Positionable injection type hydrogel lacrimal passage embolism as well as preparation method and application thereof

Abstract

The invention discloses a positionable injection type hydrogel lacrimal passage embolism as well as a preparation method and application thereof. The hydrogel lacrimal passage embolism comprises the following components by mass concentration: 78 to 80 g / L of methacrylated sericin SerMA, 0.2 to 0.22 g / L of fluorescence localization nanoparticles FTN and 3.7 to 4 g / L of a photoinitiator LAP. The hydrogel lacrimal passage embolism is used for treating xerophthalmia. According to the locatable injection type hydrogel lacrimal passage suppository, methylacryloyl sericin SerMA is selected as one of raw materials, the locatable injection type hydrogel lacrimal passage suppository has good biocompatibility while having good mechanical properties, complications are reduced, non-contact positioning and degradation condition monitoring of the lacrimal passage suppository in a living body state are achieved through FTN particles, and the locatable injection type hydrogel lacrimal passage suppository has good application prospects. The problem that whether the lacrimal passage plug falls off or is degraded or not cannot be monitored due to the fact that the lacrimal passage structure is bent and hidden clinically is solved, and meanwhile, whether the lacrimal passage plug is dislocated or not can be detected in a non-invasive mode by adding the indocyanine green nanoparticles.

Description

Technical Field

[0001] The invention relates to the technical field of ophthalmic medical devices, and in particular to a positionable injectable hydrogel lacrimal duct plug and a preparation method and an application method thereof. Background Art

[0002] Dry eyes are a common chronic ocular surface disease in clinical practice, which can cause discomfort symptoms such as dry eyes, foreign body sensation, blurred vision, etc., seriously affecting the normal work and life of patients. Dry eyes are also related to the incidence of diseases such as migraine and chronic fatigue syndrome.

[0003] Tear duct embolism can treat dry eyes by blocking the tear duct, reducing tear loss, and prolonging the time tears stay on the ocular surface. Studies have shown that tear duct embolism can effectively improve the symptoms of dry eye patients, prolong the tear film breakup time, reduce corneal fluorescent staining, significantly reduce the frequency of artificial tear use, and effectively treat moderate to severe dry eyes. The International Dry Eye Working Group and the American Academy of Ophthalmology recommend it as one of the important methods for treating moderate to severe dry eyes.

[0004] Currently, most tear duct plug products on the market are made of artificial synthetic polymers such as silicone, acrylic polymers, and polydioxanone, or collagen, and are specifically designed for fixed shapes. However, the shape of each person's tear duct is not exactly the same, and the pre-formed tear duct plug / punctal plug does not completely match the tear duct, and the probability of spontaneous displacement and dislocation is as high as 50%. At the same time, artificial synthetic polymers have poor biocompatibility and are prone to cause complications such as irritation symptoms, infection, allergies, and granulomas; although collagen has good biocompatibility, its degradation time is only a few days, which cannot meet the long-term treatment needs of dry eye patients. In addition, the existing tear duct plugs cannot be detected in a non-invasive way to determine whether they are dislocated, and cannot guide clinical re-implantation.

[0005] Patent CN111773178A discloses a hydrogel lacrimal duct plug and a preparation method thereof. The hydrogel lacrimal duct plug is a hydrogel plug of a size that can pass through the lacrimal point, which contains a dehydrated hydrophilic polymer hydrogel. After the dry gel absorbs physiological water, it expands to at least 2 times in cross-sectional width to expand the plug and can be placed in the lacrimal duct. The hydrogel lacrimal duct plug can be used as a drug delivery system. The gel is dried once at room temperature to a suitable state and then taken out and placed at room temperature. The production process conditions are mild, and the tensile properties of the prepared gel are greatly improved, reducing the probability of breakage during the stretching process and improving production efficiency. The lacrimal duct plug product does not contain bubbles, has a smooth appearance, uniform and stable quality, good in vivo compliance, and a degradation cycle of up to 180 days or more. It can be used as a device for treating dry eye, improving the ocular surface environment, and alleviating dry eye symptoms. However, the dry gel expands to at least 2 times in cross-sectional width after absorbing physiological water, which produces a large expansion of the lacrimal duct of different patients, which may cause problems such as damage to the lacrimal duct. Summary of the invention

[0006] In view of the above-mentioned problems, the present invention provides a positionable injectable hydrogel lacrimal duct plug and a preparation method and application thereof.

[0007] The technical solution of the present invention is:

[0008] A locatable injectable hydrogel lacrimal duct plug comprises, by mass concentration, 78-80 g / L methacrylylated sericin SerMA, 0.2-0.22 g / L fluorescent locatable nanoparticles FTN and 3.7-4 g / L photoinitiator LAP.

[0009] The present invention also discloses a method for preparing the above-mentioned positionable injectable hydrogel lacrimal duct plug, comprising the following steps:

[0010] S1. Preparation of methacryloyl sericin SerMA: silkworm cocoons were heated in a Na2CO3 solution with a molar concentration of 0.02 M for 2 times, each heating reaction time was 1 to 1.5 h, and the heating reaction temperature was 80 to 100°C. The liquid was filtered and dialyzed for 2 to 3 days to remove calcium carbonate, and then the liquid was freeze-dried to obtain solid sericin. The solid sericin was dissolved in a PBS solution, and then glycidyl methacrylate was added. The solution was stirred at room temperature for 10 to 12 h to fully dissolve, and then dialyzed for 7 to 8 days to obtain a methacryloyl sericin SerMA solution. The ratio of solid sericin, PBS solution and glycidyl methacrylate was 5 g: 20 mL: 1 mL.

[0011] S2. Preparation of fluorescent localization nanoparticles FTN: adding indocyanine green ICG to the methacryloyl sericin SerMA solution with a mass concentration of 100 g / L, then dropping it into an acetone solution, stirring at room temperature for 10 to 12 hours to obtain a mixed solution, centrifuging the mixed solution to remove acetone, placing the remaining mixture in distilled water for ultrasonic treatment for 15 to 20 minutes to obtain a secondary mixed solution, ultrafiltering the secondary mixed solution and freeze-drying it to obtain fluorescent localization nanoparticles FTN, the ratio of indocyanine green ICG, methacryloyl sericin SerMA solution and acetone solution is 0.2 g: 5 mL: 12 mL;

[0012] S3. Preparation of viscosity factor: dissolve 3-methacryloyl dopamine in dimethyl sulfoxide solution at a ratio of 1 mg:1 ul to obtain a viscosity factor;

[0013] S4, mixing and molding: dissolving the fluorescent positioning nanoparticles FTN in deionized water to obtain a fluorescent positioning nanoparticle FTN solution with a mass concentration of 2 to 2.3 g / L, mixing the methacryloyl sericin SerMA solution with a mass concentration of 96 to 100 g / L and the fluorescent positioning nanoparticle FTN solution with a mass concentration of 1.8 to 2 g / L in a volume ratio of 8 to 10:1, adding the viscosity factor prepared in step S3, controlling the molar concentration of the viscosity factor to be 1 to 1.05 m / mL, and then adding 1 volume of a photoinitiator LAP solution with a mass concentration of 37 to 40 g / L. After mixing completely, 0.2 mL of a mixed solution of methacryloyl sericin SerMA, fluorescent positioning nanoparticles FTN, and photoinitiator LAP is obtained, and the mixed solution is irradiated with blue light for 1 min to form a hydrogel lacrimal duct plug.

[0014] Furthermore, in step S1, the addition ratio of silkworm cocoons to Na2CO3 solution is 4-6 g:2 L.

[0015] Note: By optimizing the weight ratio of silkworm cocoons to Na2CO3 solution, the silkworm cocoons are completely dissolved, which is beneficial to the preparation of methacrylylated sericin SerMA.

[0016] Furthermore, the interval between the two heating reactions in step S1 is 0.5 to 1 hour, and after the first heating reaction is completed, the temperature is allowed to stand and cool to below 40°C.

[0017] Furthermore, the specification of the dialysis bag in step S1 is a regenerated cellulose ester membrane Mwco3.5kDa×MD45mm.

[0018] Description: The purity of methacryloyl sericin SerMA is improved by optimizing the specifications of the dialysis bag and the filter pore size.

[0019] Furthermore, the molar concentration of the acetone solution in step S2 is 13.5M.

[0020] Furthermore, in step S2, the room temperature is 25-28° C., the stirring speed is 300-400 rpm, the centrifugal speed is 3500-5000 rpm, the amplitude of the ultrasonic treatment is 200 W, and the ultrasonic pulses are 1s ON and 1s OFF.

[0021] Note: The dispersion effect is further improved by using the pulse ultrasonic treatment method, making the prepared fluorescent positioning nanoparticles FTN more uniform.

[0022] Furthermore, in step S4, the mixed solution of methacrylylated sericin SerMA, fluorescent localization nanoparticles FTN, and photoinitiator LAP is 0.2-0.25 mL.

[0023] The present invention also discloses application of the above-mentioned positionable injectable hydrogel lacrimal duct plug, and the hydrogel lacrimal duct plug is used for treating dry eye.

[0024] The beneficial effects of the present invention are:

[0025] (1) The method for preparing a locatable injectable hydrogel tear duct plug of the present invention uses methacryloyl sericin SerMA as the main raw material. The main material has better viscosity. After being injected into the tear duct, it forms a hydrogel in situ through blue light irradiation. The prepared tear duct plug completely matches the shape of the tear duct, reducing the shedding rate. At the same time, by adding the viscosity factor dopamine derivative, the formed tear duct plug adheres more tightly to the inner wall of the tear duct, providing triple insurance to reduce the shedding rate.

[0026] (2) The present invention provides a locatable injectable hydrogel lacrimal duct plug that uses FTN particles to achieve non-contact positioning and degradation monitoring of the lacrimal duct plug in a living state, thereby resolving the difficulty of being unable to monitor whether the lacrimal duct plug has fallen off or degraded due to the curved and hidden structure of the lacrimal duct, and achieving non-invasive detection and positioning of the lacrimal punctum plug.

[0027] (3) The present invention is a locatable injectable hydrogel lacrimal duct plug that uses methacryloyl sericin SerMA as one of its raw materials. It has good mechanical properties and good biocompatibility, which can reduce the occurrence of complications such as scars, foreign body granulomas, and dacryocystitis in the lacrimal duct. At the same time, the addition of indocyanine green nanoparticles has photothermal antibacterial and antibacterial functions, which can inhibit the synthesis of bacterial cell walls and destroy the structure of bacterial cell membranes. It has better antibacterial properties and reduces the incidence of lacrimal duct plug-related infections. Ultimately, an injectable degradable lacrimal duct plug with in vivo positioning and antibacterial effects is developed, which can improve the symptoms and signs of dry eyes in patients and reduce local complications, and is expected to provide a safer and more effective solution for the clinical treatment of dry eyes.

[0028] (4) The use of the locatable injectable hydrogel lacrimal duct plug of the present invention can effectively prolong the residence time of the lacrimal duct plug in the patient's lacrimal duct when treating dry eye syndrome, with a low rate of dislodgmentation and good use effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 This is a schematic diagram of a positionable injectable hydrogel lacrimal duct plug before injection;

[0030] Figure 2 It is a schematic diagram of the injection site of a locatable injectable hydrogel lacrimal duct plug of the present invention;

[0031] Figure 3 It is a schematic diagram of a positionable injectable hydrogel lacrimal duct plug of the present invention during lacrimal duct injection;

[0032] Figure 4 It is a schematic diagram of a locatable injectable hydrogel lacrimal duct plug of the present invention during blue light irradiation in step S3. DETAILED DESCRIPTION

[0033] Example 1

[0034] A locatable injectable hydrogel lacrimal duct plug comprises, by mass concentration, 80 g / L methacrylylated sericin SerMA, 0.2 g / L fluorescent locatable nanoparticles FTN and 4 g / L photoinitiator LAP.

[0035] Example 2

[0036] A positionable injectable hydrogel lacrimal duct plug comprises, by mass concentration, 78 g / L methacrylylated sericin SerMA, 0.21 g / L fluorescent positioning nanoparticles FTN and 3.8 g / L photoinitiator LAP.

[0037] Example 3

[0038] A positionable injectable hydrogel lacrimal duct plug comprises, by mass concentration, 79 g / L methacrylylated sericin SerMA, 0.22 g / L fluorescent positioning nanoparticles FTN and 3.7 g / L photoinitiator LAP.

[0039] Example 4

[0040] This embodiment is a method for preparing a locatable injectable hydrogel lacrimal duct plug based on the embodiment 1, comprising the following steps:

[0041] S1. Preparation of methacryloyl sericin SerMA: silkworm cocoons were heated in a Na2CO3 solution for two times, each time for 1.2 hours at 90°C, with an interval of 0.75 hours between the two heating reactions. After the first heating reaction, the cocoons were allowed to stand and cooled to 35°C. The molar concentration of the Na2CO3 solution was 0.02M, and the ratio of silkworm cocoons to the Na2CO3 solution was 5g:2L. The liquid was filtered and dialyzed for 2 days to remove calcium carbonate, and then the liquid was freeze-dried to obtain solid sericin. The solid sericin was dissolved in a PBS solution, and then glycidyl methacrylate was added. The solution was stirred at room temperature for 12 hours to fully dissolve and then dialyzed for 8 days to obtain a methacryloyl sericin SerMA solution. The ratio of solid sericin, PBS solution and glycidyl methacrylate was 5g:20mL:1mL. The specification of the dialysis bag was a regenerated cellulose ester membrane Mwco3.5kDa×MD45mm.

[0042] S2. Preparation of fluorescent localization nanoparticles FTN: 0.2 g of indocyanine green ICG was added to 5 mL of methacryloyl sericin SerMA solution with a mass concentration of 100 g / L, and then added dropwise to 12 mL of acetone solution with a molar concentration of 13.5 M. The mixture was stirred for 12 h at room temperature (26° C.) and a stirring speed of 350 rpm to obtain a mixed solution. The mixed solution was centrifuged to remove acetone at a centrifugal speed of 4000 rpm. The remaining mixture was placed in distilled water for ultrasonic treatment for 20 min at an amplitude of 200 W and ultrasonic pulses of 1sON and 1sOFF to obtain a secondary mixed solution. The secondary mixed solution was ultrafiltered and freeze-dried to obtain fluorescent localization nanoparticles FTN.

[0043] S3. Preparation of viscosity factor: dissolve 3-methacryloyl dopamine in dimethyl sulfoxide solution at a ratio of 1 mg:1 ul to obtain a viscosity factor;

[0044] S4, mixing and molding: dissolve the fluorescent positioning nanoparticles FTN in deionized water to obtain a fluorescent positioning nanoparticle FTN solution with a mass concentration of 2.1 g / L, mix the methacryloyl sericin SerMA solution with a mass concentration of 98 g / L and the fluorescent positioning nanoparticle FTN solution with a mass concentration of 1.9 g / L in a volume ratio of 9:1, add the viscosity factor prepared in step S3, control the molar concentration of the viscosity factor to be 1.02 m / mL, and then add 1 volume of a photoinitiator LAP solution with a mass concentration of 38 g / L. After complete mixing, 0.23 mL of a mixed solution of methacryloyl sericin SerMA, fluorescent positioning nanoparticles FTN, and photoinitiator LAP is obtained, and the mixed solution is irradiated with blue light for 1 min to form a hydrogel lacrimal duct plug.

[0045] Example 5

[0046] The difference between this embodiment and embodiment 4 is that the specific parameters in steps S1 and S2 are different.

[0047] S1. Preparation of methacryloyl sericin SerMA: silkworm cocoons were heated in a Na2CO3 solution for two times, each time for 1.5 hours at 80°C, with an interval of 0.5 hours between the two heating reactions. After the first heating reaction, the cocoons were allowed to stand and cooled to below 40°C. The molar concentration of the Na2CO3 solution was 0.02M, and the ratio of silkworm cocoons to the Na2CO3 solution was 4g:2L. The liquid was filtered and dialyzed for 2 days to remove calcium carbonate, and then the liquid was freeze-dried to obtain solid sericin. The solid sericin was dissolved in a PBS solution, and then glycidyl methacrylate was added. The solution was stirred at room temperature for 10 hours to fully dissolve, and then dialyzed for 7 days to obtain a methacryloyl sericin SerMA solution. The ratio of solid sericin, PBS solution and glycidyl methacrylate was 5g:20mL:1mL, and the specification of the dialysis bag was a regenerated cellulose ester membrane Mwco3.5kDa×MD45mm.

[0048] S2. Preparation of fluorescent localization nanoparticles FTN: Add 0.2 g of indocyanine green ICG to 5 mL of methacryloyl sericin SerMA solution with a mass concentration of 99 g / L, and then add it dropwise into 12 mL of acetone solution with a molar concentration of 13.5 M. Stir for 12 h at room temperature (28°C) and a stirring speed of 400 rpm to obtain a mixed solution. Centrifuge the mixed solution to remove acetone at a centrifugal speed of 5000 rpm. Place the remaining mixture in distilled water and ultrasonically treat it for 20 min. The amplitude of the ultrasonic treatment is 200 W, and the ultrasonic pulses are 1sON and 1sOFF to obtain a secondary mixed solution. Ultrafilter the secondary mixed solution and freeze-dry it to obtain fluorescent localization nanoparticles FTN.

[0049] Example 6

[0050] The difference between this embodiment and Embodiment 1 is that the specific parameters in steps S1 and S2 are different.

[0051] S1. Preparation of methacryloyl sericin SerMA: silkworm cocoons were heated in a Na2CO3 solution for two times, each time for 1 hour, the heating reaction temperature was 100°C, the interval between the two heating reactions was 1 hour, after the first heating reaction, the cocoons were allowed to stand and cooled to below 40°C, the molar concentration of the Na2CO3 solution was 0.02M, the addition ratio of silkworm cocoons to the Na2CO3 solution was 6g:2L, the liquid was filtered and dialyzed for 3 days to remove calcium carbonate, and then the liquid was freeze-dried to obtain solid sericin, the solid sericin was dissolved in a PBS solution, and then glycidyl methacrylate was added, stirred at room temperature for 12 hours to fully dissolve, and then dialyzed for 8 days to obtain a methacryloyl sericin SerMA solution, the ratio of solid sericin, PBS solution and glycidyl methacrylate was 5g:20mL:1mL, and the specification of the dialysis bag was a regenerated cellulose ester membrane Mwco3.5kDa×MD45mm;

[0052] S2. Preparation of fluorescent localization nanoparticles FTN: Add 0.2 g of indocyanine green ICG to 5 mL of methacryloyl sericin SerMA solution with a mass concentration of 96 g / L, and then add it dropwise into 12 mL of acetone solution with a molar concentration of 13.5 M. Stir for 12 h at room temperature (28°C) and a stirring speed of 400 rpm to obtain a mixed solution. Centrifuge the mixed solution to remove acetone at a centrifugal speed of 5000 rpm. Place the remaining mixture in distilled water and ultrasonically treat it for 20 min. The amplitude of the ultrasonic treatment is 200 W, and the ultrasonic pulses are 1sON and 1sOFF to obtain a secondary mixed solution. Ultrafilter the secondary mixed solution and freeze-dry it to obtain fluorescent localization nanoparticles FTN.

[0053] Example 7

[0054] The difference between this embodiment and Embodiment 1 is that the specific parameters in step S4 are different.

[0055] S4, mixing and molding: dissolve the fluorescent positioning nanoparticles FTN in deionized water to obtain a fluorescent positioning nanoparticle FTN solution with a mass concentration of 2 g / L, mix the methacryloyl sericin SerMA solution with a mass concentration of 96 g / L and the fluorescent positioning nanoparticle FTN solution with a mass concentration of 1.8 g / L in a volume ratio of 8:1, add the viscosity factor prepared in step S3, control the molar concentration of the viscosity factor to be 1 m / mL, and then add 1 volume of a photoinitiator LAP solution with a mass concentration of 37 g / L. After complete mixing, 0.2 mL of a mixed solution of methacryloyl sericin SerMA, fluorescent positioning nanoparticles FTN, and photoinitiator LAP is obtained, and the mixed solution is irradiated with blue light for 1 min to form a hydrogel lacrimal duct plug.

[0056] Example 8

[0057] The difference between this embodiment and Embodiment 1 is that the specific parameters in step S4 are different.

[0058] S4, mixing and molding: dissolve the fluorescent positioning nanoparticles FTN in deionized water to obtain a fluorescent positioning nanoparticle FTN solution with a mass concentration of 2.3 g / L, mix the methacryloyl sericin SerMA solution with a mass concentration of 100 g / L and the fluorescent positioning nanoparticle FTN solution with a mass concentration of 2 g / L in a volume ratio of 10:1, add the viscosity factor prepared in step S3, control the molar concentration of the viscosity factor to be 1.05 m / mL, and then add 1 volume of a photoinitiator LAP solution with a mass concentration of 40 g / L. After mixing completely, 0.25 mL of a mixed solution of methacryloyl sericin SerMA, fluorescent positioning nanoparticles FTN, and photoinitiator LAP is obtained, and the mixed solution is irradiated with blue light for 1 min to form a hydrogel lacrimal duct plug.

[0059] Example 9

[0060] This embodiment is an application of a locatable injectable hydrogel lacrimal duct plug in Embodiment 1, and the hydrogel lacrimal duct plug is used for the treatment of dry eye.

[0061] Experimental example

[0062] The effect of the locatable injectable hydrogel tear duct plug of the present invention was tested below. 20 patients with dry eye were used as test subjects for the test. It was found that after the hydrogel tear duct plug was implanted in 43 patients according to the method of the present invention, the dry eye began to be significantly alleviated within 1 to 2 weeks, and in the subsequent process, infrared detection could be used to quickly and non-destructively detect whether the hydrogel tear duct plug was dislodged. It was observed that from the first week, the dry eye symptoms of all patients were improved; only one patient had the hydrogel tear duct plug fall off and be lost at the 7th to 8th week, and the rest of the patients kept the hydrogel tear duct plug in the tear duct. At the 12th week, 2 patients had the hydrogel tear duct plug dislodged, which may be related to the patient's own eye structure. At the 6th month, all hydrogel tear duct plugs were completely degraded, and no side effects such as infection occurred during the treatment.

Claims

1. A locatable injectable hydrogel lacrimal duct plug, characterized in that: Calculated by mass concentration, it includes 78-80 g / L methacrylylated sericin SerMA, 0.2-0.22 g / L fluorescent positioning nanoparticles FTN and 3.7-4 g / L photoinitiator LAP.

2. The method for preparing a locatable injectable hydrogel lacrimal duct plug according to claim 1, characterized in that: The following steps are involved: S1. Preparation of methacryloyl sericin SerMA: silkworm cocoons were heated in a Na2CO3 solution with a molar concentration of 0.02 M for 2 times, each heating reaction time was 1 to 1.5 h, and the heating reaction temperature was 80 to 100°C. The liquid was filtered and dialyzed for 2 to 3 days to remove calcium carbonate, and then the liquid was freeze-dried to obtain solid sericin. The solid sericin was dissolved in a PBS solution, and then glycidyl methacrylate was added. The solution was stirred at room temperature for 10 to 12 h to fully dissolve, and then dialyzed for 7 to 8 days to obtain a methacryloyl sericin SerMA solution. The ratio of solid sericin, PBS solution and glycidyl methacrylate was 5 g: 20 mL: 1 mL. S2. Preparation of fluorescent localization nanoparticles FTN: adding indocyanine green ICG to the methacryloyl sericin SerMA solution with a mass concentration of 100 g / L, then dropping it into an acetone solution, stirring at room temperature for 10 to 12 hours to obtain a mixed solution, centrifuging the mixed solution to remove acetone, placing the remaining mixture in distilled water for ultrasonic treatment for 15 to 20 minutes to obtain a secondary mixed solution, ultrafiltering the secondary mixed solution and freeze-drying it to obtain fluorescent localization nanoparticles FTN, the ratio of indocyanine green ICG, methacryloyl sericin SerMA solution and acetone solution is 0.2 g: 5 mL: 12 mL; S3. Preparation of viscosity factor: dissolve 3-methacryloyl dopamine in dimethyl sulfoxide solution at a ratio of 1 mg:1 ul to obtain a viscosity factor; S4, mixing and molding: dissolving the fluorescent positioning nanoparticles FTN in deionized water to obtain a fluorescent positioning nanoparticle FTN solution with a mass concentration of 2 to 2.3 g / L, mixing the methacryloyl sericin SerMA solution with a mass concentration of 96 to 100 g / L and the fluorescent positioning nanoparticle FTN solution with a mass concentration of 1.8 to 2 g / L in a volume ratio of 8 to 10:1, adding the viscosity factor prepared in step S3, controlling the molar concentration of the viscosity factor to be 1 to 1.05 m / mL, and then adding 1 volume of a photoinitiator LAP solution with a mass concentration of 37 to 40 g / L. After mixing completely, a mixed solution of methacryloyl sericin SerMA, fluorescent positioning nanoparticles FTN, and photoinitiator LAP is obtained, and the mixed solution is irradiated with blue light for 1 min to form a hydrogel lacrimal duct plug.

3. The method for preparing a locatable injectable hydrogel lacrimal duct plug according to claim 2, characterized in that: In the step S1, the addition ratio of silkworm cocoons to Na2CO3 solution is 4-6 g:2 L.

4. The method for preparing a locatable injectable hydrogel lacrimal duct plug according to claim 2, characterized in that: The interval between the two heating reactions in step S1 is 0.5 to 1 hour, and after the first heating reaction is completed, the temperature is allowed to stand and cool to below 40° C.

5. The method for preparing a locatable injectable hydrogel lacrimal duct plug according to claim 2, characterized in that: The molar concentration of the acetone solution in step S2 is 13.5M.

6. The method for preparing a locatable injectable hydrogel lacrimal duct plug according to claim 2, characterized in that: In step S2, the room temperature is 25-28° C., the stirring speed is 300-400 rpm, the centrifugal speed is 3500-5000 rpm, the amplitude of ultrasonic treatment is 200 W, and the ultrasonic pulse is 1s ON and 1s OFF.

7. The use of a positionable injectable hydrogel lacrimal duct plug according to claim 1, characterized in that: In the step S4, the mixed solution of methacrylylated sericin SerMA, fluorescent localization nanoparticles FTN, and photoinitiator LAP is 0.2-0.25 mL.

8. The use of a positionable injectable hydrogel lacrimal duct plug according to claim 1, characterized in that: The hydrogel tear duct plug is used for treating dry eye.

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