Glutaraldehyde gel and preparation method thereof

Abstract

The invention relates to the technical field of medical gel, in particular to glutaraldehyde gel and a preparation method thereof. Comprising the following raw materials: poloxamer, glutaraldehyde, modified nano magnesium silicide, a modified nano polyvinyl alcohol-vinyl acetate copolymer, glycerol, potassium sorbate, menthol, sodium hyaluronate, polyethylene glycol, aloe, angelica sinensis, dandelion, centella asiatica, ginseng, poria cocos, fructus kochiae, honeysuckle, propylene glycol and purified water. The glutaraldehyde, the modified nano magnesium silicide and the modified nano polyvinyl alcohol-vinyl acetate copolymer play a role through a synergistic effect, effective release of the glutaraldehyde and the modified nano magnesium silicide is ensured by a continuous release mechanism of the modified nano polyvinyl alcohol-vinyl acetate copolymer, and the glutaraldehyde directly attacks the HPV virus; and the modified nano magnesium silicide enhances the antiviral effect of glutaraldehyde, promotes skin repair, accelerates skin regeneration and reduces the recurrence rate.

Description

Technical Field

[0001] The present invention relates to the technical field of medical gels, and specifically to a glutaraldehyde gel and a preparation method thereof. Background Art

[0002] Warts are common skin diseases caused by the human papillomavirus (HPV), usually manifested as small papules or nodules with keratinous hyperplasia, and can form obvious verrucous lesions on the skin surface. According to the morphology and location of warts, warts can be divided into common warts, plantar warts, flat warts, genital warts and other types. Although most warts are benign lesions, their existence often causes aesthetic problems, and even causes pain, infection and further spread, seriously affecting the quality of life of patients. Glutaraldehyde is a fast-acting and broad-spectrum chemical sterilant, which can not only inhibit the growth of a variety of pathogenic microorganisms, but also cause irreversible damage to virus particles through cross-linking. At room temperature, a low-concentration aqueous solution of glutaraldehyde can exhibit activity against many microorganisms, and has a high sterilization effect on reproductive bacteria, viruses, mycobacteria, pathogenic molds and bacterial spores. Especially for warts caused by HPV, glutaraldehyde can reduce virus replication and spread through cross-linking with the surface proteins of the virus, so it has a good antiviral effect and very low toxicity to humans, and is known as the third milestone of chemical bactericidal disinfectants. To enhance the antiviral persistence of glutaraldehyde, improve its stability and sustained release, by preparing a gel preparation, not only can the release rate of glutaraldehyde be effectively controlled, but also the action time of the drug at the affected area can be prolonged, irritation can be reduced, and the discomfort and side effects of patients can be alleviated by local retention and slow penetration. Summary of the Invention

[0003] (1) Technical Problems to be Solved

[0004] The purpose of the present invention is to provide a glutaraldehyde gel and a preparation method thereof. By optimizing the chemical formula of the glutaraldehyde gel, combining modern nanotechnology and adding traditional Chinese medicine extracts at the same time, the antiviral persistence of glutaraldehyde can be enhanced, irritation can be reduced, the virus inactivation ability can be enhanced, while promoting skin repair and reducing the recurrence rate, and the discomfort and side effects of patients can be alleviated.

[0005] (2) Technical Solutions

[0006] To achieve the above object, on the one hand, the present invention provides a glutaraldehyde gel, comprising the following raw materials in parts by weight: 6-12 parts of poloxamer, 5-10 parts of glutaraldehyde, 1-3 parts of modified nano magnesium silicate, 15-20 parts of glycerol, 0.5-1 part of potassium sorbate, 0.1-0.5 part of menthol, 0.1-0.5 part of sodium hyaluronate, 1-5 parts of polyethylene glycol, 1-3 parts of aloe vera, 0.5-1 part of angelica, 0.5-1 part of dandelion, 0.5-1 part of centella asiatica, 0.5-1 part of ginseng, 0.5-1 part of poria cocos, 0.5-1 part of Kochia scoparia, 0.5-1 part of honeysuckle, 8-10 parts of propylene glycol, 15-25 parts of purified water;

[0007] The glutaraldehyde gel further comprises:

[0008] Modified nano polyvinyl alcohol-vinyl acetate copolymer;

[0009] The weight ratio of the modified nano polyvinyl alcohol-vinyl acetate copolymer to poloxamer is 2:(6-12);

[0010] The modified nano polyvinyl alcohol-vinyl acetate copolymer is prepared by nano-sizing polyvinyl alcohol-vinyl acetate copolymer and grafting cystamine molecules on its surface. The particle size of the modified nano polyvinyl alcohol-vinyl acetate copolymer is 50-80 nm, and the specific surface area is 180-200 m 2 / g.

[0011] Furthermore, the preparation method of the modified nano polyvinyl alcohol-vinyl acetate copolymer comprises:

[0012] S11. Dissolve polyvinyl alcohol-vinyl acetate copolymer in purified water under stirring, heat up to 75-85 °C, stir for 0.5-1 h, and then filter with a 0.45 μm filter membrane to obtain a polyvinyl alcohol-vinyl acetate copolymer solution;

[0013] S12. Dissolve Span 80 in toluene under stirring, stir at room temperature for 0.5-1 h, then slowly drop the polyvinyl alcohol-vinyl acetate copolymer solution into it, continue to stir for 0.5-1 h, and then place it in a vacuum homogenizing emulsifier. Set the rotation speed to 12000-15000 rpm, emulsify for 15-20 min to obtain a first mixed solution;

[0014] S13. Slowly drop glutaraldehyde and 0.1 mol / L hydrochloric acid solution into the first mixed solution, heat up to 45-55 °C, stir for 6-8 h, then add acetone, and continue to stir for 0.5-1 h to obtain a second mixed solution;

[0015] S14. Centrifuge the second mixed solution at a high speed at a rotation speed of 12,000 - 15,000 rpm for 15 - 20 minutes. The separated solid is washed alternately with acetone and purified water three times and then dried under vacuum at a drying temperature of 55 - 65°C for 18 - 24 hours to obtain a nano polyvinyl alcohol - vinyl acetate copolymer, which is ground into a powder form for standby;

[0016] S15. Disperse the nano polyvinyl alcohol - vinyl acetate copolymer powder in phosphate buffered saline and perform ultrasonic treatment at an ultrasonic frequency of 40 - 50 kHz. After ultrasonic treatment at room temperature for 0.5 - 1 hour, a nano polyvinyl alcohol - vinyl acetate copolymer dispersion is obtained;

[0017] S16. Add epichlorohydrin to the nano polyvinyl alcohol - vinyl acetate copolymer dispersion under stirring. After stirring for 0.5 - 1 hour, slowly add 0.1 mol / L sodium hydroxide solution, heat up to 45 - 55°C, and stir for 4 - 6 hours to obtain a third mixed solution;

[0018] S17. Centrifuge the third mixed solution at a high speed at a rotation speed of 12,000 - 15,000 rpm for 15 - 20 minutes. The separated solid is washed alternately with phosphate buffered saline and purified water three times and then dried under vacuum at a drying temperature of 55 - 65°C for 18 - 24 hours to obtain a nano polyvinyl alcohol - vinyl acetate copolymer intermediate, which is ground into a powder form for standby;

[0019] S18. Disperse the nano polyvinyl alcohol - vinyl acetate copolymer intermediate powder in phosphate buffered saline and perform ultrasonic treatment at an ultrasonic frequency of 40 - 50 kHz. After ultrasonic treatment at room temperature for 0.5 - 1 hour, a nano polyvinyl alcohol - vinyl acetate copolymer intermediate dispersion is obtained;

[0020] S19. Slowly add cystamine dihydrochloride to the nano polyvinyl alcohol - vinyl acetate copolymer intermediate dispersion under stirring, and at the same time heat up to 55 - 60°C. After stirring for 12 - 15 hours, adjust the reaction solution to a pH value of 8.8 - 9.2 with 0.1 mol / L hydrochloric acid solution, add sodium borohydride and continue stirring for 2 - 4 hours to obtain a fourth mixed solution;

[0021] S20. Centrifuge the fourth mixed solution at a high speed at a rotation speed of 8,000 - 10,000 rpm for 15 - 20 minutes. The separated solid is washed with purified water five times and then freeze - dried at a drying temperature of - 40 - 60°C for 12 - 18 hours to obtain a modified nano polyvinyl alcohol - vinyl acetate copolymer, which is ground into a powder form for standby.

[0022] Further, the mass ratio of the polyvinyl alcohol-vinyl acetate copolymer to cystamine dihydrochloride is 1:(0.1 - 0.5).

[0023] Further, the preparation method of the modified magnesium silicide nanometer includes:

[0024] S21. Dispersing magnesium silicide nanometer in phosphate buffered saline and performing ultrasonic treatment, with an ultrasonic frequency of 40 - 50 kHz, and performing ultrasonic treatment at room temperature for 0.5 - 1 h to obtain a magnesium silicide nanometer dispersion;

[0025] S22. Slowly adding 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide to the magnesium silicide nanometer dispersion under stirring, and adjusting the pH value of the reaction solution to 7.2 - 7.4 with phosphate buffered saline, and performing a stirring reaction for 4 - 6 h to obtain a fifth mixed solution;

[0026] S23. Performing high-speed centrifugal separation on the fifth mixed solution, with a rotation speed of 8000 - 10000 rpm, centrifuging for 15 - 20 min, washing the separated solid alternately with phosphate buffered saline and purified water 3 times, then performing freeze-drying, with a drying temperature of -40 - -60 °C, drying for 12 - 18 h to obtain a magnesium silicide nanometer intermediate and grinding it into a powder for standby;

[0027] S24. Dissolving the antibacterial peptide in phosphate buffered saline under stirring, controlling the ice bath temperature at 0 - 4 °C, stirring for 0.5 - 1 h, then slowly adding the magnesium silicide nanometer intermediate powder, and then continuing to perform a stirring reaction for 18 - 24 h to obtain a sixth mixed solution;

[0028] S25. Performing high-speed centrifugal separation on the sixth mixed solution, with a rotation speed of 8000 - 10000 rpm, centrifuging for 15 - 20 min, washing the separated solid alternately with phosphate buffered saline and purified water 3 times, then performing freeze-drying, with a drying temperature of -40 - -60 °C, drying for 12 - 18 h to obtain the modified magnesium silicide nanometer and grinding it into a powder for standby.

[0029] Further, the modified magnesium silicide nanometer is prepared by covalently binding an antibacterial peptide on the surface of magnesium silicide nanometer, and the particle size of the modified magnesium silicide nanometer is 80 - 100 nm, and the specific surface area is 120 - 150 m 2 / g.

[0030] Further, the mass ratio of the magnesium silicide nanometer to the antibacterial peptide is 1:(0.05 - 0.1).

[0031] On the other hand, based on the same inventive concept, the present invention also provides a preparation method of a glutaraldehyde gel, which is applied to the described glutaraldehyde gel, and includes the following steps:

[0032] S31. Add purified water into a container, and sequentially add propylene glycol and modified nano polyvinyl alcohol-vinyl acetate copolymer under stirring. After stirring for 0.5 - 1 h, perform ultrasonic treatment. The ultrasonic frequency is 40 - 50 kHz. After ultrasonic treatment at room temperature for 4 - 6 h, let it stand at 0 - 4 °C for 12 - 14 h to obtain the seventh mixed solution;

[0033] S32. Sequentially add glutaraldehyde and modified nano magnesium silicate to the seventh mixed solution under stirring. After stirring for 0.5 - 1 h, perform ultrasonic treatment. After ultrasonic treatment for 0.5 - 1 h, sequentially add poloxamer, glycerol, potassium sorbate, menthol, sodium hyaluronate and polyethylene glycol and continue stirring until completely dissolved to obtain the eighth mixed solution;

[0034] S33. Wash aloe, angelica, dandelion, centella asiatica, ginseng, poria cocos, Kochia scoparia and honeysuckle, dry them in an oven, pulverize them, add purified water and 60 - 80% ethanol, and place them in an ultrasonic extractor. The extraction temperature is 55 - 65 °C. After extraction for 2 - 4 h, obtain the first extract;

[0035] Add purified water and 60 - 80% ethanol again for continuous extraction twice to obtain the second extract and the third extract respectively. Mix the extracts and perform vacuum concentration to obtain the traditional Chinese medicine extract;

[0036] S35. Add the traditional Chinese medicine extract to the eighth mixed solution under stirring. After stirring for 2 - 4 h, transfer it to a high-pressure homogenizer, set the pressure to 800 - 1000 bar, circulate 5 - 10 times, then filter through a 0.22 μm filter membrane, and let it stand at 0 - 4 °C for 12 - 14 h to obtain the glutaraldehyde gel.

[0037] Further, the usage method of the glutaraldehyde gel is as follows: For skin with a relatively thin and sensitive cutin layer, before using the gel, it is necessary to apply vaseline or the like on the intact skin around the wart to play a role in isolating the gel; For skin with a relatively thick and non-sensitive cutin layer, the gel can be directly applied on the surface of the wart. One course of treatment is 7 - 9 days, depending on the degree of wound recovery.

[0038] The mechanism of action of the above raw material components is as follows:

[0039] Poloxamer has the functions of thickening, suspending and stabilizing, and is commonly used as a pharmaceutical thickener and emulsifier. Moreover, the gel prepared using poloxamer as the thickening agent raw material is a thermosensitive gel, which is in a liquid state at room temperature and below. After being applied to the skin surface, it will turn into a gel state. At the same time, with the fluidity of the liquid, it can completely wrap the wart within a short time, enabling the active ingredients of the drug to fully act on the wart. Glycerol is a commonly used humectant with strong hygroscopicity, which can help maintain the moist state of the skin, reduce the dryness and tightness during use, and can also help other drug components better penetrate into the skin by increasing the skin permeability, enhancing the curative effect. Potassium sorbate is a commonly used preservative, which can inhibit the growth of microorganisms and improve the product stability, enabling the product to maintain high activity within a wide pH range and extending the product shelf life. Sodium hyaluronate is a natural polysaccharide with powerful moisturizing and repairing effects, which can promote the hydration of the skin, improve the elasticity of the skin, and help reduce the cracking or inflammatory reactions of the skin during drug use. In addition, sodium hyaluronate can also accelerate the repair of the skin barrier and promote skin repair. Polyethylene glycol is a water-soluble polymer, which can form a protective film on the skin and improve the stability of the drug. In the gel formulation, polyethylene glycol is often used as a solubilizer and excipient to improve the solubility of drug components and enhance the skin absorption of drug components. Propylene glycol is a common solvent and penetration enhancer, which can improve the skin permeability of the drug. By increasing the humidity of the stratum corneum of the skin and changing the structure of the skin barrier, it helps the drug components more effectively penetrate into the skin.

[0040] Menthol has significant analgesic and cooling effects. It mainly produces a cool feeling by activating temperature receptors in the skin, helping to reduce the irritation of patients and improve their comfort. Aloe vera extract has a wide range of anti-inflammatory, analgesic, and wound-healing-promoting effects. It can reduce skin redness, stinging, and allergic reactions that occur during drug use, helping to soothe the skin and promote wound healing. In addition, aloe vera also contains abundant polysaccharides and amino acids, which can help skin repair by promoting collagen synthesis. Angelica sinensis has significant anti-inflammatory, blood circulation-promoting, and immune-regulating effects. By improving local blood flow and promoting cell metabolism, it helps to accelerate skin repair and healing, and at the same time can reduce inflammatory reactions. Dandelion extract has strong antibacterial and antiviral effects, and can help reduce local inflammatory reactions caused by virus infections. Centella asiatica is rich in triterpenoids and has good anti-inflammatory and wound-healing effects. It can promote collagen synthesis in the skin, accelerate wound healing, and reduce scar formation. Ginseng has good immune-regulating, antioxidant, and anti-inflammatory effects. It can inhibit the activity of the HPV virus by enhancing the immunity of the skin and reduce the recurrence of warts. Poria cocos has significant diuretic, anti-inflammatory, and immune-regulating effects, and can help improve the hydration state of the skin, reduce swelling and redness, and promote skin healing. Kochia scoparia has strong anti-inflammatory, antibacterial, and antiviral effects, and can effectively inhibit virus replication and reduce reinfection of warts. Honeysuckle extract has powerful antibacterial, anti-inflammatory, and heat-clearing and detoxifying effects, which helps to reduce the inflammatory reaction around warts and promote skin repair.

[0041] In glutaraldehyde gel, glutaraldehyde, modified nano magnesium silicate, and modified nano polyvinyl alcohol-vinyl acetate copolymer act through a synergistic effect. Polyvinyl alcohol-vinyl acetate copolymer is a biodegradable polymer material formed by the polymerization of two monomers, polyvinyl alcohol and vinyl acetate. Due to its good biocompatibility and controllable degradability, it is often used in drug delivery systems and the biomedical field. By nano-sizing the polyvinyl alcohol-vinyl acetate copolymer and grafting cystamine molecules with an intelligent response mechanism on its surface, the modified nano polyvinyl alcohol-vinyl acetate copolymer is obtained, further enhancing the functionality of the modified nano polyvinyl alcohol-vinyl acetate copolymer, enabling it to adjust the drug release rate according to the biochemical characteristics of the wart. And the modified nano polyvinyl alcohol-vinyl acetate copolymer prepared by the high-energy ultrasonic emulsification-precipitation method can be used as a drug sustained-release carrier due to its high specific surface area and rich pore structure, and can encapsulate drug active ingredients such as traditional Chinese medicine extracts, glutaraldehyde, and modified nano magnesium silicate through physical adsorption and chemical action to form a stable modified nano polyvinyl alcohol-vinyl acetate copolymer composite network structure. Wart cells and infected skin usually have a high expression of glutathione. When this glutaraldehyde gel is applied to the wart site, due to the high local glutathione level, glutathione, as a strong reducing agent, will react with the disulfide bond of the cystamine molecule on the surface of the modified nano polyvinyl alcohol-vinyl acetate copolymer, breaking the disulfide bond, and then leading to the relaxation of the modified nano polyvinyl alcohol-vinyl acetate copolymer composite network structure, releasing drug active ingredients such as traditional Chinese medicine extracts, glutaraldehyde, and modified nano magnesium silicate. Through this intelligent response mechanism, the local concentration and release time of the drug active ingredients can be effectively controlled, and the side effects of the drug on healthy skin can be minimized. At the same time, the cystamine molecules on the surface of the modified nano polyvinyl alcohol-vinyl acetate copolymer can also interact with the thiol groups in skin cells, directly promoting skin repair and regeneration and accelerating skin healing. The released glutaraldehyde acts directly on the HPV virus, binds to the protein on the virus surface, and denatures the virus protein through cross-linking, inhibiting virus replication and destroying its structure. The slow-release glutaraldehyde mechanism avoids the problems of poor drug efficacy persistence and strong local irritation caused by the high toxicity and volatility of glutaraldehyde when used alone. Nano magnesium silicate is a nanomaterial with a high specific surface area, biodegradability, and antibacterial properties, widely used in drug delivery systems, tissue repair, antibacterial, and other fields. By covalently binding antibacterial peptides on the surface of nano magnesium silicate, the modified nano magnesium silicate is obtained. When hydrolyzed, the modified nano magnesium silicate will release Mg 2+and silicic acid, thereby providing an alkaline microenvironment. The alkaline environment can destroy the structure of HPV and reduce the virus stability, thus enhancing the virus inactivation ability of glutaraldehyde. Meanwhile, the additional antibacterial function provided by the antibacterial peptide covalently bound to the surface of the modified magnesium nanosilicate can effectively prevent local bacterial and fungal infections after skin breakage, thereby effectively preventing secondary infections. And the Mg released during the hydrolysis process 2+ can soothe the skin and thereby reduce the local inflammatory response. In addition, the modified magnesium nanosilicate can further promote skin repair, help the wound surface to heal, avoid infections and scar formation by accelerating local blood circulation and promoting collagen synthesis. With the natural metabolism of the human body, the modified polyvinyl alcohol-vinyl acetate copolymer is gradually decomposed into lactic acid, ethanol, acetic acid, etc., which are absorbed and utilized by the human body. The released lactic acid further promotes the synthesis of collagen in the injured tissue. At the same time, the modified polyvinyl alcohol-vinyl acetate copolymer particles themselves can serve as the framework structure for cell growth, creating a good immune microenvironment for the repair of tissue cells. In summary, in the glutaraldehyde gel, glutaraldehyde directly attacks the HPV virus through cross-linking. The modified magnesium nanosilicate enhances the antiviral effect of glutaraldehyde through the combined action of its alkaline microenvironment and surface antibacterial peptide, reduces local irritation and inflammatory response, and ensures the effective release of glutaraldehyde and the modified magnesium nanosilicate through the sustained release mechanism of the modified polyvinyl alcohol-vinyl acetate copolymer, ensuring the long-lasting antiviral effect of glutaraldehyde. At the same time, the modified magnesium nanosilicate and the modified polyvinyl alcohol-vinyl acetate copolymer jointly promote skin repair, accelerate skin regeneration, reduce wound surface infections and scars, and reduce the recurrence rate.

[0042] (3) Beneficial effects

[0043] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0044] 1. Glutaraldehyde, the modified magnesium nanosilicate and the modified polyvinyl alcohol-vinyl acetate copolymer act through a synergistic effect. The modified polyvinyl alcohol-vinyl acetate copolymer encapsulates drug active ingredients such as traditional Chinese medicine extracts, glutaraldehyde and the modified magnesium nanosilicate through physical adsorption and chemical action to form a stable modified polyvinyl alcohol-vinyl acetate copolymer composite network structure;

[0045] 2. The cystamine molecules on the surface of the modified polyvinyl alcohol-vinyl acetate copolymer undergo a reduction reaction with glutathione, making the modified polyvinyl alcohol-vinyl acetate copolymer composite network structure loose, releasing drug active ingredients such as traditional Chinese medicine extracts, glutaraldehyde and the modified magnesium nanosilicate. At the same time, the cystamine molecules can also interact with the thiol groups in skin cells to directly promote the repair and regeneration of the skin;

[0046] 3. Glutaraldehyde acts directly on the HPV virus, binds to the proteins on the virus surface, denatures the viral proteins through cross-linking, inhibits the replication of the virus and destroys its structure;

[0047] 4. The modified nano magnesium silicate provides an alkaline microenvironment, destroys the structure of HPV, reduces the stability of the virus, enhances the virus-inactivating ability of glutaraldehyde, and at the same time the antibacterial peptide covalently bound to its surface can effectively prevent local bacterial and fungal infections after skin damage and prevent secondary infections;

[0048] 5. The modified nano magnesium silicate further promotes skin repair, helps wound healing, avoids infection and scar formation by accelerating local blood circulation and promoting collagen synthesis. Brief Description of the Drawings

[0049] Figure 1 It is the SEM image of the modified nano polyvinyl alcohol-vinyl acetate copolymer in Example 1 of the present invention;

[0050] Figure 2 It is the SEM image of the modified nano magnesium silicate in Example 1 of the present invention. Detailed Description of the Invention

[0051] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

[0052] The test equipment and preparations in the following embodiments are as follows: electronic balance (Sartorius, Germany), electrothermal constant temperature water bath (Kedao, Jiangsu), magnetic stirrer (Meiyingpu, Shanghai), ultrasonic instrument (Yixin, Shanghai), high-speed centrifuge (Jidi, Guangzhou), ultrasonic extractor (Jiemeng, Guangdong), vacuum homogenizing emulsifier (Nuoze, Shanghai), scanning electron microscope (Zeiss, Germany), specific surface area analyzer (Beijing Beishide Instrument Technology), freeze dryer (Pudong Freeze Drying, Shanghai), pH meter (Yidian, Shanghai), variable magnification stereomicroscope (Olympus Corporation, Japan), constant temperature incubator (Hetian, Shanghai), flow cytometer (Jiyuan, Guangzhou); Chinese medicinal materials are purchased from Tongrentang Pharmacy, and chemical drugs and reagents are purchased from Sigma-Aldrich Company.

[0053] Example 1: This example discloses a glutaraldehyde gel, which comprises the following raw materials in parts by weight: 9 parts of poloxamer, 7.5 parts of glutaraldehyde, 2 parts of modified nano magnesium silicate, 17.5 parts of glycerol, 0.75 part of potassium sorbate, 0.3 part of menthol, 0.3 part of sodium hyaluronate, 3 parts of polyethylene glycol, 2 parts of aloe vera, 0.75 part of angelica, 0.75 part of dandelion, 0.75 part of centella asiatica, 0.75 part of ginseng, 0.75 part of poria cocos, 0.75 part of Kochia scoparia, 0.75 part of honeysuckle, 9 parts of propylene glycol, and 20 parts of purified water. The glutaraldehyde gel further comprises a modified nano polyvinyl alcohol-vinyl acetate copolymer, and the weight ratio of the modified nano polyvinyl alcohol-vinyl acetate copolymer to poloxamer is 2:9. The modified nano polyvinyl alcohol-vinyl acetate copolymer is prepared by nano-sizing a polyvinyl alcohol-vinyl acetate copolymer and grafting cystamine molecules on its surface. The particle size of the modified nano polyvinyl alcohol-vinyl acetate copolymer is 50 - 80 nm, and the specific surface area is 180 - 200 m 2 / g.

[0054] In the glutaraldehyde gel, glutaraldehyde, modified nano magnesium silicate and modified nano polyvinyl alcohol-vinyl acetate copolymer act through a synergistic effect. The polyvinyl alcohol-vinyl acetate copolymer is a biodegradable polymer material formed by polymerizing two monomers, polyvinyl alcohol and vinyl acetate. Due to its good biocompatibility and controllable degradability, it is often used in drug delivery systems and the biomedical field. By nano-sizing the polyvinyl alcohol-vinyl acetate copolymer and grafting cystamine molecules with an intelligent response mechanism on its surface, the modified nano polyvinyl alcohol-vinyl acetate copolymer is obtained, further enhancing the functionality of the modified nano polyvinyl alcohol-vinyl acetate copolymer, enabling the modified nano polyvinyl alcohol-vinyl acetate copolymer to adjust the drug release rate according to the biochemical characteristics of the wart, Figure 1SEM image of the modified nano polyvinyl alcohol-vinyl acetate copolymer. It can be seen that the modified nano polyvinyl alcohol-vinyl acetate copolymer prepared by high-energy ultrasonic emulsification-precipitation method has a rich pore structure and a large specific surface area, which can be used as a drug sustained-release carrier. Its high specific surface area and large porosity provide a large number of adsorption sites for drug active ingredients such as traditional Chinese medicine extracts, glutaraldehyde, and modified nano magnesium silicate. At the same time, through electrostatic interaction and covalent interaction, these drug active ingredients are firmly attached to the porous structure of the modified nano polyvinyl alcohol-vinyl acetate copolymer to form a stable modified nano polyvinyl alcohol-vinyl acetate copolymer composite network structure. Verruca cells and infected skin usually have a high expression of glutathione. Glutathione is a strong reducing agent that is widely present in human cells, especially in areas of virus infection and cell abnormalities, where the glutathione concentration will increase significantly. When the glutaraldehyde gel is applied to the verruca site, due to the high local glutathione level, the sulfhydryl group (-SH) on the surface of glutathione will react with the disulfide bond (–S–S–) of the cystamine molecule on the surface of the modified nano polyvinyl alcohol-vinyl acetate copolymer, breaking the disulfide bond to form two sulfhydryl groups (-SH), which in turn leads to the relaxation of the modified nano polyvinyl alcohol-vinyl acetate copolymer composite network structure, and then the disintegration of the modified nano polyvinyl alcohol-vinyl acetate copolymer composite network structure, releasing drug active ingredients such as traditional Chinese medicine extracts, glutaraldehyde, and modified nano magnesium silicate. Through this intelligent response mechanism, the drug release process is specific and localized, so the local concentration and release time of the drug active ingredients can be effectively controlled, and the side effects of the drug on healthy skin can be minimized, avoiding the irritation and allergic reactions caused by drug overdose to the skin. At the same time, the cystamine molecule on the surface of the modified nano polyvinyl alcohol-vinyl acetate copolymer can also interact with the thiol group in skin cells to activate fibroblasts, directly promoting skin repair and regeneration by promoting cell proliferation and collagen synthesis, and accelerating skin healing. The released glutaraldehyde directly acts on the HPV virus, binds to the protein on the virus surface, and denatures the virus protein through cross-linking, inhibiting virus replication and destroying its structure. The sustained-release glutaraldehyde mechanism avoids the problems of poor drug efficacy persistence and strong local irritation caused by the high toxicity and volatility of glutaraldehyde when used alone. Nano magnesium silicate is a nanomaterial with a high specific surface area, biodegradability, and antibacterial properties, which is widely used in drug delivery systems, tissue repair, antibacterial and other fields. Antibacterial peptides are covalently bound to the surface of nano magnesium silicate to obtain modified nano magnesium silicate, Figure 2 SEM image of the modified nano magnesium silicate. It can be seen that the modified nano magnesium silicate has a cluster structure, and Mg will be released when the modified nano magnesium silicate hydrolyzes 2+And silicic acid, thereby providing an alkaline microenvironment. The alkaline environment can destroy the structure of HPV, cause the three-dimensional structure of viral proteins to denature, reduce the stability of the virus, inhibit its infectivity and replication ability, thereby enhancing the virus inactivation ability of glutaraldehyde. At the same time, the additional antibacterial function provided by the antibacterial peptide covalently bound to the surface of the modified magnesium nanosilicate can effectively prevent local bacterial and fungal infections after skin damage, thereby effectively preventing secondary infections and avoiding the exacerbation of inflammation and infection. Moreover, the trace element Mg released during hydrolysis 2+ can soothe the skin and thereby reduce the local inflammatory response. In addition, the modified magnesium nanosilicate can further promote skin repair, help the wound surface heal, avoid infection and scar formation by accelerating local blood circulation and promoting collagen synthesis. With the natural metabolism of the human body, the modified polyvinyl alcohol-vinyl acetate copolymer is gradually decomposed into lactic acid, ethanol, acetic acid, etc., which are absorbed and utilized by the human body. The released lactic acid further promotes the synthesis of collagen in the injured tissue. At the same time, the modified polyvinyl alcohol-vinyl acetate copolymer particles themselves can serve as the skeletal structure for cell growth, creating a good immune microenvironment for the repair of tissue cells. In short, in the glutaraldehyde gel, glutaraldehyde directly attacks the HPV virus through cross-linking. The modified magnesium nanosilicate enhances the antiviral effect of glutaraldehyde through the combined action of its alkaline microenvironment and surface antibacterial peptide, reduces local irritation and inflammatory response, and ensures the effective release of glutaraldehyde and the modified magnesium nanosilicate through the sustained release mechanism of the modified polyvinyl alcohol-vinyl acetate copolymer, ensuring the long-lasting antiviral effect of glutaraldehyde. At the same time, the modified magnesium nanosilicate and the modified polyvinyl alcohol-vinyl acetate copolymer jointly promote skin repair, accelerate skin regeneration, reduce wound surface infection and scarring, and reduce the recurrence rate of warts.

[0055] The preparation method of the modified polyvinyl alcohol-vinyl acetate copolymer includes:

[0056] S11. Dissolve the polyvinyl alcohol-vinyl acetate copolymer in purified water under stirring, heat up to 75-85 °C, stir for 0.5-1 h, and then filter with a 0.45 μm filter membrane to obtain a polyvinyl alcohol-vinyl acetate copolymer solution;

[0057] S12. Dissolve Span 80 in toluene under stirring, stir at room temperature for 0.5-1 h, then slowly drop the polyvinyl alcohol-vinyl acetate copolymer solution into it, continue to stir for 0.5-1 h, and then place it in a vacuum homogenizing emulsifier, set the rotation speed to 12000-15000 rpm, and emulsify for 15-20 min to obtain a first mixed solution;

[0058] S13. Slowly drop glutaraldehyde and 0.1 mol / L hydrochloric acid solution into the first mixed solution, heat up to 45 - 55 °C, stir for 6 - 8 h, then add acetone, and continue to stir for 0.5 - 1 h to obtain the second mixed solution;

[0059] S14. Centrifuge the second mixed solution at a high speed, with a rotation speed of 12000 - 15000 rpm, centrifuge for 15 - 20 min. The separated solid is washed alternately with acetone and purified water 3 times, then dried in vacuum. The drying temperature is 55 - 65 °C, and after drying for 18 - 24 h, a nano polyvinyl alcohol - vinyl acetate copolymer is obtained and ground into a powder for standby;

[0060] S15. Disperse the nano polyvinyl alcohol - vinyl acetate copolymer powder in phosphate buffered saline and perform ultrasonic treatment. The ultrasonic frequency is 40 - 50 kHz, and after ultrasonic treatment at room temperature for 0.5 - 1 h, a nano polyvinyl alcohol - vinyl acetate copolymer dispersion is obtained;

[0061] S16. Add epichlorohydrin to the nano polyvinyl alcohol - vinyl acetate copolymer dispersion under stirring, stir for 0.5 - 1 h, then slowly add 0.1 mol / L sodium hydroxide solution, heat up to 45 - 55 °C, and stir for 4 - 6 h to obtain the third mixed solution;

[0062] S17. Centrifuge the third mixed solution at a high speed, with a rotation speed of 12000 - 15000 rpm, centrifuge for 15 - 20 min. The separated solid is washed alternately with phosphate buffered saline and purified water 3 times, then dried in vacuum. The drying temperature is 55 - 65 °C, and after drying for 18 - 24 h, a nano polyvinyl alcohol - vinyl acetate copolymer intermediate is obtained and ground into a powder for standby;

[0063] S18. Disperse the nano polyvinyl alcohol - vinyl acetate copolymer intermediate powder in phosphate buffered saline and perform ultrasonic treatment. The ultrasonic frequency is 40 - 50 kHz, and after ultrasonic treatment at room temperature for 0.5 - 1 h, a nano polyvinyl alcohol - vinyl acetate copolymer intermediate dispersion is obtained;

[0064] S19. Slowly add cystamine dihydrochloride to the nano polyvinyl alcohol - vinyl acetate copolymer intermediate dispersion under stirring, simultaneously heat up to 55 - 60 °C, stir for 12 - 15 h, then adjust the reaction solution to a pH value of 8.8 - 9.2 with 0.1 mol / L hydrochloric acid solution, add sodium borohydride and continue to stir for 2 - 4 h to obtain the fourth mixed solution;

[0065] S20. Centrifuge the fourth mixed solution at a high speed at a rotation speed of 8000 - 10000 rpm for 15 - 20 min. Wash the separated solid 5 times with purified water and then perform freeze-drying. The drying temperature is -40 - -60 °C. After drying for 12 - 18 h, a modified nano polyvinyl alcohol-vinyl acetate copolymer is obtained and ground into a powder for standby.

[0066] The mass ratio of the polyvinyl alcohol-vinyl acetate copolymer to cystamine dihydrochloride is 1:(0.1 - 0.5).

[0067] The preparation method of the modified nano magnesium silicide includes:

[0068] S21. Disperse nano magnesium silicide in phosphate buffered saline and perform ultrasonic treatment. The ultrasonic frequency is 40 - 50 kHz. After ultrasonic treatment at room temperature for 0.5 - 1 h, a nano magnesium silicide dispersion is obtained.

[0069] S22. Slowly add 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide to the nano magnesium silicide dispersion under stirring, and adjust the pH value of the reaction solution to 7.2 - 7.4 with phosphate buffered saline. After stirring and reacting for 4 - 6 h, a fifth mixed solution is obtained.

[0070] S23. Centrifuge the fifth mixed solution at a high speed at a rotation speed of 8000 - 10000 rpm for 15 - 20 min. Wash the separated solid 3 times alternately with phosphate buffered saline and purified water and then perform freeze-drying. The drying temperature is -40 - -60 °C. After drying for 12 - 18 h, a nano magnesium silicide intermediate is obtained and ground into a powder for standby.

[0071] S24. Dissolve the antimicrobial peptide in phosphate buffered saline under stirring, control the ice bath temperature at 0 - 4 °C, stir for 0.5 - 1 h, and then slowly add the nano magnesium silicide intermediate powder. Subsequently, continue stirring and reacting for 18 - 24 h to obtain a sixth mixed solution.

[0072] S25. Centrifuge the sixth mixed solution at a high speed at a rotation speed of 8000 - 10000 rpm for 15 - 20 min. Wash the separated solid 3 times alternately with phosphate buffered saline and purified water and then perform freeze-drying. The drying temperature is -40 - -60 °C. After drying for 12 - 18 h, a modified nano magnesium silicide is obtained and ground into a powder for standby.

[0073] The modified nano magnesium silicide is prepared by covalently binding an antimicrobial peptide on the surface of nano magnesium silicide, and the particle size of the modified nano magnesium silicide is 80 - 100 nm, and the specific surface area is 120 - 150 m 2 / g.

[0074] The mass ratio of the magnesium silicide nanometer and the antibacterial peptide is 1:(0.05 - 0.1).

[0075] A preparation method of glutaraldehyde gel, applied to the described glutaraldehyde gel, comprises the following steps:

[0076] S31. Add purified water into a container, and sequentially add propylene glycol and modified nano polyvinyl alcohol-vinyl acetate copolymer under stirring. After stirring for 0.5 - 1 h, perform ultrasonic treatment. The ultrasonic frequency is 40 - 50 kHz. After ultrasonic treatment at room temperature for 4 - 6 h, let it stand at 0 - 4 °C for 12 - 14 h to obtain a seventh mixed solution;

[0077] S32. Sequentially add glutaraldehyde and modified magnesium silicide nanometer to the seventh mixed solution under stirring. After stirring for 0.5 - 1 h, perform ultrasonic treatment. After ultrasonic treatment for 0.5 - 1 h, sequentially add poloxamer, glycerol, potassium sorbate, menthol, sodium hyaluronate and polyethylene glycol and continue stirring until completely dissolved to obtain an eighth mixed solution;

[0078] S33. Wash aloe, angelica, dandelion, centella asiatica, ginseng, poria cocos, Kochia scoparia and honeysuckle, dry them, pulverize them, add purified water and 60 - 80% ethanol, and place them in an ultrasonic extractor. The extraction temperature is 55 - 65 °C. After extraction for 2 - 4 h, obtain a first extract;

[0079] S34. Add purified water and 60 - 80% ethanol again for continuous extraction twice to obtain a second extract and a third extract respectively. Mix the extracts and perform vacuum concentration to obtain a traditional Chinese medicine extract;

[0080] S35. Add the traditional Chinese medicine extract to the eighth mixed solution under stirring. After stirring for 2 - 4 h, transfer it to a high-pressure homogenizer, set the pressure at 800 - 1000 bar, circulate for 5 - 10 times, then filter through a 0.22 μm filter membrane, and let it stand at 0 - 4 °C for 12 - 14 h to obtain glutaraldehyde gel.

[0081] The using method of the described glutaraldehyde gel is as follows: For skin with a relatively thin and sensitive cutin layer, before using the gel, it is necessary to apply vaseline or the like on the intact skin around the wart to play a role in isolating the gel; For skin with a relatively thick and non-sensitive cutin layer, the gel can be directly applied on the surface of the wart. One course of treatment is 7 - 9 days, depending on the degree of injury recovery.

[0082] Example 2: This example discloses a glutaraldehyde gel, which comprises the following raw materials in parts by weight: 6 parts of poloxamer, 5 parts of glutaraldehyde, 1 part of modified nano magnesium silicate, 15 parts of glycerol, 0.5 part of potassium sorbate, 0.1 part of menthol, 0.1 part of sodium hyaluronate, 1 part of polyethylene glycol, 1 part of aloe vera, 0.5 part of angelica sinensis, 0.5 part of dandelion, 0.5 part of centella asiatica, 0.5 part of ginseng, 0.5 part of poria cocos, 0.5 part of Kochia scoparia, 0.5 part of honeysuckle, 8 parts of propylene glycol, and 15 parts of purified water. The glutaraldehyde gel further comprises a modified nano polyvinyl alcohol-vinyl acetate copolymer, and the weight ratio of the modified nano polyvinyl alcohol-vinyl acetate copolymer to poloxamer is 2:6. The modified nano polyvinyl alcohol-vinyl acetate copolymer is prepared by nano-sizing a polyvinyl alcohol-vinyl acetate copolymer and grafting cystamine molecules on its surface. The particle size of the modified nano polyvinyl alcohol-vinyl acetate copolymer is 50-80 nm, and the specific surface area is 180-200 m 2 / g. The preparation methods of the modified nano polyvinyl alcohol-vinyl acetate copolymer and the modified nano magnesium silicate in this example are the same as those in Example 1. The preparation method of a glutaraldehyde gel in this example is the same as that in Example 1.

[0083] Example 3: This example discloses a glutaraldehyde gel, which comprises the following raw materials in parts by weight: 12 parts of poloxamer, 10 parts of glutaraldehyde, 3 parts of modified nano magnesium silicate, 20 parts of glycerol, 1 part of potassium sorbate, 0.5 part of menthol, 0.5 part of sodium hyaluronate, 5 parts of polyethylene glycol, 3 parts of aloe vera, 1 part of angelica sinensis, 1 part of dandelion, 1 part of centella asiatica, 1 part of ginseng, 1 part of poria cocos, 1 part of Kochia scoparia, 1 part of honeysuckle, 10 parts of propylene glycol, and 25 parts of purified water. The glutaraldehyde gel further comprises a modified nano polyvinyl alcohol-vinyl acetate copolymer, and the weight ratio of the modified nano polyvinyl alcohol-vinyl acetate copolymer to poloxamer is 2:12. The modified nano polyvinyl alcohol-vinyl acetate copolymer is prepared by nano-sizing a polyvinyl alcohol-vinyl acetate copolymer and grafting cystamine molecules on its surface. The particle size of the modified nano polyvinyl alcohol-vinyl acetate copolymer is 50-80 nm, and the specific surface area is 180-200 m 2 / g. The preparation methods of the modified nano polyvinyl alcohol-vinyl acetate copolymer and the modified nano magnesium silicate in this example are the same as those in Example 1. The preparation method of a glutaraldehyde gel in this example is the same as that in Example 1.

[0084] Control Group 1: The difference between this example and Example 1 is that it does not contain glutaraldehyde. This example discloses a glutaraldehyde gel, which comprises the following raw materials in parts by weight: 9 parts of poloxamer, 2 parts of modified nano magnesium silicate, 17.5 parts of glycerol, 0.75 part of potassium sorbate, 0.3 part of menthol, 0.3 part of sodium hyaluronate, 3 parts of polyethylene glycol, 2 parts of aloe vera, 0.75 part of angelica, 0.75 part of dandelion, 0.75 part of centella asiatica, 0.75 part of ginseng, 0.75 part of poria cocos, 0.75 part of Kochia scoparia, 0.75 part of honeysuckle, 9 parts of propylene glycol, and 20 parts of purified water. The glutaraldehyde gel further comprises a modified nano polyvinyl alcohol-vinyl acetate copolymer, and the weight ratio of the modified nano polyvinyl alcohol-vinyl acetate copolymer to poloxamer is 2:9. The modified nano polyvinyl alcohol-vinyl acetate copolymer is prepared by nano-sizing a polyvinyl alcohol-vinyl acetate copolymer and grafting cystamine molecules on its surface. The particle size of the modified nano polyvinyl alcohol-vinyl acetate copolymer is 50 - 80 nm, and the specific surface area is 180 - 200 m 2 / g. The preparation methods of the modified nano polyvinyl alcohol-vinyl acetate copolymer and the modified nano magnesium silicate in this example are the same as those in Example 1. The preparation method of a glutaraldehyde gel in this example is the same as that in Example 1.

[0085] Control Group 2: The difference between this example and Example 1 is that it does not contain modified nano magnesium silicate. This example discloses a glutaraldehyde gel, which comprises the following raw materials in parts by weight: 9 parts of poloxamer, 7.5 parts of glutaraldehyde, 17.5 parts of glycerol, 0.75 part of potassium sorbate, 0.3 part of menthol, 0.3 part of sodium hyaluronate, 3 parts of polyethylene glycol, 2 parts of aloe vera, 0.75 part of angelica, 0.75 part of dandelion, 0.75 part of centella asiatica, 0.75 part of ginseng, 0.75 part of poria cocos, 0.75 part of Kochia scoparia, 0.75 part of honeysuckle, 9 parts of propylene glycol, and 20 parts of purified water. The glutaraldehyde gel further comprises a modified nano polyvinyl alcohol-vinyl acetate copolymer, and the weight ratio of the modified nano polyvinyl alcohol-vinyl acetate copolymer to poloxamer is 2:9. The modified nano polyvinyl alcohol-vinyl acetate copolymer is prepared by nano-sizing a polyvinyl alcohol-vinyl acetate copolymer and grafting cystamine molecules on its surface. The particle size of the modified nano polyvinyl alcohol-vinyl acetate copolymer is 50 - 80 nm, and the specific surface area is 180 - 200 m 2 / g. The preparation method of the modified nano polyvinyl alcohol-vinyl acetate copolymer in this example is the same as that in Example 1. The preparation method of a glutaraldehyde gel in this example is the same as that in Example 1.

[0086] Control Group 3: The difference between this example and Example 1 is that it does not contain modified nano polyvinyl alcohol-vinyl acetate copolymer. This example discloses a glutaraldehyde gel, which comprises the following raw materials in parts by weight: 9 parts of poloxamer, 7.5 parts of glutaraldehyde, 2 parts of modified nano magnesium silicate, 17.5 parts of glycerol, 0.75 part of potassium sorbate, 0.3 part of menthol, 0.3 part of sodium hyaluronate, 3 parts of polyethylene glycol, 2 parts of aloe, 0.75 part of angelica, 0.75 part of dandelion, 0.75 part of centella asiatica, 0.75 part of ginseng, 0.75 part of poria cocos, 0.75 part of Kochia scoparia, 0.75 part of honeysuckle, 9 parts of propylene glycol, and 20 parts of purified water. The preparation method of the modified nano magnesium silicate in this example is the same as that in Example 1. The preparation method of a glutaraldehyde gel in this example is the same as that in Example 1.

[0087] Effect evaluation: The anti-HPV virus activity of the glutaraldehyde gel was evaluated by in vitro experiments. The specific experimental steps were as follows: (1) Cell seeding: DMEM / F12 medium was used, supplemented with 10% fetal bovine serum and 5% CO 2 HaCaT cells (human skin keratinocytes) were seeded, and 1×10 6 cells were seeded in each well and cultured until 60-70% confluence; (2) HPV virus inoculation: HPV viruses such as HPV-16 and HPV-18 were inoculated into HaCaT cells and cultured for 24 h to ensure the completion of HPV virus infection; (3) Glutaraldehyde gel treatment: The glutaraldehyde gels prepared from each experimental group were added to the cell culture medium after infection and gently mixed. Incubate at 37 °C and 5% CO 2 for 2 h, 6 h, and 24 h, and observe the effect of glutaraldehyde gel treatment on virus inhibition. The blank group was the group without drug administration; (4) Virus infection monitoring: After glutaraldehyde gel treatment, the cell culture medium was taken to extract total cell DNA. The cell growth inhibition rate was detected by MTT colorimetric method, cell apoptosis was detected by flow cytometry, and the levels of HPV16E6 mRNA and HPV18E7 mRNA in the cells were detected by PCR technology to evaluate the inhibitory effect of the glutaraldehyde gel on virus DNA replication. The experimental data were statistically analyzed in Table 1.

[0088] Table 1 Statistical table of the growth inhibitory effect of glutaraldehyde gels in each experimental group on HPV virus

[0089]

[0090] As can be seen from Table 1, the blank group without drug administration has almost no growth inhibitory effect on HPV virus and does not significantly inhibit the expression of viral genes. By comparing the growth inhibitory effects of the glutaraldehyde gels prepared in Examples 1 to 3 on HPV virus, it can be found that the glutaraldehyde gel prepared in Example 1 has the most significant growth inhibitory effect on HPV virus, showing the highest growth inhibition rate, apoptosis rate and the lowest relative expression level of HPV virus mRNA. It indicates that the glutaraldehyde gel has an obvious inhibitory effect on cell growth, also shows excellent apoptosis induction effect, can effectively inhibit the expression of viral genes, and almost completely inhibits virus replication. Its effect is significantly higher than that of other experimental groups. By comparing the growth inhibitory effects of the glutaraldehyde gels prepared in Example 1 and Control Groups 1 to 3 on HPV virus, it can be found that when the three components of glutaraldehyde, modified nano-magnesium silicate and modified nano-poly(vinyl alcohol)-vinyl acetate copolymer are added simultaneously during the preparation of the gel, the antiviral persistence of glutaraldehyde can be significantly enhanced and the virus inactivating ability can be enhanced.

[0091] A skin wound model was used to evaluate the skin repair situation of rats after using glutaraldehyde gel. Thirty-six healthy rats, half male and half female, with a body weight of 200 - 250 g, were provided by Hunan Slack Jingda Experimental Animal Company. All experimental rats were adaptively cultured for 7 days under the conditions of temperature (22 ± 2) °C, humidity 50% ± 10%, noise below 85 dB, and a 12 h light-dark cycle, with free access to water and food to ensure their good health status. After 7 days of feeding, the rats were randomly divided into 7 groups, with 6 rats in each group and half male and half female. Establishment of a skin wound rat model: The skin surface layer on the back of the mice was scraped off using a laser knife, with a thickness of about 1 - 2 mm, and local laser burning was used to produce wounds, ensuring that the deep tissues were not damaged, and only the surface skin was scraped off to simulate the skin wounds of warts. 24 h after the model establishment, the rats in each experimental group were administered according to the usage method of glutaraldehyde gel, twice a day, with a dosage of 50 - 100 μL / rat wound area, and the administration continued for 15 days. Ensure that other feeding conditions are the same, and record the skin repair situation of the rats in each experimental group on the 1st, 5th, 10th, and 15th days.

[0092] According to the symptoms shown in the skin repair situation of the rats in the skin wound model, it was divided into 5 grades, namely completely unhealed (A), severely poorly healed (B), mildly healed (C), moderately healed (D), and completely healed (E), and the specific manifestations were as follows:

[0093] Completely unhealed (A): The wound area was severely infected and enlarged, the skin was not healed and showed a deteriorating state, the wound area continuously oozed fluid, accompanied by purulent secretions, and there was obvious necrotic tissue on the wound surface.

[0094] Severe poor healing (B): The wound area fails to heal, the wound remains exposed and continues to exude, there are obvious inflammatory reactions such as local redness, swelling, suppuration, and continuous bleeding, the wound area is accompanied by pus or obvious ulceration, and excessive scars are formed during the healing process, and they are relatively rough.

[0095] Mild healing (C): The wound area has not yet healed completely, the wound is partially exposed, there is still obvious epidermal defect, there is obvious redness and swelling, accompanied by mild pain, uneven collagen deposition, and the healing process is accompanied by obvious scar formation.

[0096] Moderate healing (D): The healing of the wound area is almost complete, but there are still slight unevenness and epidermal defects. The wound area is slightly red and swollen, but there is no obvious exudate. The inflammatory reaction is mild, collagen deposition is relatively normal, the epidermis in some areas is well repaired, and there are slight scars or pigmentation.

[0097] Complete healing (E): The wound is completely healed, with no surface defects, the skin is smooth and consistent with the surrounding normal skin, collagen deposition is abundant, the structure of the epidermis and dermis is well restored, capillary formation is obvious, there is no pain or discomfort, and the skin in the trauma area has completely restored its elasticity and function.

[0098] Table 2 Statistical results of skin repair in rats with skin trauma model in each experimental group

[0099] Group Day 1 Day 5 Day 10 Day 15 Example 1 AAAAAA BBCCBC DCDDCD EEEEDE Example 2 AAAAAA BCBBCC CDCCDD DEDDEE Example 3 AAAAAA CBCBCB DCDDDC EDEEED Control Group 1 AAAAAA AABABB BBBBCC CCCCCD Control Group 2 AAAAAA BBBAAB CCCBBD DDECCD Control Group 3 AAAAAA AABABB BBCBCC CCDCDD

[0100] Table 2 is the statistical results of skin repair of rats with skin trauma models in each experimental group. It can be seen from Table 2 that when the glutaraldehyde gel prepared in Example 1 is used on the injured part of rats, the recovery of the rats is the best and can significantly promote wound healing. From the 5th day and the 10th day to the 15th day, the skin repair of the rats is better than that of the other experimental groups. By comparing Examples 1 to 3 with Control Groups 1 to 3, it can be found that the skin repair of the rats in Examples 1 to 3 is also significantly better than that in Control Groups 1 to 3, which shows that by adding the three components of glutaraldehyde, modified nano-magnesium silicide and modified nano-polyvinyl alcohol-vinyl acetate copolymer at the same time during the gel preparation process, a glutaraldehyde gel that can significantly promote skin repair can be obtained.

[0101] Through the above limited experiments, the application effect of a glutaraldehyde gel in Example 1 of the present invention is significant. By optimizing the chemical formula of the glutaraldehyde gel, combining modern nanotechnology and adding Chinese medicine extracts, the antiviral persistence and virus inactivation ability of glutaraldehyde can be significantly enhanced. Glutaraldehyde directly attacks the HPV virus, and the modified nano magnesium silicide enhances the antiviral effect of glutaraldehyde through the combined action of its alkaline microenvironment and surface antimicrobial peptides, and promotes skin repair together with the modified nano polyvinyl alcohol-vinyl acetate copolymer, accelerates skin regeneration, and reduces the recurrence rate.

[0102] Finally, it should be noted that: Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments, or perform equivalent replacements for some of the technical features. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. A glutaraldehyde gel, characterized in that The invention comprises the following raw materials in parts by weight: 6-12 parts of poloxamer, 5-10 parts of glutaraldehyde, 1-3 parts of modified nano magnesium silicide, 15-20 parts of glycerol, 0.5-1 parts of potassium sorbate, 0.1-0.5 parts of menthol, 0.1-0.5 parts of sodium hyaluronate, 1-5 parts of polyethylene glycol, 1-3 parts of aloe vera, 0.5-1 parts of angelica sinensis, 0.5-1 parts of dandelion, 0.5-1 parts of Centella asiatica, 0.5-1 parts of ginseng, 0.5-1 parts of Poria cocos, 0.5-1 parts of Kochia scoparia, 0.5-1 parts of honeysuckle, 8-10 parts of propylene glycol, and 15-25 parts of purified water; The glutaraldehyde gel also includes: Modified nano polyvinyl alcohol-vinyl acetate copolymer; The modified nano polyvinyl alcohol-vinyl acetate copolymer and poloxamer are in a weight ratio of 2: (6-12); The modified nano polyvinyl alcohol-vinyl acetate copolymer is prepared by nano-scaling the polyvinyl alcohol-vinyl acetate copolymer and grafting cystamine molecules on its surface. The particle size of the modified nano polyvinyl alcohol-vinyl acetate copolymer is 50-80 nm, and the specific surface area is 180-200 m 2 / g.

2. A glutaraldehyde gel according to claim 1, characterized in that: The preparation method of the modified nano polyvinyl alcohol-vinyl acetate copolymer comprises: S11. The polyvinyl alcohol-vinyl acetate copolymer was dissolved in purified water under stirring, the temperature was raised to 75-85°C, and the mixture was stirred for 0.5-1h and filtered through a 0.45 μm filter membrane to obtain a polyvinyl alcohol-vinyl acetate copolymer solution; S12. Span 80 was dissolved in toluene under stirring, and the polyvinyl alcohol-vinyl acetate copolymer solution was slowly added dropwise thereto after stirring at room temperature for 0.5 to 1 h, and the mixture was placed in a vacuum homogenizer at a speed of 12000 to 15000 rpm, and emulsified for 15 to 20 min to obtain a first mixed solution; S13. Slowly add glutaraldehyde and 0.1 mol / L hydrochloric acid solution to the first mixed solution, raise the temperature to 45-55°C, stir for 6-8h, add acetone, and continue stirring for 0.5-1h to obtain a second mixed solution; S14. The second mixed solution was subjected to high-speed centrifugation at a speed of 12000 to 15000 rpm for 15 to 20 min. The separated solid was washed alternately with acetone and purified water three times and then vacuum dried at a drying temperature of 55 to 65 ° C. After drying for 18 to 24 h, a nano-polyvinyl alcohol-vinyl acetate copolymer was obtained and ground into a powder for standby use; S15. The nano-polyvinyl alcohol-vinyl acetate copolymer powder is dispersed in a phosphate buffer solution and subjected to ultrasonic treatment at an ultrasonic frequency of 40 to 50 kHz. The nano-polyvinyl alcohol-vinyl acetate copolymer dispersion is obtained after ultrasonic treatment at room temperature for 0.5 to 1 h; S16. epichlorohydrin was added to the nano-polyvinyl alcohol-vinyl acetate copolymer dispersion under stirring, and 0.1 mol / L sodium hydroxide solution was slowly added after stirring for 0.5 to 1 h, and the temperature was raised to 45 to 55 ° C. and stirred for 4 to 6 h to obtain a third mixed solution; S17. The third mixed solution is subjected to high-speed centrifugation at a speed of 12000 to 15000 rpm for 15 to 20 min, and the separated solid is washed alternately with phosphate buffered saline and purified water three times and then vacuum dried at a drying temperature of 55 to 65 ° C. After drying for 18 to 24 h, a nano-polyvinyl alcohol-vinyl acetate copolymer intermediate is obtained and ground into a powder for standby use; S18. The nano-polyvinyl alcohol-vinyl acetate copolymer intermediate powder is dispersed in a phosphate buffer solution and subjected to ultrasonic treatment at an ultrasonic frequency of 40 to 50 kHz. The nano-polyvinyl alcohol-vinyl acetate copolymer intermediate dispersion is obtained after ultrasonic treatment at room temperature for 0.5 to 1 h; S19. Slowly add cystamine dihydrochloride to the nano-polyvinyl alcohol-vinyl acetate copolymer intermediate dispersion under stirring, and raise the temperature to 55-60° C., stir for 12-15 hours, adjust the reaction solution to a pH of 8.8-9.2 with 0.1 mol / L hydrochloric acid solution, add sodium borohydride and continue stirring for 2-4 hours to obtain a fourth mixed solution; S20. The fourth mixed solution is subjected to high-speed centrifugation at a rotation speed of 8000 to 10000 rpm for 15 to 20 min. The separated solid is washed 5 times with purified water and then freeze-dried at a drying temperature of -40 to -60°C. After drying for 12 to 18 hours, a modified nano-polyvinyl alcohol-vinyl acetate copolymer is obtained and ground into powder for later use.

3. A glutaraldehyde gel according to claim 2, characterized in that: The mass ratio of the polyvinyl alcohol-vinyl acetate copolymer to cystamine dihydrochloride is 1:(0.1-0.5).

4. A glutaraldehyde gel according to claim 1, characterized in that: The preparation method of the modified nano magnesium silicide comprises: S21. The nano-magnesium silicide is dispersed in a phosphate buffer solution and subjected to ultrasonic treatment at an ultrasonic frequency of 40 to 50 kHz. The nano-magnesium silicide dispersion is obtained after ultrasonic treatment at room temperature for 0.5 to 1 h; S22. Slowly add 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide to the nano-magnesium silicide dispersion under stirring, and adjust the pH value of the reaction solution to 7.2 to 7.4 with phosphate buffered saline, and stir the reaction for 4 to 6 hours to obtain a fifth mixed solution; S23. The fifth mixed solution was subjected to high-speed centrifugation at a speed of 8000 to 10000 rpm for 15 to 20 min, and the separated solid was washed three times with phosphate buffered saline and purified water alternately and then freeze-dried at a drying temperature of -40 to -60 ° C. After drying for 12 to 18 h, the nano-magnesium silicide intermediate was obtained and ground into a powder for standby use; S24. The antimicrobial peptide was dissolved in a phosphate buffered saline solution under stirring, the ice bath temperature was controlled to be 0 to 4°C, and the nano-magnesium silicide intermediate powder was slowly added after stirring for 0.5 to 1 h, and then the reaction was continued with stirring for 18 to 24 h to obtain a sixth mixed solution; S25. The sixth mixed solution is subjected to high-speed centrifugation at a rotation speed of 8000 to 10000 rpm for 15 to 20 min. The separated solid is washed alternately with phosphate buffered saline and purified water for 3 times and then freeze-dried at a drying temperature of -40 to -60°C. After drying for 12 to 18 hours, the modified nano-magnesium silicide is obtained and ground into powder for later use.

5. A glutaraldehyde gel according to claim 4, characterized in that: The modified nano magnesium silicide is prepared by covalently bonding antimicrobial peptides on the surface of nano magnesium silicide, and the particle size of the modified nano magnesium silicide is 80-100 nm, and the specific surface area is 120-150 m 2 / g.

6. A glutaraldehyde gel according to claim 4, characterized in that: The mass ratio of the nano magnesium silicide to the antimicrobial peptide is 1:(0.05-0.1).

7. A method for preparing glutaraldehyde gel, used for preparing the glutaraldehyde gel as claimed in any one of claims 1 to 6, characterized in that: The method comprises the following steps: S31. Purified water was added to the container, and propylene glycol and modified nano-polyvinyl alcohol-vinyl acetate copolymer were added sequentially under stirring, and ultrasonic treatment was performed after stirring for 0.5 to 1 hour at an ultrasonic frequency of 40 to 50 kHz. After ultrasonic treatment at room temperature for 4 to 6 hours, the mixture was allowed to stand at 0 to 4 ° C for 12 to 14 hours to obtain a seventh mixed solution; S32. Glutaraldehyde and modified nano-magnesium silicide were sequentially added to the seventh mixed solution under stirring, and ultrasonic treatment was performed after stirring for 0.5 to 1 h. After ultrasonic treatment for 0.5 to 1 h, poloxamer, glycerol, potassium sorbate, menthol, sodium hyaluronate and polyethylene glycol were sequentially added and stirred until fully dissolved to obtain an eighth mixed solution; S33. Wash and dry aloe vera, angelica, dandelion, Centella asiatica, ginseng, Poria, Kochia scoparia and honeysuckle, crush and add purified water and 60-80% ethanol, place in an ultrasonic extractor, extract at 55-65 ° C, extract for 2-4 hours to obtain a first extract; S34. Purified water and 60-80% ethanol were added again to continue extraction, twice in a row, to obtain a second extract and a third extract, respectively, and the extracts were mixed and concentrated under reduced pressure to obtain a Chinese medicine extract; S35. Add the Chinese medicine extract to the eighth mixed solution under stirring, transfer to a high-pressure homogenizer after stirring for 2 to 4 hours, set the pressure to 800 to 1000 bar, filter through a 0.22 μm filter membrane after circulating 5 to 10 times, and obtain glutaraldehyde gel after standing at 0 to 4° C. for 12 to 14 hours.

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