Bacteria-blocking and inflammation-diminishing gel and preparation method thereof
By using a photocrosslinking method with modified silk fibroin and methacrylamide hyaluronic acid, an antibacterial and anti-inflammatory gel was prepared, which solved the problems of easy detachment and poor biocompatibility of existing products, achieving efficient adhesion and long-lasting bactericidal effect, and improving the patient's medication experience.
Patent Information
- Application Number
- CN202512049138.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-12-31
- Publication Date
- 2026-03-03
AI Technical Summary
Existing antibacterial and anti-inflammatory gels tend to detach easily from oily skin areas, exhibiting poor adhesion, which affects treatment compliance and efficacy. Furthermore, their biocompatibility is poor, easily triggering skin irritation.
An antibacterial and anti-inflammatory gel was prepared by using a photocrosslinking method with modified silk fibroin, methacrylamide hyaluronic acid, cyclodextrin and salicylic acid. The crosslinking network structure was used to improve adhesion, and the gel was cured by ultraviolet light.
It achieves good adhesion of the antibacterial and anti-inflammatory gel to skin wounds and affected areas, effectively releases antibacterial ingredients, promotes metabolism, improves the patient's medication experience, and enhances treatment efficacy.
Smart Images
Figure CN121588028A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of hydrogel technology, and more specifically, to an antibacterial and anti-inflammatory gel and its preparation method. Background Technology
[0002] Antibacterial and anti-inflammatory gels are widely used in the treatment of skin inflammation and wound care due to their advantages such as convenient application, good adhesion, and sustained release of active ingredients. However, most existing antibacterial and anti-inflammatory gels used to treat skin wounds, acne, and onychomycosis tend to detach from oily areas of the skin due to poor fluidity or adhesion, affecting treatment compliance and efficacy. Furthermore, many products have poor biocompatibility, causing skin irritation, and prolonged application or wearing can easily lead to adverse reactions such as allergies and redness. Therefore, developing a gel formulation that maintains good adhesion to the affected area, is not prone to detachment, and possesses excellent antibacterial and anti-inflammatory effects is of significant practical importance for improving treatment efficacy and enhancing the patient's medication experience. Summary of the Invention
[0003] The purpose of this invention is to overcome the shortcomings of the prior art and provide an antibacterial and anti-inflammatory gel and its preparation method.
[0004] To achieve the above objectives, the present invention adopts the following technical solution:
[0005] A method for preparing an antibacterial and anti-inflammatory gel includes the following steps:
[0006] S1. Mix the modified silk fibroin aqueous solution with the methacryloyl hyaluronic acid aqueous solution, the cyclodextrin aqueous solution, the 1,2-propanediol and the salicylic acid ethanol aqueous solution in a certain proportion to obtain a mixture;
[0007] S2. Mix the mixture with the photoinitiator evenly in the dark to obtain the antibacterial and anti-inflammatory gel precursor solution;
[0008] S3. The precursor solution of the antibacterial and anti-inflammatory gel is cured under ultraviolet light to obtain the antibacterial and anti-inflammatory gel.
[0009] The present invention is further configured such that, in step S1, the mass ratio of the modified silk fibroin aqueous solution to the aqueous solution of methacryloyl hyaluronic acid, the aqueous solution of cyclodextrin, the aqueous solution of 1,2-propanediol and the aqueous solution of salicylic acid in ethanol is 5:(3-4):(4-5):(1-2):(1-2); and in step S2, the mass ratio of the modified silk fibroin aqueous solution to the photoinitiator in the mixture is 5:0.5-0.6.
[0010] The modified silk fibroin concentration in the aqueous solution is 15-20 wt%; the preparation steps of the modified silk fibroin are as follows:
[0011] (a) After heating and stirring degummed silk with CaCl2-C2H6O-H2O solution, the mixture was cooled and centrifuged. The supernatant obtained by centrifugation was dialyzed and freeze-dried to obtain regenerated silk fibroin.
[0012] (b) Regenerated silk fibroin was mixed with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide, and glutathione and reacted. The solution after reaction was dialyzed and freeze-dried to obtain modified silk fibroin.
[0013] The present invention is further configured such that, in step (a), the molar ratio of CaCl2, C2H6O, and H2O is 1:2:8; and the volume ratio of degummed silk to CaCl2-C2H6O-H2O solution is 0.1~2g:10~30mL.
[0014] The present invention is further configured such that, in step (b), the mass ratio of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide, glutathione, and regenerated silk fibroin is (1.6~2.3):(1~1.5):(0.5~2):1.
[0015] The present invention is further configured such that the concentration of methacrylamide hyaluronic acid in the aqueous solution of methacrylamide hyaluronic acid is 1~20wt%; sodium hyaluronate is dissolved in water, DMF and methacrylic anhydride are added, the pH of the solution is adjusted to 8~9 and the reaction is carried out, the product is separated and purified after the reaction, and the product is freeze-dried to obtain methacrylamide hyaluronic acid.
[0016] The present invention is further configured such that the ratio of sodium hyaluronate to water and DMF is 0.1~2g:30~150mL:20~100mL, and the mass ratio of methacrylic anhydride to sodium hyaluronate is 1~2:1.
[0017] The present invention is further configured such that the cyclodextrin aqueous solution is made of cyclodextrin, antibacterial component and water; the mass ratio of cyclodextrin, antibacterial component and water in the cyclodextrin aqueous solution is (10~20):(0.5~3):(77~89.5), and the antibacterial component is at least one of tea tree oil, thymol, cinnamaldehyde and allicin.
[0018] The present invention is further configured such that the salicylic acid ethanol aqueous solution is prepared by mixing salicylic acid with an ethanol aqueous solution with a concentration of 70-95%, wherein the concentration of salicylic acid in the salicylic acid ethanol aqueous solution is 5-15 wt%.
[0019] An antibacterial and anti-inflammatory gel prepared by the method described above.
[0020] In summary, the present invention has the following beneficial effects:
[0021] This invention enables the rapid formation of antibacterial and anti-inflammatory gel on medical tape through photocrosslinking. Simultaneously, by leveraging the crosslinked network structure as a carrier and the permeability of the material, along with the anti-inflammatory and healing-promoting effects of silk fibroin, the gel's adhesion is significantly improved. Furthermore, it effectively releases antibacterial components into deep tissue layers, achieving a highly efficient, long-lasting, and thorough bactericidal effect. This promotes the metabolism of tissues such as skin wounds, acne, and onychomycosis, improving the patient's medication experience and ultimately achieving a cure. Attached Figure Description
[0022] Figure 1 This is a photograph of the antibacterial and anti-inflammatory gel prepared in Example 1. Detailed Implementation
[0023] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.
[0024] The preparation steps of the antibacterial and anti-inflammatory gel of this invention are as follows:
[0025] S1. Preparation of modified silk fibroin aqueous solution:
[0026] (a) Add silkworm cocoons to a 0.05 mol / L Na2CO3 aqueous solution and boil at 100°C (the ratio of silkworm cocoons to Na2CO3 aqueous solution is 0.5~2g: 50~400mL). After removing the cocoons, place them in a new 6000mL 0.05 mol / L Na2CO3 aqueous solution and boil again at 100°C. Remove the cocoons, wash and dry them to obtain degummed silk.
[0027] (b) Degummed silk and CaCl2-C2H6O-H2O solution were heated in a water bath at 60-65℃ and stirred for 4-5 hours (the molar ratio of CaCl2, C2H6O, and H2O was 1:2:8; the volume ratio of degummed silk to CaCl2-C2H6O-H2O solution was 0.1~2g:10~30mL). After cooling and centrifugation, the supernatant was obtained. The supernatant was placed in a dialysis bag and dialyzed at 3-4℃ for 3 days. After freeze-drying, regenerated silk fibroin was obtained (the molecular weight of regenerated silk fibroin was 10~130 kDa).
[0028] (c) After dissolving regenerated silk fibroin in water (the ratio of regenerated silk fibroin to water is 1~30g: 50~200mL), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide are added and stirred for reaction. Then glutathione is added and reacted at room temperature for 24h. The mass ratio of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide, glutathione and regenerated silk fibroin is (1.6~2.3):(1~1.5):(0.5~2):1. The solution after reaction is dialyzed and freeze-dried to obtain modified silk fibroin.
[0029] (d) Dissolve the modified silk fibroin in water to prepare a modified silk fibroin aqueous solution with a concentration of 15~20wt%.
[0030] S2. Preparation of aqueous solution of methacrylamide hyaluronic acid: Dissolve sodium hyaluronate in water, add DMF while stirring at 4℃ (the ratio of sodium hyaluronate to water and DMF is 0.1~2g:30~150mL:20~100mL), then add methacrylic anhydride dropwise (the mass ratio of methacrylic anhydride to sodium hyaluronate is 1~2:1), adjust the pH of the solution to 8~9 with 1mol / L NaOH solution, and react for 24h; after the reaction is completed, add NaCl and continue stirring for 1h (the mass ratio of NaCl to sodium hyaluronate is 0.1~1:1), then add the solution dropwise to anhydrous ethanol to precipitate (the volume ratio of anhydrous ethanol to the reaction solution is 3~5:1), centrifuge to obtain the lower precipitate, redissolve the lower precipitate in 100~200mL of water, place it in a 7000Da dialysis bag and dialyze at room temperature for 3 days, and freeze-dry to obtain methacrylamide hyaluronic acid. Methacrylamide hyaluronic acid was dissolved in water to prepare an aqueous solution of methacrylamide hyaluronic acid with a concentration of 1~20wt%.
[0031] S3. Preparation of cyclodextrin aqueous solution: Dissolve cyclodextrin in purified water, and then add antibacterial component (at least one of tea tree oil, thymol, cinnamaldehyde and allicin) dropwise at 60°C. After stirring continuously for 1-2 hours, a cyclodextrin aqueous solution is obtained. The mass ratio of cyclodextrin, antibacterial component and purified water is (10-20):(0.5-3):(77-89.5).
[0032] S4. Preparation of salicylic acid ethanol aqueous solution: Prepare an ethanol aqueous solution with an ethanol concentration of 70~95%; dissolve salicylic acid in the ethanol aqueous solution and stir evenly to obtain a salicylic acid ethanol aqueous solution with a salicylic acid concentration of 5~15wt%.
[0033] S5. The preparation method of the gel is as follows:
[0034] Step 1: Mix the modified silk fibroin aqueous solution, methacrylamide hyaluronic acid aqueous solution, cyclodextrin aqueous solution, 1,2-propanediol and salicylic acid ethanol aqueous solution, dipotassium glycyrrhizate, and Sapindus saponin B in a mass ratio of 5:(3-4):(4-5):(1-2):(1-2):(0-0.5):(0-0.3) to obtain a mixture.
[0035] Step 2: Mix the mixed solution with the photoinitiator in the dark (the mass ratio of the modified silk fibroin aqueous solution to the photoinitiator in the mixed solution is 5:0.5-0.6) to obtain the antibacterial and anti-inflammatory gel precursor solution;
[0036] Step 3: Cut the medical tape into strips, peel off the release paper, and heat it on a hot plate at 80-100℃ for 30-60 minutes, applying 0.5-1.0 mL / 10cm. 2 Pour the amount of antibacterial and anti-inflammatory gel precursor solution onto medical tape, at a concentration of 40~80 W / cm². 2 After curing and setting under ultraviolet light for 20-60 seconds, an antibacterial and anti-inflammatory gel can be obtained.
[0037] The preferred embodiment is as follows:
[0038] Example 1
[0039] S1. Add 15g of silkworm cocoons to 6000mL of 0.05mol / L Na2CO3 aqueous solution and boil at 100℃ for 30 minutes. Remove the cocoons and place them in a fresh 6000mL 0.05mol / L Na2CO3 aqueous solution, boil at 100℃ for another 30 minutes. Remove the cocoons, wash and dry them to obtain degummed silk. In a 250mL beaker, add 10g of degummed silk and 150mL of CaCl2-C2H6O-H2O solution, heat in a water bath at 60℃ and stir for 4h (Molar ratio of CaCl2, C2H6O, H2O is 1:2:8). After cooling and centrifugation, obtain the supernatant. Place the supernatant in a dialysis bag and dialyze at 4℃ for 3 days. After freeze-drying, obtain regenerated silk fibroin with a molecular weight of 30KDa. In a 250 mL beaker, 8 g of regenerated silk fibroin and 200 mL of water were added and stirred to dissolve. Then, 16 g of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and 11.8 g of N-hydroxysuccinimide were added and stirred to react. Subsequently, 12 g of glutathione was added and reacted at room temperature for 24 h. The resulting solution was dialyzed and freeze-dried to obtain modified silk fibroin. In a 100 mL beaker, 9 g of modified silk fibroin and 41 g of water were added and stirred thoroughly to dissolve, resulting in an aqueous solution of modified silk fibroin.
[0040] S2. In a 1000mL blue-capped reagent bottle, add 9g of sodium hyaluronate and 450mL of water. After stirring thoroughly to dissolve, add 300mL of DMF at 4℃ and stir for half an hour. Then, add 13.5g of methacrylic anhydride dropwise. Adjust the pH of the solution to 8 with 1mol / L NaOH solution and react for 24 hours. After the reaction is complete, add 6.75g of NaCl and continue stirring for 1 hour. Then, add the reacted solution dropwise to 2400mL of anhydrous ethanol to precipitate. After centrifugation, obtain the lower precipitate. Redissolve the lower precipitate in 100mL of water and dialyze it in a 7000Da dialysis bag at room temperature for 3 days. After freeze-drying, obtain methacrylamide hyaluronic acid. In a 50mL beaker, add 1g of methacrylamide hyaluronic acid and 9g of water. After stirring thoroughly to dissolve, obtain an aqueous solution of methacrylamide hyaluronic acid.
[0041] S3. In a 50mL beaker, add 1.5g of cyclodextrin and 8.3g of water, stir thoroughly to dissolve, heat to 60℃, then add 0.2g of thymol dropwise, and continue stirring for 2 hours to obtain an aqueous solution of cyclodextrin.
[0042] S4. In a 20mL beaker, add 9.5mL of anhydrous ethanol and 0.5mL of water, and mix thoroughly by ultrasonic vibration to obtain an ethanol-water solution; in a 20mL beaker, add 0.25g of salicylic acid and 4.75g of ethanol-water solution, and stir thoroughly to dissolve to obtain a salicylic acid-ethanol-water solution.
[0043] S5. The preparation method of the gel is as follows:
[0044] Step 1: In a 25mL beaker, add 5g of modified silk fibroin aqueous solution, 3.96g of methacrylamide hyaluronic acid aqueous solution, 4.48g of cyclodextrin aqueous solution, 1.34g of 1,2-propanediol and 1.64g of salicylic acid ethanol aqueous solution in sequence, and stir thoroughly to obtain a mixture.
[0045] Step 2: Add 0.58g of LAP photoinitiator (lithium phenyl (2,4,6-trimethylbenzoyl)phosphate) to the beaker of the mixture, stir and dissolve evenly in the dark, centrifuge and transfer the clear upper layer to a brown tube bottle, which is the precursor solution for antibacterial and anti-inflammatory gel. Wrap it in aluminum foil for later use.
[0046] Step 3: Cut the medical tape into strips, peel off the release paper, and heat it on an 80℃ hot plate for 30 minutes. Pour the antibacterial and anti-inflammatory gel precursor solution onto the medical tape at a ratio of 0.5 mL / 10 cm² of medical tape. After curing and setting under an 80 W / cm² UV lamp for 60 seconds, the antibacterial and anti-inflammatory gel is obtained.
[0047] Example 2
[0048] The antibacterial and anti-inflammatory gel was prepared according to the method in Example 1, except that in step S1 of step S5, 0.3g of dipotassium glycyrrhizate and 0.2g of Sapindus mukorossi saponin B (purchased from Shanghai Tongtian Biotechnology Co., Ltd., catalog number E-4494) were added to obtain a mixture.
[0049] Example 3
[0050] The antibacterial and anti-inflammatory gel was prepared according to the method in Example 1, except that in step S1 of step S5, 0.3g of dipotassium glycyrrhizate was added to obtain a mixture.
[0051] Example 4
[0052] The antibacterial and anti-inflammatory gel was prepared according to the method in Example 1, except that in step S1 of step S5, 0.2g of Sapindus mukorossi saponin B was added to obtain a mixture.
[0053] The adhesive properties of the antibacterial and anti-inflammatory gel products in Examples 1-4 were tested respectively (the method was as follows: prepare a piece of pigskin 20mm long, 10mm wide, and 2mm thick, apply 75% medical alcohol to the surface of the pigskin, and then apply a 10×10mm area...). 2 The antibacterial and anti-inflammatory gel tape was applied to the surface of pigskin, and the adhesion strength was tested after 14 days after pressing for 2 minutes. The results showed that the adhesion strengths of the gels in Examples 1-4 were 38 kPa, 54 kPa, 45 kPa, and 42 kPa, respectively.
[0054] The skin irritation of the antibacterial and anti-inflammatory gel products in Examples 1-4 were tested respectively (the method was as follows: prepare a piece of pigskin 20mm long, 10mm wide, and 2mm thick, apply 75% medical alcohol to the surface of the pigskin, and then apply a 10×10mm area...). 2 The antibacterial and anti-inflammatory gel tape was applied to the surface of pigskin, and the skin condition was observed after pressing for 2 minutes. The results showed that after 96 hours of gel application in Example 2, no redness or erythema appeared on the pigskin, while after 72 hours of gel application in Examples 1, 3, and 4, the skin showed redness and slight swelling.
[0055] The antibacterial properties of the antibacterial and anti-inflammatory gel of this invention were evaluated using *Escherichia coli*, *Staphylococcus aureus*, *Trichophyton rubrum*, and *Propionibacterium acnes* as pathogenic models (method: 0.1g of the antibacterial and anti-inflammatory gel was added to a bacterial suspension with a bacterial concentration of 10⁸ CFU / mL, cultured at 37°C for 24 h, and the inhibition rate was tested). The results showed that the inhibition rates of the gels in Examples 1-4 against *Escherichia coli* were 86.5%, 98%, 92.6%, and 90.2%, respectively; against *Staphylococcus aureus*, 90.3%, 99%, 95.1%, and 93.4%, respectively; against *Trichophyton rubrum*, 81.2%, 95.4%, 90.5%, and 89%, respectively; and against *Propionibacterium acnes*, 84%, 97.6%, 92.3%, and 88%, respectively.
[0056] The above description is merely a preferred embodiment of the present invention. The scope of protection of the present invention is not limited to the above embodiments. All technical solutions falling within the scope of the present invention's concept are within the scope of protection of the present invention. It should be noted that for those skilled in the art, any improvements and modifications made without departing from the principles of the present invention should also be considered within the scope of protection of the present invention.
Claims
1. A method for preparing an antibacterial and anti-inflammatory gel, characterized in that, Includes the following steps: S1. Mix the modified silk fibroin aqueous solution with the methacryloyl hyaluronic acid aqueous solution, the cyclodextrin aqueous solution, the 1,2-propanediol and the salicylic acid ethanol aqueous solution in a certain proportion to obtain a mixture; S2. Mix the mixture with the photoinitiator evenly in the dark to obtain the antibacterial and anti-inflammatory gel precursor solution; S3. The precursor solution of the antibacterial and anti-inflammatory gel is cured under ultraviolet light to obtain the antibacterial and anti-inflammatory gel.
2. The method for preparing an antibacterial and anti-inflammatory gel according to claim 1, characterized in that, In step S1, the mass ratio of the modified silk fibroin aqueous solution to the methacryloyl hyaluronic acid aqueous solution, the cyclodextrin aqueous solution, the 1,2-propanediol and the salicylic acid ethanol aqueous solution is 5:(3-4):(4-5):(1-2):(1-2); in step S2, the mass ratio of the modified silk fibroin aqueous solution to the photoinitiator in the mixture is 5:0.5-0.
6.
3. The method for preparing an antibacterial and anti-inflammatory gel according to claim 1, characterized in that, The modified silk fibroin concentration in the aqueous solution is 15-20 wt%; the preparation steps of the modified silk fibroin are as follows: (a) After heating and stirring degummed silk with CaCl2-C2H6O-H2O solution, the mixture was cooled and centrifuged. The supernatant obtained by centrifugation was dialyzed and freeze-dried to obtain regenerated silk fibroin. (b) Regenerated silk fibroin was mixed with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide, and glutathione and reacted. The solution after reaction was dialyzed and freeze-dried to obtain modified silk fibroin.
4. The method for preparing an antibacterial and anti-inflammatory gel according to claim 3, characterized in that, In step (a), the molar ratio of CaCl2, C2H6O, and H2O is 1:2:8; the volume ratio of degummed silk to CaCl2-C2H6O-H2O solution is 0.1~2g:10~30mL.
5. The method for preparing an antibacterial and anti-inflammatory gel according to claim 1, characterized in that, In step (b), the mass ratio of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide, glutathione, and regenerated silk fibroin is (1.6~2.3):(1~1.5):(0.5~2):
1.
6. The method for preparing an antibacterial and anti-inflammatory gel according to claim 1, characterized in that, The concentration of methacrylated hyaluronic acid in the aqueous solution is 1~20wt%; sodium hyaluronate is dissolved in water, DMF and methacrylic anhydride are added, the pH of the solution is adjusted to 8~9 and the reaction is carried out. After the reaction, the product is separated and purified, and the product is freeze-dried to obtain methacrylated hyaluronic acid.
7. The method for preparing an antibacterial and anti-inflammatory gel according to claim 6, characterized in that, The ratio of sodium hyaluronate to water and DMF is 0.1~2g:30~150mL:20~100mL, and the mass ratio of methacrylic anhydride to sodium hyaluronate is 1~2:
1.
8. The method for preparing an antibacterial and anti-inflammatory gel according to claim 1, characterized in that, The cyclodextrin aqueous solution is made of cyclodextrin, antibacterial component, and water; the mass ratio of cyclodextrin, antibacterial component, and water in the cyclodextrin aqueous solution is (10~20):(0.5~3):(77~89.5), and the antibacterial component is at least one of tea tree oil, thymol, cinnamaldehyde, and allicin.
9. The method for preparing an antibacterial and anti-inflammatory gel according to claim 1, characterized in that, The salicylic acid ethanol aqueous solution is prepared by mixing salicylic acid with an ethanol aqueous solution with a concentration of 70-95%, and the concentration of salicylic acid in the salicylic acid ethanol aqueous solution is 5-15 wt%.
10. An antibacterial and anti-inflammatory gel prepared by the method according to any one of claims 1-9.