Magnetic nano eyedrops for adjuvant treatment of lacrimal passage obstruction and preparation method and application of magnetic nano eyedrops

Abstract

The invention discloses magnetic nano eyedrops for adjuvant treatment of lacrimal passage obstruction and a preparation method and application thereof, and every 100 mL of eyedrops comprise the following raw materials: 3-5 g of magnetic nanoparticles, 0.3-0.6 g of a buffering agent, 0.3-0.6 g of an antioxidant, 0.2-0.5 g of an osmotic pressure regulator, and the balance of a solvent. According to the magnetic nano eyedrops, the buffering agent, the antioxidant and the osmotic pressure regulator are accurately controlled, meanwhile, a proper amount of the pH regulator is added, the pH value of the eyedrops is stabilized between 7 and 7.5, the osmotic pressure is maintained between 295 mOsm / l and 309 mOsm / l, the pH value is highly consistent with the physiological environment of human tears, the stability of the eyedrops is guaranteed, and the magnetic nano eyedrops are suitable for being used as eye drops. Eye stimulation or discomfort caused by deviation of the pH value or osmotic pressure is effectively avoided, and the safety and comfort of treatment are further improved.

Description

Technical Field

[0001] The present invention belongs to the technical field of eye drops, and particularly relates to a magnetic nano eye drop for assisting in the treatment of lacrimal duct obstruction, its preparation method and application. Background Art

[0002] Lacrimal duct obstruction is a common ophthalmic disease. The main clinical manifestations of this disease include epiphora, swelling in the lacrimal sac area, and symptoms such as eyelid redness and swelling, and purulent secretions. In severe cases, it may affect vision and quality of life. Research shows that about 90% of lacrimal duct obstructions are due to the failure of the Hasner valve at the lower end of the nasolacrimal duct to open in time after birth, resulting in the obstruction of tear drainage.

[0003] At present, the treatment methods for dacryocystitis mainly include conservative treatment and surgical intervention. Conservative treatment usually involves lacrimal sac massage and the use of antibiotic eye drops. However, this method has problems such as insufficient standardized operation and a long treatment cycle, often resulting in poor patient compliance and limited treatment effects, thus bringing additional psychological burdens to the parents of patients. Surgical intervention, especially lacrimal duct probing, has been proven to be a rapid and effective method for treating lacrimal duct obstruction, and its success rate can be as high as over 95%. However, surgery also has some disadvantages: First, the surgery needs to be performed by professional medical staff in the hospital; second, as an invasive operation, improper operation may cause iatrogenic damage to the lacrimal duct and there is a risk of inducing systemic infection after surgery; in addition, the patient needs to be pressed during local anesthesia, which may cause discomfort and fear, and there may be pain during the surgery. General anesthesia may increase the anesthesia risk and economic burden.

[0004] Therefore, there is an urgent need in clinical practice for a safe, painless, non-invasive treatment method that does not require professional skills to improve treatment compliance, reduce the consumption of medical resources, and provide better medical services for the majority of patients. Summary of the Invention

[0005] Aiming at the deficiencies of the prior art, the purpose of the present invention is to provide a magnetic nano eye drop for assisting in the treatment of lacrimal duct obstruction, its preparation method and application.

[0006] To achieve the above purpose, the present invention provides the following technical solutions:

[0007] A magnetic nano eye drop for assisting in the treatment of lacrimal duct obstruction, in every 100 mL of the eye drop, includes the following raw materials:

[0008] 3 - 5 g of magnetic nanoparticles, 0.3 - 0.6 g of buffer, 0.3 - 0.6 g of antioxidant, 0.2 - 0.5 g of osmotic pressure regulator, and the balance is solvent.

[0009] Preferably, a magnetic nano-eye drop for adjuvant treatment of lacrimal duct obstruction, in every 100 mL of the eye drop, there are 4 - 5 g of magnetic nanoparticles, 0.3 - 0.5 g of buffer, 0.4 - 0.6 g of antioxidant, 0.2 - 0.4 g of osmotic pressure regulator, and the balance is solvent.

[0010] In the present invention, by precisely controlling the dosages of the buffer, antioxidant, and osmotic pressure regulator in this magnetic nano-eye drop, and adding an appropriate amount of pH regulator at the same time, the pH value of the eye drop is stabilized at about 7.5, and the osmotic pressure is maintained at 295 - 309 mOsm / l, which is highly consistent with the physiological environment of human tears. This not only ensures the stability of the eye drop, but also effectively avoids eye irritation or discomfort caused by pH value or osmotic pressure deviation, further improving the safety and comfort of treatment.

[0011] Preferably, the buffer is sodium dihydrogen phosphate, the antioxidant is sodium tartrate, the osmotic pressure regulator is sodium chloride, the solvent is injection water, and the pH regulator is 0.1 mol / L sodium hydroxide solution.

[0012] Preferably, the osmotic pressure of the eye drop is 295 - 309 mOsm / l.

[0013] Preferably, the preparation method of the magnetic nanoparticles includes the following steps:

[0014] S1. Add FeCl3·6H2O solution, FeCl2·4H2O, dextran, and deionized water into a reaction flask protected by inert gas, then add ammonia water, and carry out stirring reaction. After the reaction is completed, centrifuge and remove the precipitate, and transfer the supernatant to an ultrafiltration tube for ultrafiltration three times to obtain a mixed solution A;

[0015] S2. Add sodium hydroxide solution and epichlorohydrin to the mixed solution A in step S1, carry out a constant temperature reaction. After the reaction is completed, add ammonia water, and continue to react at 50 °C for 3 - 4 h. After the reaction is completed, adjust the pH to neutral and carry out ultrafiltration to obtain a mixed solution B;

[0016] S3. Add succinimidyl ester-polyethylene glycol-maleimide (NHS-PEG-MAL) to the mixed solution B in step S2, carry out a heating reaction. After the reaction is completed, add succinimidyl ester-polyethylene glycol (NHS-PEG), and continue to react for 2 - 3 h. After the reaction is completed, carry out ultrafiltration to obtain magnetic nanoparticles.

[0017] Preferably, in step S1, the concentration of the FeCl3·6H2O solution is 10-15 mmol / L, the mass concentration of the ammonia water is 15-20%, and the volume-mass ratio of the FeCl3·6H2O solution, FeCl2·4H2O, dextran, deionized water, and ammonia water is 5-10 mL: 0.5-1 g: 5-8 g: 100-105 mL: 5-8 mL. The temperature of the stirring reaction is 20-25 °C, and the time is 0.5-1 h. The cut-off molecular weight of the ultrafiltration tube is 30 k. After ultrafiltration, the iron concentration in the mixed solution A is controlled to be 6-8 mg / mL.

[0018] In the present invention, through the coprecipitation method, under the protection of inert gas, FeCl3·6H2O and FeCl2·4H2O react under alkaline conditions to generate Fe3O4 nanoparticles. The addition of dextran plays the role of a stabilizer to prevent nanoparticle aggregation. By strictly controlling the reaction conditions (such as temperature, time, and raw material ratio) and the ultrafiltration process, the particle size uniformity and dispersibility of the nanoparticles are ensured, and the iron concentration in the mixed solution A is controlled, laying a foundation for subsequent modification.

[0019] Preferably, in step S2, the mass concentration of the ammonia water is 15-20%, the pH of the sodium hydroxide solution is 10-11, and the volume ratio of the mixed solution A, sodium hydroxide solution, epichlorohydrin, and ammonia water is 1-1.5: 5-8: 0.4-0.6: 0.6-0.9. The temperature of the constant temperature reaction is 50-60 °C, and the time is 3-4 h. After ultrafiltration, the iron concentration in the mixed solution B is controlled to be 7-9 mg / mL.

[0020] In the present invention, the nanoparticles prepared in S1 are surface-modified by epichlorohydrin. On the one hand, crosslinking between nanoparticles can be achieved. This crosslinking effect increases the particle size of the nanoparticles, forming magnetic nanoclusters with a larger magnetic moment, which can not only enhance their magnetic responsiveness but also reduce their penetration into the eye through the cornea. On the other hand, amino groups can be introduced to provide active sites for subsequent PEG grafting reactions.

[0021] Preferably, in step S3, the mass-volume ratio of the mixed solution B, NHS-PEG-MAL, and NHS-PEG is 2 mL: 110-150 mg: 30-40 mg. The temperature of the heating reaction is 20-25 °C, and the time is 2-3 h.

[0022] In the present invention, double PEGylation modification of the nanoparticles is carried out using NHS-PEG-MAL and NHS-PEG. By grafting long-chain PEG, the biocompatibility of the nanoparticles and their stability in tears are improved. The introduction of NHS-PEG further blocks the unreacted active sites and reduces the potential toxicity of the nanoparticles.

[0023] The present invention also protects a method for preparing the magnetic nano-eye drops for assisting in the treatment of lacrimal duct obstruction as described above, comprising the following steps:

[0024] Take 80% of the formula amount of injection water, sequentially add a buffer, an antioxidant, and an osmotic pressure regulator, stir until completely dissolved, then add magnetic nanoparticles, stir evenly, add a pH regulator, adjust the pH to 7.5, supplement injection water to the full volume, stir evenly, and sequentially filter through 0.45 μm and 0.22 μm filters under sterile conditions to obtain the product.

[0025] The present invention also protects the application of the magnetic nano-eye drops as described above in assisting in the treatment of lacrimal duct obstruction. The specific implementation method is as follows: Drop the eye drops into the eye, and along with the tear fluid flowing into the lacrimal duct, they finally accumulate at the obstruction site. After 5 - 10 minutes, place a magnetic rod with a magnetic field in the nasal cavity. The eye drops in the lacrimal duct break through the obstruction membrane in the lacrimal duct by the action of magnetic force, so as to achieve the purpose of restoring the patency of the lacrimal duct and solve the lacrimal duct obstruction.

[0026] Compared with the prior art, the present invention has the following beneficial effects:

[0027] (1) The magnetic nano-eye drops for assisting in the treatment of lacrimal duct obstruction provided by the present invention precisely control the buffer, antioxidant, and osmotic pressure regulator, and at the same time add an appropriate amount of pH regulator, so that the pH value of the eye drops is stably maintained at about 7.5, and the osmotic pressure is maintained at 295 - 309 mOsm / l. This is highly consistent with the physiological environment of human tear fluid, not only ensuring the stability of the eye drops, but also effectively avoiding eye irritation or discomfort caused by pH value or osmotic pressure deviation, and further improving the safety and comfort of the treatment.

[0028] (2) The magnetic nano-eye drops for assisting in the treatment of lacrimal duct obstruction provided by the present invention use the prepared magnetic nanoparticles as the core component of the eye drops. By finely regulating the ratio of each raw material, combined with the stabilizing effect of dextran and subsequent PEGylation modification, it is ensured that the magnetic nanoparticles are stably dispersed in the tear fluid environment and have no toxic or side effects on eye tissues; more importantly, after these magnetic nanoparticles dredge the lacrimal duct, they can be gradually absorbed by the lacrimal duct mucosal tissue, avoiding potential risks that may be brought by long-term retention.

[0029] (3) The present invention ingeniously combines magnetic nano-eye drops with external magnetic field guidance to achieve precise and non-invasive intervention for lacrimal duct obstruction. Compared with traditional conservative treatment and surgical intervention methods for treating lacrimal duct obstruction, this eye drop does not require professional assistance and can be used at home; secondly, this operation is non-invasive and painless, and patients have no discomfort, avoiding the trauma, pain and potential infection risks brought by surgery, greatly improving the treatment comfort and compliance of patients; thirdly, this eye drop has biocompatibility, is non-toxic and harmless to the lacrimal duct and eye tissues, and also has absorbability, and can be absorbed by the mucosal tissues in the lacrimal duct even if it breaks through the obstruction site; finally, this operation can be repeated multiple times. Even if it is not successful once, it can be repeated multiple times until the treatment effect is achieved. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 It is the particle size distribution diagram before and after crosslinking of the magnetic nanoparticles prepared in Example 1 of the present invention;

[0031] Figure 2 It is the relaxation rate diagram before and after crosslinking of the magnetic nanoparticles prepared in Example 1 of the present invention;

[0032] Figure 3 It is the infrared diagram before and after crosslinking of the magnetic nanoparticles prepared in Example 1 of the present invention;

[0033] Figure 4 It is the pH and conductivity change diagram before and after ammoniation crosslinking of the magnetic nanoparticles prepared in Example 1 of the present invention;

[0034] Figure 5 It is the particle size distribution diagram of the magnetic nanoparticles grafted with PEG and not grafted with PEG prepared in Example 1 of the present invention;

[0035] Figure 6 It is the cytotoxicity diagram of the magnetic nanoparticles prepared in Example 1 of the present invention;

[0036] Figure 7 It is the electron microscope diagram of the magnetic nanoparticles prepared in Example 1 of the present invention;

[0037] Figure 8 It is the diagram of lacrimal duct obstruction of the patient;

[0038] Figure 9 It is the diagram of the membrane rupture opening under nasal endoscopy after treating lacrimal duct obstruction with the magnetic nano-eye drops prepared in Example 1 of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0039] The following will clearly and completely describe the technical solutions in the embodiments of the present invention with reference to the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0040] Example 1

[0041] A magnetic nano-eye drop for adjuvant treatment of lacrimal duct obstruction, in every 100 mL of the eye drop, includes the following raw materials:

[0042] 4 g of magnetic nanoparticles, 0.5 g of sodium dihydrogen phosphate, 0.4 g of sodium tartrate, 0.3 g of sodium chloride, and the balance is injection water.

[0043] Among them, the preparation method of the magnetic nanoparticles includes the following steps:

[0044] S1. Add 8 mL of a FeCl3·6H2O solution with a concentration of 13 mmol / L, 0.8 g of FeCl2·4H2O, 7 g of dextran, and 102 mL of deionized water into a reaction flask protected by an inert gas, and then add 7 mL of ammonia water with a mass concentration of 20%. Stir and react at 23°C for 1 h. After the reaction is completed, centrifuge and remove the precipitate, and transfer the supernatant to an ultrafiltration tube (cut-off molecular weight is 30k) for ultrafiltration three times to obtain a mixed solution A with an iron concentration of 7 mg / mL.

[0045] S2. Add 7 mL of a sodium hydroxide solution with a pH of 10 and 0.5 mL of epichlorohydrin to 1.3 mL of the mixed solution A in step S1, and react at a constant temperature of 55°C for 3.5 h. After the reaction is completed, add 0.8 mL of ammonia water with a mass concentration of 15%, and continue to react at 50°C for 3.5 h. After the reaction is completed, adjust the pH to neutral with 2 wt% hydrochloric acid, and ultrafilter to obtain a mixed solution B with an iron concentration of 8 mg / mL.

[0046] Test the particle size distribution, relaxation rate, and infrared of the magnetic nanoparticles in the mixed solution B before and after crosslinking, as Figures 1-3 ; as Figure 1 shown, comparing the particle size distribution before crosslinking, the particle size after crosslinking has increased, which to a certain extent indicates that the particle crosslinking is successful. A suitable size is beneficial to increasing the magnetic force of the eye drop and helps to achieve the breakthrough force on the lacrimal duct obstruction membrane. On the other hand, the successful crosslinking increases the diameter of the magnetic nanoparticles and reduces the possibility of their penetrating the cornea and entering the eye, thereby reducing the damage to the intraocular tissues caused by their entry into the eye, especially the blockage of the anterior chamber angle. As Figure 2 shown, comparing the particle size distribution before crosslinking, the transverse relaxation rate of the particles after crosslinking has increased, providing imaging support for subsequent MRI monitoring of whether the lacrimal duct is unobstructed. AsFigure 3 As shown, by comparing the Fourier transform infrared spectra before crosslinking, stretching vibration peaks of -C-O-C- can be observed at 1225 - 1060, and bending vibration absorption peaks of -N-H- can be observed at 1650 - 1550, indicating that amino groups are introduced after the particles are successfully crosslinked.

[0047] Another 500 μL of mixture B was taken, an appropriate amount of water was added, the pH was first adjusted to about 3.5 with 0.037% hydrochloric acid, and a 0.2 mg / ml sodium hydroxide solution was slowly added. The changes in pH and conductivity during the titration process were recorded, as Figure 4 ; By conducting conductivity titration on the crosslinked particles, the number of amino groups on the particle surface was accurately quantified. There are approximately 300 - 600 times as many active amino sites on the surface of one particle, providing a quantitative range for subsequent NHS-PEG and NHS-PEG-MAL modifications.

[0048] S3. Add 140 mg of NHS-PEG-MAL to 2 mL of mixture B in step S2, react at 23 °C for 2.5 h. After the reaction is completed, add 35 mg of NHS-PEG and continue to react for 2.5 h. After the reaction is completed, ultrafiltration is carried out to obtain magnetic nanoparticles.

[0049] The particle size distribution of the magnetic nanoparticles before and after grafting PEG was tested, as Figure 5 shown. The particle size distribution of the magnetic nanoparticles after grafting is not significantly affected, indicating that grafting PEG has little effect on the particle size change of the magnetic nanoparticles; the cytotoxicity of the magnetic nanoparticles was tested, as Figure 6 shown. The magnetic nanoparticles basically do not damage the cell viability, demonstrating the biosafety of the magnetic particles and laying a foundation for subsequent lacrimal duct probing.

[0050] A preparation method of a magnetic nanoparticle eye drop for assisting in the treatment of lacrimal duct obstruction, comprising the following steps:

[0051] Take 80% of the formula amount of injection water, sequentially add sodium dihydrogen phosphate, sodium tartrate, and sodium chloride, stir until completely dissolved, then add magnetic nanoparticles, stir evenly, add 0.1 mol / L sodium hydroxide solution to adjust the pH to 7.5, make up the injection water to the full volume, stir evenly, and filter through 0.45 μm and 0.22 μm filters in sequence under sterile conditions to obtain the product.

[0052] The osmotic pressure of the magnetic nanoparticle eye drop prepared in this example is 304 mOsm / l.

[0053] The magnetic nanoparticle eye drop prepared by the present invention is used for assisting in the treatment of lacrimal duct obstruction, and the treatment effect is as Figure 8 and Figure 9 shown. From Figure 9It can be seen that the magnetic nano-eye drops prepared by the present invention can successfully break through the obstructive membrane in the lacrimal duct, thus achieving the effect of restoring the patency of the lacrimal duct.

[0054] Example 2

[0055] A magnetic nano-eye drop for adjuvant treatment of lacrimal duct obstruction, in every 100 mL of the eye drops, includes the following raw materials:

[0056] 3 g of magnetic nanoparticles, 0.3 g of sodium dihydrogen phosphate, 0.3 g of sodium tartrate, 0.2 g of sodium chloride, and the balance is water for injection.

[0057] Among them, the preparation method of the magnetic nanoparticles includes the following steps:

[0058] S1. Add 5 mL of a FeCl3·6H2O solution with a concentration of 10 mmol / L, 0.5 g of FeCl2·4H2O, 5 g of dextran, and 105 mL of deionized water into a reaction flask protected by inert gas, then add 5 mL of ammonia water with a mass concentration of 20%, stir and react at 20 °C for 1 h. After the reaction is completed, centrifuge and remove the precipitate, transfer the supernatant to an ultrafiltration tube (cut-off molecular weight is 30k) for ultrafiltration three times to obtain a mixed solution A with an iron concentration of 6 mg / mL;

[0059] S2. Add 5 mL of a sodium hydroxide solution with a pH of 11 and 0.4 mL of epichlorohydrin to 1 mL of the mixed solution A in step S1, react at a constant temperature of 50 °C for 4 h. After the reaction is completed, add 0.6 mL of ammonia water with a mass concentration of 20%, continue to react at 50 °C for 3 h. After the reaction is completed, adjust the pH to neutral with 2 wt% hydrochloric acid, and perform ultrafiltration to obtain a mixed solution B with an iron concentration of 7 mg / mL;

[0060] S3. Add 110 mg of NHS-PEG-MAL to 2 mL of the mixed solution B in step S2, react at 20 °C for 3 h. After the reaction is completed, add 30 mg of NHS-PEG, continue to react for 3 h. After the reaction is completed, perform ultrafiltration to obtain magnetic nanoparticles.

[0061] A preparation method of a magnetic nano-eye drop for adjuvant treatment of lacrimal duct obstruction includes the following steps:

[0062] Take 80% of the formula amount of water for injection, sequentially add sodium dihydrogen phosphate, sodium tartrate, and sodium chloride, stir until completely dissolved, then add magnetic nanoparticles, stir evenly, add 0.1 mol / L sodium hydroxide solution to adjust the pH to 7.5, make up the volume to the full amount with water for injection, stir evenly, and sequentially filter through 0.45 μm and 0.22 μm filters under sterile conditions to obtain the product.

[0063] The osmotic pressure of the magnetic nano-eye drops prepared in this example is 295 mOsm / l.

[0064] Example 3

[0065] A magnetic nano-eye drop for adjuvant treatment of lacrimal duct obstruction, in every 100 mL of the eye drop, includes the following raw materials:

[0066] 5 g of magnetic nanoparticles, 0.6 g of sodium dihydrogen phosphate, 0.6 g of sodium tartrate, 0.5 g of sodium chloride, and the balance is water for injection.

[0067] Among them, the preparation method of the magnetic nanoparticles includes the following steps:

[0068] S1. Add 10 mL of a FeCl3·6H2O solution with a concentration of 15 mmol / L, 1 g of FeCl2·4H2O, 8 g of dextran, and 100 mL of deionized water into a reaction flask protected by inert gas, then add 8 mL of ammonia water with a mass concentration of 15%, stir and react at 25°C for 0.5 h. After the reaction is completed, centrifuge and remove the precipitate, transfer the supernatant to an ultrafiltration tube (with a molecular weight cut-off of 30k) for ultrafiltration three times to obtain a mixed solution A with an iron concentration of 8 mg / mL;

[0069] S2. Add 8 mL of a sodium hydroxide solution with a pH of 10 and 0.6 mL of epichlorohydrin to 1.5 mL of the mixed solution A in step S1, react at a constant temperature of 60°C for 3 h. After the reaction is completed, add 0.9 mL of ammonia water with a mass concentration of 15%, continue to react at 50°C for 4 h. After the reaction is completed, adjust the pH to neutral with 2 wt% hydrochloric acid and perform ultrafiltration to obtain a mixed solution B with an iron concentration of 9 mg / mL;

[0070] S3. Add 150 mg of NHS-PEG-MAL to 2 mL of the mixed solution B in step S2, react at 25°C for 2 h. After the reaction is completed, add 40 mg of NHS-PEG and continue to react for 2 h. After the reaction is completed, perform ultrafiltration to obtain magnetic nanoparticles.

[0071] A preparation method of a magnetic nano-eye drop for adjuvant treatment of lacrimal duct obstruction includes the following steps:

[0072] Take 80% of the formula amount of water for injection, sequentially add sodium dihydrogen phosphate, sodium tartrate, and sodium chloride, stir until completely dissolved, then add magnetic nanoparticles, stir evenly, add 0.1 mol / L sodium hydroxide solution to adjust the pH to 7.5, make up the volume to the full amount with water for injection, stir evenly, and filter successively through 0.45 μm and 0.22 μm filters under sterile conditions to obtain the product.

[0073] The osmotic pressure of the magnetic nano-eye drop prepared in this example is 309 mOsm / l.

[0074] Although embodiments of the present invention have been shown and described, those of ordinary skill in the art will appreciate that various changes, modifications, substitutions, and variations can be made to these embodiments without departing from the principles and spirit of the present invention. The scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A magnetic nano-eye drop for adjuvant treatment of lacrimal duct obstruction, characterized in that, In every 100 mL of the eye drops, the following raw materials are included: 3 - 5 g of magnetic nanoparticles, 0.3 - 0.6 g of buffer, 0.3 - 0.6 g of antioxidant, 0.2 - 0.5 g of osmotic pressure regulator, and the balance is solvent.

2. The magnetic nano-eye drops for adjuvant treatment of lacrimal duct obstruction according to claim 1, wherein, In every 100 mL of the eye drops, 4 - 5 g of magnetic nanoparticles, 0.3 - 0.5 g of buffer, 0.4 - 0.6 g of antioxidant, 0.2 - 0.4 g of osmotic pressure regulator, and the balance is solvent.

3. The magnetic nano-eye drops for adjuvant treatment of lacrimal duct obstruction according to claim 1, wherein, The buffer is sodium dihydrogen phosphate, the antioxidant is sodium tartrate, the osmotic pressure regulator is sodium chloride, and the solvent is water for injection.

4. The magnetic nano-eye drops for adjuvant treatment of lacrimal duct obstruction according to claim 1, characterized in that, The osmotic pressure of the eye drops is 295 - 309 mOsm / l.

5. The magnetic nano-eye drops for assisting in the treatment of lacrimal duct obstruction according to claim 1, wherein The preparation method of the magnetic nanoparticles includes the following steps: S1. Add FeCl3·6H2O solution, FeCl2·4H2O, dextran, and deionized water into a reaction flask protected by inert gas, then add ammonia water, and carry out stirring reaction. After the reaction is completed, centrifuge and remove the precipitate, transfer the supernatant to an ultrafiltration tube and perform ultrafiltration three times to obtain mixture A; S2. Add sodium hydroxide solution and epichlorohydrin to mixture A in step S1, carry out a constant temperature reaction. After the reaction is completed, add ammonia water and continue to react at 50 °C for 3 - 4 h. After the reaction is completed, adjust the pH to neutral and perform ultrafiltration to obtain mixture B; S3. Add NHS - PEG - MAL to mixture B in step S2, carry out a heating reaction. After the reaction is completed, add NHS - PEG and continue to react for 2 - 3 h. After the reaction is completed, perform ultrafiltration to obtain magnetic nanoparticles.

6. The magnetic nano-eye drops for adjuvant treatment of lacrimal duct obstruction according to claim 5, characterized in that, In step S1, the concentration of the FeCl3·6H2O solution is 10 - 15 mmol / L, the mass concentration of the ammonia water is 15 - 20%, the volume - mass ratio of the FeCl3·6H2O solution, FeCl2·4H2O, dextran, deionized water, and ammonia water is 5 - 10 mL:0.5 - 1 g:5 - 8 g:100 - 105 mL:5 - 8 mL, the temperature of the stirring reaction is 20 - 25 °C, the time is 0.5 - 1 h, the cut - off molecular weight of the ultrafiltration tube is 30 k, and after ultrafiltration, the iron concentration in mixture A is controlled to be 6 - 8 mg / mL.

7. The magnetic nano-eye drops for adjuvant treatment of lacrimal duct obstruction according to claim 5, characterized in that, In step S2, the mass concentration of the ammonia water is 15 - 20%, the pH of the sodium hydroxide solution is 10 - 11, the volume ratio of mixture A, sodium hydroxide solution, epichlorohydrin, and ammonia water is 1 - 1.5:5 - 8:0.4 - 0.6:0.6 - 0.9, the temperature of the constant temperature reaction is 50 - 60 °C, the time is 3 - 4 h; after ultrafiltration, the iron concentration in mixture B is controlled to be 7 - 9 mg / mL.

8. The magnetic nano-eye drops for adjuvant treatment of lacrimal duct obstruction according to claim 5, wherein, In step S3, the mass - volume ratio of mixture B, NHS - PEG - MAL, and NHS - PEG is 2 mL:110 - 150 mg:30 - 40 mg, the temperature of the heating reaction is 20 - 25 °C, and the time is 2 - 3 h.

9. A method for preparing a magnetic nano-eye drop for adjuvant treatment of lacrimal duct obstruction according to any one of claims 1-8, characterized in that, It includes the following steps: Take 80% of the formula amount of water for injection, sequentially add a buffer, an antioxidant, and an osmotic pressure regulator, stir until completely dissolved, then add magnetic nanoparticles, stir evenly, add a pH regulator, adjust the pH to 7.5, make up the volume with water for injection to the full amount, stir evenly, and sequentially filter through 0.45 μm and 0.22 μm filters under sterile conditions to obtain the product.

10. Use of a magnetic nanoparticle eye drop according to any one of claims 1-8 for treating lacrimal duct obstruction.

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