Anti-HPV (human papillomavirus) gel dressing and preparation method thereof

Abstract

The invention discloses an anti-HPV (human papillomavirus) gel dressing and a preparation method thereof, and belongs to the technical field of dressings, and the preparation method comprises the following steps: dissolving lopinavir in methanol to obtain an organic phase, adding poloxamer 407 into deionized water to obtain a water phase, dropwise adding the organic phase into the water phase at a constant speed while stirring under a room temperature condition, and after dropwise adding is finished, performing suction filtration and drying to obtain the anti-HPV gel dressing. Stirring in a fuming cupboard to volatilize methanol, and carrying out particle size treatment on the obtained solution by using a high-pressure homogenizer to obtain a lopinavir nanoparticle solution; the preparation method comprises the following steps: adding a chitosan-based functional component, poloxamer 407 and poloxamer 188 into a lopinavir nanoparticle solution, stirring at the temperature of 4 DEG C and the speed of 100-200r / min for 2-4 hours, and treating in a refrigerator at the temperature of 4 DEG C for 48 hours to obtain the anti-HPV gel dressing, the anti-HPV gel dressing has good drug sustained release performance, mucous membrane adhesion and viscosity permeability, and the bioavailability of lopinavir is greatly improved.

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. Human skin, digestive tract, respiratory tract, etc. carry HPV. 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 for the treatment of AIDS, has anti-HPV activity, mainly because lopinavir inhibits the degradation of P53 proteasome regulated by HPV E6. However, lopinavir has low water solubility, strong crystallization tendency and low oral bioavailability. Considering the many advantages of existing hydrogel vaginal drug delivery preparations in application, such as easy use, little pain and irritation, it is necessary to provide an anti-HPV gel dressing containing lopinavir. Summary of the invention

[0004] The purpose of the present invention is to provide an anti-HPV virus gel dressing. The preparation method is simple. First, lopinavir and poloxamer 407 are used as main raw materials, and a lopinavir nanoparticle solution is prepared 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 permeability, and greatly improves 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 dropwise addition is completed, stirring 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, in step (1), the high pressure homogenization conditions 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] Further, 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 under stirring, react at 50-60°C for 4-6h, 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, placing epoxidized chitosan and sodium hydroxide solution in a flask, adding dopamine hydrochloride after stirring, stirring and reacting at 65-75°C for 6-7h, cooling to room temperature, washing the filter cake with anhydrous ethanol and deionized water respectively, and distilling and drying 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 the reaction is completed, pouring the reaction product into a sodium hydroxide solution with a total volume of 2 times, filtering, washing the filter cake, and drying to obtain an intermediate product;

[0016] S4. The intermediate product is placed in a hydrochloric acid ethanol solution, and after magnetic stirring for 24 hours, the ethanol is removed by rotary evaporation at 80°C, deionized water is added to dissolve it, and then precipitated with acetone, filtered, and vacuum dried at 60°C to obtain a chitosan-based functional component.

[0017] Firstly, under alkaline conditions, the hydroxyl groups in amino-protected chitosan are halogenated with epichlorohydrin to obtain epoxidized chitosan, and then the epoxy groups in the epoxidized chitosan are used to undergo a ring-opening reaction with the amino groups to introduce a catechol structure into the chitosan molecular chain and form a new hydroxyl group to obtain dopamine-grafted chitosan. Subsequently, under the catalysis of 4-dimethylaminopyridine and dicyclohexylcarbodiimide, carboxyl-terminated poly-N-isopropylacrylamide and dopamine-grafted chitosan are esterified 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 dosage 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 to the ethanol hydrochloride solution is 10 g:100 mL, and the concentration of the ethanol hydrochloride solution is 0.5 mol / L.

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

[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 constant stirring at 50-60°C for 12 hours under nitrogen protection. Remove methanol by vacuum distillation, dissolve the distillation product in tetrahydrofuran and 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 main raw materials, and a lopinavir nanoparticle solution is prepared by a nanoprecipitation-high pressure homogenization method. 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 permeability, and greatly improves the bioavailability of lopinavir.

[0028] 2. The anti-HPV virus 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 is in low viscosity at room temperature, which is convenient for vaginal administration. After administration, it contacts the human body and is converted into a gel network at a slightly higher temperature, which prolongs 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, have good adhesion to the mucosa, further increase the residence time of the drug on the mucosal tissue, achieve continuous penetration of the drug, and improve the bioavailability of the drug. BRIEF DESCRIPTION OF THE DRAWINGS

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

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

[0031] Example 1

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

[0033] 1 g of chitosan (deacetylation degree 91.5%, average molecular weight 3000) was added to 100 mL of 1 wt% acetic acid solution, and magnetically stirred for 5 min. Then, a mixed solution consisting of 6.57 g of benzaldehyde and 30 mL of anhydrous ethanol was added dropwise. After the addition was completed, the mixture was reacted at 60 ° C for 6 h, and the pH was adjusted to 7 with 0.4 mol / L sodium hydroxide solution. The mixture was filtered, and 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 amino-protected chitosan of Example 1 and 100 mL of 0.4 mol / L sodium hydroxide solution were placed in a flask, and 8.9 g of epichlorohydrin was added dropwise under 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, 10g of epoxidized chitosan and 200mL of 0.05mol / L sodium hydroxide solution were placed in a flask, and 11.7g of dopamine hydrochloride was added after stirring, and the mixture was stirred at 65°C for 6h. After cooling to room temperature, the filter cake was washed with anhydrous ethanol and deionized water respectively, and distilled and dried at 60°C to obtain dopamine-grafted chitosan;

[0038] S3, add 100mL of dimethyl sulfoxide, 3.7g of carboxyl-terminated poly (N-isopropylacrylamide) and 10g of dopamine-grafted chitosan into a flask, stir for 5min, then add 0.1g of 4-dimethylaminopyridine and 0.3g of dicyclohexylcarbodiimide, stir at room temperature for 3h, after the reaction is completed, pour the reaction product into a sodium hydroxide solution with a total volume of 2 times, filter with suction, wash and dry the filter cake 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 dry in vacuo at 60 °C to obtain chitosan-based functional components. The concentration of the hydrochloric acid ethanol solution is 0.5 mol / L.

[0040] Wherein, the carboxyl-terminated poly N-isopropylacrylamide is obtained specifically 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. Distill under reduced pressure to remove methanol. 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 amino-protected chitosan of Example 1 and 100 mL of 0.4 mol / L sodium hydroxide solution were placed in a flask, and 11.4 g of epichlorohydrin was added dropwise under stirring. After the addition was completed, the mixture was reacted at 60° C. for 6 h, cooled to room temperature, 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, 10g of epoxidized chitosan and 300mL of 0.1mol / L sodium hydroxide solution were placed in a flask, and 12.5g of dopamine hydrochloride was added after stirring. The mixture was stirred at 75°C for 7h. After cooling to room temperature, the filter cake was washed with anhydrous ethanol and deionized water respectively, and distilled and dried at 60°C to obtain dopamine-grafted chitosan;

[0046] S3, add 100mL of dimethyl sulfoxide, 5.1g of carboxyl-terminated poly (N-isopropylacrylamide) and 10g of dopamine-grafted chitosan into a flask, stir for 10min, then add 0.1g of 4-dimethylaminopyridine and 0.3g of dicyclohexylcarbodiimide, stir at room temperature for 5h, after the reaction is completed, pour the reaction product into a sodium hydroxide solution with a total volume of 2 times, filter with suction, wash and dry the filter cake 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 dry in vacuo at 60 °C to obtain chitosan-based functional components. The concentration of the hydrochloric acid ethanol solution is 0.5 mol / L.

[0048] Wherein, the carboxyl-terminated poly N-isopropylacrylamide is obtained specifically 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. Distill under reduced pressure to remove methanol. 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, and after magnetic stirring for 24 h, the ethanol was removed by rotary evaporation at 80 ° C. Deionized water was added to dissolve it, and then precipitated with acetone, filtered, and vacuum dried at 60 ° C to obtain chitosan-based functional components. 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 obtained solution was subjected to particle size treatment by 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, the mixture was stirred at 4° C. and 100-200 r / min for 2 h, and placed in a 4° C. refrigerator for 48 h to obtain an anti-HPV virus 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 obtained solution was subjected to particle size treatment by 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, the mixture was stirred at 4° C. and 150 r / min for 3 h, and the mixture was placed in a 4° C. refrigerator for 48 h to obtain an anti-HPV virus 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 obtained solution was subjected to particle size treatment by a high-pressure homogenizer (1500 bar, homogenization 10 times, temperature 4° C.) to obtain a lopinavir nanoparticle solution;

[0066] (2) Add 1 g of the chitosan-based functional component of Example 3, 20 g of poloxamer 407, and 6 g of poloxamer 188 to 75 g of the lopinavir nanoparticle solution, stir at 4°C and 200 r / min for 4 h, and place in a 4°C refrigerator for 48 h to obtain an anti-HPV virus 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 virus gel dressings obtained in Examples 4 to 6 and Comparative Examples 3 to 4 were subjected to safety testing. The "Vaginal Irritation Test" was conducted in accordance with the provisions of B7 in Appendix B of GB / T16886.10-2005. The identification results all 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 to 6 and Comparative Examples 3 to 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 14000 Da. The dialysis bags of each group were placed in 30 mL of a phosphate buffer solution (PBS) with a pH of 4.5, the phosphate buffer solution containing 1% volume fraction of Tween 80, the temperature was 37±0.5°C, the speed was 200 r / min, and the samples were taken at fixed time intervals (2 mL). After each sampling, an equal amount of fresh diffusion medium was added, and the absorbance of the samples 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 Figure 1 As shown;

[0076] Depend on Figure 1It can be seen that the 72h drug release rate of the gel dressings obtained in Examples 4-6 reaches 95-97%, indicating that the gel dressings prepared by the present invention have good sustained release effect and sustained release advantage under acidic regulation, and have better cumulative release amount compared with the gel dressings obtained in Comparative Examples 3 and 4. The reason is that the presence of poly-N-isopropylacrylamide and dopamine components on the chitosan-based functional component molecules in Examples 4-6 has a higher cross-linking strength at 37°C, and the aggregation and collapse between molecules are more serious, 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] Temperature sensitivity: The anti-HPV gel dressings obtained from each group were placed in sample tubes and placed in an oven at 37°C. After 5 minutes, the samples were observed to see if they were gelled. The test results are shown in Table 1.

[0078] Mucosal permeation performance: After continuous permeation for 12 hours, the permeability of lopinavir was calculated. 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 regular shape of the mucosa was washed with saline, and the mucosa was transferred to VSF vaginal simulation fluid and soaked for 0.5h before use; the in vitro drug permeation test was performed using an intelligent transdermal diffusion cell, the temperature was set to 37°C, and the stirring speed was 100r / min; the vaginal mucosa was placed between the donor and receptor chambers, 1mL of sample was added to the donor chamber, and 0.75mL of VSF vaginal simulation fluid was added to simulate the vaginal environment, and the receptor chamber was filled with 15mL of phosphate buffer (pH=4.5), 2mL of receptor permeation solution was taken out regularly, and an equal amount of fresh phosphate buffer was added; then the absorbance value at 260nm was measured, and the cumulative dose of drug penetration was calculated according to the following formula:

[0080]

[0081] Wherein: 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 at time i to t-1, Ci is the drug concentration of the sample at time i to t, and A is the surface area of ​​the mucosa; the permeability of lopinavir (%) = Qt / the 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 article, relational terms such as first and second, etc. are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "include", "comprise" or any other variants thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or device.

[0086] Although 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 the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A method for preparing an anti-HPV virus 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 dropwise addition is completed, stirring 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 h, and placing in a 4° C. refrigerator for 48 h to obtain an anti-HPV virus 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 under stirring, and react at 50-60° C. for 4-6 hours to obtain epoxidized chitosan; S2, placing epoxidized chitosan and sodium hydroxide solution in a flask, adding dopamine hydrochloride after stirring, and reacting 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, and after magnetic stirring for 24 hours, the ethanol is removed by rotary evaporation at 80°C, deionized water is added to dissolve it, and then 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 method for preparing the anti-HPV gel dressing according to claim 1, characterized in that: In step (2), the mass ratio of 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, characterized in that: 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 to the ethanol hydrochloride solution is 10 g:100 mL, and the concentration of the ethanol hydrochloride 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 via 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 constant stirring at 50-60°C for 12 hours under nitrogen protection. Remove methanol by vacuum distillation, dissolve the distillation product in tetrahydrofuran and 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. An anti-HPV virus gel dressing, characterized in that: Prepared by the preparation method described in any one of claims 1 to 8.

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