Rare-earth-based anticoagulant coating for PVC pipeline and preparation method of rare-earth-based anticoagulant coating

Abstract

The invention provides a rare-earth-based anticoagulant coating for a PVC pipeline and a preparation method thereof, and the preparation method comprises the following steps: uniformly mixing a rare-earth-based complex with chitosan, citric acid, glycerol and deionized water, heating to obtain a colloidal mixed system, smearing the mixed system on the inner wall of the PVC pipeline, and drying to obtain the rare-earth-based anticoagulant coating for the PVC pipeline. And cooling and curing to obtain the rare earth-based anticoagulant coating. According to the rare-earth-based anticoagulant coating for the PVC pipeline, quaternary ammonium groups (N + (CH3) 3) of chitosan quaternary ammonium salt and a coordination hydration layer of rare earth ions have a synergistic effect, so that platelet adhesion is remarkably inhibited; the quaternary ammonium group is positively charged and can compete for adsorption with electronegative glycoprotein (GP Ib / IX / V) on the surface of the blood platelet through electrostatic interaction, so that the initial adhesion of the blood platelet is reduced.

Description

Technical Field

[0001] This invention belongs to the field of medical devices, and in particular relates to a rare earth-based anticoagulant coating for PVC pipes and its preparation method. Background Technology

[0002] Chitosan, a deacetylated product of chitin, possesses biocompatibility, biodegradability, and antibacterial properties, but its poor water solubility limits its applications. By introducing amino and quaternary ammonium groups through quaternization modification, the solubility of chitosan quaternary ammonium salt (CTSQ) is significantly improved, and its positive charge density increases, allowing it to interact more efficiently with negatively charged cell membranes (such as platelets) and proteins, thereby inhibiting adhesion and activation. Furthermore, the amino group of CTSQ can form coordination bonds with rare earth ions, stabilizing the rare earth complex structure and avoiding the toxicity risks caused by ion leakage. The anticoagulant mechanism of rare earth chlorides is mainly based on the antagonistic effect between rare earth ions and calcium ions. Rare earth ions and calcium ions are very similar in terms of ionic radius, Lewis acidity / basicity, oxygen affinity, and coordination properties. This similarity allows rare earth ions to mimic the role of calcium ions in the coagulation process, thereby interfering with it. Simultaneously, rare earth ions have one more positive charge than calcium ions, resulting in a higher charge density and a stronger binding capacity for oxygen-containing ligands. During coagulation, rare earth ions can competitively replace calcium ions and bind to γ-carboxylic acid glutamate residues in coagulation factors on phospholipids, forming more stable compounds. Furthermore, the stable compounds formed after rare earth ions bind to coagulation factors may affect the intact protein structure necessary for the coagulation process. This effect may disrupt the normal conformation of coagulation factors, thereby inhibiting thrombin activation and fibrin formation, achieving an anticoagulant effect.

[0003] In the selection of materials for practical medical devices, a single material is generally insufficient to meet various performance requirements. Therefore, the selection of materials for medical devices often involves the use of mixed ligands of multiple materials. In reality, the contact process between medical materials and human blood occurs within a portion of the material's surface atomic layer. Therefore, surface coating treatment is a direct, economical, and rapid solution to improve the anticoagulant properties of materials. By combining the advantages of coatings and substrates, medical devices can be developed towards superior performance, more stable quality, and lower costs. Summary of the Invention

[0004] In view of this, the present invention aims to overcome the defects in the prior art and proposes a rare earth-based anticoagulant coating for PVC pipes and its preparation method.

[0005] To achieve the above objectives, the technical solution of the present invention is implemented as follows: A method for preparing a rare earth-based anticoagulant coating for polyvinyl chloride (PVC) pipes includes the following steps: a rare earth-based complex is mixed evenly with chitosan, citric acid, glycerol, and deionized water, and then heated to obtain a gel-like mixture. This mixture is then applied to the inner wall of the PVC pipe, and after cooling and curing, the rare earth-based anticoagulant coating is obtained. Polyvinyl chloride (PVC) is a mainstream material for extracorporeal blood circulation tubing, possessing advantages such as low cost, good processability, and high transparency, facilitating clinical observation of blood conditions.

[0006] Furthermore, the solid-liquid ratio of the rare earth-based complex to chitosan, citric acid, glycerol, and deionized water is (8-12) g: (4-6) g: (2-4) g: (1-2) g: (90-100) mL.

[0007] Furthermore, the heating step is performed at a temperature of 80-100℃ for 2-4 hours; the curing step is performed at a time of 20-30 hours and a temperature of 20-25℃.

[0008] Furthermore, the rare earth-based complex is formed by doping rare earth compounds with chitosan quaternary ammonium salts.

[0009] Furthermore, the preparation method of the rare earth-based complex includes the following steps: dissolving chitosan quaternary ammonium salt in N,N-dimethylformamide solution, adding rare earth compound solution dropwise under heating conditions, cooling, filtering, and rinsing after reaction, then mixing the obtained precipitate with zirconium oxide and ball milling, and finally drying under vacuum to obtain the rare earth-based complex.

[0010] Furthermore, the mass ratio of the rare earth compound to the chitosan quaternary ammonium salt in the rare earth compound solution is 2:(1-2); the mass concentration of the rare earth compound solution is 15-25%.

[0011] Furthermore, the heating temperature in the preparation method of the rare earth-based complex is 40-60℃; the reaction time in the preparation method of the rare earth-based complex is 2-4 h; and the temperature of the vacuum drying step in the preparation method of the rare earth-based complex is 55-65℃.

[0012] Furthermore, the rare earth compound is at least one of yttrium chloride hexahydrate, gadolinium chloride hexahydrate, lanthanum chloride heptahydrate, or cerium chloride heptahydrate; the chitosan quaternary ammonium salt is hydroxypropyltrimethylammonium chloride chitosan.

[0013] The present invention also provides a rare earth-based anticoagulant coating for PVC pipes prepared by the aforementioned preparation method.

[0014] The present invention also provides a PVC pipe with the aforementioned rare earth-based anticoagulant coating on its surface.

[0015] Compared with the prior art, the present invention has the following advantages: The quaternary ammonium group (N) of the chitosan quaternary ammonium salt in the rare earth-based anticoagulant coating for PVC pipes described in this invention + (CH3)3) and the coordination hydration layer of rare earth ions synergistically inhibit platelet adhesion; the positively charged quaternary ammonium groups can compete with negatively charged glycoproteins (GP Ib / IX / V) on the platelet surface for adsorption through electrostatic interactions, reducing initial platelet adhesion; simultaneously, rare earth ions (such as Y) 3+ Gd 3+ Through hydration, a dynamic hydration layer is formed, covering the coating surface and hindering conformational changes of platelet membrane proteins (such as integrin αIIbβ3), thereby blocking the platelet activation signaling pathway. In addition, the 4f orbital electrons of rare earth ions can form weak coordination bonds with the carbonyl oxygen (C=O) in platelet membrane phospholipids, further stabilizing the platelet membrane structure and preventing the release of particulate contents (such as ADP and thromboxane A2), thus inhibiting thrombus formation at its source.

[0016] The rare earth ions (such as La) in the rare earth-based anticoagulant coating for PVC pipes described in this invention 3+ Ce 3+ Coordination competition can interfere with the activity of key enzymes in the coagulation cascade. For example, the active sites of coagulation factors Xa and IXa contain histidine residues (His), and the nitrogen atom of their imidazole groups can form a five-membered ring chelate structure with rare earth ions, causing conformational distortion of the enzyme active site and preventing it from binding to substrates (such as prothrombin). At the same time, the hydroxyl groups (-OH) of chitosan quaternary ammonium salts form a hydrogen bond network with rare earth ions, enhancing the stability of rare earth ions on the coating surface and prolonging their inhibitory effect on coagulation factors.

[0017] The rare earth ions (such as Y) in the rare earth-based anticoagulant coating for PVC pipes described in this invention 3+ Gd 3+ It can mimic the Ca in calmodulin. 2+The coating binds to specific sites, activating the integrin β1 subunit on the surface of endothelial cells (ECs), promoting their adhesion to fibronectin (FN), and accelerating endothelial regeneration. Simultaneously, the amino group (-NH2) of the chitosan quaternary ammonium salt binds to the tyrosine kinase receptor (VEGFR-2) of vascular endothelial growth factor (VEGF), forming a hydrogen-electrostatic complex that enhances the biological activity of VEGF and stimulates endothelial cell proliferation and migration. Furthermore, the 4f electron transition of rare earth ions generates weak photon radiation, activating nitric oxide synthase (eNOS) within endothelial cells, promoting nitric oxide (NO) synthesis, further inhibiting platelet aggregation and dilating blood vessels, forming a dual protective mechanism of "anticoagulation-promoting repair." This synergistic effect enables the coating to inhibit thrombosis while accelerating vascular endothelialization, reducing the risk of restenosis after long-term implantation. Attached Figure Description

[0018] Figure 1 This is a bar chart showing the blood clotting time in PVC pipes after applying a rare earth-based anticoagulant coating, as described in the embodiments and comparative examples of the present invention. Detailed Implementation

[0019] Unless otherwise defined, the technical terms used in the following embodiments have the same meanings as commonly understood by those skilled in the art. Unless otherwise specified, the experimental reagents used in the following embodiments are conventional biochemical reagents; and the experimental methods described are conventional methods.

[0020] The reagents and conventional consumables used in this invention, including chitosan quaternary ammonium salt, polyvinyl alcohol (PVA) particles, lanthanum chloride heptahydrate, cerium chloride heptahydrate, yttrium chloride hexahydrate, gadolinium chloride hexahydrate, anhydrous ethanol, glycerol, and hydrochloric acid, were all purchased from Maclean Chemical Company.

[0021] The present invention will be described in detail below with reference to the embodiments.

[0022] Example 1 A method for preparing a rare earth-based anticoagulant coating for PVC pipes includes the following steps: (1) Add 10 g of hydroxypropyltrimethylammonium chloride chitosan to 90 mL of N,N-dimethylformamide solution, and then place it on a 50℃ constant temperature magnetic stirrer and stir until it is completely dissolved to form a uniform transparent solution. Dissolve 20 g of cerium chloride heptahydrate in 100 mL of 3 mol / L dilute hydrochloric acid, keep the temperature at 50℃ and stir continuously for 3 h. After the reaction is completed, take out the reaction system and let it cool naturally to room temperature. At this time, a precipitate is formed. Use a vacuum filter to filter the precipitate at the bottom of the beaker. After collecting the precipitate, wash it with anhydrous ethanol 3-4 times to remove impurities and unreacted raw materials. Transfer the washed precipitate to a ball mill jar, add an appropriate amount of zirconia grinding balls, and use wet ball milling for 2 h to reduce the particle size of the material and make the particle distribution uniform. After the ball milling is completed, take out the material. Finally, put the processed material into a vacuum drying oven and vacuum dry it at 60℃ until the mass no longer changes, thus obtaining modified rare earth cerium chloride (Ce@HF) with anticoagulant effect. (2) Mix modified rare earth cerium chloride, chitosan particles, citric acid, glycerol and deionized water in a mass ratio of 10 g: 5 g: 3 g: 1 g: 95 mL (chitosan particles need to be deacetylated in advance to improve their solubility and reactivity), place in an oil bath, turn on the stirrer, set the temperature to 80℃, stir slowly to fully dissolve the chitosan, and at the same time, evenly disperse the modified rare earth cerium chloride powder in the solution, and add a small amount of 2% dilute acetic acid to assist in dissolution. Continue stirring to allow the citric acid and chitosan to fully cross-link and interact with the modified rare earth cerium chloride powder to form a uniform adhesive solution (total heating time is 2 h). During the reaction, closely observe the state of the adhesive solution to ensure that it is completely melted but not solidified. Use a homemade brush to apply it evenly to the inner wall of the PVC pipe, and then let it stand at room temperature for 24 h to complete the curing.

[0023] Example 2 The only difference from Example 1 is that the rare earth compound is yttrium chloride hexahydrate.

[0024] Example 3 The only difference from Example 1 is that the rare earth compound is lanthanum chloride heptahydrate.

[0025] Example 4 The only difference from Example 1 is that the rare earth compound is gadolinium chloride hexahydrate.

[0026] Comparative Example 1 The only difference from Example 1 is that the rare earth compound is replaced with silicon dioxide.

[0027] Comparative Example 2 The only difference from Example 1 is that the solid-liquid ratio of the rare earth-based complex to chitosan, citric acid, glycerol, and deionized water is 5g:5g:3g:2g:95mL.

[0028] Comparative Example 3 The only difference from Example 1 is that the solid-liquid ratio of the rare earth-based complex to chitosan, citric acid, glycerol, and deionized water is 10g:8g:3g:2g:95mL.

[0029] Comparative Example 4 The only difference from Example 1 is that the solid-liquid ratio of the rare earth-based complex to chitosan, citric acid, glycerol, and deionized water is 10g:5g:3g:0.5g:95mL.

[0030] Experiments were conducted on PVC pipes with rare earth-based anticoagulant coatings obtained from the various examples and comparative examples. Fresh blood from cattle slaughtered on the same day at the Tianjin Meat Processing Plant was used in the experiments. Approximately 1000 mL of the cattle blood was collected immediately and 500 U / L of heparin sodium was added. After mixing evenly, 7.0 mL of the blood was added to pipes without coating, as well as pipes prepared by Examples 1, 2, 3, 4, Comparative Examples 1, 2, 3, and 4, respectively. Three sets of experiments were conducted for each different pipe. The ends of the pipes were tightly sealed with hemostatic forceps and the timing was started. During the timing, the pipes were shaken once every 10-15 seconds, and the coagulation condition was observed and the time was recorded. In this experiment, the coagulation time was considered to be when the blood in the pipe was obviously viscous and adhered significantly to the pipe wall.

[0031] Blood clotting time in PVC pipes containing various rare earth-based anticoagulant coatings, such as Figure 1As shown, compared to the blank control tubing, the clotting time in the other four tubing types was prolonged, demonstrating that the rare earth-chitosan quaternary ammonium salt anticoagulant coating has a certain anticoagulant effect. Among them, Ce@HF showed the most significant effect, with a clotting time 12′13″ longer than the control group. Examples 2, 3, and 4 used yttrium chloride hexahydrate, lanthanum chloride heptahydrate, and gadolinium chloride hexahydrate as rare earth compounds, respectively. These differ from the modified rare earth cerium chloride (Ce@HF) used in Example 1. From the perspective of anticoagulant mechanism, different rare earth elements exhibit different anticoagulant properties due to their unique electronic structures and chemical properties. Cerium (Ce) has a special electronic configuration, and its modified cerium chloride (Ce@HF) may have... Superior ability to interact with blood components. For example, cerium ions may more easily interact with clotting factors and platelets in the blood, interfering with the initiation and progression of the coagulation process, thereby effectively inhibiting thrombus formation; while rare earth elements such as yttrium (Y), lanthanum (La), and gadolinium (Gd), although they also have certain biological activities, have different interaction patterns and intensities with blood components than cerium, and may not be able to interfere with the coagulation process as efficiently as cerium, resulting in a less effective anticoagulant effect than in Example 1; Comparative Examples 2, 3, and 4 mainly changed the solid-liquid ratio of the rare earth-based complex with chitosan, citric acid, glycerol, and deionized water, which affects the composition and properties of the coating, and thus affects the anticoagulant effect.

[0032] In Example 1, the chitosan, citric acid, glycerol, and other components underwent a suitable cross-linking reaction, forming a uniform, stable, and well-coagulated solution. In Comparative Example 2, the solid-liquid ratio of the rare earth-based complex to chitosan, citric acid, glycerol, and deionized water was 5g:5g:3g:2g:95mL. The reduced proportion of the rare earth-based complex may have weakened its effect in the coating, preventing it from fully interacting with blood components to exert its anticoagulant effect. Simultaneously, the relatively increased proportion of citric acid may have led to excessive cross-linking, resulting in a poorly coated solution. The structure is too dense, which affects its interaction with blood and reduces the anticoagulant effect; in Comparative Example 3, the solid-liquid ratio is 10g:8g:3g:2g:95mL, the proportion of chitosan is too high, which may change the aggregation state of chitosan in the coating, affecting its synergistic effect with rare earth complexes and other components, and is not conducive to the performance of anticoagulant properties; in Comparative Example 4, the solid-liquid ratio is 10g:5g:3g:0.5g:95mL, the proportion of citric acid is too low, which may lead to insufficient cross-linking reaction, unstable coating structure, and inability to effectively maintain the performance required for anticoagulation.

[0033] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing a rare earth-based anticoagulant coating for PVC pipes, characterized in that: The process includes the following steps: mixing a rare earth-based complex with chitosan, citric acid, glycerol, and deionized water until homogeneous, then heating the mixture to obtain a gel-like mixture. The mixture is then applied to the inner wall of a PVC pipe, and after cooling and curing, the rare earth-based anticoagulant coating is obtained.

2. The method for preparing a rare earth-based anticoagulant coating for PVC pipes according to claim 1, characterized in that: The solid-liquid ratio of the rare earth-based complex to chitosan, citric acid, glycerol, and deionized water is (8-12) g: (4-6) g: (2-4) g: (1-2) g: (90-100) mL.

3. The method for preparing a rare earth-based anticoagulant coating for PVC pipes according to claim 1, characterized in that: The heating step is performed at a temperature of 80-100℃ for 2-4 hours; the curing step is performed at a temperature of 20-25℃ for 20-30 hours.

4. The method for preparing a rare earth-based anticoagulant coating for PVC pipes according to claim 1, characterized in that: The rare earth-based complex is formed by doping rare earth compounds with chitosan quaternary ammonium salt.

5. The method for preparing a rare earth-based anticoagulant coating for PVC pipes according to claim 4, characterized in that: The preparation method of the rare earth-based complex includes the following steps: dissolving chitosan quaternary ammonium salt in N,N-dimethylformamide solution, adding rare earth compound solution dropwise under heating conditions, cooling, filtering and rinsing after reaction, mixing the obtained precipitate with zirconium oxide and ball milling, and finally drying under vacuum to obtain the rare earth-based complex.

6. The method for preparing a rare earth-based anticoagulant coating for PVC pipes according to claim 5, characterized in that: The mass ratio of rare earth compounds to chitosan quaternary ammonium salt in the rare earth compound solution is 2:(1-2); the mass concentration of the rare earth compound solution is 15-25%.

7. The method for preparing a rare earth-based anticoagulant coating for PVC pipes according to claim 5, characterized in that: The heating temperature in the preparation method of the rare earth-based complex is 40-60℃; the reaction time in the preparation method of the rare earth-based complex is 2-4 h; and the temperature of the vacuum drying step in the preparation method of the rare earth-based complex is 55-65℃.

8. The method for preparing a rare earth-based anticoagulant coating for PVC pipes according to claim 5, characterized in that: The rare earth compound is at least one of yttrium chloride hexahydrate, gadolinium chloride hexahydrate, lanthanum chloride heptahydrate, or cerium chloride heptahydrate; the chitosan quaternary ammonium salt is hydroxypropyltrimethylammonium chloride chitosan.

9. A rare earth-based anticoagulant coating for PVC pipes prepared by the preparation method according to any one of claims 5-8.

10. A PVC pipe with a surface coated with the rare earth-based anticoagulant coating of claim 9.

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