Functionalized nanofiber material, method for preparing the same and use thereof

Abstract

The application provides a functionalized nanofiber material and a preparation method and application thereof, and the preparation method comprises the following steps: (1) adding raw materials into water to form an electrospinning solution; and obtaining a nanofiber membrane after electrospinning; (2) performing crosslinking on the nanofiber membrane in an organic solvent under acid catalysis to obtain a crosslinked nanofiber membrane; (3) performing grafting reaction on the crosslinked nanofiber membrane in a polyamine crosslinking agent, and then performing reaction with a sulfur-containing reagent to obtain the functionalized nanofiber material; the functionalized nanofiber material prepared by the application has the advantages of large adsorption capacity, fast adsorption rate, strong selectivity, good biocompatibility and stable structure, and can efficiently and safely remove heavy metal ions in blood plasma, and solves many defects existing in the prior art adsorption materials.

Description

Technical Field

[0001] This invention relates to the field of membrane separation technology, and in particular to a functionalized nanofiber material, its preparation method, and its application. Background Technology

[0002] Heavy metals (such as lead, mercury, cadmium, etc.) are a class of environmental pollutants with significant biotoxicity. With the acceleration of industrialization and the aggravation of environmental pollution, the risk of human exposure to heavy metals through the respiratory tract, digestive tract, and skin is increasing daily. Heavy metals that enter the human body are difficult to biodegrade and tend to accumulate, especially after binding with proteins in the blood (such as albumin). They can then circulate throughout the body, causing irreversible damage to the nervous system, kidneys, liver, and skeletal system, leading to chronic poisoning and even cancer.

[0003] Traditional treatments for heavy metal poisoning primarily rely on chelation therapy. However, this method has significant limitations: First, it is non-specific. While chelating agents bind toxic heavy metals, they also chelate essential metal ions in the body (such as calcium, zinc, and copper), leading to electrolyte imbalances and trace element deficiencies. Second, it has side effects: long-term or high-dose use of chelating agents may cause serious side effects such as liver and kidney damage and allergic reactions. Third, it has limited efficiency: for heavy metals tightly bound to proteins or already deposited in deep tissues, the removal efficiency of chelating agents is low.

[0004] Against this backdrop, technologies for the direct physical removal of heavy metals from blood or plasma have emerged and demonstrated enormous potential. Blood, as the primary carrier for the transport and distribution of heavy metals in the body, has become an ideal target for in vitro removal strategies. Plasma, comprising over 55% of blood volume, is the site of the vast majority of heavy metals and their protein-bound complexes. Therefore, developing technologies that can efficiently, selectively, and safely remove heavy metals from plasma can not only provide rapid and effective life support for patients with acute severe poisoning but also open up new therapeutic avenues for long-term health management and reducing the heavy metal load in the body of patients with chronic exposure. This research direction integrates multiple disciplines, including clinical toxicology, blood purification technology, materials science, and environmental health, and has significant scientific and clinical application value.

[0005] Currently, research on removing heavy metals from plasma mainly focuses on using advanced adsorption materials and membrane separation technology to construct efficient and biocompatible extracorporeal circulation purification systems. The current research status can be summarized into the following directions: (1) Adsorption therapy based on chelating functional materials, which is the current mainstream and hot topic of research. Its core is to develop functionalized adsorbents with high affinity and high selectivity for specific heavy metal ions and use them for blood perfusion or plasma perfusion. (2) Development of functional groups: Researchers are committed to fixing efficient chelating groups (such as EDTA, DTPA, mercapto, amino, and amine oxime groups) onto various carrier materials through chemical bonding. Among them, mercapto has a strong affinity for soft acid heavy metals such as mercury and lead and is one of the most studied functional groups. (3) Optimization of carrier materials: The selection of carrier materials is crucial to ensure blood compatibility and adsorption efficiency. For example, polymer microspheres / resins, such as polystyrene-divinylbenzene and polyacrylate, have high specific surface area and good mechanical strength and are classic adsorbent carriers. For example, nanomaterials such as mesoporous silica, magnetic nanoparticles (Fe3O4), carbon nanotubes, and graphene, due to their huge specific surface area, tunable pore structure, and abundant surface functional groups, have become ideal platforms for constructing highly efficient adsorbents. For instance, thiol-modified mesoporous silica used in plasma perfusion exhibits extremely high lead ion adsorption capacity and rate. Furthermore, biomaterials such as chitosan, sodium alginate, and cellulose, which possess good biocompatibility, can become safe and efficient adsorbents after functionalization.

[0006] The integrated strategy based on membrane separation technology combines adsorption function with membrane separation process, which is a cutting-edge direction that has emerged in recent years and aims to achieve the integration of "separation-purification". It includes: (1) Mixed matrix membrane: Nanoparticles with heavy metal adsorption function (such as functionalized silica, metal-organic framework MOFs) are used as fillers and mixed into polymer casting solution to prepare mixed matrix membrane. While physically retaining macromolecules, the nanofillers inside the membrane can actively adsorb the heavy metal ions flowing through it, achieving a dual removal effect. (2) Surface functionalized separation membrane: Chelating groups are directly grafted onto the surface or pores of plasma filtration membrane (such as polysulfone hollow fiber membrane). When plasma flows through the membrane surface, heavy metals are selectively captured, while large molecules such as plasma proteins pass through smoothly. This method avoids the risk of adsorbent particles falling into the blood, making the system safer and more integrated.

[0007] Despite significant progress, several challenges remain: (1) Selectivity challenges. Achieving ultra-high selectivity adsorption of target heavy metals in complex plasma environments without affecting the balance of endogenous essential metal ions remains a core challenge. (2) Biosafety. The long-term biosafety of nanomaterials and their potential metabolic pathways in vivo require more in-depth and systematic evaluation. (3) Clinical translation. Currently, most research remains at the laboratory stage. There is still a long way to go from material preparation and performance evaluation to large-scale production and clinical validation that meet medical device standards.

[0008] CN115945172A discloses a composite nanofiber material and its preparation method and application, comprising the following steps: mixing an aqueous solution of polyvinyl alcohol and an aqueous solution of polyacrylic acid to obtain a mixed solution A; adding 2,5-dimercapto-1,3,4-thiadiazole to the mixed solution A, mixing, electrospinning, and then drying and thermally crosslinking to obtain the composite nanofiber material. The composite nanofiber material prepared by this invention introduces 2,5-dimercapto-1,3,4-thiadiazole into the polyvinyl alcohol and polyacrylic acid system, endowing the membrane material with resistance to Pb in the environment. 2+ The method utilizes highly selective adsorption capacity; the composite nanofiber membrane material prepared by electrospinning technology has the advantages of easy separation and recovery, effectively avoiding the secondary pollution problem of adsorbent materials being difficult to recover in liquid food environments. However, this method mainly achieves specific adsorption of lead ions by using specific components, and the adsorption effect is limited.

[0009] Therefore, existing technologies cannot yet prepare good membranes to solve the adsorption bottleneck problem. Developing a new type of adsorption membrane is of great significance for clinical applications. Summary of the Invention

[0010] The technical problem that this invention aims to solve is that existing membranes have poor adsorption capacity, poor adsorption selectivity, and low biosafety.

[0011] To address the aforementioned technical problems, in a first aspect, a method for preparing functionalized nanofiber materials is provided, the method comprising:

[0012] (1) Add the raw materials to water to form an electrospinning solution; after electrospinning, nanofiber membranes are obtained;

[0013] (2) Crosslink the nanofiber membrane in an organic solvent under acid catalysis to obtain a crosslinked nanofiber membrane;

[0014] (3) The cross-linked nanofiber membrane is grafted onto a polyamine cross-linking agent and then reacted with a sulfur-containing reagent to obtain the functionalized nanofiber material.

[0015] The method of this invention utilizes electrospun nanofiber technology to form a dense and fine pore structure, which improves the specific surface area and mass transfer efficiency of the membrane, and the surface functional groups have a strong coordination ability for heavy metals, thus achieving high adsorption efficiency and good heavy metal removal performance.

[0016] Preferably, the raw material in step (1) is polyvinyl alcohol; the mass concentration of the electrospinning solution formed by the polyvinyl alcohol in water is 10%~30%, for example, it can be 10%, 15%, 20%, 25% or 30%, etc.

[0017] Preferably, the mass concentration of the electrospinning solution formed by polyvinyl alcohol in water in step (1) is 12%. In this invention, polyvinyl alcohol is heated and refluxed in water to form an electrospinning solution. The reflux temperature is 100~130℃ and the time can be 24h.

[0018] Preferably, the conditions for electrospinning in step (1) are: the spinning voltage is 10~25kV, the flow rate of the electrospinning solution is 10~30μL / min, and the spinning distance is 15~25cm.

[0019] Preferably, the organic solvent in step (2) is an acetone solution containing glutaraldehyde, wherein the volume concentration of glutaraldehyde in acetone is 10% to 50%, for example, it can be 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50%, etc. Preferably, it is 30%.

[0020] The crosslinking time in step (2) is 1 to 24 hours; the preferred reaction time is 6 hours.

[0021] Preferably, the thickness of the cross-linked nanofiber membrane in step (2) is 100~300μm, preferably 200μm, the fiber diameter is 300~600nm, the porosity is 75%~85%, the degree of cross-linking is 20%~80%, and the degree of cross-linking is preferably 50%.

[0022] In this invention, the acid in step (2) can be hydrochloric acid, acetic acid, phosphoric acid, or other acidic substances.

[0023] Preferably, the concentration of the polyamine crosslinking agent in step (3) is 1% to 10%, for example, it can be 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10%, preferably 2.1%. In this invention, the concentration of the polyamine crosslinking agent refers to the mass concentration of the polyamine crosslinking agent in water. The polyamine crosslinking agent can be one or more of ethylenediamine, diethylenetriamine, and triethylenetetramine. The polyamine crosslinking agent molecule contains multiple amino groups (-NH2, -NH-), which can react with the hydroxyl or aldehyde groups remaining on the surface of the crosslinked nanofiber membrane to achieve stable grafting; on the other hand, amino groups are good adsorption sites for heavy metal ions, and can bind to heavy metal ions in plasma through coordination to achieve preliminary adsorption.

[0024] The specific process of grafting with polyamine crosslinking agent can be as follows: at room temperature, soak the crosslinked nanofiber membrane in a 2.1% (w / w) aqueous solution of polyamine crosslinking agent for 24 hours.

[0025] Preferably, the sulfur-containing reagent in step (3) includes cysteine; the concentration of the sulfur-containing reagent is 1% to 10%, for example, it can be 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9% or 10%, etc., preferably 2%.

[0026] In this invention, the system reacting with cysteine ​​is an aqueous solution, the concentration of cysteine ​​is preferably 2%, the reaction time is 24 hours, and the reaction temperature is 25°C.

[0027] In this invention, the sulfur-containing reagent cysteine ​​molecule contains a thiol group (-SH) and an amino group (-NH2), wherein the thiol group reacts with heavy metal ions (such as Hg). 2+ Pb 2+ Cd 2+ The coordination constants of cysteine ​​(e.g., amino groups) are much higher than those of single amino groups, exhibiting extremely strong specific adsorption capabilities. In particular, cysteine, with its thiol group, demonstrates an even more prominent coordination effect. Cysteine ​​can react with the active groups on the surface of the polyamine crosslinking agent through its amino group, stably grafting onto the nanofiber membrane and forming bifunctional adsorption sites of amino and thiol groups on the fiber surface.

[0028] Secondly, the present invention provides a functionalized nanofiber material prepared by the preparation method described in the first aspect.

[0029] In a third aspect, the present invention provides the application of the functionalized nanofiber material described in the second aspect in the preparation of medical devices for removing heavy metal ions from plasma.

[0030] The functionalized electrospun nanofiber plasma adsorption membrane prepared by this invention can be used in plasma filtration as an adsorption membrane responsible for removing heavy metals.

[0031] In this invention, the heavy metals are mainly lead and mercury in blood plasma.

[0032] Implementing this invention has the following beneficial effects:

[0033] This invention utilizes multi-nozzle electrospinning technology to prepare functionalized nanofiber membranes for plasma filtration. The introduction of nanofiber membrane carriers solves the problem of adsorption capacity; the introduction of sulfur-containing dimercapto groups solves the problem of adsorption selectivity; and the selection of environmentally friendly materials solves the problem of biosafety.

[0034] The functionalized nanofiber material prepared by this invention combines the good biocompatibility of polyvinyl alcohol, the high specific surface area and high porosity of nanofibers, and the synergistic adsorption effect of polyamine crosslinking agent and cysteine. It has the advantages of large adsorption capacity, fast adsorption rate, strong selectivity, good biocompatibility and structural stability. It can efficiently and safely remove heavy metal ions from plasma and solve many defects of existing adsorption materials. Detailed Implementation

[0035] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0036] Example 1

[0037] The preparation method of the functionalized nanofiber material in this embodiment is as follows:

[0038] (1) Place 10 g of polyvinyl alcohol with a degree of hydrolysis of 99% in 90 mL of water and reflux at 120 °C for 24 hours to dissolve. Add 1% Triton 100 to prepare a 10% spinning solution.

[0039] Nanofiber membranes were obtained by spinning a 30 mL polyvinyl alcohol solution on a multi-nozzle electrospinning machine. The spinning voltage was 20 kV, the flow rate was 20 μL / min, the spinning distance was 15 cm, and the collecting roller speed was 60 rpm.

[0040] (2) The spun electrospun nanofiber membrane was placed in 500 ml of acetone and glutaraldehyde solution (concentration of 30%) for cross-linking reaction. The reaction temperature was 25℃ and the reaction time was 6 hours. A few drops of acid were added as a catalyst.

[0041] (3) The cross-linked nanofiber membrane was immersed in a 2.1% aqueous solution of the polyamine cross-linking agent triethylenetetramine and reacted at room temperature for 24 hours. The electrospun membrane grafted with the polyamine cross-linking agent was immersed in a 2% aqueous solution of cysteine ​​and reacted for 24 hours, washed with water and dried to obtain the nanofiber material.

[0042] Example 2

[0043] The preparation method of the functionalized nanofiber material in this embodiment is as follows:

[0044] (1) Place 20 g of polyvinyl alcohol with a degree of hydrolysis of 99% in 80 mL of water and reflux at 120 °C for 24 hours to dissolve. Add 1% of Triton 100 to prepare a 20% spinning solution.

[0045] Polyvinyl alcohol solution was used for spinning on a multi-nozzle electrospinning machine. The spinning voltage was 22 kV, the flow rate was 22 μL / min, the spinning distance was 20 cm, and the collecting roller speed was 60 rpm. Nanofiber membranes were obtained.

[0046] (2) The spun electrospun nanofiber membrane was placed in 250 ml of acetone and glutaraldehyde solution (concentration of 25%) for cross-linking reaction. The reaction temperature was 25℃ and the reaction time was 6 hours. A few drops of acid were added as a catalyst.

[0047] (3) The cross-linked nanofiber membrane was immersed in a 2.5% aqueous solution of triethylenetetramine, a polyamine cross-linking agent, and reacted at room temperature for 24 hours. The electrospun membrane grafted with the polyamine cross-linking agent was immersed in a 2.3% aqueous solution of cysteine ​​and reacted for 24 hours. After washing with water and drying, the nanofiber material was obtained.

[0048] Example 3

[0049] The preparation method of the functionalized nanofiber material in this embodiment is as follows:

[0050] (1) Place 15 g of polyvinyl alcohol with a degree of hydrolysis of 99% in 85 mL of water and reflux at 120 °C for 24 hours to dissolve. Add 1% Triton 100 to prepare a 15% spinning solution.

[0051] Nanofiber membranes were obtained by spinning a 25 mL polyvinyl alcohol solution on a multi-nozzle electrospinning machine. The spinning voltage was 22 kV, the flow rate was 22 μL / min, the spinning distance was 20 cm, and the collecting roller speed was 60 rpm.

[0052] (2) The spun electrospun nanofiber membrane was placed in 280 ml of acetone and glutaraldehyde solution (concentration of 27%) for cross-linking reaction. The reaction temperature was 25℃ and the reaction time was 6 hours. A few drops of acid were added as a catalyst.

[0053] (3) The cross-linked nanofiber membrane was immersed in a 3% aqueous solution of diethylenetriamine, a polyamine cross-linking agent, and reacted at room temperature for 24 hours. The electrospun membrane grafted with the polyamine cross-linking agent was immersed in a 2.2% aqueous solution of cysteine ​​and reacted for 24 hours. After washing with water and drying, the nanofiber material was obtained.

[0054] Comparative Example 1

[0055] In Example 1, the amount of spinning solution was reduced to 5 ml, while other conditions remained unchanged. The resulting electrospun film had a thickness of 30 micrometers.

[0056] Comparative Example 2

[0057] Replace cysteine ​​in Example 1 with mercaptoethylamine, keeping other conditions unchanged.

[0058] Comparative Example 3

[0059] The polyamine crosslinking agent grafting step in Example 1 was removed, while other conditions remained unchanged.

[0060] Performance testing:

[0061] Plasma filtration tests were conducted on the functionalized electrospun nanofiber membranes in Example 1 and Comparative Examples 1-3.

[0062] Traditional plasma filtration membranes were cut into 47 mm diameter pieces. Two plasma filtration membranes were stacked with an electrospun membrane and placed in a filter. The flow rate was controlled at 0.2 mL / min using a syringe pump. The filtrate was collected and the corresponding heavy metal concentrations were determined by ICP. Details are shown in Table 1 below.

[0063] Table 1

[0064]

[0065] As shown in Table 1, the functionalized nanofiber material prepared in this invention has a significant effect on Hg levels in plasma. 2+ Pb 2 + It exhibits extremely high removal rates for heavy metal ions, significantly outperforming unmodified polyvinyl alcohol nanofiber membranes.

[0066] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. The application of a functionalized nanofiber material in the preparation of medical devices for removing heavy metal ions from blood plasma, characterized in that, The preparation method of the functionalized nanofiber material includes: (1) Polyvinyl alcohol is added to water to form an electrospinning solution; nanofiber membranes are obtained after electrospinning. (2) The nanofiber membrane was cross-linked in an acetone solution containing glutaraldehyde under acid catalysis to obtain a cross-linked nanofiber membrane; (3) The cross-linked nanofiber membrane is grafted onto a polyamine cross-linking agent and then reacted with cysteine ​​to obtain the functionalized nanofiber material. The electrospinning solution formed by polyvinyl alcohol in water in step (1) has a mass concentration of 10% to 30%. The thickness of the cross-linked nanofiber membrane in step (2) is 100~300μm, the fiber diameter is 300~600nm, the porosity is 75%~85%, and the degree of cross-linking is 20%~80%. The concentration of the polyamine crosslinking agent in step (3) is 1%~10%; The concentration of cysteine ​​in step (3) is 1% to 10%.

2. The application according to claim 1, characterized in that, The electrospinning solution formed by polyvinyl alcohol in water in step (1) has a mass concentration of 12%.

3. The application according to claim 1, characterized in that, The conditions for electrospinning in step (1) are: the spinning voltage is 10~25kV, the flow rate of the electrospinning solution is 10~30μL / min, and the spinning distance is 15~25cm.

4. The application according to claim 1, characterized in that, The volume concentration of glutaraldehyde in acetone in step (2) is 10%~50%.

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