Anti-HPV virus gel dressing and preparation method thereof

Abstract

The invention discloses an anti-HPV gel dressing and a preparation method thereof, belonging to the technical field of dressings. The invention comprises the following steps: dissolving lopinavir in methanol to obtain an organic phase, adding poloxamer 407 to deionized water to obtain an aqueous phase, dripping the organic phase into the aqueous phase at a uniform speed while stirring under room temperature, stirring in a fume hood to volatilize methanol after the dripping is completed, and subjecting the obtained solution to particle size treatment using a high-pressure homogenizer to obtain a lopinavir nanoparticle solution; and adding a chitosan-based functional component, poloxamer 407, and poloxamer 188 to the lopinavir nanoparticle solution, stirring at 4°C and 100-200 r / min for 2-4 hours, and placing the dressing in a 4°C refrigerator for treatment for 48 hours to obtain the anti-HPV gel dressing. The anti-HPV gel dressing has good drug sustained-release performance, mucosal adhesion, and viscosity permeability, and greatly improves the bioavailability of lopinavir.

Description

Technical Field

[0001] The invention belongs to the technical field of dressings, and in particular relates to an anti-HPV gel dressing and a preparation method thereof. Background Art

[0002] Cervical cancer is currently a common gynecological malignancy. More than 99% of cervical cancer patients are related to human papillomavirus (HPV) infection. HPV is a small, non-enveloped DNA virus that is widely present in nature. HPV is carried by human skin, digestive tract, respiratory tract, etc. All women who have sexual life may be infected with HPV through sexual contact. Currently, HPV vaccines are mainly used to prevent HPV viruses, but cannot treat related diseases caused by HPV viruses. Therefore, the development of simple and effective drug preparations will be beneficial to the control of HPV-infected diseases.

[0003] Studies have found that lopinavir (LPV), a protease inhibitor used to treat AIDS, has anti-HPV activity, mainly because lopinavir inhibits the degradation of the P53 proteasome regulated by HPV E6. However, lopinavir has low water solubility, a strong tendency to crystallize, and low oral bioavailability. Considering the many advantages of existing hydrogel vaginal drug delivery preparations in application, such as ease of use, low pain and irritation, it is necessary to provide an anti-HPV gel dressing containing lopinavir. Summary of the Invention

[0004] The present invention aims to provide an anti-HPV virus gel dressing with a simple preparation method. First, lopinavir and poloxamer 407 are used as main raw materials to prepare a lopinavir nanoparticle solution by a nanoprecipitation-high-pressure homogenization method. Then, a chitosan-based functional component, poloxamer 407, and poloxamer 188 are added to obtain an anti-HPV virus gel dressing. The dressing has good drug sustained-release performance, mucosal adhesion, and viscosity-penetration performance, thereby greatly improving the bioavailability of lopinavir.

[0005] The purpose of the present invention can be achieved through the following technical solutions:

[0006] The preparation method of the anti-HPV gel dressing comprises the following steps:

[0007] (1) dissolving lopinavir in methanol to obtain an organic phase, adding poloxamer 407 to deionized water to obtain an aqueous phase, and dropping the organic phase into the aqueous phase at a uniform rate while stirring at room temperature. After the addition is completed, stirring is performed in a fume hood to evaporate the methanol, and the resulting solution is subjected to particle size treatment using a high-pressure homogenizer to obtain a lopinavir nanoparticle solution;

[0008] (2) Adding chitosan-based functional components, poloxamer 407, and poloxamer 188 to the lopinavir nanoparticle solution, stirring at 4°C and 100-200 r / min for 2-4 hours, and placing in a 4°C refrigerator for 48 hours to obtain an anti-HPV virus gel dressing.

[0009] Furthermore, in step (1), the usage ratio of lopinavir, methanol, poloxamer 407 and deionized water is 10 mg:1 mL:100 mg:10 mL.

[0010] Furthermore, the high-pressure homogenization conditions in step (1) are: 1500 bar, homogenization 10 times, and temperature 4°C.

[0011] Furthermore, in step (2), the mass ratio of the lopinavir nanoparticle solution, poloxamer 407, poloxamer 188 and chitosan-based functional component is 70-75:20:6:0.6-1.

[0012] Furthermore, the chitosan-based functional component is obtained by the following steps:

[0013] S1. Place amino-protected chitosan and sodium hydroxide solution in a flask, add epichlorohydrin dropwise with stirring, react at 50-60°C for 4-6 hours, cool to room temperature, filter, wash the filter cake with anhydrous ethanol and deionized water, respectively, and distill and dry at 60°C to obtain epoxidized chitosan;

[0014] S2. Place epoxidized chitosan and sodium hydroxide solution in a flask, add dopamine hydrochloride after stirring, react at 65-75°C with stirring for 6-7 hours, cool to room temperature, wash the filter cake with anhydrous ethanol and deionized water respectively, and distill and dry at 60°C to obtain dopamine-grafted chitosan;

[0015] S3, adding dimethyl sulfoxide, carboxyl-terminated poly (N-isopropylacrylamide) and dopamine-grafted chitosan into a flask, stirring for 5-10 minutes, then adding 4-dimethylaminopyridine and dicyclohexylcarbodiimide, stirring at room temperature for 3-5 hours, after which the reaction is completed, pouring the reaction product into a sodium hydroxide solution twice the total volume, filtering with suction, washing the filter cake, and drying to obtain an intermediate product;

[0016] S4. The intermediate product is placed in a hydrochloric acid ethanol solution, magnetically stirred for 24 hours, and then rotary evaporated at 80°C to remove the ethanol. After adding deionized water to dissolve, it is precipitated with acetone, filtered, and vacuum dried at 60°C to obtain a chitosan-based functional component.

[0017] First, under alkaline conditions, the hydroxyl groups in amino-protected chitosan react with epichlorohydrin to undergo a halogenation reaction to obtain epoxidized chitosan. Then, the epoxy groups in the epoxidized chitosan react with the amino groups to undergo a ring-opening reaction, introducing a catechol structure into the chitosan molecular chain and forming a new hydroxyl group to obtain dopamine-grafted chitosan. Subsequently, under the catalysis of 4-dimethylaminopyridine and dicyclohexylcarbodiimide, the carboxyl-terminated poly (N-isopropylacrylamide) and the dopamine-grafted chitosan undergo an esterification reaction at room temperature to obtain an intermediate product. Finally, the amino protecting group of the intermediate product is removed in a hydrochloric acid solution to obtain a chitosan-based functional component.

[0018] Furthermore, in step S1, the usage ratio of amino-protected chitosan, sodium hydroxide solution and epichlorohydrin is 10 g:100 mL:8.9-11.4 g, and the concentration of the sodium hydroxide solution is 0.4 mol / L.

[0019] Furthermore, in step S2, the usage ratio of epoxidized chitosan, sodium hydroxide solution and dopamine hydrochloride is 10 g:200-300 mL:11.7-12.5 g, and the concentration of the sodium hydroxide solution is 0.05-0.1 mol / L.

[0020] Furthermore, in step S3, the mass ratio of carboxyl-terminated poly (N-isopropylacrylamide) and dopamine-grafted chitosan is 3.7-5.1:10, the amount of 4-dimethylaminopyridine is 3% of the mass of carboxyl-terminated poly (N-isopropylacrylamide), and the amount of dicyclohexylcarbodiimide is 3 times the mass of 4-dimethylaminopyridine.

[0021] Furthermore, in step S4, the usage ratio of the intermediate product and the hydrochloric acid ethanol solution is 10 g:100 mL, and the concentration of the hydrochloric acid ethanol solution is 0.5 mol / L.

[0022] Furthermore, the amino-protected chitosan is obtained by reacting chitosan with benzaldehyde via a Schiff base, using benzaldehyde as an amino-protecting agent.

[0023] Furthermore, the carboxyl-terminated poly N-isopropylacrylamide is obtained by free radical polymerization using azobisisobutyronitrile as an initiator, thioglycolic acid as a chain transfer agent, and N-isopropylacrylamide as a monomer, and is specifically obtained by the following steps:

[0024] Place N-isopropylacrylamide, azobisisobutyronitrile and methanol in a flask, stir to dissolve, then add thioglycolic acid, and react with stirring at a constant temperature of 50-60°C for 12 hours under nitrogen protection. Remove methanol by distillation under reduced pressure, dissolve the distillation product in tetrahydrofuran, precipitate in ether, filter, and dry the solid product. The mass ratio of N-isopropylacrylamide, azobisisobutyronitrile, methanol and thioglycolic acid is 15:0.3:150-200:0.8-1.3.

[0025] Furthermore, the anti-HPV virus gel dressing is prepared by the above preparation method.

[0026] Beneficial effects of the present invention:

[0027] 1. The present invention provides an anti-HPV virus gel dressing. First, lopinavir and poloxamer 407 (emulsifier and solubilizer) are used as the main raw materials, and a lopinavir nanoparticle solution is prepared by nanoprecipitation-high pressure homogenization. Then, chitosan-based functional components, poloxamer 407, and poloxamer 188 are added to obtain an anti-HPV virus gel dressing. The dressing has good drug sustained release performance, mucosal adhesion, and viscosity and permeability, greatly improving the bioavailability of lopinavir.

[0028] 2. The anti-HPV gel dressing obtained by the present invention contains a homemade chitosan-based functional component, which contains thermosensitive poly N-isopropylacrylamide, which can give the gel dressing good thermosensitivity and has low viscosity at room temperature, making it convenient for vaginal administration. After administration, it contacts the human body and is converted into a gel network at a slightly higher temperature, thereby prolonging the retention time of lopinavir in the vagina. In addition, the chitosan-based functional component also contains active amino groups and catechol structures, which can form electrostatic interactions with the vaginal mucosa, promote mucosal penetration effects, and have good adhesion to the mucosa, further increasing the residence time of the drug on the mucosal tissue, achieving continuous penetration of the drug, and improving the bioavailability of the drug. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] The present invention will be further described below with reference to the accompanying drawings.

[0030] Figure 1 1 is a graph showing the in vitro drug release performance test results of the anti-HPV gel dressings obtained in the examples and comparative examples of the present invention. DETAILED DESCRIPTION

[0031] Example 1

[0032] Amino-protected chitosan is obtained by the following steps:

[0033] 1 g of chitosan (degree of deacetylation 91.5%, average molecular weight 3000) was added to 100 mL of 1 wt% acetic acid solution and magnetically stirred for 5 min. A mixed solution consisting of 6.57 g of benzaldehyde and 30 mL of anhydrous ethanol was then added dropwise. After the addition was completed, the mixture was reacted at 60°C for 6 h. The pH was adjusted to 7 with 0.4 mol / L sodium hydroxide solution, and the mixture was filtered. The filter cake was washed with deionized water and vacuum dried at 60°C to obtain amino-protected chitosan.

[0034] Example 2

[0035] The chitosan-based functional component is obtained by the following steps:

[0036] S1. 10 g of the amino-protected chitosan of Example 1 and 100 mL of a 0.4 mol / L sodium hydroxide solution were placed in a flask, and 8.9 g of epichlorohydrin was added dropwise with stirring. After the addition was completed, the mixture was reacted at 50° C. for 4 h. After cooling to room temperature, the mixture was filtered, and the filter cake was washed with anhydrous ethanol and deionized water, respectively, and distilled and dried at 60° C. to obtain epoxidized chitosan.

[0037] S2. Place 10 g of epoxidized chitosan and 200 mL of 0.05 mol / L sodium hydroxide solution in a flask, stir, add 11.7 g of dopamine hydrochloride, and react at 65°C with stirring for 6 h. After cooling to room temperature, wash the filter cake with anhydrous ethanol and deionized water, respectively, and distill and dry at 60°C to obtain dopamine-grafted chitosan;

[0038] S3, 100 mL of dimethyl sulfoxide, 3.7 g of carboxyl-terminated poly (N-isopropylacrylamide) and 10 g of dopamine-grafted chitosan were added to a flask, stirred for 5 min, and then 0.1 g of 4-dimethylaminopyridine and 0.3 g of dicyclohexylcarbodiimide were added. The mixture was stirred at room temperature for 3 h. After the reaction was completed, the reaction product was poured into a sodium hydroxide solution with a total volume of 2 times, filtered, and the filter cake was washed and dried to obtain an intermediate product;

[0039] S4. Place 10 g of the intermediate product in 100 mL of hydrochloric acid ethanol solution, stir magnetically for 24 h, remove ethanol by rotary evaporation at 80 ° C, add deionized water to dissolve, precipitate with acetone, filter, and vacuum dry at 60 ° C to obtain chitosan-based functional components. The concentration of the hydrochloric acid ethanol solution is 0.5 mol / L.

[0040] The carboxyl-terminated poly (N-isopropylacrylamide) is obtained by the following steps:

[0041] Place 15 g of N-isopropylacrylamide, 0.3 g of azobisisobutyronitrile and 150 g of methanol in a flask, stir to dissolve, then add 0.8 g of thioglycolic acid. Under nitrogen protection, stir and react at a constant temperature of 50°C for 12 h. Remove methanol by vacuum distillation. Dissolve the distillation product in tetrahydrofuran and precipitate in ether. Filter and dry the solid product.

[0042] Example 3

[0043] The chitosan-based functional component is obtained by the following steps:

[0044] S1. 10 g of the amino-protected chitosan of Example 1 and 100 mL of a 0.4 mol / L sodium hydroxide solution were placed in a flask, and 11.4 g of epichlorohydrin was added dropwise with stirring. After the addition was completed, the mixture was reacted at 60° C. for 6 h. After cooling to room temperature, the mixture was filtered, and the filter cake was washed with anhydrous ethanol and deionized water, respectively, and distilled and dried at 60° C. to obtain epoxidized chitosan.

[0045] S2. Place 10 g of epoxidized chitosan and 300 mL of 0.1 mol / L sodium hydroxide solution in a flask, stir, then add 12.5 g of dopamine hydrochloride. Stir and react at 75°C for 7 h. After cooling to room temperature, wash the filter cake with anhydrous ethanol and deionized water, respectively, and distill and dry at 60°C to obtain dopamine-grafted chitosan.

[0046] S3, 100 mL of dimethyl sulfoxide, 5.1 g of carboxyl-terminated poly (N-isopropylacrylamide) and 10 g of dopamine-grafted chitosan were added to a flask, stirred for 10 min, and then 0.1 g of 4-dimethylaminopyridine and 0.3 g of dicyclohexylcarbodiimide were added. The mixture was stirred at room temperature for 5 h. After the reaction was completed, the reaction product was poured into a sodium hydroxide solution with a total volume of 2 times, filtered, and the filter cake was washed and dried to obtain an intermediate product;

[0047] S4. Place 10 g of the intermediate product in 100 mL of hydrochloric acid ethanol solution, stir magnetically for 24 h, remove ethanol by rotary evaporation at 80 ° C, add deionized water to dissolve, precipitate with acetone, filter, and vacuum dry at 60 ° C to obtain chitosan-based functional components. The concentration of the hydrochloric acid ethanol solution is 0.5 mol / L.

[0048] The carboxyl-terminated poly (N-isopropylacrylamide) is obtained by the following steps:

[0049] Place 15 g of N-isopropylacrylamide, 0.3 g of azobisisobutyronitrile and 200 g of methanol in a flask, stir to dissolve, then add 1.3 g of thioglycolic acid. Under nitrogen protection, stir and react at a constant temperature of 60°C for 12 h. Remove methanol by vacuum distillation. Dissolve the distillation product in tetrahydrofuran and precipitate in ether. Filter and dry the solid product.

[0050] Comparative Example 1

[0051] The chitosan-based functional component is obtained by the following steps:

[0052] 10 g of dopamine-grafted chitosan was placed in 100 mL of hydrochloric acid-ethanol solution, magnetically stirred for 24 h, and then the ethanol was removed by rotary evaporation at 80°C. Deionized water was added to dissolve the chitosan, and the chitosan-based functional component was obtained by filtration and vacuum drying at 60°C. The concentration of the hydrochloric acid-ethanol solution was 0.5 mol / L. The preparation process of dopamine-grafted chitosan was the same as that in Example 1.

[0053] Comparative Example 2

[0054] This comparative example is carboxymethyl chitosan, and the number average molecular weight is 3000.

[0055] Example 4

[0056] The preparation method of the anti-HPV gel dressing comprises the following steps:

[0057] (1) 100 mg of lopinavir was dissolved in 10 mL of methanol to obtain an organic phase, 1000 mg of poloxamer 407 was added to 100 mL of deionized water to obtain an aqueous phase, and the organic phase was uniformly added dropwise to the aqueous phase while stirring at room temperature. After the addition was completed, the methanol was evaporated by stirring in a fume hood, and the resulting solution was subjected to particle size treatment using a high-pressure homogenizer (1500 bar, homogenization 10 times, temperature 4°C) to obtain a lopinavir nanoparticle solution;

[0058] (2) To 70 g of the lopinavir nanoparticle solution, 0.6 g of the chitosan-based functional component of Example 2, 20 g of poloxamer 407, and 6 g of poloxamer 188 were added, and the mixture was stirred at 4°C and 100-200 r / min for 2 h. The mixture was placed in a refrigerator at 4°C for 48 h to obtain an anti-HPV gel dressing.

[0059] Example 5

[0060] The preparation method of the anti-HPV gel dressing comprises the following steps:

[0061] (1) 100 mg of lopinavir was dissolved in 10 mL of methanol to obtain an organic phase, 1000 mg of poloxamer 407 was added to 100 mL of deionized water to obtain an aqueous phase, and the organic phase was uniformly added dropwise to the aqueous phase while stirring at room temperature. After the addition was completed, the methanol was evaporated by stirring in a fume hood, and the resulting solution was subjected to particle size treatment using a high-pressure homogenizer (1500 bar, homogenization 10 times, temperature 4°C) to obtain a lopinavir nanoparticle solution;

[0062] (2) To 72 g of the lopinavir nanoparticle solution, 0.8 g of the chitosan-based functional component of Example 2, 20 g of poloxamer 407, and 6 g of poloxamer 188 were added, and the mixture was stirred at 4°C and 150 r / min for 3 h. The mixture was placed in a refrigerator at 4°C for 48 h to obtain an anti-HPV gel dressing.

[0063] Example 6

[0064] The preparation method of the anti-HPV gel dressing comprises the following steps:

[0065] (1) 100 mg of lopinavir was dissolved in 10 mL of methanol to obtain an organic phase, 1000 mg of poloxamer 407 was added to 100 mL of deionized water to obtain an aqueous phase, and the organic phase was uniformly added dropwise to the aqueous phase while stirring at room temperature. After the addition was completed, the methanol was evaporated by stirring in a fume hood, and the resulting solution was subjected to particle size treatment using a high-pressure homogenizer (1500 bar, homogenization 10 times, temperature 4°C) to obtain a lopinavir nanoparticle solution;

[0066] (2) To 75 g of the lopinavir nanoparticle solution, 1 g of the chitosan-based functional component of Example 3, 20 g of poloxamer 407, and 6 g of poloxamer 188 were added, and the mixture was stirred at 4°C and 200 r / min for 4 h. The mixture was placed in a refrigerator at 4°C for 48 h to obtain an anti-HPV gel dressing.

[0067] Comparative Example 3

[0068] The preparation method of the anti-HPV gel dressing comprises the following steps:

[0069] Compared with Example 4, the chitosan-based functional component in Example 4 was replaced by the product prepared in Comparative Example 1, and the remaining raw materials and preparation process were the same as in Example 4.

[0070] Comparative Example 4

[0071] The preparation method of the anti-HPV gel dressing comprises the following steps:

[0072] Compared with Example 4, the chitosan-based functional component in Example 4 was replaced by the substance in Comparative Example 2, and the remaining raw materials and preparation process were the same as in Example 4.

[0073] The anti-HPV gel dressings obtained in Examples 4 to 6 and Comparative Examples 3 and 4 were subjected to safety testing. The "Vaginal Irritation Test" was conducted in accordance with B7 in Appendix B of GB / T 16886.10-2005. The identification results showed that the degree of vaginal irritation reaction was none, and no skin allergic reaction was observed.

[0074] The anti-HPV gel dressings obtained in Examples 4-6 and Comparative Examples 3-4 were tested, and the testing process was as follows:

[0075] In vitro drug release performance: 2 mL of the gel dressing obtained from each group was placed in a dialysis bag with a molecular weight cutoff of 14,000 Da. The dialysis bag of each group was placed in 30 mL of phosphate buffer solution (PBS) with a pH of 4.5, containing 1% volume fraction of Tween 80, at a temperature of 37±0.5°C and a rotation speed of 200 r / min. Samples (2 mL) were taken at fixed time intervals. After each sampling, an equal amount of fresh diffusion medium was added. The absorbance of the sample at 260 nm was measured to analyze the drug release. The experiment was repeated three times and the average value was taken. The experimental results are shown in the figure. Figure 1 As shown;

[0076] Depend on Figure 1It can be seen that the 72-h drug release rate of the gel dressings obtained in Examples 4-6 reached 95-97%, indicating that the gel dressings prepared by the present invention have good sustained-release effects and sustained-release advantages under acidic conditions, and have better cumulative release amounts than the gel dressings obtained in Comparative Examples 3 and 4. This is because the presence of poly (N-isopropylacrylamide) and dopamine components on the chitosan-based functional component molecules in Examples 4-6 has higher cross-linking strength at 37°C, resulting in more severe intermolecular aggregation and collapse, which makes it easier for small drug molecules to be squeezed out of the gel voids, resulting in a faster drug release rate and cumulative release amount.

[0077] Thermosensitivity: The anti-HPV gel dressings obtained from each group were placed in sample tubes and placed in a 37°C oven. After 5 minutes, the samples were observed to see if they had gelled. The test results are shown in Table 1.

[0078] Mucosal permeation performance: Continuous permeation for 12 hours and calculation of the permeability of lopinavir. The test process is as follows:

[0079] Using the pig vaginal mucosa to simulate the experiment, the pig's tubular vaginal tissue was cut vertically, and the inner wall epithelial mucosa was taken and each piece was cut into 4cm 2 The mucosa was placed between the donor and recipient chambers. 1 mL of sample was added to the donor chamber, along with 0.75 mL of VSF vaginal simulating fluid to simulate the vaginal environment. The recipient chamber was filled with 15 mL of phosphate buffer (pH 4.5). 2 mL of the receptor permeation solution was periodically removed and supplemented with an equal amount of fresh phosphate buffer. The absorbance at 260 nm was measured, and the cumulative drug permeation dose was calculated according to the following formula:

[0080]

[0081] Where: Qt is the cumulative drug permeation per unit surface area of ​​the mucosa at time t, Vr is the volume of the receptor compartment, Ct is the drug concentration in the receptor compartment at time t, VS is the volume of the sample from time i to t-1, Ci is the drug concentration of the sample from time i to t, and A is the surface area of ​​the mucosa; Lopinavir permeability (%) = Qt / total amount of lopinavir in the sample. The test results are shown in Table 1.

[0082] Table 1

[0083]

[0084] It can be seen from the data recorded in Table 1 that compared with Comparative Example 3 and Comparative Example 4, the anti-HPV virus gel dressings obtained in Example 4, Example 5, and Example 6 have good temperature sensitivity and mucosal permeability, and achieve the bioavailability of lopinavir.

[0085] It should be noted that, in this document, relational terms such as first and second, etc., are used only to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any actual relationship or order between these entities or operations. Moreover, the terms "comprises," "comprising," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that includes a list of elements includes not only those elements but also other elements not explicitly listed, or elements inherent to such process, method, article, or apparatus.

[0086] While embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions, and variations may be made to these embodiments without departing from the principles and spirit of the invention, and that the scope of the invention is defined by the appended claims and their equivalents.

Claims

1. A method for preparing an anti-HPV gel dressing, characterized in that: The following steps are involved: (1) dissolving lopinavir in methanol to obtain an organic phase, adding poloxamer 407 to deionized water to obtain an aqueous phase, and dropping the organic phase into the aqueous phase at a uniform rate while stirring at room temperature. After the addition is completed, stirring is performed in a fume hood to evaporate the methanol, and the resulting solution is subjected to particle size treatment using a high-pressure homogenizer to obtain a lopinavir nanoparticle solution; (2) adding chitosan-based functional components, poloxamer 407, and poloxamer 188 to the lopinavir nanoparticle solution, stirring at 4°C and 100-200 r / min for 2-4 hours, and placing in a 4°C refrigerator for 48 hours to obtain an anti-HPV gel dressing; The chitosan-based functional component is obtained by the following steps: S1. Place amino-protected chitosan and sodium hydroxide solution in a flask, add epichlorohydrin dropwise with stirring, and react at 50-60° C. for 4-6 hours to obtain epoxidized chitosan; S2. Place epoxidized chitosan and sodium hydroxide solution in a flask, stir, then add dopamine hydrochloride, and react at 65-75° C. with stirring for 6-7 hours to obtain dopamine-grafted chitosan; S3, adding dimethyl sulfoxide, carboxyl-terminated poly (N-isopropylacrylamide) and dopamine-grafted chitosan into a flask, stirring for 5-10 minutes, then adding 4-dimethylaminopyridine and dicyclohexylcarbodiimide, stirring at room temperature for 3-5 hours to obtain an intermediate product; S4. The intermediate product is placed in a hydrochloric acid ethanol solution, magnetically stirred for 24 hours, and then rotary evaporated at 80°C to remove the ethanol. After adding deionized water to dissolve, it is precipitated with acetone, filtered, and vacuum dried at 60°C to obtain a chitosan-based functional component.

2. The method for preparing the anti-HPV gel dressing according to claim 1, characterized in that: In step (1), the dosage ratio of lopinavir, methanol, poloxamer 407 and deionized water is 10 mg:1 mL:100 mg:10 mL.

3. The preparation method of the anti-HPV gel dressing according to claim 1, characterized in that: In step (2), the mass ratio of the lopinavir nanoparticle solution, poloxamer 407, poloxamer 188 and chitosan-based functional component is 70-75:20:6:0.6-1.

4. The method for preparing the anti-HPV gel dressing according to claim 1, wherein: In step S2, the usage ratio of epoxidized chitosan, sodium hydroxide solution and dopamine hydrochloride is 10 g:200-300 mL:11.7-12.5 g, and the concentration of the sodium hydroxide solution is 0.05-0.1 mol / L.

5. The method for preparing the anti-HPV gel dressing according to claim 1, characterized in that: In step S3, the mass ratio of carboxyl-terminated poly (N-isopropylacrylamide) and dopamine-grafted chitosan is 3.7-5.1:10, the amount of 4-dimethylaminopyridine is 3% of the mass of carboxyl-terminated poly (N-isopropylacrylamide), and the amount of dicyclohexylcarbodiimide is 3 times the mass of 4-dimethylaminopyridine.

6. The method for preparing the anti-HPV gel dressing according to claim 1, characterized in that: In step S4, the usage ratio of the intermediate product and the hydrochloric acid ethanol solution is 10 g:100 mL, and the concentration of the hydrochloric acid ethanol solution is 0.5 mol / L.

7. The method for preparing the anti-HPV gel dressing according to claim 1, characterized in that: Amino-protected chitosan is obtained by using benzaldehyde as an amino-protecting agent and reacting chitosan with benzaldehyde through a Schiff base reaction.

8. The method for preparing the anti-HPV gel dressing according to claim 1, characterized in that: Carboxyl-terminated poly (N-isopropylacrylamide) is obtained by the following steps: Place N-isopropylacrylamide, azobisisobutyronitrile and methanol in a flask, stir to dissolve, then add thioglycolic acid, and react with stirring at a constant temperature of 50-60°C for 12 hours under nitrogen protection. Remove methanol by distillation under reduced pressure, dissolve the distillation product in tetrahydrofuran, precipitate in ether, filter, and dry the solid product. The mass ratio of N-isopropylacrylamide, azobisisobutyronitrile, methanol and thioglycolic acid is 15:0.3:150-200:0.8-1.

3.

9. Anti-HPV virus gel dressing, characterized in that, Prepared by the preparation method according to any one of claims 1 to 8.

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