A retinal filling hydrogel and its preparation method and application

Abstract

The present invention discloses a retinal filling hydrogel and a preparation method and application thereof, wherein the method comprises the following steps: mixing an arginine-modified amino-containing polymer and a aldehyde-modified polysaccharide for reaction to obtain the retinal filling hydrogel. The raw material source of the hydrogel of the present invention is natural and non-toxic, the hydrogel has good adhesion ability and mechanical strength, the modulus is adjustable at 1 kPa-3 kPa, the modulus of the hydrogel matches the intraocular pressure of the human body, and it has good elasticity and deformation recovery ability, which is beneficial to the patient's postoperative recovery. The degradation cycle of the hydrogel matches the postoperative recovery cycle of retinal surgery patients, it degrades stably and slowly during the recovery cycle, and disintegrates rapidly after recovery, and can be absorbed by the human body, so there is no need to remove it after surgery, thereby reducing the patient's pain. The retinal filling hydrogel of the present invention is used to prepare a cushion for recovery surgery after retinal detachment.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedical polymer materials, and in particular relates to a retina filling hydrogel and a preparation method and application thereof. Background Art

[0002] Retinal detachment is the separation of the retinal neuroepithelium and the pigment epithelium. After retinal detachment, the choroidal blood supply is lost, and the pigment epithelium is prone to free and atrophy. If it is not reset and restored in time, vision will not be easy to recover. It may cause severe vision loss or even blindness. It is a more serious eye disease. The most common causes of retinal detachment are the following two: one is the change of vitreous fluid. Changes in vitreous fluid (such as fluid exudation, increase, etc.) may cause retinal displacement; the other is the death or detachment of nerve cells on the retina, resulting in retinal holes, which will further lead to retinal detachment. In addition, eye diseases and age are also important factors causing retinal detachment, such as: high myopia, eye trauma, other causes including uveitis, fundus hemorrhage, eye trauma, etc. can also cause retinal detachment. With age, the inherent support structure of the retina will become fragile, which will also increase the risk of retinal detachment. This leads to retinal detachment concentrated in people aged 60 to 70, as well as those with high myopia (degrees above 600 degrees), patients with eye trauma, the elderly, and patients with a family history of retinal detachment. Retinal detachment is an ophthalmic disease with a high incidence rate.

[0003] Retinal detachment can have a great impact on the patient's vision and field of vision, such as decreased vision, blindness, eyeball atrophy, etc. In addition, retinal detachment can also cause many complications, such as floaters, abnormal light spots, vision loss, blurred vision, etc., which have a great impact on the patient's quality of life.

[0004] Scleral episcleral pressure surgery, implantation of foldable artificial vitreous balloon, and laser treatment are the main methods for treating retinal detachment. These three methods are widely used in the treatment of retinal detachment due to their different advantages. For example, scleral episcleral pressure has the advantages of relatively small damage, fast recovery, low recurrence rate, and no position restriction after surgery; the advantage of implantation of foldable balloon is that it does not require retrobulbar anesthesia, muscle traction line, retinal freezing, subretinal fluid, scleral fixation sutures, and retinal tear positioning during surgery. The operation is simple, with little damage and few complications; laser treatment uses the heat energy generated by the laser beam to form a scar on the retina to fix the detached or about to detach retina. It is a minimally invasive, safe, and effective treatment method. When considering the treatment of retinal detachment, doctors usually consider the patient's specific situation to choose the most appropriate treatment plan.

[0005] The above three conventional treatment methods also have their own shortcomings: when using external padding materials, displacement, extrusion, infection, pain or foreign body sensation may occur, and secondary surgery is required to remove them. Retinal detachment may occur again after the external padding materials are removed; some patients will have varying degrees of anterior chamber hemorrhage, low intraocular pressure, shallow anterior chamber, corneal white, exudative membrane and inflammatory reaction after implantation of foldable fovea (FCVB). At the same time, the surgical incision for FCVB implantation is larger than that for simple silicone oil injection, which increases the incidence of postoperative cataracts. In addition, the oxygen transport, metabolism and toxicity of FCVB need further study; the recurrence rate of laser treatment of retinal detachment is high, and laser treatment may cause retinal burns or other complications, especially for severe detachment cases, the treatment risk is relatively high. Laser treatment is only suitable for retinal detachment of specific types and locations, and may have limited effect on some complex or extensive cases. Therefore, the study of new and safe vitreous substitutes plays an important role in promoting the treatment of fundus diseases.

[0006] Compared with conventional treatment methods such as folding balloons, episcleral pad surgery, and laser therapy, injectable hydrogels overcome most of the shortcomings of existing vitreous substitutes and reduce the occurrence of complications. They have good mechanical, optical, and biocompatibility. When in direct contact with intraocular tissues, the material is also stable and safe. In the treatment of retinal detachment, it can be used in a local targeted or minimally invasive manner through a narrow syringe without the need for invasive surgery. At the same time, the hydrogel can be formed into the desired shape in a confined space for filling irregular wounds. Therefore, injectable hydrogels are expected to become a new generation of vitreous substitutes for the treatment of retinal detachment. However, the high strength of the hydrogel material itself will inevitably cause the material to be highly brittle, and there are problems such as insufficient elastic modulus. The storage modulus of the hydrogel prepared by the prior art is only about 50~350Pa. The low elastic modulus leads to its insufficient elasticity, thereby weakening the extrusion support effect of the hydrogel. It is necessary to develop hydrogel materials with higher storage modulus and better elasticity.

[0007] In addition, the recovery period after retinal surgery is 12-15 weeks. Therefore, the degradation period of retinal filling hydrogels also needs to match the recovery period after surgery. It should be stable for at least 3 months and maintain a low degradation rate to facilitate patient recovery. Then, after the 3-month recovery period after surgery, when the patient has basically recovered, the hydrogel needs to disintegrate quickly and be absorbed by the human body without the need for postoperative removal. It is necessary to develop retinal filling hydrogels with a degradation period that matches the recovery period of retinal surgery patients. Summary of the invention

[0008] The present invention develops a biomedical polymer material called hydrogel, which is injectable, self-healing, has good light transmittance and biocompatibility, to treat retinal detachment. The refractive index of hydrogel is close to that of natural vitreous. Studies have shown that hydrogel has many advantages in the application of new intraocular implant materials. At the same time, the new application of hydrogel in intraocular drug sustained release system, scleral outer pad pressure, etc., provides a basis for further new technologies for the treatment of retinal detachment.

[0009] The present invention aims to solve the problem that existing injectable hydrogels have high brittleness, low modulus and weak supporting and extruding effect when used as retinal detachment surgical materials. The present invention provides an injectable, degradable and absorbable hydrogel with excellent biocompatibility and a preparation method thereof. The padding effect and adhesion performance of the hydrogel of the present invention in the animal eyeball are tested using a pig eye model and New Zealand rabbit in vivo absorption, and its stability in the animal eyeball is evaluated.

[0010] The technical solution adopted by the present invention is:

[0011] A retina filling hydrogel is prepared according to the following method: an arginine-modified amino-containing polymer and a aldehyde-modified polysaccharide are mixed and reacted to prepare the retina filling hydrogel.

[0012] The retinal filling hydrogel of the present invention is an injectable retinal filling hydrogel, which can be prepared by mixing and reacting an arginine-modified amino-containing polymer and a aldehyde-modified polysaccharide through injection.

[0013] Furthermore, the amine-containing polymer includes but is not limited to one or more of chitosan, gelatin, polylysine, and collagen, preferably chitosan.

[0014] The polysaccharide is one or more of starch, sodium alginate, dextran and hyaluronic acid.

[0015] The retinal filling hydrogel provided by the present invention has a modulus of 1-3 kPa, a large elastic modulus, and better elasticity and deformation recovery ability.

[0016] The degradation rate of the retinal filling hydrogel provided by the present invention is 40-60% within 120 days, which is consistent with the postoperative recovery period.

[0017] The present invention also provides a method for preparing a retinal filling hydrogel, the method comprising: mixing an arginine-modified amino-containing polymer and a aldehyde-modified polysaccharide for reaction to prepare the retinal filling hydrogel.

[0018] Furthermore, the arginine-modified amine-containing polymer and the aldehyde-modified polysaccharide are mixed and reacted by injection to prepare the retinal filling hydrogel.

[0019] Further, the method is preferably carried out according to the following steps:

[0020] The arginine-modified amine-containing polymer was prepared into a 3-5 wt% arginine-modified amine-containing polymer solution using PBS buffer, which was recorded as solution A;

[0021] The aldehyde-modified polysaccharide was prepared into a aldehyde-modified polysaccharide solution with a mass concentration of 5-10 wt% using PBS buffer, which was recorded as solution B;

[0022] Solution A and solution B are injected according to the proportion and mixed evenly to form a gel.

[0023] The volume ratio of solution A to solution B is preferably 1:0.5-2, and more preferably solution A and solution B are injected in an equal volume ratio.

[0024] It can be injected using a double syringe and mixed evenly to form a gel, which can form a gel within 30 seconds.

[0025] The PBS buffer is generally a 1×PBS solution with a pH of 7 to 7.5.

[0026] The present invention uses amine-containing polymer materials as raw materials, which have the advantages of excellent biocompatibility, low price and easy availability. This type of molecular chain is rich in a large number of active groups such as amino groups and hydroxyl groups, and can meet the Schiff base reaction conditions through modification. The resulting hydrogel can quickly gel in situ and has a certain self-repair ability, which better meets the actual situation that the target position is easily squeezed.

[0027] The arginine-modified amine-containing polymer can be prepared by the following method:

[0028] The amine-containing polymer and NaOH are dissolved in a water solvent or a mixed solvent of isopropanol and water, and then 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC), N-hydroxysuccinimide (NHS) and arginine are added and stirred at room temperature to react to obtain an arginine-modified amine-containing polymer.

[0029] The mass ratio of the amine-containing polymer, NaOH, 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC), N-hydroxysuccinimide (NHS), and arginine is 1:1-2:2-3:1-2:3-4, preferably 1:1:2:1:3.

[0030] The amine-containing polymer and NaOH are dissolved in water or a mixed solvent of isopropanol and water. The preferred dissolution process is: stirring and swelling at 40-50° C. for 1-2 hours for more uniform mixing.

[0031] In the mixed solvent of isopropanol and water, the volume ratio of isopropanol to water is preferably 1:0.5 to 2, more preferably 1:1.

[0032] The reaction time is preferably 6 to 24 hours.

[0033] After the reaction is completed, the reaction solution is post-treated to obtain the arginine-modified amine-containing polymer. The post-treatment method is generally: alcohol precipitation and washing of the reaction solution to obtain the arginine-modified amine-containing polymer.

[0034] Furthermore, the specific steps of the post-processing are preferably:

[0035] After the reaction, ethanol was added to the reaction solution for precipitation, the filter cake was filtered and washed, and deionized water was added to dissolve it. The pH was adjusted to neutral using a dilute hydrochloric acid solution. At this time, white flocs were precipitated. The upper liquid was taken out after centrifugation and freeze-dried to obtain the product arginine-modified amino-containing polymer, which was recorded as ACMCs.

[0036] Polysaccharides (starch, dextran, etc.) have the characteristics of special surface area, wide source, non-immunogenicity, and can be absorbed by the human body, and are widely used in the field of biomedical hydrogels.

[0037] Furthermore, the present invention modifies polysaccharides into aldehyde-modified polysaccharides. The product obtained by reacting polysaccharides with oxidants in acid, alkali, and neutral media is ODS. The oxidation reaction can not only break the glycosidic bonds, but also introduce carbonyl and carboxyl groups to the molecular chain to a limited extent, thereby minimizing the precipitation effect of straight-chain starch and greatly improving the stability, film-forming properties, adhesion, and transparency of the paste. Since ODS has the above-mentioned advantages, coupled with simple process and low price, it is also used in biomedicine. At the same time, the introduction of aldehyde groups into polysaccharides can increase their cross-linking ability and adhesion.

[0038] The hydroformylation-modified polysaccharide of the present invention is prepared by subjecting the polysaccharide to an oxidation reaction with hydrogen peroxide, and the specific steps are as follows:

[0039] The polysaccharide is dispersed in water, hydrogen peroxide is added, and oxidation reaction is carried out in the dark to obtain the aldehyde-modified polysaccharide;

[0040] The molar ratio of polysaccharide to hydrogen peroxide is 1:0.2 to 1.0, preferably 1:0.6 to 0.8. The molar ratio of hydrogen peroxide refers to the molar ratio of H2O2 in hydrogen peroxide.

[0041] The temperature of the oxidation reaction is preferably 30-35° C., and the reaction time is preferably 3-5 h.

[0042] After the oxidation reaction is completed, ethylene glycol is added and stirred to terminate the reaction, and the hydroformylation-modified polysaccharide is obtained by dialysis and freeze-drying.

[0043] The mass concentration of hydrogen peroxide is 25~30%.

[0044] The present invention also provides the use of the retinal filling hydrogel in preparing a cushion for recovery surgery after retinal detachment.

[0045] Furthermore, in the application, the retinal filling hydrogel is used as a cushion for episcleral cushioning in the recovery surgery after retinal detachment. The retinal filling hydrogel can replace the foldable artificial vitreous balloon and does not need to be removed after surgery.

[0046] The hydrogel of the present invention has the following advantages:

[0047] (1) The hydrogel substrate is made of natural bio-based raw materials, which are cheap and easy to obtain. After simple modification, they can meet the Schiff base reaction conditions and can quickly generate gel in situ at the injection site. Arginine grafting modification of amino-containing polymers also improves the low solubility of amino-containing polymers in neutral aqueous solutions. It has excellent water solubility and good biocompatibility. At the same time, it can enhance the adhesion ability of hydrogels, improve mechanical strength, and improve its brittleness and support extrusion effect.

[0048] (2) The second component of the hydrogel, the hydroformyl modified polysaccharide, can be combined with the arginine modified amino-containing polymer ACMC s The cross-linking is sufficient to form Schiff base cross-linking sites and the final degradation products are completely non-immunotoxic to the human body.

[0049] (3) The modulus of the hydrogel is one order of magnitude higher than that of the existing technology, and it has stronger elastic deformation ability and can be adjusted according to the size of the intraocular pressure. By controlling the degree of hydroformylation of ODS, the dosage ratio of the two components can adjust the cross-linking density of the hydrogel and the molecular weight between the cross-linking points, so that the modulus of the hydrogel can be adjusted between 1 kPa and 3 kPa. The normal intraocular pressure of the human body is between 10 mmHg and 21 mmHg (corresponding to the modulus of 1.33 kPa and 2.80 kPa). Therefore, the modulus of the hydrogel just matches the intraocular pressure of the human body, and it has good elasticity and deformation recovery ability, which is beneficial to the patient's postoperative recovery.

[0050] (4) The degradation cycle of the hydrogel of the present invention matches the postoperative recovery cycle of retinal surgery patients. The hydrogel of the present invention can achieve a degradation rate of 60% in 120 days, maintaining a slower stable degradation rate, which is slower than the degradation rate of the prior art and is just in line with the use cycle of retinal recovery surgery (12 weeks to 15 weeks). After a recovery period of 120 days, the hydrogel can quickly disintegrate and can be absorbed by the human body, without the need for postoperative removal, thereby reducing the patient's pain. BRIEF DESCRIPTION OF THE DRAWINGS

[0051] Figure 1 The infrared spectra of the amino-containing polymer raw material and the product ACMCs in Example 1 of the present invention are shown.

[0052] Figure 2This is the relationship between the ODS hydroformylation degree and the feed ratio in Example 2 of the present invention.

[0053] Figure 3 The storage modulus and loss modulus and microscopic morphology of hydrogels with different formulations in Example 3 of the present invention are shown in FIG. Figure 3 Figure a) shows the test results of storage modulus and loss modulus of hydrogels with different formulas, and Figures b) to f) show the microscopic morphologies of hydrogels prepared with ODS with hydroformylation degrees of 0.2, 0.4, 0.6, 0.8, and 1.0, respectively.

[0054] Figure 4 This is a diagram showing the adhesion of the hydrogel prepared in Example 4 of the present invention to an isolated pig eye.

[0055] Figure 5 This is a graph showing the change in in vitro mass residual ratio of the hydrogel prepared in Example 5 of the present invention over time.

[0056] Figure 6 The injectability and postoperative observation diagram of the hydrogel prepared in Example 6 of the present invention in the New Zealand rabbit eye model. DETAILED DESCRIPTION

[0057] In order to facilitate a better understanding of the present invention, the present invention is further described in detail below in conjunction with embodiments and drawings, but the protection content of the present invention is not limited thereto.

[0058] Example 1: Modification and preparation of Class A raw materials

[0059] Take the amino-containing polymer raw material A (5 g chitosan) and 5 g sodium hydroxide in a three-necked flask and mix them evenly, add 50 mL of a mixed solvent of isopropanol and water (volume ratio of isopropanol: water = 1:1) (or pure water), stir and swell at 50 °C for 1 hour, and record it as solution A. Add 10 g of 1-ethyl-(3-dimethylaminopropyl) carbodiimide (EDC) and 5 g of N-hydroxysuccinimide (NHS) to solution A, then add 15 g of L-arginine, stir and react for 12 hours, then add ethanol to precipitate the reaction product, filter and wash three times, then add 250 mL of deionized water to dissolve, use 0.1 M dilute hydrochloric acid solution to adjust Ph to neutral, at this time, white floccules precipitate, take out the upper liquid after centrifugation, and freeze-dry to obtain a white or light yellow product ACMCs. Amino-containing polymer raw material A and product ACMC s The infrared spectrum of Figure 1 As shown, Figure 1 This indicates that after grafting arginine, the -1 The obvious absorption peak is due to the presence of more -CH2 bonds in arginine; at 1586 cm -1The absorption peak of chitosan was strengthened, which was due to the stretching vibration of C=O and the bending vibration of NH formed by the amide bond between the carboxyl group of arginine and the hydroxyl group of chitosan, and the stretching vibration of CN. The results of infrared analysis also showed that arginine had been successfully introduced into the macromolecular chain of chitosan.

[0060] Similarly, amino-containing polymer raw materials such as polylysine, gelatin, collagen, etc. can be grafted and modified according to the above method; the specific formula is modified according to the amino content in each raw material, and the amino content is determined by sodium nitrite titration.

[0061] Example 2: Aldehyde ODS modification and preparation method:

[0062] 1 g of polysaccharide raw material B (starch) was dispersed in 100 mL of deionized water and rapidly stirred at room temperature to disperse it in water. The number of structural units in 1 g of starch was calculated to be 6.17 mmol. Then, 30 wt% aqueous hydrogen peroxide solution was added according to different molar ratios (0.2, 0.4, 0.6, 0.8), and the mixture was reacted at 35 °C for 3 h in the dark. 3 mL of ethylene glycol was added and stirred for 30 min to terminate the reaction. The mixture was dialyzed in deionized water for 3 d and freeze-dried to obtain the product, aldehyde-modified ODS.

[0063] Similarly, other polysaccharide raw materials such as sodium alginate, dextran, and hyaluronic acid can be oxidatively modified using the above method.

[0064] Example 3 Preparation of hydrogel system

[0065] ACMCs powder was prepared into 5 wt% solution using sterile 1×PBS solution with Ph=7.4, and the different degrees of hydroformylation (distribution of degree of hydroformylation as shown in Table 1) obtained by oxidation reaction and titration reaction with hydroxylamine hydrochloride were added. Figure 2 As shown in the figure, ODS is prepared into a 10 wt% solution; the two components are mixed evenly in a vial according to a mass ratio of 1:1 to form a gel or mixed evenly using a syringe to form a gel. The storage modulus and loss modulus test results and scanning electron microscopy morphology of the hydrogels prepared from ODS with hydroformylation degrees of 0.2, 0.4, 0.6, 0.8, and 1.0 are shown in the figure. Figure 3 As shown, Figure 3 Figure a) shows the rheological curve of the hydrogel; it can be seen that the storage modulus of ACMCs-ODSX is adjustable in the range of 1 kPa – 4 kPa, proving that the elastic properties of the hydrogel can be adjusted by the oxidation degree of ODS. Figure 3Figures b)-f) are microscopic morphologies of hydrogels made from ODS with hydroformylation degrees of 0.2, 0.4, 0.6, 0.8, and 1.0, respectively. It can be seen that the gel after liquid nitrogen quenching and freeze-drying has a good continuous, tight, porous network structure, and the gel formation is relatively uniform. With the increase of hydroformylation degree, the gel mesh becomes denser, which is due to the formation of more cross-linking sites. Example 4: Tissue Adhesion of ACMCs-ODS Hydrogel to Excised Pig Eyes

[0066] ACMCs powder was prepared into 5 wt% solution A using sterile PBS solution, and 80% hydroformylation degree ODS was prepared into 10 wt% solution B. Solution A and solution B were mixed and extruded through a double syringe, which could form a gel in about 30 s. The gel was then injection molded on the sclera of the eyeball peeled off from a living pig.

[0067] The gel time of the hydrogel prepared in this embodiment after extrusion was 39±4 s, which had good injectability and rapid gelation ability; Figure 4 Figure a) shows the adhesion of the hydrogel outside the pig eye tissue. Figure 4 b) shows the adhesion and support properties of the hydrogel injected under the sclera of a pig eye. Figure 4 Display, ACMCs-ODS 0.8 The hydrogel has excellent bioadhesion on the sclera of the eyeball. Example 5: In vitro biodegradation experiment of the hydrogel

[0068] The materials used to restore the detached retina through episcleral pad surgery should have good biodegradability and should be absorbed by the human body after degradation to avoid the risks and complicated postoperative treatment process of surgical removal of the pad material after the retina has recovered. Therefore, it is necessary for the material to be biodegradable and harmless to absorption by organisms.

[0069] The present invention uses all-biobased degradable materials as raw materials to prepare a degradable hydrogel for use in episcleral pad surgery. Therefore, the degradation cycle matches the postoperative retinal recovery cycle to better reduce postoperative treatment for patients. The degradation cycle of the hydrogel was studied by using PBS buffer in vitro. The degradation rate of the hydrogel prepared using ODS and ACMCs with different degrees of hydroformylation changes over time as shown in the figure. Figure 5 shown. Figure 5It is shown that at 120 days, the remaining mass is 40%~60%, that is, the degradation rate is about 60%~40%. It can be seen that within 120 days, the hydrogel degrades stably at a slower rate. The patient's postoperative recovery period is 12-15 weeks. The degradation period of the hydrogel of this system matches the postoperative recovery time. As the retina recovers after surgery, the volume of the hydrogel slowly decreases, which is more conducive to stable recovery after surgery. And three months after surgery, the hydrogel of the present invention has a faster degradation rate than the first three months, which is called the disintegration of the hydrogel. The hydrogel degrades rapidly and does not remain in the body for a longer time. This allows the hydrogel to stably exist during the postoperative recovery period during application, and can be quickly disintegrated and absorbed by the human body after the patient recovers, without the need for postoperative removal, thereby reducing the patient's pain.

[0070] Example 6: Adhesion, safety and degradation performance testing of hydrogels in New Zealand rabbit model

[0071] The hydrogel of the present invention is used as a cushioning material for human scleral external cushioning surgery, and should have biosafety, and its degradation products should be absorbable by the human body and have good adhesion properties. After being injected under the human sclera, the position should be fixed without movement or falling off (it is known that existing external cushioning materials require the surgeon to fix the material by suturing).

[0072] In this example, ACMCs powder was prepared into a 5 wt% solution A using a sterile PBS solution, and 80% hydroformylation degree oxidized starch was prepared into a 10 wt% solution B. Solution A and solution B were injected into the sclera of the eyeball of New Zealand rabbits through a double syringe. Figure 6 Experimental observations in Figure 6 In the figure, a) is a preoperative animal experiment, and the actual picture of the injection into the sclera of the eyeball before the experiment, and b) is a picture of the injection, indicating that the hydrogel has good injectability and is combined with Figure 6 Figure c) shows the rabbit eye after injection. It can be seen that the hydrogel can stably open the eyeball to form a cushioning effect. After the experiment, the New Zealand rabbit did not have any overreaction. Figure 6 Figure d) shows the residual state of the hydrogel in the eyes of New Zealand rabbits 3 months after the experiment. It can be seen that the hydrogel did not shift in position 3 months after the operation, had certain wet tissue adhesion, and had good biological safety. This example confirms that the ACMCs-ODS0.8 hydrogel has good biological safety, its degradation products can be absorbed by the human body, and it has good wet tissue adhesion.

[0073] The present invention innovatively prepares a retinal filling hydrogel which is a cushioning material for retinal recovery surgery after retinal detachment. The hydrogel has good biodegradability by using bio-based polysaccharide as raw material, and is slowly degraded and absorbed while the patient's retina is recovering, saving the step of postoperative removal. The hydrogel has good adhesion and antibacterial properties, and can effectively serve as a cushioning material for human episcleral cushioning surgery. This method effectively reduces the difficulty of surgery and alleviates the pain of patients during treatment.

Claims

1. A retinal filling hydrogel, characterized in that The retinal filling hydrogel is prepared by the following method: the arginine-modified amine-containing polymer is prepared into an arginine-modified amine-containing polymer solution with a mass concentration of 3-5 wt % using PBS buffer, which is recorded as solution A; The aldehyde-modified polysaccharide was prepared into a aldehyde-modified polysaccharide solution with a mass concentration of 5-10 wt% using PBS buffer, which was recorded as solution B; Solution A and solution B are injected at a volume ratio of 1:0.5-2, mixed evenly to form a gel, and the retinal filling hydrogel is prepared; The arginine-modified amino-containing polymer and the aldehyde-modified polysaccharide are mixed and reacted to obtain the retinal filling hydrogel; the modulus of the retinal filling hydrogel is 1 kPa to 3 kPa; the degradation rate of the retinal filling hydrogel in 120 days is 40 to 60%; The amino-containing polymer is chitosan; the polysaccharide is starch; The arginine-modified amine-containing polymer is prepared by the following method: Chitosan and NaOH are dissolved in water or a mixed solvent of isopropanol and water, and then 1-ethyl-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide and arginine are added, and stirred at room temperature to react to obtain an arginine-modified amine-containing polymer; The mass ratio of chitosan, NaOH, 1-ethyl-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide, and arginine is 1:1~2:2~3:1~2:3~4; The hydroformylation-modified polysaccharide is prepared by the following method: starch is dispersed in water, hydrogen peroxide is added, the molar ratio of polysaccharide to hydrogen peroxide is 1:0.2-1.0, oxidation reaction is carried out in the dark to prepare the hydroformylation-modified polysaccharide.

2. The method for preparing the retinal filling hydrogel according to claim 1, characterized in that The method comprises: preparing an arginine-modified amine-containing polymer solution with a mass concentration of 3-5 wt% using a PBS buffer solution, which is recorded as solution A; The aldehyde-modified polysaccharide was prepared into a aldehyde-modified polysaccharide solution with a mass concentration of 5-10 wt% using PBS buffer, which was recorded as solution B; Solution A and solution B are injected at a volume ratio of 1:0.5-2, mixed evenly to form a gel, and the retinal filling hydrogel is prepared; The amino-containing polymer is chitosan; the polysaccharide is starch; The arginine-modified amine-containing polymer is prepared by the following method: Chitosan and NaOH are dissolved in water or a mixed solvent of isopropanol and water, and then 1-ethyl-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide and arginine are added, and stirred at room temperature to react to obtain an arginine-modified amine-containing polymer; The mass ratio of chitosan, NaOH, 1-ethyl-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide, and arginine is 1:1~2:2~3:1~2:3~4; The hydroformylation-modified polysaccharide is prepared by the following method: starch is dispersed in water, hydrogen peroxide is added, the molar ratio of polysaccharide to hydrogen peroxide is 1:0.2-1.0, oxidation reaction is carried out in the dark to prepare the hydroformylation-modified polysaccharide.

3. The method according to claim 2, characterized in that The temperature of the oxidation reaction is 30-35°C and the reaction time is 3-5h.

4. Use of a retinal filling hydrogel as claimed in claim 1 or a retinal filling hydrogel prepared by the preparation method of a retinal filling hydrogel as claimed in any one of claims 2 or 3 in preparing a substitute for a foldable artificial vitreous balloon.

5. Use of the retinal filling hydrogel as claimed in claim 1 or the retinal filling hydrogel prepared by the preparation method of the retinal filling hydrogel as claimed in any one of claims 2 or 3 in preparing a cushion for recovery surgery after retinal detachment.

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