Slow-release antibacterial ophthalmic postoperative dressing and preparation method thereof

Abstract

The invention provides a sustained-release antibacterial ophthalmic postoperative dressing and a preparation method thereof, and belongs to the technical field of drug sustained release. A core-shell structure is formed by coating a medicine with calcium alginate, and a gel network is prepared by crosslinking poly (N-vinylcaprolactam) microgel and sodium alginate. Sodium alginate can form a moist environment on the surface of a wound and promote healing due to the high water absorption of sodium alginate, forms a gel barrier through calcium ion exchange, delays drug release, complements with the temperature sensitivity of poly (N-vinylcaprolactam) and prolongs the drug action time. The chitosan grafted on the outer layer has natural broad-spectrum antibacterial property, can inhibit early infection by destroying bacterial cell membranes, and reduces the risk of bacterial colonization in the early stage after operation. Dynamic regulation and control of drug release, double antibacterial protection and biocompatibility optimization are achieved, and the preparation is particularly suitable for scenes with strict requirements for precise treatment and high safety after ophthalmology.

Description

Technical Field

[0001] The present invention relates to the technical field of drug sustained-release technology, in particular to a sustained-release antibacterial ophthalmic postoperative dressing and a preparation method thereof. Background Art

[0002] To prevent wound infection, wound dressings should have good antimicrobial activity. Ideally, an antimicrobial dressing would effectively kill bacteria or fungi in wound infections, prevent bacterial biofilm formation, and prevent reinfection during wound healing, wound inspection, surgery, or dressing changes. Currently, commonly used antimicrobial dressings are made by physically mixing small molecule drugs into the material, providing a viable option for treating wound infections. However, due to the rapid release rate of the antimicrobial drug from such antimicrobial dressings, the concentration of the antimicrobial drug in the wound tissue can be excessively high within a short period of time, allowing the antimicrobial drug to further enter the body and negatively impact vital organs. This is particularly true for ocular surgery, where the wound is located in a unique location and nerves are concentrated beneath the wound. High drug concentrations can be highly irritating, leading to adverse consequences. Furthermore, since the antimicrobial efficacy of these antimicrobial dressings does not last longer than 48 hours, frequent dressing changes are necessary to maintain the antimicrobial efficacy at the wound site, increasing care costs and patient suffering.

[0003] Sodium alginate has excellent biocompatibility, is non-immunogenic, and has good compatibility with human tissues. It can quickly form a gel at room temperature or physiological conditions, making it suitable for encapsulating drugs, cells, or growth factors, and has good adsorption and drug-loading capabilities. However, natural sodium alginate hydrogels have low mechanical strength, are brittle, and are easily broken. They also suffer from burst release, making it difficult to achieve long-term sustained release, which affects therapeutic efficacy.

[0004] Traditional antimicrobial hydrogel dressings, which often use a polyurethane carrier and glutaraldehyde as a crosslinker, have poor biocompatibility, can trigger inflammatory reactions, and easily adhere to wounds after absorbing fluid. Therefore, there is an urgent need to develop a wound dressing with sustained-release antimicrobial activity. Summary of the Invention

[0005] The purpose of the present invention is to provide a sustained-release antibacterial ophthalmic postoperative dressing and a preparation method thereof, so as to overcome the technical problems in the prior art of postoperative ophthalmic dressings, such as poor antibacterial performance and biosafety, poor sustained-release effect, and the resulting high concentration of antibacterial drugs in a short period of time.

[0006] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0007] The present invention provides a method for preparing a sustained-release antibacterial ophthalmic postoperative dressing, comprising the following steps:

[0008] Step 1) dropping tiny droplets of drug-containing sodium alginate solution formed in a high-voltage electrostatic field into a calcium chloride solution for solidification, and obtaining drug-loaded calcium alginate microspheres after washing;

[0009] Step 2), mixing N-vinyl caprolactam, methacrylic acid and water, adding methylene bisacrylamide and ammonium persulfate for micro-crosslinking to obtain poly (N-vinyl caprolactam) microgel, which is purified by dialysis and freeze-dried for later use;

[0010] Step 3) Dispersing poly(N-vinyl caprolactam) microgel in sodium alginate solution, adding drug-loaded calcium alginate microspheres and calcium chloride solution under magnetic stirring conditions for pre-crosslinking, then adding modified chitosan solution dropwise, and continuing to stir to obtain a sustained-release antibacterial ophthalmic postoperative dressing.

[0011] Furthermore, in step 1), the drug includes a growth factor, an antibiotic or an anti-inflammatory drug;

[0012] The concentration of the sodium alginate solution is 1-3 mg / mL, and the concentration of the calcium chloride solution is 2-5 mg / mL.

[0013] Furthermore, in step 2), the molar ratio of N-vinylcaprolactam to methacrylic acid is 7 to 12:1;

[0014] The amount of methylene bisacrylamide added is 1 to 3% of the sum of the mass of N-vinyl caprolactam and methacrylic acid;

[0015] The amount of ammonium persulfate added is 0.5-1% of the total mass of N-vinylcaprolactam and methacrylic acid.

[0016] Furthermore, in step 2), the micro-crosslinking is carried out in an inert gas atmosphere, the micro-crosslinking temperature is 50-70° C., and the micro-crosslinking time is 3-10 hours.

[0017] Furthermore, in step 3), the concentration of the sodium alginate solution is 10-30 mg / mL, and the concentration of the calcium chloride solution is 0.5-6 mg / mL.

[0018] Furthermore, in step 3), the amount of the drug-loaded calcium alginate microspheres added is 5 to 12 wt % of the mass of the poly(N-vinylcaprolactam) microgel.

[0019] Furthermore, in step 3), the pre-crosslinking temperature is 20-30° C., and the pre-crosslinking time is 8-20 min.

[0020] Furthermore, in step 3), the concentration of the modified chitosan solution is 0.5 to 1.2 wt%;

[0021] The modified chitosan solution is obtained by dissolving chitosan in an acetic acid solution, wherein the concentration of the acetic acid solution is 0.8-1 wt %.

[0022] Furthermore, in step 3), the volume ratio of the modified chitosan solution to the sodium alginate solution is 1:0.5-2;

[0023] The modified chitosan solution is added at a rate of 2 to 5 mL / min and a magnetic stirring speed of 300 to 600 rpm;

[0024] The stirring time is 20 to 40 minutes;

[0025] The volume ratio of poly(N-vinyl caprolactam) microgel to sodium alginate in the sustained-release antibacterial ophthalmic postoperative dressing is 1:0.8-1.3.

[0026] The present invention provides a sustained-release antibacterial ophthalmic postoperative dressing prepared by the above-mentioned preparation method.

[0027] Beneficial effects of the present invention:

[0028] The present invention uses calcium alginate to encapsulate drug factors, creating a core-shell structure that enhances sustained-release effects. Calcium alginate is also hydrophilic. When it comes into contact with sodium-containing exudate from a wound, the sodium ions in the exudate exchange with the calcium ions in the calcium alginate, rapidly transforming the solid alginate fibers into a hydrophilic, moist gel, creating a moist environment conducive to wound healing. This gel not only encapsulates and locks bacteria and necrotic tissue debris from the wound surface within the gel, helping to quickly stop bleeding and promote healing, but also increases the volume ratio of the sodium alginate gel in the dressing, further enhancing the sustained-release effect. This gel can be easily removed from the wound by rinsing with 0.9% saline.

[0029] The present invention uses poly(N-vinyl caprolactam) and sodium alginate to construct a gel system. Drug molecules are coated with calcium alginate gel and loaded into the gel in the form of a core-shell structure. Chitosan, which has antibacterial effects, is grafted onto the outside of the gel. During the wound recovery period, the sustained-release antibacterial dressing of the present invention produces an initial antibacterial effect through the chitosan on the outside. At the same time, the thermosensitive poly(N-vinyl caprolactam) undergoes a slight phase change within the human body temperature range, making the sustained release of the drug molecules thermosensitive and adjustable. The composite structure of core-shell loading and outer grafting simultaneously achieves rapid antibacterial, sustained-release therapy, and physical barrier functions. DETAILED DESCRIPTION

[0030] The present invention provides a method for preparing a sustained-release antibacterial ophthalmic postoperative dressing, comprising the following steps:

[0031] Step 1) dropping tiny droplets of drug-containing sodium alginate solution formed in a high-voltage electrostatic field into a calcium chloride solution for solidification, and obtaining drug-loaded calcium alginate microspheres after washing;

[0032] Step 2), mixing N-vinyl caprolactam, methacrylic acid and water, adding methylene bisacrylamide and ammonium persulfate for micro-crosslinking to obtain poly (N-vinyl caprolactam) microgel, which is purified by dialysis and freeze-dried for later use;

[0033] Step 3) Dispersing poly(N-vinyl caprolactam) microgel in sodium alginate solution, adding drug-loaded calcium alginate microspheres and calcium chloride solution under magnetic stirring conditions for pre-crosslinking, then adding modified chitosan solution dropwise, and continuing to stir to obtain a sustained-release antibacterial ophthalmic postoperative dressing.

[0034] In the present invention, in step 1), the drug includes a growth factor, an antibiotic or an anti-inflammatory drug;

[0035] The concentration of the sodium alginate solution is 1-3 mg / mL, preferably 2 mg / mL; the concentration of the calcium chloride solution is 2-5 mg / mL, preferably 3 mg / mL.

[0036] In the present invention, as a preferred embodiment, in order to prevent the inactivation of the drug, a stabilizer is added to the calcium chloride solution, and the stabilizer is preferably mannitol.

[0037] In the present invention, the voltage of the high-voltage electrostatic field is 8 to 12 kV, preferably 10 kV; the needle diameter is preferably 0.4 mm; the receiving distance is 5 to 12 cm, preferably 8 cm; and the flow rate is 0.5 to 2 mL / h, preferably 1 mL / h.

[0038] In the present invention, in step 2), the molar ratio of N-vinylcaprolactam to methacrylic acid is 7 to 12:1, preferably 10:1;

[0039] The amount of methylene bisacrylamide added is 1 to 3% of the sum of the mass of N-vinyl caprolactam and methacrylic acid, preferably 2%;

[0040] The amount of ammonium persulfate added is 0.5-1% of the total mass of N-vinylcaprolactam and methacrylic acid, preferably 0.8%.

[0041] In the present invention, the poly(N-vinyl caprolactam) is temperature-sensitive. After adjusting the solution concentration, the lower critical solution temperature of the obtained microgel is in the range of 32 to 40°C. As the body temperature rises due to inflammation, the microgel will shrink, thereby avoiding sudden release of the drug.

[0042] In the present invention, in step 2), the micro-crosslinking is carried out in an inert gas atmosphere, the micro-crosslinking temperature is 50-70° C., preferably 60° C.; the micro-crosslinking time is 3-10 h, preferably 5-7 h, and more preferably 6 h.

[0043] In the present invention, in step 3), the concentration of the sodium alginate solution is 10-30 mg / mL, preferably 20 mg / mL; the concentration of the calcium chloride solution is 0.5-6 mg / mL, preferably 1-4 mg / mL, and more preferably 3 mg / mL.

[0044] In the present invention, in step 3), the amount of the drug-loaded calcium alginate microspheres added is 5-12 wt %, preferably 8-10 wt %, and more preferably 9 wt % of the mass of the poly(N-vinylcaprolactam) microgel.

[0045] In the present invention, the sodium alginate has good water absorption and is used to absorb wound exudate.

[0046] In the present invention, the phase change of the sodium alginate is affected by ions / pH. With the increase of calcium ion concentration in wound exudate and the influence of the pH value of the exudate, sodium alginate forms a denser calcium alginate network when encountering calcium, providing a sustained release effect of the drug in the middle and late stages.

[0047] In the present invention, in step 3), the pre-crosslinking temperature is 20-30°C, preferably 22-28°C, more preferably 24°C; the pre-crosslinking time is 8-20 min, preferably 10-18 min, more preferably 15 min.

[0048] In the present invention, in step 3), the concentration of the modified chitosan solution is 0.5 to 1.2 wt%, preferably 0.8 to 1 wt%;

[0049] The modified chitosan solution is obtained by dissolving chitosan in an acetic acid solution, wherein the concentration of the acetic acid solution is 0.8-1 wt%, preferably 0.8 wt%.

[0050] In the present invention, in step 3), the volume ratio of the modified chitosan solution to the sodium alginate solution is 1:0.5-2, preferably 1:1;

[0051] The dropwise acceleration rate of the modified chitosan solution is 2-5 mL / min, preferably 3 mL / min; the speed of the magnetic stirring is 300-600 rpm, preferably 400 rpm;

[0052] The stirring time is 20 to 40 minutes, preferably 30 minutes.

[0053] In the present invention, in the sustained-release antibacterial ophthalmic postoperative dressing, the volume ratio of poly(N-vinylcaprolactam) to sodium alginate is 1:0.8-1.3, preferably 1:1.

[0054] In the present invention, chitosan has natural broad-spectrum antibacterial properties and can inhibit early infection by destroying bacterial cell membranes, thereby reducing the risk of bacterial colonization in the early postoperative period.

[0055] The present invention provides a sustained-release antibacterial ophthalmic postoperative dressing prepared by the above-mentioned preparation method.

[0056] In the present invention, after the sustained-release antibacterial ophthalmic postoperative dressing of the present invention is applied to the wound, chitosan provides an initial antibacterial environment, and the drug-loaded calcium alginate microspheres are initially sustained-released due to the phase change of poly (N-vinyl caprolactam), and the calcium alginate microspheres release Ca 2+ It can enhance the positive charge density of chitosan and improve the efficiency of destroying bacterial membranes.

[0057] As chitosan is consumed and wound tissue fluid exudes, the drug-loaded calcium alginate microspheres come into contact with the wound exudate. The higher concentration of sodium ions in the exudate is exchanged with calcium ions in the drug-loaded calcium alginate microspheres to obtain sodium alginate and release drug components. Sodium alginate absorbs water and swells, forming a protective gel film with therapeutic effects on the wound.

[0058] With the release of calcium ions and the consumption of sodium in the microspheres, the exudate containing a higher concentration of calcium ions gradually penetrates into the gel, cross-links with the sodium alginate in the structure for the second time, forms a dense calcium alginate network, and releases the drug-loaded calcium alginate microspheres for the second time.

[0059] In the present invention, the simulated body fluid is MX0952-500ML (SBF) simulated body fluid sterile cell culture, purchased from Shanghai Maokang Biotechnology Co., Ltd.

[0060] The technical solutions provided by the present invention are described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0061] Example 1

[0062] 10 mg / mL tobramycin and 2 mg / mL sodium alginate aqueous solution were used as raw materials, 3 mg / mL CaCl2 aqueous solution was used as the receiver, a needle with an inner diameter of 200 μm was selected, the distance between the needle tip and the liquid surface of the CaCl2 solution was maintained at 20 cm, the electric field voltage was 10 kV, the flow rate was 1 mL / h, and after curing for 10 minutes, the microspheres were washed three times with deionized water and the water on the microspheres was filtered off with filter paper to obtain drug-loaded calcium alginate microspheres;

[0063] N-vinylcaprolactam and methacrylic acid at a molar ratio of 10:1 were dissolved in water, and then methylene bisacrylamide (2% of the total mass of N-vinylcaprolactam and methacrylic acid) and ammonium persulfate (0.8% of the total mass of N-vinylcaprolactam and methacrylic acid) were added. The mixture was micro-crosslinked at 60°C for 6 hours to obtain poly(N-vinylcaprolactam) microgel, which was purified by dialysis and freeze-dried at -80°C for 6 hours before use.

[0064] Under magnetic stirring at a speed of 600 rpm, poly(N-vinyl caprolactam) microgel was dispersed in a sodium alginate solution with a concentration of 30 mg / mL. Based on the mass of the microgel, 10 wt% of drug-loaded calcium alginate microspheres and a sufficient amount of calcium chloride solution with a concentration of 3 mg / mL were added. The mixture was pre-crosslinked at 20°C for 15 minutes to make the volume ratio of poly(N-vinyl caprolactam) microgel to sodium alginate be 1:1. Then, a modified chitosan solution with a concentration of 1.2 wt% (obtained by dissolving chitosan with a concentration of 1 wt% in an acetic acid solution) was added dropwise to the mixed system at a rate of 3 mL / min. The mixture was stirred for 30 minutes. After washing and drying, a sustained-release antibacterial ophthalmic postoperative dressing was obtained.

[0065] Example 2

[0066] 8 mg / mL tobramycin and 20 mg / mL sodium alginate aqueous solution were used as raw materials, 3 mg / mL CaCl2 aqueous solution was used as the receiver, a needle with an inner diameter of 200 μm was selected, the distance between the needle tip and the liquid surface of the CaCl2 solution was maintained at 20 cm, the electric field voltage was 12 kV, the flow rate was 1 mL / h, and the curing time was 10 min. After washing three times with deionized water, the water on the microspheres was filtered off with filter paper to obtain drug-loaded calcium alginate microspheres;

[0067] N-vinylcaprolactam and methacrylic acid at a molar ratio of 12:1 were dissolved in water, and then methylene bisacrylamide (1% of the total mass of N-vinylcaprolactam and methacrylic acid) and ammonium persulfate (0.8% of the total mass of N-vinylcaprolactam and methacrylic acid) were added. Micro-crosslinking was carried out at 56°C for 6 hours to obtain poly(N-vinylcaprolactam) microgel, which was purified by dialysis and freeze-dried at -80°C for 6 hours before use.

[0068] Under magnetic stirring at a speed of 400 rpm, poly (N-vinyl caprolactam) microgel was dispersed in a sodium alginate solution with a concentration of 30 mg / mL. Based on the mass of the microgel, 7 wt% of drug-loaded calcium alginate microspheres and a sufficient amount of calcium chloride solution with a concentration of 3 mg / mL were added. The mixture was pre-crosslinked at 20°C for 15 minutes so that the volume ratio of poly (N-vinyl caprolactam) microgel to sodium alginate was 1:1.15. Then, a modified chitosan solution with a concentration of 1 wt% (obtained by dissolving chitosan with a concentration of 1 wt% in an acetic acid solution) was added dropwise to the mixed system at a rate of 3 mL / min. The mixture was stirred for 30 minutes. After washing and drying, a sustained-release antibacterial ophthalmic postoperative dressing was obtained.

[0069] Example 3

[0070] Different from Example 1, in this example, the volume ratio of poly (N-vinyl caprolactam) microgel to sodium alginate in the gel is 1:1.3.

[0071] Example 4

[0072] Different from Example 1, in this example, the volume ratio of poly (N-vinyl caprolactam) microgel to sodium alginate in the gel is 1:0.8.

[0073] Comparative Example 1

[0074] Different from Example 1, in this comparative example, tobramycin was mixed in the form of a single drug with poly (N-vinyl caprolactam) microgel and sodium alginate solution to prepare a dressing.

[0075] Comparative Example 2

[0076] Different from Example 1, in this comparative example, the molar ratio of N-vinylcaprolactam to methacrylic acid is 5:1.

[0077] Comparative Example 3

[0078] Different from Example 1, in this comparative example, the volume ratio of poly (N-vinyl caprolactam) microgel to sodium alginate is 1:5.

[0079] Comparative Example 4

[0080] Different from Example 1, in this comparative example, the volume ratio of poly (N-vinyl caprolactam) microgel to sodium alginate is 3:1.

[0081] Drug sustained release experiment: The gel dressings obtained in Example 1 and Comparative Examples 1 to 4 were placed in simulated body fluid and subjected to in vitro drug release in a constant temperature oscillator at 36°C and 40 rpm. At specific time points, 1 mL of supernatant was collected and added to the same volume of fresh simulated body fluid. The tobramycin content was measured and the cumulative drug release rate was calculated.

[0082] Table 1 shows the cumulative drug release of the dressings obtained in Examples 1 to 4 and Comparative Examples 1 to 4 at specific times.

[0083] Table 1 Cumulative drug release of Examples 1 to 4 and Comparative Examples 1 to 4

[0084] 4h 12h 1d 5d 8d 12d Example 1 5.62％ 8.68％ 24.11％ 35.69％ 48.84％ 56.62％ Example 2 5.88％ 8.76％ 25.15％ 34.46％ 48.68％ 57.19％ Example 3 6.65％ 9.66％ 25.32％ 32.64％ 42.76％ 52.76％ Example 4 4.26％ 8.24％ 19.88％ 36.16％ 49..53％ 61.52％ Comparative Example 1 15.49％ 36.49％ 52.89％ 76.19％ 92.49％ 96.46％ Comparative Example 2 9.26％ 27.65％ 36.19％ 57.68％ 76.35％ 89.89％ Comparative Example 3 3.31％ 8.28％ 56.33％ 85.69％ 96.54％ 98.76％ Comparative Example 4 12.33％ 18.36％ 27.63％ 75.69％ 86.46％ 94.64％

[0085] As shown in Table 1, the sustained-release antibacterial ophthalmic postoperative dressing obtained in Example 1 has an excellent sustained-release effect. It can provide a stable and continuous recovery environment during the wound recovery period, and significantly reduces the risk of sudden release compared to the sustained-release gel in Comparative Example 1.

[0086] Comparative Example 2 shows that when preparing poly(N-vinyl caprolactam) microgel, the addition amount of the two monomers affects the gel structure of the poly(N-vinyl caprolactam) microgel. Compared with Example 1, its structure is looser and cannot achieve sustained release. In addition, the LCST is significantly different from the normal human body temperature, making temperature control impossible.

[0087] According to the comparison of Example 1, Example 3 and Example 4, it can be seen that as the volume distribution of poly (N-vinyl caprolactam) microgel and sodium alginate gel in the gel changes, the drug sustained release effect is also different. Comparative Examples 3 to 4 magnify the impact of this volume distribution change on the sustained release effect and burst release. In Comparative Example 3, the higher poly (N-vinyl caprolactam) microgel content played a greater sustained release effect in the early stage. However, due to the significant decrease in the overall hydrophilicity of the dressing, the gel drug loading rate decreased, and in the later stage of the experiment, the gel structure partially collapsed, causing irregular drug release. In Comparative Example 4, the excessively high proportion of sodium alginate made the gel absorb water and swell more significantly, resulting in a loose network structure, a decrease in mechanical strength, and an increase in the drug burst release effect. The low content of poly (N-vinyl caprolactam) microgel weakened the temperature response characteristics of the dressing, so a higher increase in drug release occurred in the early stage of the experiment.

[0088] As can be seen from the above embodiments, the present invention provides a sustained-release antibacterial ophthalmic postoperative dressing and a preparation method thereof. The present invention uses poly (N-vinyl caprolactam) and sodium alginate to jointly construct a gel system, coats the drug molecules with calcium alginate gel, and loads them in the gel in the form of a core-shell structure, and grafts chitosan with antibacterial effect on the outside of the gel. During the wound recovery period, the sustained-release antibacterial dressing of the present invention produces an initial antibacterial effect through the chitosan on the outside, while the thermosensitive poly (N-vinyl caprolactam) produces a slight phase change within the human body temperature range, so that the sustained release of the drug molecules has thermosensitive adjustability. The composite architecture of core-shell loading + outer grafting simultaneously achieves rapid antibacterial, sustained-release therapy and physical barrier functions, solving the technical problems of traditional ophthalmic dressings with short antibacterial time, uncontrollable drug release and insufficient biocompatibility.

[0089] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. A method for preparing a sustained-release antibacterial ophthalmic postoperative dressing, characterized in that: The following steps are involved: Step 1) dropping tiny droplets of drug-containing sodium alginate solution formed in a high-voltage electrostatic field into a calcium chloride solution for solidification, and obtaining drug-loaded calcium alginate microspheres after washing; Step 2), mixing N-vinyl caprolactam, methacrylic acid and water, adding methylene bisacrylamide and ammonium persulfate for micro-crosslinking to obtain poly (N-vinyl caprolactam) microgel, which is purified by dialysis and freeze-dried for later use; Step 3) Dispersing poly(N-vinyl caprolactam) microgel in sodium alginate solution, adding drug-loaded calcium alginate microspheres and calcium chloride solution under magnetic stirring conditions for pre-crosslinking, then adding modified chitosan solution dropwise, and continuing to stir to obtain a sustained-release antibacterial ophthalmic postoperative dressing.

2. The method for preparing a sustained-release antibacterial ophthalmic postoperative dressing according to claim 1, characterized in that: In step 1), the drug includes a growth factor, an antibiotic or an anti-inflammatory drug; The concentration of the sodium alginate solution is 1-3 mg / mL, and the concentration of the calcium chloride solution is 2-5 mg / mL.

3. The method for preparing a sustained-release antibacterial ophthalmic postoperative dressing according to claim 2, characterized in that: In step 2), the molar ratio of N-vinylcaprolactam to methacrylic acid is 7 to 12:1; The amount of methylene bisacrylamide added is 1 to 3% of the sum of the mass of N-vinyl caprolactam and methacrylic acid; The amount of ammonium persulfate added is 0.5-1% of the total mass of N-vinylcaprolactam and methacrylic acid.

4. The method for preparing a sustained-release antibacterial ophthalmic postoperative dressing according to claim 2 or 3, characterized in that: In step 2), the micro-crosslinking is carried out in an inert gas atmosphere, the micro-crosslinking temperature is 50-70° C., and the micro-crosslinking time is 3-10 hours.

5. The method for preparing a sustained-release antibacterial ophthalmic postoperative dressing according to claim 4, characterized in that: In step 3), the concentration of the sodium alginate solution is 10-30 mg / mL, and the concentration of the calcium chloride solution is 0.5-6 mg / mL.

6. The method for preparing a sustained-release antibacterial ophthalmic postoperative dressing according to claim 1 or 5, characterized in that: In step 3), the amount of the drug-loaded calcium alginate microspheres added is 5 to 12 wt% of the mass of the poly(N-vinyl caprolactam) microgel.

7. The method for preparing a sustained-release antibacterial ophthalmic postoperative dressing according to claim 6, characterized in that: In step 3), the pre-crosslinking temperature is 20-30° C., and the pre-crosslinking time is 8-20 minutes.

8. The method for preparing a sustained-release antibacterial ophthalmic postoperative dressing according to claim 1, 5 or 7, characterized in that: In step 3), the concentration of the modified chitosan solution is 0.5 to 1.2 wt%; The modified chitosan solution is obtained by dissolving chitosan in an acetic acid solution, wherein the concentration of the acetic acid solution is 0.8-1 wt %.

9. The method for preparing a sustained-release antibacterial ophthalmic postoperative dressing according to claim 8, characterized in that: In step 3), the volume ratio of the modified chitosan solution to the sodium alginate solution is 1:0.5-2; The modified chitosan solution is added at a rate of 2 to 5 mL / min and a magnetic stirring speed of 300 to 600 rpm; The stirring time is 20 to 40 minutes; The volume ratio of poly(N-vinyl caprolactam) microgel to sodium alginate in the sustained-release antibacterial ophthalmic postoperative dressing is 1:0.8-1.

3.

10. The sustained-release antibacterial ophthalmic postoperative dressing prepared by the preparation method according to any one of claims 1 to 9.