A method for preparing a medical high-absorbency resin having an anticoagulant function enriched in a surface layer

Abstract

The present application belongs to the technical field of functional polymer materials, and particularly relates to a preparation method of medical high-absorbability resin with surface layer enriched with anticoagulation function. The method comprises: preparing an anticoagulation function monomer in water phase coupling; obtaining a base resin by polymerization after neutralization of an acrylic acid system, and obtaining base particles by drying and screening; performing surface cross-linking on the base particles; spraying the functional monomer and a second initiation system on the surface layer of the particles in liquid atomization, controlling only the outer surface layer to be wetted, and drying the whole particles after low-temperature grafting and fixing at 20-50 DEG C. Through the process of "base forming, surface cross-linking and low-temperature surface layer grafting", the anticoagulation function is enriched on the outer layer of the particles, the surface aggregation and liquid path blockage risk after contact with blood-containing body fluid are significantly reduced while the high water absorption and pressure liquid retention performance are maintained, the covalent fixation stability of the functional component and the anti-clumping property of the finished product are improved, and the method is suitable for postoperative drainage and high-protein body fluid absorption scenarios.

Description

Technical Field

[0001] This invention relates to the field of functional polymer materials technology, and more specifically, to a method for preparing a medical superabsorbent resin with surface enrichment of anticoagulant function. Background Technology

[0002] Superabsorbent polymers (SAPs) are a class of polymeric absorbent materials with a three-dimensional cross-linked network structure. They can absorb and retain large amounts of water or body fluids and are now widely used in absorbent products and some medical and health-related products. With the segmentation of medical scenarios, the absorption and management of body fluids such as postoperative drainage fluids, blood-containing high-protein exudates, and pericatheter exudates have placed new demands on superabsorbent polymers. These demands not only require high absorbency but also good continuous fluid permeability and low risk of blockage during the absorption process.

[0003] However, postoperative drainage fluids or high-protein, blood-containing body fluids typically contain high concentrations of protein, blood cells, fibrinogen, immunoglobulins, and electrolytes, and their flow rate is often large and the duration is long. In such environments, ordinary superabsorbent resins are prone to blockage of the fluid pathways during absorption due to the rapid formation of a high-viscosity gel layer or localized agglomeration layer on the particle surface, leading to a decrease in continuous absorption capacity and, in severe cases, even poor drainage.

[0004] In existing technologies, one approach involves directly introducing free anticoagulants, such as heparin, into the superabsorbent resin to alleviate coagulation and blockage after blood contact. However, this approach typically suffers from issues such as easy migration and loss of the anticoagulant components, poor duration of action, and insufficient stability during storage and use. Another approach involves uniformly introducing anticoagulant functional units into the overall superabsorbent resin network. While this can improve the binding stability of the anticoagulant functional units, it often interferes with the liquid absorption structure of the resin matrix, affecting the absorption ratio, absorption rate, and particle liquid flow capacity. A third approach involves simply spraying or physically loading the surface of the superabsorbent resin particles. Although this can impart anticoagulant functionality to the surface to some extent, the limited binding force makes it prone to detachment, deactivation, or surface clumping under continuous liquid scouring.

[0005] Therefore, current technology lacks a suitable medical superabsorbent resin for the absorption of postoperative drainage fluids or high-protein blood-containing body fluids. It needs to meet the following requirements simultaneously: First, the anticoagulant functional components should be stably fixed on the surface of the resin particles to reduce the tendency of aggregation and blockage at the liquid contact interface; Second, the superabsorbent resin main network should still be maintained inside the resin particles to ensure liquid absorption capacity and pressure absorption performance; Third, the preparation process should also take into account the needs of particle processing stability, agglomeration and clumping control, residue control, and subsequent blood compatibility. Summary of the Invention

[0006] In view of the shortcomings of the existing technology, the purpose of this application is to provide a method for preparing a medical superabsorbent resin with surface enrichment of anticoagulant function.

[0007] To achieve the above objectives, this application provides the following technical solution: A method for preparing a medical superabsorbent resin with surface enrichment of anticoagulant function, characterized by comprising the following steps: S1, heparin-like oligosaccharides are coupled in an aqueous phase with a modifier having polyethylene glycol spacer arms and polymerizable unsaturated groups, and then purified to obtain an anticoagulant monomer. S2, after mixing acrylic acid with water and partially neutralizing it, yields a monomer system containing acrylic acid and acrylate. S3, an internal crosslinking agent and a first initiator are added to the monomer system to carry out free radical polymerization to obtain a gel polymer; S4, the gel polymer is crushed, dried, pulverized and sieved to obtain basic resin particles; S5, the surface crosslinking agent is prepared into a surface crosslinking liquid and sprayed onto the surface of the base resin particles, followed by heat treatment to obtain surface crosslinked matrix resin particles. S6, the anticoagulant functional monomer and the second initiation system are formulated into a grafting solution and sprayed onto the surface of the surface cross-linked matrix resin particles. The grafting solution is controlled to only wet the outer surface layer of the particles. Under low temperature conditions, the anticoagulant functional monomer is grafted and fixed onto the surface of the surface cross-linked matrix resin particles. Then, the particles are dried and granulated to obtain a medical high absorbency resin with anticoagulant functional units enriched on the surface.

[0008] In a preferred embodiment, the coupling reaction in step S1 includes: Heparin oligosaccharides were dissolved in buffer solution and activated at pH 4.5–6.0. ​​Then, a modifier with polyethylene glycol spacer arms and polymerizable unsaturated groups was added to carry out a coupling reaction. The coupling reaction is carried out at a temperature of 0–25°C for 2–24 hours. After the coupling reaction is completed, the anticoagulant functional monomer is obtained by dialysis, ultrafiltration or precipitation purification.

[0009] In a preferred embodiment, the molecular weight of the heparin-like oligosaccharide is 1–6 kDa; The molecular weight of the polyethylene glycol spacer arm is 400–2000 Da; The polymerizable unsaturated group is an acrylate group or a methacrylate group.

[0010] In a preferred embodiment, in step S2, after mixing acrylic acid with water, an alkaline neutralizing agent is added at a temperature below 40°C for partial neutralization until the degree of neutralization reaches 60% to 80%; wherein, by mass, acrylic acid is 100 parts and water is 120 to 180 parts.

[0011] In a preferred embodiment, in step S3, an internal crosslinking agent is first added to the monomer system and stirred until homogeneous, and then a first initiator system is added to carry out free radical polymerization; The initiation temperature for the free radical polymerization is 20–60 °C.

[0012] In a preferred embodiment, the internal crosslinking agent is methylenebisacrylamide or polyethylene glycol diacrylate; The amount of the internal crosslinking agent added is 0.05–1 wt% based on the mass of acrylic acid; The first initiation system is a redox initiation system composed of persulfate, bisulfite and ascorbic acid, and the total amount of the first initiation system is 0.05 to 0.5 wt% based on the mass of acrylic acid.

[0013] In a preferred embodiment, the drying temperature in step S4 is 130–190°C; The basic resin particles obtained after sieving have a particle size of 100-800 μm, of which the content of micro powder with a particle size of less than 106 μm does not exceed 1 wt%.

[0014] In a preferred embodiment, in step S5, the surface crosslinking liquid is sprayed onto the surface of the base resin particles in 2 to 4 applications, and the mixture is stirred for 1 to 5 minutes after each application before the next application. The amount of the surface crosslinking agent used is 0.2 to 1 wt% of the mass of the base resin particles; The heat treatment temperature is 140–190°C, and the treatment time is 5–60 min.

[0015] In a preferred embodiment, the surface crosslinking agent is selected from one or more of polyethylene glycol diglycidyl ether, ethylene glycol diglycidyl ether, and ethylene carbonate.

[0016] In a preferred embodiment, in step S6, the concentration of the grafting treatment solution is 3-8 wt%, and the amount sprayed is 0.1-0.5 wt% of the mass of the surface crosslinking matrix resin particles; The grafting treatment solution is applied by atomization spraying. The second initiation system is a redox initiation system composed of persulfate, bisulfite, and ascorbic acid, and the total amount of the second initiation system is 0.005–0.05 wt% of the mass of the surface crosslinked matrix resin particles; The grafting temperature is 20–50°C; After grafting and fixation, the grains are dried and granulated at 50–70°C.

[0017] By adopting the above technical solution, the beneficial effects of the present invention are as follows: This invention employs a process route of "matrix resin formation, surface crosslinking, and low-temperature surface grafting fixation" to immobilize anticoagulant functional monomers primarily on the outer surface of resin particles. While maintaining the resin's main liquid-absorbing structure, this reduces surface aggregation and fluid path blockage after contact with blood or high-protein blood-containing body fluids. By using aqueous coupling to prepare the anticoagulant functional monomers and employing a second initiation system for surface grafting fixation at a lower temperature, the binding stability of the anticoagulant functional monomers is improved, reducing migration and loss under simple physical spraying methods. Through synergistic control of the base resin particle size, micron powder content, surface crosslinking, and surface grafting spraying conditions, the risks of aggregation, clumping, and hygroscopic adhesion are reduced, improving preparation stability and the uniformity of the finished particles. This invention is suitable for postoperative drainage or high-protein blood-containing body fluid absorption scenarios, achieving a balance between absorption performance and anti-blocking properties in such complex fluid environments. Attached Figure Description

[0018] Figure 1 A schematic flowchart of the method of the present invention. Detailed Implementation

[0019] The present invention will be further described below with reference to specific embodiments. It should be understood that the following embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the scope of protection of the present invention. Equivalent substitutions or conventional adjustments made by those skilled in the art to the types of raw materials, amounts added, process parameters, and testing conditions without departing from the technical concept of the present invention should all fall within the scope of protection of the present invention.

[0020] like Figure 1 As shown, this invention provides a method for preparing a medical-grade superabsorbent resin with surface-enriched anticoagulant function. The method employs a technical route of "aqueous coupling preparation of anticoagulant functional monomers—partial neutralization of the acrylic acid system—internal crosslinking polymerization—formation of base resin particles—surface crosslinking—low-temperature grafting fixation of the surface layer—drying and granulation." Specifically, a first initiating system is used for free radical polymerization of the main monomer liquid to form a superabsorbent resin base network; a second initiating system is used for low-temperature grafting of the surface-crosslinked matrix resin particles to fix the anticoagulant functional monomers to the outer surface of the particles, thereby forming a surface-enriched anticoagulant functional structure.

[0021] The main raw materials used in this embodiment are as follows: The preferred heparin-like oligosaccharide is low-molecular-weight heparin oligosaccharide sodium, with a number-average molecular weight of 2.5–5.0 kDa, a sulfate group content of 0.8–1.5 mmol / g, and a carboxyl group content of 0.2–0.6 mmol / g. The preferred modifier is methacrylate-terminated amino-terminated polyethylene glycol, i.e., NH2-PEG-MA, where the PEG spacer arms have a number-average molecular weight of 400–2000 Da, preferably 600–1000 Da, an amino group value of 0.8–1.2 mmol / g, and a purity of not less than 95%. The preferred buffer is MES buffer, with a concentration of… The concentration is 0.05–0.20 M, preferably 0.10 M; the pH is 4.5–6.0, preferably 5.0; the purity of acrylic acid is not less than 99.0%; the sodium hydroxide is analytical grade or industrial grade; the conductivity of deionized water is not higher than 10 μS / cm; the internal crosslinking agent is methylene bisacrylamide or polyethylene glycol diacrylate; the surface crosslinking agent is selected from one or more of polyethylene glycol diglycidyl ether, ethylene glycol diglycidyl ether, and ethylene carbonate; both the first and second initiation systems are preferably redox initiation systems composed of persulfate, bisulfite, and ascorbic acid.

[0022] It should be noted that the composition of the first initiation system and the second initiation system can be the same, but their timing of addition, target molecules, and dosages differ. The first initiation system is used for the bulk polymerization of the main monomer in step S3 to rapidly form a highly absorbent resin matrix network; the second initiation system is used for the low-temperature grafting of the surface layer in step S6 to fix the anticoagulant functional monomer to the outer surface of the particles at a lower temperature. Typically, the dosage of the second initiation system is significantly lower than that of the first initiation system to avoid excessive surface reaction or deactivation of the functional structure.

[0023] Preparation and characterization of anticoagulant functional monomers in this embodiment: 10.0 g of low molecular weight heparin oligosaccharide sodium was added to 100 mL of 0.10 MMES buffer, and the pH was adjusted to 5.0. The solution was stirred and dissolved at 0–5 °C. Then, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl) and N-hydroxysuccinimide (NHS) were added to activate the carboxyl groups of the heparin oligosaccharide. The preferred molar ratio of the heparin oligosaccharide carboxyl groups, EDC·HCl, and NHS was 1:(1.0–1.5):(1.0–1.5), more preferably 1:1.2:1.2. After activation for 20–40 min, NH2-PEG-MA was added dropwise. The preferred molar ratio of the heparin oligosaccharide carboxyl groups to NH2-PEG-MA was 1:(0.8–1.2), more preferably 1:1.0. The reaction system temperature was maintained at 5–15 °C, and the reaction was continued for 8–12 h.

[0024] After the reaction was completed, the solution was dialyzed in deionized water for 24 hours using a dialysis bag with a molecular weight cutoff of 3500 Da, with the dialysate being replaced every 4 hours. Subsequently, ultrafiltration was used to further remove unreacted small molecules and inorganic salts. Finally, the resulting solution was lyophilized to obtain anticoagulant functional monomer powder.

[0025] The obtained anticoagulant functional monomer was characterized by ATR-FTIR, ¹H NMR, and elemental analysis. ATR-FTIR should show characteristic absorption peaks for sulfate and ester groups; ¹H NMR should show proton peaks for the PEG segment and proton peaks related to the methacrylate double bond; and the sulfur content in the sample should be significantly higher than that in the blank matrix resin. These results confirm the successful preparation of the anticoagulant functional monomer.

[0026] Example 1:

[0027] Preparation of S1 anticoagulant functional monomer: The anticoagulant functional monomer was prepared according to the above-mentioned method of "Preparation and characterization of anticoagulant functional monomer" and set aside for later use.

[0028] Preparation of S2 monomer system: 100 parts of acrylic acid and 150 parts of deionized water were added to the reactor. Sodium hydroxide solution was slowly added at 40°C under stirring conditions to partially neutralize the mixture until the degree of neutralization reached 70%, thus obtaining a monomer system containing acrylic acid and acrylate.

[0029] S3 polymerization into a gel: First, add 0.20 parts of the internal crosslinking agent polyethylene glycol diacrylate to the monomer system and stir for 10 min to disperse it evenly; then add the first initiator system for free radical polymerization. The first initiator system consists of potassium persulfate, sodium bisulfite, and ascorbic acid, with a preferred mass ratio of 1:(0.6-1.0):(0.2-0.5), preferably 1:0.8:0.4; the total amount of the first initiator system is 0.10 wt% based on the mass of acrylic acid. Polymerization is started at 35-45℃ and reacted for 2-5 min to obtain a gel polymer.

[0030] S4 base resin particle formation: The gel polymer is crushed, pre-dried at 80°C for 1 hour, and then dried at 150°C until the moisture content is less than 10%; then it is pulverized and sieved to obtain base resin particles with a particle size of 100-800 μm, of which the content of micro powder smaller than 106 μm is controlled below 1 wt%.

[0031] S5 Surface Crosslinking Treatment: Prepare a surface crosslinking solution by mixing 0.40 parts of ethylene carbonate and 0.20 parts of ethylene glycol diglycidyl ether, and spray it onto the surface of the base resin particles in two applications, mixing for 3 minutes after each application; then heat-treat at 165°C for 20 minutes to obtain surface crosslinked matrix resin particles.

[0032] S6 Surface Low-Temperature Grafting Fixation: The anticoagulant functional monomer and the second initiation system are formulated into a grafting treatment solution with a concentration of 5 wt%, and the spraying amount is 0.30 wt% of the mass of the surface cross-linked matrix resin particles. The second initiation system consists of potassium persulfate, sodium bisulfite, and ascorbic acid, and the preferred mass ratio of the three is 1:(0.8-1.2):(0.3-0.6), preferably 1:1.0:0.5; the total amount of the second initiation system is 0.02 wt% of the mass of the surface cross-linked matrix resin particles.

[0033] A dual-fluid pneumatic atomizing nozzle is used for spraying. The nozzle orifice diameter is preferably 0.3–0.5 mm, the atomization pressure is preferably 0.15–0.25 MPa, the spray rate is preferably 0.5–1.5 mL / min, and the median droplet size (D50) is preferably 20–60 μm. During spraying, the particle bed temperature is controlled at 25–30 °C, and the mixing speed is controlled at 30–60 rpm. By controlling the total spray volume, atomization pressure, and spray rate, the particles are kept in a free-flowing dynamic state without bridging or agglomeration. After spraying, particle slices are stained with toluidine blue, and the thickness of the stained layer accounts for 5%–25% of the particle radius. This is used as the criterion for "wetting only the outer surface of the particles".

[0034] After spraying, grafting and fixing are performed at 35°C for 30 minutes, followed by drying and granulation at 60°C for 40 minutes to obtain the medical-grade superabsorbent resin with anticoagulant function enriched on the surface of the present invention.

[0035] Preliminary experiments have verified that effective grafting can be achieved with a grafting solution concentration ranging from 3 to 8 wt%, with 5 wt% showing the best overall effect. The sample performance changes positively with the increase of the anticoagulant functional monomer spraying amount ranging from 0.1 to 0.5 wt%, with 0.30 wt% achieving a good balance between grafting efficiency and anti-agglomeration risk. Therefore, the above conditions are preferred in this embodiment.

[0036] Post-processing and residue control: The obtained samples were tested for residual acrylic acid, extractable small molecules, and water content. Residual acrylic acid was determined by liquid chromatography; extractable small molecules were extracted with pure water and then the total organic carbon was determined; the water content of the finished product was determined by loss on drying. Preferably, the residual acrylic acid was controlled to ≤500 ppm, the total amount of extractable small molecules was controlled to ≤1.0 wt%, and the water content of the finished product was controlled to 3%–8%.

[0037] Example 2:

[0038] Except for the grafting fixation temperature in step S6 being changed to 20°C, all other raw material specifications, atomization spraying parameters, initiation system composition, ratio, steps, and post-treatment conditions are the same as in Example 1. This example serves as a low-temperature boundary example to verify the surface grafting effect at a lower grafting temperature.

[0039] Example 3:

[0040] Except for the grafting fixation temperature in step S6 being changed to 50°C, all other raw material specifications, atomization spraying parameters, initiation system composition, ratio, steps, and post-treatment conditions are the same as in Example 1. This example serves as a high-temperature boundary example to verify the surface grafting effect at higher grafting temperatures.

[0041] Comparative Example 1: Basic resin particles and surface cross-linked matrix resin particles were prepared according to the method of Example 1, but the anticoagulant functional monomer grafting and fixation treatment in step S6 was not performed, resulting in blank surface cross-linked matrix resin particles.

[0042] Comparative Example 2: The base resin particles and the surface cross-linked matrix resin particles were prepared according to the method of Example 1; the anticoagulant functional monomer was directly sprayed onto the surface of the surface cross-linked matrix resin particles and then dried and granulated, but no second initiation system was added or grafting was performed, to obtain a physically sprayed sample.

[0043] Comparative Example 3: The basic resin particles were prepared according to the method of Example 1, but without the surface crosslinking treatment in step S5; then, surface grafting fixation was performed according to step S6 of Example 1 to obtain a grafted sample without surface crosslinking.

[0044] Test method: Grafting rate and surface enrichment characterization: The grafting rate was determined by elemental analysis. Since heparin-like oligosaccharides contain sulfur, while the blank matrix resin is essentially sulfur-free, the blank sample was used as a control. The grafting amount of anticoagulant functional monomers was calculated based on the total sulfur content of the sample, thus characterizing the grafting rate. The calculation method was: Grafting rate (%) = (Ssample - Smatrix) / Sfunctional monomer (theoretical value) × 100% (where Ssample is the sulfur content of the grafted sample, Smatrix is the sulfur content of the blank matrix resin, and Sfunctional monomer is the theoretical sulfur content calculated based on the sulfate content of heparin-like oligosaccharides in the anticoagulant functional monomers. In this embodiment, the theoretical value of Sfunctional monomer was calculated based on a heparin-like oligosaccharide sulfate content of 1.2 mmol / g and its molecular structure). Surface enrichment was determined by X-ray photoelectron spectroscopy (XPS) to measure the S2p content on the sample surface, compared with the blank sample; simultaneously, ATR-FTIR was used to detect changes in functional groups on the sample surface. Preferably, the percentage of sulfur atoms on the surface of the example sample is significantly higher than that of the blank sample, and the degree of sulfur enrichment on the surface is higher than the overall sulfur content change trend, to prove the formation of the anticoagulant functional structure enriched on the surface.

[0045] Centrifugal water retention ratio (CRC): Tested according to the method specified in GB / T22875—2018. After aspirating the sample from 0.9% physiological saline, centrifuge and calculate the CRC, in g / g.

[0046] Pressure Absorption Ratio (AUL): Tested according to the method specified in GB / T22875—2018. The amount of liquid absorbed by the resin sample in 0.9% physiological saline was determined under a pressure of 2.0 kPa, and the result is expressed in g / g.

[0047] Activated partial thromboplastin time (APTT) test: 0.10 g of sample powder was mixed with 1.0 mL of platelet-poor plasma obtained by anticoagulation with sodium citrate and centrifugation, and incubated at 37°C for 10 min; after adding APTT reagent and CaCl2 solution to the supernatant, APTT was measured using a fully automated coagulation analyzer, and the extension time was calculated based on the blank control sample.

[0048] This test uses platelet-poor plasma to eliminate interference from platelet coagulation activity, thereby specifically evaluating the material's inhibitory activity on the coagulation cascade (intrinsic pathway); the material's anti-clogging performance in actual blood-containing body fluid environments is comprehensively verified by dynamic clogging time testing.

[0049] Platelet adhesion rate test: The sample was pressed into a test piece with a diameter of 10 mm and a thickness of about 1 mm, and incubated with platelet-enriched plasma at 37°C for 30 min. After washing with PBS buffer to remove unadhered platelets, the number of platelets adhering to the sample surface was quantitatively analyzed by the lactate dehydrogenase (LDH) method, and the adhesion rate of the blank control sample was taken as 100%.

[0050] Dynamic clogging time test: A microfluidic clogging model was used for testing. The preferred chip channel width was 100 μm, and the preferred height was 80 μm. 0.50 g of sample was dispersed in 10 mL of simulated blood-containing high-protein body fluid, preferably containing 0.9% sodium chloride, 10 mg / mL bovine serum albumin, 2 mg / mL fibrinogen, and 2% red blood cell volume fraction. The sample was pumped into the channel at a constant flow rate of 0.20 mL / min, and pressure changes were monitored in real time. The clogging time was recorded when the channel pressure reached three times the initial pressure.

[0051] Moisture absorption and adhesion rate test: Take 5.0g of sample and place it in a constant temperature and humidity chamber at 40℃ and 75% relative humidity for 24h. Then pass it through a 250μm sieve, weigh the mass of the agglomerated part, and calculate the moisture absorption and adhesion rate according to the percentage of the mass of the agglomerated part to the total mass of the sample.

[0052] The main formulations and process parameters of the examples and comparative examples are shown below: Table 1. Comparison of main formulations and process parameters for examples and comparative examples.

[0053] The performance tests for the embodiments and comparative examples are as follows: Table 2 Comparison of Performance Test Results of Examples and Comparative Examples

[0054] As shown in Table 2, under the premise that CRC and AUL are basically maintained at a high level, Example 1 has the highest grafting rate, the highest surface sulfur content, the longest APTT extension time, the lowest platelet adhesion rate, and the longest clogging time. This indicates that when the surface is grafted at 35°C, the surface fixation effect of the anticoagulant functional monomer is the best, which can take into account both absorption performance and anti-clogging performance.

[0055] Although Example 2 achieved surface grafting, the grafting temperature was low, resulting in insufficient motive force for the second initiating system to initiate surface grafting. Therefore, the grafting rate, surface sulfur content, APTT extension time, and clogging time were all lower than those of Example 1. Although Example 3 could also form a grafted layer at a higher temperature, the increased side reactions led to a decrease in effective grafting efficiency. Consequently, its grafting rate, surface sulfur content, and overall performance were also lower than those of Example 1.

[0056] Comparative Example 1 shows that, without the introduction of anticoagulant functional monomers, although the basic absorption performance is acceptable, the anticoagulant and anti-clogging performance is significantly insufficient. Comparative Example 2 shows that, when only physical spraying is used without surface grafting fixation, the grafting rate and surface sulfur content are both low, the improvement in anticoagulant function is limited, and the clogging time is significantly shorter than in Example 1, indicating that surface covalent fixation is superior to simple physical loading. Comparative Example 3 shows that, without surface crosslinking treatment, even with surface grafting, the pressure absorption performance and clogging time of the sample still decrease significantly, and the hygroscopic adhesion rate increases significantly, indicating that surface crosslinking treatment plays an important role in maintaining particle surface strength, reducing adhesion, and improving anti-clogging performance.

[0057] In summary, this invention, through three grafting temperature examples (20℃, 35℃, and 50℃) and comparative examples of blank samples, physically sprayed samples, and uncrosslinked samples, demonstrates that the adopted "surface crosslinking and low-temperature surface grafting fixation" technique can improve anticoagulant properties and prolong clogging time while maintaining the absorption performance of the highly absorbent resin matrix. Among these, 35℃ is the optimal grafting temperature, achieving a good balance between absorption performance, anticoagulant properties, and anti-clogging performance.

[0058] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any ordinary changes and substitutions made by those skilled in the art within the scope of the technical solution of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing a medical-grade superabsorbent resin with surface enrichment of anticoagulant function, characterized in that, Includes the following steps: S1, heparin-like oligosaccharides are coupled in an aqueous phase with a modifier having polyethylene glycol spacer arms and polymerizable unsaturated groups, and then purified to obtain an anticoagulant monomer. S2, after mixing acrylic acid with water and partially neutralizing it, yields a monomer system containing acrylic acid and acrylate. S3, an internal crosslinking agent and a first initiator are added to the monomer system to carry out free radical polymerization to obtain a gel polymer; S4, the gel polymer is crushed, dried, pulverized and sieved to obtain basic resin particles; S5, the surface crosslinking agent is prepared into a surface crosslinking liquid and sprayed onto the surface of the base resin particles, followed by heat treatment to obtain surface crosslinked matrix resin particles. S6, the anticoagulant functional monomer and the second initiation system are formulated into a grafting solution and sprayed onto the surface of the surface cross-linked matrix resin particles. The grafting solution is controlled to only wet the outer surface layer of the particles. Under low temperature conditions, the anticoagulant functional monomer is grafted and fixed onto the surface of the surface cross-linked matrix resin particles. Then, the particles are dried and granulated to obtain a medical high absorbency resin with anticoagulant functional units enriched on the surface.

2. The method for preparing the medical superabsorbent resin with surface enrichment of anticoagulant function according to claim 1, characterized in that, The coupling reaction in step S1 includes: Heparin oligosaccharides were dissolved in buffer solution and activated at pH 4.5–6.

0. ​​Then, a modifier with polyethylene glycol spacer arms and polymerizable unsaturated groups was added to carry out a coupling reaction. The coupling reaction is carried out at a temperature of 0–25°C for 2–24 hours. After the coupling reaction is completed, the anticoagulant functional monomer is obtained by dialysis, ultrafiltration or precipitation purification.

3. The method for preparing the medical superabsorbent resin with surface enrichment of anticoagulant function according to claim 2, characterized in that, The molecular weight of the heparin-like oligosaccharide is 1–6 kDa; The molecular weight of the polyethylene glycol spacer arm is 400–2000 Da; The polymerizable unsaturated group is an acrylate group or a methacrylate group.

4. The method for preparing the medical superabsorbent resin with surface enrichment of anticoagulant function according to claim 3, characterized in that, In step S2, acrylic acid and water are mixed, and an alkaline neutralizing agent is added at a temperature below 40°C for partial neutralization until the degree of neutralization reaches 60% to 80%. The acrylic acid is 100 parts by mass, and the water is 120 to 180 parts by mass.

5. The method for preparing the medical superabsorbent resin with surface enrichment of anticoagulant function according to claim 4, characterized in that, In step S3, an internal crosslinking agent is first added to the monomer system and stirred evenly, and then the first initiation system is added to carry out free radical polymerization. The initiation temperature for the free radical polymerization is 20–60 °C.

6. The method for preparing the medical superabsorbent resin with surface enrichment of anticoagulant function according to claim 5, characterized in that, The internal crosslinking agent is methylene bisacrylamide or polyethylene glycol diacrylate; The amount of the internal crosslinking agent added is 0.05–1 wt% based on the mass of acrylic acid; The first initiation system is a redox initiation system composed of persulfate, bisulfite and ascorbic acid, and the total amount of the first initiation system is 0.05 to 0.5 wt% based on the mass of acrylic acid.

7. The method for preparing the medical superabsorbent resin with surface enrichment of anticoagulant function according to claim 6, characterized in that, The drying temperature in step S4 is 130–190°C; The basic resin particles obtained after sieving have a particle size of 100-800 μm, of which the content of micro powder with a particle size of less than 106 μm does not exceed 1 wt%.

8. The method for preparing the medical superabsorbent resin with surface enrichment of anticoagulant function according to claim 7, characterized in that, In step S5, the surface crosslinking liquid is sprayed onto the surface of the base resin particles in 2 to 4 applications. After each application, the mixture is mixed for 1 to 5 minutes before the next application. The amount of the surface crosslinking agent used is 0.2 to 1 wt% of the mass of the base resin particles; The heat treatment temperature is 140–190°C, and the treatment time is 5–60 min.

9. The method for preparing the medical superabsorbent resin with surface enrichment of anticoagulant function according to claim 8, characterized in that, The surface crosslinking agent is selected from one or more of polyethylene glycol diglycidyl ether, ethylene glycol diglycidyl ether, and ethylene carbonate.

10. The method for preparing the medical superabsorbent resin with surface enrichment of anticoagulant function according to claim 9, characterized in that, In step S6, the concentration of the grafting treatment solution is 3-8 wt%, and the amount sprayed is 0.1-0.5 wt% of the mass of the surface crosslinking matrix resin particles. The grafting treatment solution is applied by atomization spraying. The second initiation system is a redox initiation system composed of persulfate, bisulfite, and ascorbic acid, and the total amount of the second initiation system is 0.005–0.05 wt% of the mass of the surface crosslinked matrix resin particles; The grafting temperature is 20–50°C; After grafting and fixation, the grains are dried and granulated at 50–70°C.

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