial activity and CBD has anti-inflammatory properties, the anti-inflammatory effect can be achieved without the use of antibiotics, avoiding the risk of drug resistance and related side effects, and providing a safer and more effective mucosal defect repair solution; MnO2 nanozyme not only has anti-inflammatory ability itself, but can also further enhance the anti-inflammatory activity of CBD in this system.

[0054] Meanwhile, the contents not described in detail in this specification belong to the prior art known to those skilled in the art.

[0055] While embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions, and variations may be made to these embodiments without departing from the principles and spirit of the invention, and that the scope of the invention is defined by the appended claims and their equivalents.

Claims

1. An oral mucosal damage repair composition, characterized in that: include: Methacryloyl-polylysine hydrogel, MnO2 nanozyme, and cannabidiol.

2. A method for preparing the oral mucosal damage repair composition according to claim 1, characterized in that: Methacryloylated polylysine hydrogel was used as a drug carrier and repair scaffold, and MnO2 nanozyme and cannabidiol were carried in the system.

3. The method for preparing an oral mucosal damage repair composition according to claim 2, wherein: The preparation method of the methacrylated polylysine hydrogel is as follows: (1) At room temperature, methacrylic acid was poured into deionized water at a volume ratio of 1:(1.5-2.5), and then N-hydroxysuccinimide and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride were added; (2) After adding ε-polylysine, adjust the pH value of the reaction system to 4-6, raise the temperature to 40-60°C, and react for 18-24 hours; (3) After the reaction is completed, the reaction product is dialyzed and purified and freeze-dried; (4) Pour the mixture into an aqueous solution 2-4 times the volume of ε-polylysine and containing 2%-5% photoinitiator, and mix well; (5) Finally, ultraviolet irradiation is used for curing to obtain a hydrogel.

4. The method for preparing an oral mucosal damage repair composition according to claim 3, wherein: In said (1), the molar ratio of N-hydroxysuccinimide, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and methacrylic acid is 1:(1-1.5); In said (2), the molecular weight of ε-polylysine is 3600-4300 Daltons, and the molar ratio of ε-polylysine to methacrylic acid is 1:(1-3); In the above (4), the photoinitiator is 2-hydroxy-2-methyl-1-phenyl-1-propanone.

5. The method for preparing an oral mucosal damage repair composition according to claim 3, wherein: In (5), the ultraviolet light irradiation time is 45-60s, the ultraviolet wavelength is 340-365nm, and the light energy density is 600-1000mJ / cm 2 .

6. The method for preparing an oral mucosal damage repair composition according to claim 1, wherein: The preparation method of the MnO2 nanozyme is: S1. dissolving manganese nitrate in deionized water to prepare a manganese nitrate solution with a concentration of 0.2-0.5 mol / L; S2. Add the complexing agent, stir evenly, then add the solvent, and while stirring, add aqueous ammonia at a rate of 1-2 mL / min to adjust the pH value of the solution to 7.8-8, and continue stirring for 2-4 h to obtain a sol; S3. Place the sol in a sealed container at room temperature for 12-24 hours; S4. Place the mixture in a drying oven at 60-80°C and dry for 12-24 hours, then place it in a muffle furnace and calcine for 2-4 hours to obtain MnO2 nanozyme.

7. The method for preparing an oral mucosal damage repair composition according to claim 6, characterized in that: In S2, the complexing agent is citric acid, and the molar ratio of the complexing agent to manganese nitrate is (1-2):

1.

8. The method for preparing an oral mucosal damage repair composition according to claim 6, characterized in that: In S2, the solvent is selected from a mixture of ethylene glycol, methyl ether and deionized water, and the volume ratio of ethylene glycol or methyl ether to deionized water is (1-3):1; the volume ratio of the solvent to manganese nitrate is (1.5-3):

1.

9. The method for preparing an oral mucosal damage repair composition according to claim 6, wherein: In the S4, the temperature in the muffle furnace is raised to 300-500° C. at a heating rate of 1-5° C. / min.

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