Recyclable blood sterilization nanoparticles, preparation method and application thereof

Abstract

The application relates to the technical field of biomedical materials, and discloses recyclable blood sterilization nano particles, a preparation method and application thereof. The preparation method of the recyclable blood sterilization nano particles comprises the following steps: reacting 2,2,6,6-tetramethyl-4-piperidinol and isocyanic acid propyl triethoxysilane to obtain a halamine precursor; adding the halamine precursor into a solvent, stirring, then adding ferric oxide nano particles to react to obtain N-Fe3O4; adding NaClO aqueous solution into deionized water to obtain a chlorination solution; adding the N-Fe3O4 into the chlorination solution to perform chlorination treatment to obtain recyclable blood sterilization nano particles; the recyclable blood sterilization nano particles have good blood compatibility and excellent antibacterial performance, can be used in blood sterilization materials, and provide auxiliary support materials for sepsis treatment.

Description

Technical Field

[0001] This invention belongs to the field of biomedical materials technology, specifically a recyclable blood sterilization nanoparticle, its preparation method, and its application. Background Technology

[0002] Sepsis is a life-threatening disease with high morbidity and mortality rates. It is a major health problem recognized worldwide. It is caused by an overgrowth of microorganisms in the circulating blood, which triggers a large amount of inflammation in the immune system, potentially damaging tissues and organs. Globally, more than 18 million people suffer from sepsis each year, with a mortality rate exceeding 20%. Furthermore, during the treatment of sepsis, the occurrence of bloodstream infections can exacerbate treatment risks and further infect organs.

[0003] Currently, blood disinfection on the market mainly relies on the physical interception of filtration membranes (such as hemodialysis membranes), primarily involving external treatment and removal before the blood is reinfused into the body. The antibacterial effect of hemodialysis membranes depends on the contact between the membrane surface and the blood, limiting the antibacterial range to the contact area and making it difficult to comprehensively eliminate pathogens circulating in the blood, resulting in low antibacterial specificity and coverage. While blood-flow contact sterilization avoids removing blood from the patient's body, recycling the sterilization materials presents challenges. Furthermore, the overuse of antibiotics and other antibacterial drugs easily leads to bacterial resistance, increasing the difficulty of treatment. Therefore, there is a need for nanoparticles with antibacterial properties that possess extremely high antibacterial performance during use, while also exhibiting good blood compatibility and recyclability. Summary of the Invention

[0004] To address the aforementioned technical problems, this invention aims to prepare and study a recyclable blood-sterilizing nanoparticle for application in blood disinfection materials in the biomedical field. This would provide auxiliary support for the treatment of sepsis, reduce the risk of blood infection during treatment, and ensure that the material possesses good biocompatibility, efficient blood sterilization performance, and recyclability.

[0005] To achieve the above objectives, the present invention provides a method for preparing recyclable blood-sterilizing nanoparticles, comprising the following steps: Step 1: Mix 2,2,6,6-tetramethyl-4-piperidinol, propyltriethoxysilane isocyanate and acetone, stir, react, and distill under reduced pressure to obtain the haloamine precursor; Step 2: Add the haloamine precursor to the solvent, stir, then add iron oxide nanoparticles, react, wash, and obtain N-Fe3O4. Step 3: Add NaClO aqueous solution to deionized water, stir, and adjust pH to obtain chlorination solution; add N-Fe3O4 to chlorination solution for chlorination treatment to obtain halogenated iron(III) oxide, from which blood sterilization nanoparticles can be recovered.

[0006] Preferably, in step one, the molar ratio of 2,2,6,6-tetramethyl-4-piperidinol to propyltriethoxysilane isocyanate is (0.5-2):1.

[0007] Preferably, in step one, the reaction conditions for 2,2,6,6-tetramethyl-4-piperidinol and propyltriethoxysilane isocyanate are: reaction at 30-50 °C for 1-3 h under a nitrogen atmosphere.

[0008] Preferably, in step two, the mass ratio of the haloamine precursor to the iron oxide nanoparticles is 1:1; and the particle size of the iron oxide nanoparticles is 15-30 nm.

[0009] Preferably, in step two, the solvent includes at least one of ethanol, water, N,N-dimethylformamide, and acetone.

[0010] Preferably, in step two, the reaction conditions for the haloamine precursor and the iron oxide nanoparticles are as follows: first, the reaction is carried out at 70-90℃ for 4-16 hours, and then the solvent is evaporated, followed by a reaction at 45-160℃ for 2-5 minutes.

[0011] Preferably, in step two, the detergent used for washing includes any one of ethanol, water, N,N-dimethylformamide, and acetone.

[0012] Preferably, in step three, the mass ratio of the NaClO aqueous solution to deionized water is 1:9; the effective chlorine content in the chlorination solution is 6-14 wt%; and the pH of the chlorination solution is 4-9.

[0013] Preferably, in step three, the mass ratio of N-Fe3O4 to chlorination liquid is (1-5):100.

[0014] Preferably, in step three, the chlorination treatment conditions are: temperature 10-37℃ and time 1-2h.

[0015] The recyclable blood sterilization nanoparticles were prepared using the aforementioned method.

[0016] The recyclable blood-sterilizing nanoparticles can be used in blood-sterilizing materials.

[0017] Compared with the prior art, the beneficial effects of the present invention are as follows: 1. This invention prepares recyclable blood-sterilizing nanoparticles (i.e., Cl-N-Fe3O4), comprising magnetic iron oxide nanoparticles and a haloamine antibacterial structure on the surface. The haloamine antibacterial structure simultaneously possesses both a six-membered ring amine haloamine structure and a linear amide haloamine structure. Due to the influence of the conjugated molecular structure and spatial structure on the electron density of nitrogen atoms, the six-membered ring structure exhibits greater stability than the linear structure. Furthermore, the lower polarity of the haloamine bond gives the amine haloamine structure superior stability compared to the amide haloamine structure. Therefore, the six-membered ring amine haloamine structure in the haloamine antibacterial structure of this invention increases the active sites of the haloamine while ensuring the long-term stability of the haloamine antibacterial structure in the blood environment. Furthermore, the carbonyl group at the ortho position in the linear amide halogen amine in the halogen amine antibacterial structure generates a strong electron-withdrawing effect on the halogen amine bond, increasing the polarity of the halogen amine bond and making it more prone to hydrolysis to release the bactericidal active chlorine component. Therefore, the linear amide halogen amine has high release properties, which can ensure rapid and efficient bactericidal performance during use. Thus, under the synergistic effect of the six-membered ring amine halogen amine structure and the linear amide halogen amine structure, blood bactericidal nanoparticles can not only completely kill all microorganisms in a short time, but also have long-lasting bactericidal effect, and also have good antibacterial properties in blood flow. They can be used in blood bactericidal materials to provide auxiliary support materials for the treatment of sepsis and reduce the risk of blood infection during treatment.

[0018] 2. The recyclable blood sterilization nanoparticles of the present invention also have good blood compatibility and recycling characteristics. Attached Figure Description

[0019] Figure 1 This is a schematic diagram of the structure of the recyclable blood sterilization nanoparticles prepared in Examples 1-3 of the present invention; Figure 2 This is a schematic diagram illustrating the synthesis of the haloamine precursors in Examples 1-3 of the present invention; Figure 3 This is the NMR spectrum of the haloamine precursor prepared in Example 1 of this invention; Figure 4 This is a TEM image of the recyclable blood sterilization nanoparticles (Cl-N-Fe3O4) prepared in Example 1 of this invention; Figure 5 Real-world images of red blood cells after testing with iron oxide nanoparticles, N-Fe3O4 prepared in Example 1, and recyclable blood sterilization nanoparticles (Cl-N-Fe3O4); Figure 6 Comparison of hemolysis rate test results in blood for Fe3O4 nanoparticles, N-Fe3O4 prepared in Example 1, and recyclable blood sterilization nanoparticles (Cl-N-Fe3O4). Detailed Implementation

[0020] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0021] Example 1 This embodiment discloses a method for preparing recyclable blood-sterilizing nanoparticles, including the following steps: Step 1: In a 150 mL round-bottom flask, add 7.86 g (0.05 mol) of 2,2,6,6-tetramethyl-4-piperidinol (TMP), 12.37 g (0.05 mol) of propyltriethoxysilane isocyanate (ICPES), and 50 mL of acetone. Stir the mixture and react at 40 °C for 2 h under a nitrogen atmosphere. Then, remove the acetone solvent by vacuum distillation at 50 °C to obtain the product, which is a haloamine precursor named TPES, with a yield of approximately 80%. Step 2: Take a certain amount of halogen amine precursor (TPES) and dissolve it in 50 mL of solvent (30 mL of water and 20 mL of ethanol). Add iron oxide nanoparticles of the same mass as the halogen amine precursor, stir evenly, and react at 80 °C for 6 h. After the solvent is evaporated, react the above mixture in an oven at 150 °C for 3 min. Wash it clean with ethanol to obtain N-Fe3O4. Step 3: Mix NaClO aqueous solution and deionized water at a mass ratio of 1:9, stir evenly, and adjust the pH to 4 with a 0.1 mol / L sulfuric acid solution to obtain a chlorination solution with an effective chlorine content of 10 wt%. Place N-Fe3O4 in the chlorination solution at a mass ratio of 1:100 to completely submerge N-Fe3O4 in the solution, and chlorinate at 37℃ for 2 h to obtain haloaminated iron(III) oxide, which is named Cl-N-Fe3O4. Blood sterilization nanoparticles can then be recovered.

[0022] Example 2 This embodiment discloses a method for preparing recyclable blood-sterilizing nanoparticles, including the following steps: Step 1: In a 150 mL round-bottom flask, add 3.93 g (0.025 mol) of 2,2,6,6-tetramethyl-4-piperidinol (TMP), 12.37 g (0.05 mol) of propyltriethoxysilane isocyanate (ICPES), and 50 mL of acetone. Stir the mixture and react at 35 °C for 2 h under a nitrogen atmosphere. Then, remove the acetone solvent by vacuum distillation at 50 °C to obtain the product, which is a haloamine precursor named TPES, with a yield of approximately 50%. Step 2: Take a certain amount of halogen amine precursor (TPES) and dissolve it in 50 mL of solvent (30 mL of water and 20 mL of ethanol). Add iron oxide nanoparticles of the same mass as the halogen amine precursor, stir evenly, and react at 80 °C for 6 h. After the solvent is evaporated, react the above mixture in an oven at 150 °C for 3 min. Wash it clean with ethanol to obtain N-Fe3O4. Step 3: Mix NaClO aqueous solution and deionized water at a mass ratio of 1:9, stir evenly, and adjust the pH to 9 with 0.1 mol / L sulfuric acid solution to obtain a chlorination solution with an effective chlorine content of 10 wt%. Place N-Fe3O4 in the chlorination solution at a mass ratio of 5:100 to completely submerge N-Fe3O4 in the solution, and chlorinate at 20℃ for 2 h to obtain haloaminated iron(III) oxide, which is named Cl-N-Fe3O4, and the blood sterilization nanoparticles can be recovered.

[0023] Example 3 This embodiment discloses a method for preparing recyclable blood-sterilizing nanoparticles, including the following steps: Step 1: In a 150 mL round-bottom flask, add 15.72 g (0.1 mol) of 2,2,6,6-tetramethyl-4-piperidinol (TMP), 12.37 g (0.05 mol) of propyltriethoxysilane isocyanate (ICPES), and 50 mL of acetone. Stir the mixture and react at 50 °C for 3 h under a nitrogen atmosphere. Then, remove the acetone solvent by vacuum distillation at 50 °C to obtain the product, which is a haloamine precursor named TPES, with a yield of approximately 90%. Step 2: Take a certain amount of halogen amine precursor (TPES) and dissolve it in 50 mL of solvent (30 mL of water and 20 mL of ethanol). Add iron oxide nanoparticles of the same mass as the halogen amine precursor, stir evenly, and react at 80 °C for 6 h. After the solvent is evaporated, react the above mixture in an oven at 150 °C for 3 min. Wash it clean with ethanol to obtain N-Fe3O4. Step 3: Mix NaClO aqueous solution and deionized water at a mass ratio of 1:9, stir evenly, and adjust the pH to 7 with a 0.1 mol / L sulfuric acid solution to obtain a chlorination solution with an effective chlorine content of 10 wt%. Place N-Fe3O4 in the chlorination solution at a mass ratio of 2:100 to completely submerge N-Fe3O4 in the solution, and chlorinate at 37℃ for 2 h to obtain haloaminated iron(III) oxide, which is named Cl-N-Fe3O4. Blood sterilization nanoparticles can then be recovered.

[0024] Comparative Example 1 This comparative example discloses a method for preparing cyclic haloamine-modified iron(III) oxide, comprising the following steps: Step 1: In a 250 mL round-bottom flask, add 7.86 g (0.05 mol) of 2,2,6,6-tetramethyl-4-piperidinol (TMP), 1.20 g (0.05 mol) of sodium hydride, and 100 mL of tetrahydrofuran. Stir the mixture and react at 25 °C for 30 min under a nitrogen atmosphere. Then add 6.11 g (0.05 mol) of bromopropene and continue the reaction at 65 °C for 4 h. After filtration and vacuum distillation, intermediate product I is obtained with a yield of approximately 80%. Intermediate product I, 8.65 g (0.05 mol) of triethoxysilane, and 150 mL of anhydrous acetone are stirred continuously under a nitrogen atmosphere. Then add 20 μL of 2 wt% chloroplatinic acid / isopropanol solution and react at 75 °C and 100 °C for 4 h, respectively. After vacuum distillation, final product II is obtained with a yield of approximately 70%. Step 2: Take a certain amount of final product II and dissolve it in 50 mL of solvent (30 mL of water and 20 mL of ethanol). Add an equal mass of iron(II) nanoparticles and stir until homogeneous. React at 80 °C for 6 h. After the solvent is evaporated, react the mixture in an oven at 150 °C for 3 min. Wash with ethanol to obtain cyclic halogen amine precursor modified Fe3O4 particles (i.e., cyclic amine halogen amine precursor modified Fe3O4 particles). Step 3: Mix NaClO aqueous solution and deionized water at a mass ratio of 1:9, stir evenly, and adjust the pH to 7 with 0.1 mol / L sulfuric acid solution to obtain a chlorination solution with an effective chlorine content of 10 wt%. Place the cyclic haloamine precursor modified Fe3O4 particles in the chlorination solution at a mass ratio of 2:100, and chlorinate at 37℃ for 2 h to obtain cyclic haloamine modified iron(III) oxide.

[0025] Comparative Example 2 This comparative example discloses a method for preparing linear haloamine-modified iron(III) oxide, comprising the following steps: Step 1: In a 250 mL round-bottom flask, add 12.37 g (0.05 mol) of propyltriethoxysilane isocyanate (ICPES), 0.01 g of dibutyltin dilaurate, 80 mL of acetone, and 70 mL of tetrahydrofuran. Stir the mixture at 50 °C under a nitrogen atmosphere until homogeneous. Then add 6.91 g (0.05 mol) of terephthalic acid and continue the reaction at 50 °C for 4 h. After separation, washing with water, and vacuum drying, the final product I is obtained, with a yield of approximately 70%. Step 2: Take a certain amount of final product I and dissolve it in 50 mL of solvent (30 mL of water and 20 mL of ethanol). Add an equal mass of iron(III) oxide nanoparticles to the final product I, stir evenly, and react at 80 °C for 6 h. After the solvent is evaporated, react the above mixture in an oven at 150 °C for 3 min. Wash it clean with ethanol to obtain linear haloamine precursor modified Fe3O4 particles (i.e., linear amide haloamine precursor modified Fe3O4 particles). Step 3: Mix NaClO aqueous solution and deionized water at a mass ratio of 1:9, stir evenly, and adjust the pH to 7 with 0.1 mol / L sulfuric acid solution to obtain a chlorination solution with an effective chlorine content of 10 wt%. Place the linear haloamine precursor modified Fe3O4 particles in the chlorination solution with a mass ratio of linear haloamine precursor modified Fe3O4 particles to chlorination solution of 2:100, and chlorinate at 37℃ for 2 h to obtain linear haloamine modified iron(III) oxide.

[0026] Experimental Example I. The haloamine precursor and recyclable blood-sterilizing nanoparticles prepared in Example 1 of this invention were characterized and tested, and the results are as follows: Figure 3-4 As shown, where, Figure 3 This is the NMR spectrum of the haloamine precursor prepared in Example 1 of this invention. Figure 3 As can be seen, the number of hydrogen atoms in the proton NMR spectrum is consistent with the molecular structure of the compound, proving the successful synthesis of the haloamine precursor. The following data can be obtained from the analysis: 7.20 (J = 5.9 Hz, 1H), 5.26 – 5.10 ( 9H), 4.35 (J = 6.7 Hz, 2H), 3.92 (J = 1.8 Hz, 2H), 3.09 (J = 13.7, 13.0, 4.1 Hz, 3H), 2.68 (1H), 2.56 (J =14.0 Hz, 12H), 2.43 (6H), 2.31 (J = 11.7 Hz, 2H), 1.94 – 1.88 (2H).

[0027] Figure 4 This is a TEM image of the recyclable blood-sterilizing nanoparticles prepared in Example 1 of this invention. Figure 4 It is known that the particle size of the recyclable blood sterilization nanoparticles (Cl-N-Fe3O4) varies from 15 to 30 nm. By comparing the lattice structure, it is confirmed that the microstructure of the synthesized material belongs to the regular cubic crystal system and has an obvious anti-spinel structure with octahedral and tetrahedral voids.

[0028] II. Blood Antibacterial Rate Test 1. Static Blood Antibacterial Rate Test: The antibacterial properties of iron oxide nanoparticles, N-Fe3O4 prepared in Example 1, recyclable blood-sterilizing nanoparticles (Cl-N-Fe3O4) prepared in Examples 1-3, cyclic halogenated amine-modified iron oxide prepared in Comparative Example 1, and linear halogenated amine-modified iron oxide prepared in Comparative Example 2 in static blood were tested. The test method is as follows: 0.1 mL of bacterial suspension is added to 10 mL of sheep blood and mixed evenly. Then, 0.1 g of sample is added and cultured for 10 min. After centrifugation and set aside, 0.5 mL of suspension is added to 4.5 mL of sodium thiosulfate solution (0.01 mol / L) for quenching. The above mixed solution is then serially diluted and dropped onto a plate. After incubation at 37 ℃ for 24 h, the colony count is calculated.

[0029] The test results are shown in Table 1: Table 1 Results of Static Blood Antibacterial Rate Test

[0030] As shown in Table 1, the antibacterial effect of Cl-N-Fe3O4 was the best in Examples 1 and 3, completely killing Staphylococcus aureus, Escherichia coli, and Candida albicans within the specified contact time. In Example 2, due to the control of process and conditions, its antibacterial effect was slightly worse, but the antibacterial rate against Staphylococcus aureus and Escherichia coli could reach over 99%, and the antibacterial rate against Candida albicans could reach over 85%. In order to intuitively analyze the role of cyclic amine haloamine structures and linear amide haloamine structures in the haloamine structure of Cl-N-Fe3O4 in the antibacterial effect of the samples in blood, the static antibacterial performance of cyclic haloamine-modified iron(III) oxide (cyclic amine, Comparative Example 1) and linear haloamine-modified iron(III) oxide (linear amide, Comparative Example 2) in blood was analyzed. It can be found that due to the high release of linear haloamine structures, Comparative Example 2 effectively killed Staphylococcus aureus, Escherichia coli, and Candida albicans within the specified time. The antibacterial rates of the two compounds reached 99.85%, 99.75%, and 98.92%, respectively. In Comparative Example 1, the haloamine is a cyclic amine structure, and its antibacterial rates against Staphylococcus aureus, Escherichia coli, and Candida albicans reached 91.64%, 95%, and 90.71%, respectively. In comprehensive comparison, under suitable conditions, Cl-N-Fe3O4 exhibits both cyclic amine haloamine structures and linear amide haloamine structures in its structure. The linear amide haloamine ensures its high bactericidal performance during use. The carbonyl group at the ortho position in the linear amide haloamine produces a strong electron-withdrawing effect on the haloamine bond, increasing the polarity of the haloamine bond and making it more prone to hydrolysis, thereby releasing the bactericidal active chlorine component. The six-membered cyclic amine haloamine, while ensuring the low polarity of its haloamine bond, further enhances the hydrolysis resistance of the haloamine bond through its conjugated molecular structure and spatial structure, thus ensuring the stability of the haloamine structure in the blood environment and achieving excellent static blood bactericidal effect.

[0031] 2. Dynamic Blood Antibacterial Rate Test: The antibacterial properties of the recyclable blood-sterilizing nanoparticles (Cl-N-Fe3O4) prepared in Examples 1-3, the cyclic haloamine-modified iron(III) oxide prepared in Comparative Example 1, and the linear haloamine-modified iron(III) oxide prepared in Comparative Example 2 in dynamic blood were tested. The test method was as follows: Using goat blood as a sample, the dynamic antibacterial properties of the blood were tested. 0.05 mL of *E. coli* bacterial suspension was poured into 5 mL of goat blood and vortexed to obtain a homogeneous bacterial blood solution. The bacterial blood solution was loaded onto a syringe pump and slowly injected into a catheter at a certain speed. 0.05 g of sterilizing nanoparticles were added to 5 mL of sterile PBS and mixed thoroughly, then mixed with the bacterial blood solution at the same rate. After the designed mixing times (2 min, 10 min, 20 min), the mixture of antibacterial solution and bacterial blood solution was collected at the end of the syringe and the sample was collected using a strong magnet. The collected blood sample was serially diluted and evenly added to an agar plate. After incubation at 37°C for 24 h, the colony count was calculated. The antibacterial rate of the sample was calculated based on the obtained colony count.

[0032] The test results are shown in Table 2: Table 2 Results of dynamic blood antibacterial rate test

[0033] As shown in Table 2, the trend of dynamic blood sterilization is consistent with that of static blood antibacterial effect; the slower the blood flow rate and the longer the contact time, the better the final antibacterial effect. For the examples, due to differences in specific processes, the antibacterial rates varied, with the highest antibacterial rate reaching 93.37%. The dynamic blood antibacterial performance of cyclic halogenated amine-modified iron oxide samples (cyclic amines, Comparative Example 1) and linear halogenated amine-modified iron oxide samples (linear amides, Comparative Example 2) was analyzed. It was found that due to the high release of the linear halogenated amine structure, Comparative Example 2 exhibited a higher antibacterial effect after 20 minutes of treatment at a flow rate of 0.25 mL / min. The minimum antibacterial rate can reach 86.36%. Similar to the static blood antibacterial performance, the carbonyl group at the ortho position in linear amide haloamines has a strong electron-withdrawing effect on the haloamine bond, increasing the polarity of the haloamine bond and making it easier to hydrolyze and release the bactericidal active chlorine component. In Comparative Example 1, the haloamine has a cyclic structure, and the antibacterial rate can reach 73.64% under the same treatment conditions. While ensuring the low polarity of its haloamine bond, the six-membered cyclic amine haloamine has a conjugated molecular structure and spatial structure that further enhances the anti-hydrolysis ability of the haloamine bond, making its antibacterial performance insufficient in the short-term action range. In summary, under suitable conditions, the examples can achieve the ideal dynamic blood sterilization effect.

[0034] III. Storage Stability Test Test method: The recyclable blood sterilization nanoparticles (Cl-N-Fe3O4) prepared in Examples 1-3, the cyclic haloamine-modified iron(III) oxide prepared in Comparative Example 1, and the linear haloamine-modified iron(III) oxide prepared in Comparative Example 2 were placed under light-protected conditions and removed at different time intervals. The chlorine content of the samples was tested, and the storage stability of the samples was judged by the retention rate of chlorine content. The relevant results are shown in Table 3. Table 3 Storage stability test results

[0035] As shown in Table 3, the initial chlorine content in Examples 1 and 3 was relatively high, while the chlorine content in Example 2 was relatively low. In all three examples, after 30 days of storage in the dark, the overall chlorine retention rate was between 60% and 65%, indicating that the nanoparticles still exhibited good antibacterial effects. However, in Comparative Example 1 (cyclic amine haloamine), although the chlorine retention rate reached 70%, its initial chlorine content was low, making it unable to achieve a high antibacterial rate in actual use. Although the cyclic structure in the haloamine structure reduces the decomposition rate of the N-Cl bonds through the conjugated system and spatial conformation, for powder samples, the chlorine content must be at least 0.5 wt% to ensure sufficient antibacterial performance in actual use. As for Comparative Example 2 (linear amide haloamine), although its initial chlorine content was high, its chlorine retention rate after 30 days was only 27%, which could not meet the basic requirements for blood disinfection. This is because the α-hydroxyl content of the halogen amine structure in the linear structure... Elimination, hydrolysis, and rearrangement processes make it easier for halogenated amine bonds to break, which inhibits their antibacterial properties to some extent. Referring to Examples 1 and 3, the introduction of the six-membered ring structure increases the active sites of the halogenated amine, and the high stability of the six-membered ring structure can ensure that the material still has good antibacterial properties after long-term storage.

[0036] IV. Blood compatibility test The hemolysis rates of iron oxide nanoparticles, N-Fe3O4 prepared in Example 1, and recyclable blood sterilization nanoparticles (Cl-N-Fe3O4) in blood were tested. A hemolysis rate of less than 5% indicates good blood compatibility. Test method: Goat blood was used as the sample to test the blood compatibility of the sample. 10 mL of goat blood was centrifuged at 3000 rpm for 5 min, the supernatant was removed, and an appropriate amount of PBS solution (PBS:H2O=1:9, the same below) was added to wash the red blood cell liquid 3 times. 1 mL of red blood cell pellet was centrifuged and 19 mL of PBS solution was added to prepare red blood cell suspension (RCS) for later use. 1 mL of RCS was added to 4 mL of PBS and mixed with 2.5 mg of sample. The mixture was then cultured in a constant temperature shaker at 37℃ for 2 h. After the culture was completed, the above mixed solution was centrifuged (2000 rpm, 5 min), and the supernatant was tested by ultraviolet spectrophotometry. The final blood compatibility of the sample was calculated according to formula (1). 5 mL of deionized water was used as the positive control sample. 1 mL of RCS was mixed with 4 mL of deionized water as the negative control sample. (1); Test results are as follows Figure 5 , Figure 6 As shown, where: Figure 5 Real-world images of red blood cells after testing with iron oxide nanoparticles, N-Fe3O4 prepared in Example 1, and recyclable blood sterilization nanoparticles (Cl-N-Fe3O4); Figure 6 Comparison of hemolysis rate test results in blood for Fe3O4 nanoparticles, N-Fe3O4 prepared in Example 1, and recyclable blood sterilization nanoparticles (Cl-N-Fe3O4); Depend on Figure 5 and Figure 6 It can be seen that, Figure 5 The compatibility of the sample with red blood cells was directly demonstrated. After long-term treatment, the red blood cells did not rupture significantly, and their compatibility with the sample was good. Depend on Figure 6 It can be seen that the hemolysis rate of iron oxide nanoparticles in blood is 1.97%, the hemolysis rate of N-Fe3O4 prepared in Example 1 in blood is 0.569%, and the hemolysis rate of Cl-N-Fe3O4 prepared in Example 1 in blood is 0.673%. The blood solubility test values ​​are all less than 5%, which proves that the Cl-N-Fe3O4 series powders prepared in the embodiments of the present invention have good blood compatibility.

[0037] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A method for preparing a recyclable blood sterilization nanoparticle, characterized by, Includes the following steps: Step 1: Mix 2,2,6,6-tetramethyl-4-piperidinol, propyltriethoxysilane isocyanate, and acetone, stir, and react at 30-50 °C for 1-3 h under a nitrogen atmosphere. Distill under reduced pressure to obtain the haloamine precursor; wherein the molar ratio of 2,2,6,6-tetramethyl-4-piperidinol to propyltriethoxysilane is (0.5-2):

1. Step 2: Add the haloamine precursor to the solvent, stir, then add iron oxide nanoparticles, react, wash, and obtain N-Fe3O4. Step 3: Add NaClO aqueous solution to deionized water, stir, and adjust pH to obtain chlorination solution; add N-Fe3O4 to chlorination solution for chlorination treatment to obtain recyclable blood sterilization nanoparticles.

2. The method for preparing recyclable blood-sterilizing nanoparticles according to claim 1, characterized in that, In step two, the mass ratio of the haloamine precursor to the iron oxide nanoparticles is 1:1; the particle size of the iron oxide nanoparticles is 15-30 nm.

3. The method for preparing recyclable blood-sterilizing nanoparticles according to claim 1, characterized in that, In step two, the reaction conditions for the haloamine precursor and the iron oxide nanoparticles are as follows: first, the reaction is carried out at 70-90 °C for 4-16 h, and then the solvent is evaporated and the reaction is carried out at 45-160 °C for 2-5 min.

4. The method for preparing recyclable blood-sterilizing nanoparticles according to claim 1, characterized in that, In step three, the mass ratio of the NaClO aqueous solution to deionized water is 1:9; the available chlorine content in the chlorination solution is 6-14 wt%; and the pH of the chlorination solution is 4-9.

5. The method for preparing recyclable blood-sterilizing nanoparticles according to claim 1, characterized in that, In step three, the mass ratio of N-Fe3O4 to chlorination liquid is (1-5):

100.

6. The method for preparing recyclable blood-sterilizing nanoparticles according to claim 1, characterized in that, In step three, the chlorination treatment conditions are: temperature 10-37℃, time 1-2 h.

7. Recyclable blood sterilization nanoparticles prepared by the method for preparing recyclable blood sterilization nanoparticles as described in any one of claims 1-6.

8. The application of the recyclable blood sterilization nanoparticles according to claim 7 in the preparation of blood sterilization materials.

Images