A conductive MOF functionalized gel and its preparation method

Abstract

This invention discloses a conductive MOF-functionalized gel and its preparation method, applicable to electroencephalogram (EEG) signal transduction, belonging to the field of medical devices. The functionalized gel of this invention uses a conductive MOF material as a proton transport matrix, further covalently grafted onto a hydrophilic polymer to obtain a MOF-modified polymer material. The modified polymer is then used as the conductive and gel matrix to prepare the gel material. This method improves the dispersibility and stability of MOFs in the gel, enhancing the stability of gel-based electrical signal transduction. The conductive MOF-functionalized gel material of this invention can be used as a conductive gel for electrical signal transduction in EEG signal monitoring during anesthesia.

Description

Technical Field

[0001] This invention relates to a conductive MOF functionalized gel and its preparation method, which can be applied in electroencephalogram (EEG) signal transmission and belongs to the field of medical devices. Background Technology

[0002] Anesthesia plays a crucial role in surgical procedures, not only ensuring patients undergo surgery painlessly but, more importantly, protecting their lives. Insufficient or excessive anesthesia can lead to a series of problems, threatening the patient's health. Therefore, accurate monitoring of anesthesia depth is of significant research importance. Clinically, a CBS dual-spectrum anesthesia depth multi-parameter monitor is commonly used to assess anesthesia depth by monitoring the patient's electroencephalogram (EEG) signals. This is achieved by attaching monitoring electrodes to the skin. However, EEG signals are weak, and the poor contact between the electrodes and skin, along with gaps, creates significant impedance, resulting in poor current signal. Therefore, a conductive gel needs to be applied between the skin and electrodes during use to reduce impedance.

[0003] Currently, conductive gels on the market still have the following problems when used for EEG signal transmission: First, EEG signals are weak, gel conductivity is poor, making it difficult for electrodes to detect EEG signals. High impedance also results in poor anti-interference capabilities of the electrodes, making them unsuitable for complex hospital environments and leading to a poor user experience. Second, gels are prone to water loss, resulting in poor product stability and inaccurate interference testing. Solving the impedance problem requires skin surface abrasion and degreasing, which can easily cause skin infections. Furthermore, while foreign manufacturers' technologies are mature, they are highly confidential, requiring breakthroughs in technological barriers.

[0004] Metal-organic frameworks (MOFs) are a novel class of porous materials containing metal ions and carbon atoms. Using MOFs as precursors, carbon materials and metal oxide materials with controllable structures and morphologies can be obtained. However, their inherent electrical conductivity is poor. Excellent electrical transport properties can be achieved through thermal excitation, photoexcitation, doping, and electron injection. Directly incorporating MOFs into hydrogels is a common approach, but simple physical blending often results in particle aggregation, making it difficult for MOFs to disperse uniformly and causing poor stability, thus affecting conductivity. This is particularly true when MOFs are used in conductive gels for anesthesia. The gel needs to be spread evenly to increase skin-electrode adhesion. Given the weak strength of the gel matrix, it is even more crucial that MOFs be uniformly dispersed within the gel and remain stable over a long period. Therefore, there is an urgent need to develop conductive MOF-functionalized hydrogel materials for electrical signal conduction during anesthesia monitoring. Summary of the Invention

[0005] The purpose of this invention is to address the shortcomings of existing technologies by providing a conductive MOF functionalized gel and its preparation method.

[0006] This invention involves covalently grafting conductive MOF materials onto a hydrophilic polymer matrix to obtain a conductive MOF-modified hydrophilic polymer, which is then compounded with water, glycerol, etc., to obtain a conductive MOF-functionalized gel. The MOF is uniformly dispersed in the gel, which exhibits excellent stability and conductivity, making it suitable for monitoring electroencephalogram (EEG) signals during anesthesia.

[0007] The conductive MOF-modified hydrophilic polymer is obtained by reacting polysaccharides, polysaccharide derivatives, or anionic polymers with a conductive MOF under the action of a condensing agent.

[0008] Preferably, the polysaccharide, polysaccharide derivative, or anionic polymer is selected from one or more of hyaluronic acid or its derivatives, sodium alginate or its derivatives, carboxymethyl cellulose, glucomannan or its derivatives, polyglutamic acid, polyaspartic acid, and polyacrylic acid.

[0009] Preferably, the condensing agent is carbodiimide or disuccinyl ...

[0010] Preferably, the conductive MOF is prepared by the following steps:

[0011] (1) A primary reactant was prepared by stirring a solution of 2,3,6,7,10,11-hexamethoxy-1,5,9-triaminotriphenyl (HMTATP), chloroform, and boron tribromide (dissolved in dichloromethane) at room temperature. Methanol was added to the primary reactant and the mixture was stirred under a nitrogen atmosphere. After removing the solvent, methanol was added and mixed thoroughly. Then, a large amount of dichloromethane was added, and the mixture was filtered and washed to obtain the ligand.

[0012] (2) The synthesized ligand, dichloromethane and an appropriate amount of copper sulfate solution are mixed evenly and reacted at a temperature of 40-80℃ for a certain period of time to obtain the crude product of MOF.

[0013] (3) The crude product was washed with DMF, DCM and hexane and then dried to obtain conductive MOF powder.

[0014] Preferably, the method for preparing the conductive MOF-modified hydrophilic polymer includes:

[0015] (1) Dissolve 85-98 parts by weight of polysaccharide, polysaccharide derivative or anionic polymer in water, add 0.5-5 parts by weight of condensing agent and react for 10-60 min. Then, add 1.5-10 parts by weight of conductive MOF (pre-dispersed evenly in water) and react at a stirring speed of 200-1000 rpm for 1-5 h.

[0016] (2) After the reaction is complete, small molecule byproducts are removed by dialysis using a dialysis bag (usually with a molecular weight cutoff of 3000 Da), and then lyophilized to obtain a hydrophilic polymer modified with conductive MOF.

[0017] Preferably, the conductive MOF-modified hydrophilic polymer is mixed with purified water and glycerol to prepare the conductive MOF-functionalized gel, wherein the mass ratio of purified water, conductive MOF-modified hydrophilic polymer and glycerol is 70-90:7-15:3-15.

[0018] Preferably, the viscosity of the conductive MOF functionalized gel is 3-15 Pa·s.

[0019] Preferably, the conductive MOF functionalized gel can be used as a conductive gel for EEG signal transmission during anesthesia monitoring.

[0020] Compared with existing technologies, the present invention has the following advantages:

[0021] 1. In this invention, conductive MOF is used as the conductive matrix in the gel. MOF materials have very high specific surface area and porosity. In this invention, the structure can be controlled by metal ions and organic ligands to enable MOF to have excellent electron transport capabilities.

[0022] 2. This invention provides a gel material obtained by covalently grafting a conductive MOF material onto a hydrophilic polymer matrix and then compounding it with water, glycerol, etc. Compared with directly incorporating MOF into the gel matrix, the covalent grafting method can enhance the interaction between the MOF and the gel network, and improve the stability of the electrical signal conduction of the conductive gel. Attached Figure Description

[0023] Figure 1 Transmission electron microscopy (TEM) image of the conductive MOF prepared in Example 1.

[0024] Figure 2 Images of the conductive gel prepared in Example 2 and the conductive gel prepared in Comparative Example 1 after being left for 24 hours.

[0025] Figure 3 The changes in resistance in different regions of the conductive gel prepared in Example 3 and the conductive gel prepared in Comparative Example 2 after 24 hours of storage. Detailed Implementation

[0026] The technical solutions of the present invention will now be described in detail with reference to the accompanying drawings and specific embodiments.

[0027] This application provides a conductive MOF functionalized gel and its preparation method.

[0028] Example 1:

[0029] 0.68 g of 2,3,6,7,10,11-hexamethoxy-1,5,9-triaminotriphenyl (HMTATP) was weighed into a 250 mL round-bottom flask and dissolved in 30 mL of anhydrous chloroform. Then, 30 mL of 1.0 M boron tribromide solution (dichloromethane as solvent) was added, and the mixture was stirred at room temperature for 24 h to obtain the primary reactant. 40 mL of methanol was added to the primary reactant, and the mixture was stirred for 3 h under a nitrogen atmosphere. The solvent was removed under reduced pressure, and 200 mL of methanol was added and mixed thoroughly. The mixture was poured into 500 mL of dichloromethane and filtered to obtain a white solid. After washing three times with dichloromethane, the solid was dried under vacuum to obtain a light gray solid as the ligand. 1 g of the ligand was added to a 1000 mL flask, along with 200 mL of DMF solution. Then, 1.1 g of copper sulfate was added to obtain a suspension. The flask was sealed with a stopper, and the reaction was carried out at 65 °C for 12 h. After cooling, the suspension was washed three times each with DMF, DCM and hexane, and then dried under vacuum to obtain MOF powder.

[0030] Next, 10g of sodium carboxymethyl cellulose was weighed into a 2000mL beaker, followed by the addition of 0.5g of EDC and NHS (both with the same molar amount) and mixed thoroughly. After reacting for 1 hour, 0.2g of MOF (pre-mixed thoroughly in 100mL of water) was slowly added to the mixture. The mixture was stirred at 700rpm until homogeneous. After reacting for 2 hours, the mixture was placed in a dialysis bag and dialyzed for 3 days. The resulting lyophilized polymer was the MOF-modified polymer. In 100mL of water, 5g of the MOF-modified polymer and 10g of glycerol were added and stirred for 1 hour to obtain a homogeneous viscous solution, which is the conductive MOF-functionalized gel.

[0031] Example 2: MOF preparation was the same as in Example 1. However, 5g of sodium polyacrylate was weighed into a 2000mL beaker, followed by the addition of 0.3g of EDC and NHS (both in equal molar amounts) and mixed thoroughly. After reacting for 30 minutes, 0.1g of MOF (pre-mixed thoroughly in 50mL of water) was slowly added to the mixture. The mixture was stirred at 200rpm until homogeneous. After reacting for 5 hours, the mixture was placed in a dialysis bag and dialyzed for 3 days. The resulting lyophilized polymer was the MOF-modified polymer. In 100mL of water, 5g of MOF-modified sodium polyacrylate and 10g of glycerol were added and stirred for 1 hour to obtain a homogeneous viscous liquid, which was the conductive MOF functionalized gel.

[0032] Example 3: MOF preparation was the same as in Example 1. However, 5g of sodium alginate was weighed into a 2000mL beaker, followed by the addition of 0.1g of EDC and NHS (both in equal molar amounts) and mixed thoroughly. After reacting for 20 minutes, 0.1g of MOF (pre-mixed thoroughly in 100mL of water) was slowly added to the mixture. The mixture was stirred at 700rpm until homogeneous. After reacting for 4 hours, the mixture was placed in a dialysis bag and dialyzed for 3 days. The resulting lyophilized polymer was the MOF-modified polymer. In 100mL of water, 5g of the MOF-modified polymer and 10g of glycerol were added and stirred for 1 hour to obtain a homogeneous viscous solution, which was the conductive MOF functionalized gel.

[0033] Comparative Example 1: The preparation of MOF was the same as in Example 1. 5g of sodium polyacrylate, 0.1g of MOF, and 10g of glycerol were added to 100mL of water and stirred for 1 hour to obtain a homogeneous viscous liquid, which is Comparative Example 1.

[0034] Comparative Example 2: Add 5g sodium alginate, 0.1g MOF and 10g glycerol to 100mL of water and stir for 1h to obtain a uniform viscous liquid, which is Comparative Example 2.

[0035] The relevant tests in the invention are described in further detail below:

[0036] Morphology testing of MOF materials: The prepared MOF was evenly dispersed in an ethanol solution, an appropriate amount of solution was dropped onto a copper grid, dried, and the morphology of the MOF was tested using a transmission electron microscope.

[0037] Analyze the experimental results, such as Figure 1 As shown, sheet-like MOF materials were synthesized. After 24 hours of storage, the MOF in the MOF blend gel (Comparative Example 1) aggregated and slightly precipitated within the gel matrix, while the MOF covalently modified gel sample (Example 2) remained stable after 24 hours. This covalent bonding significantly improved the gel's stability (e.g., Figure 2 (As shown). Furthermore, as... Figure 3 As shown, the resistance of the blended gel (Comparative Example 2) also changed significantly due to the precipitation of MOF, which can lead to instability in electrical signal conduction during use and affect the shelf life of the product. In contrast, the resistance of the covalently modified gel (Example 3) was stable.

[0038] The experimental results above show that the conductive gel based on MOF covalently modified polymer in this invention has excellent conductivity and stability, and has significant beneficial effects.

Claims

1. A conductive MOF functionalized gel, characterized in that, The conductive MOF material is covalently grafted onto a hydrophilic polymer matrix to obtain a hydrophilic polymer modified with conductive MOF, which is then compounded with water and glycerol to obtain a conductive MOF functionalized gel material; wherein the conductive MOF is prepared through the following steps: (1) 2,3,6,7,10,11-hexamethoxy-1,5,9-triaminotriphenylene (HMTATP), chloroform and boron tribromide solution dissolved in dichloromethane were stirred at room temperature to obtain a primary reactant. Methanol was added to the primary reactant and stirred under N2 atmosphere. After removing the solvent, methanol was added and mixed well. The mixture was then added to dichloromethane, filtered and washed to obtain the ligand. (2) The synthesized ligand, dichloromethane and copper sulfate solution were mixed evenly and reacted at a temperature of 40-80℃ to obtain the crude product of MOF; (3) The crude product was washed with DMF, DCM and hexane and then dried to obtain conductive MOF powder; The method for preparing the conductive MOF-modified hydrophilic polymer includes: 1) Disperse 1.5-10 parts by weight of conductive MOF in water beforehand, dissolve 85-98 parts by weight of polysaccharide or anionic polymer in water, add 0.5-5 parts by weight of condensing agent and react for 10-60 min, then add the dispersion of conductive MOF and react at a stirring speed of 200-1000 rpm for 1-5 h. 2) After the reaction is complete, small molecule byproducts are removed by dialysis, and the conductive MOF-modified hydrophilic polymer is obtained by lyophilization.

2. The conductive MOF functionalized gel according to claim 1, characterized in that, The polysaccharide or anionic polymer is selected from one or more of hyaluronic acid, sodium alginate, carboxymethyl cellulose, glucomannan, polyglutamic acid, polyaspartic acid, and polyacrylic acid.

3. The conductive MOF functionalized gel according to claim 1, characterized in that, The condensing agent is carbodiimide or disuccinyl ...

4. The conductive MOF functionalized gel according to claim 1, characterized in that, The conductive MOF-modified hydrophilic polymer was mixed with purified water and glycerol to prepare the conductive MOF-functionalized gel, wherein the mass ratio of purified water, conductive MOF-modified hydrophilic polymer and glycerol was 70-90:7-15:3-15.

5. The conductive MOF functionalized gel according to claim 1, characterized in that, The viscosity of the conductive MOF functionalized gel is 3-15 Pa·s.

6. The use of the conductive MOF functionalized gel according to any one of claims 1-5, characterized in that, It is used as a conductive gel for transduction of electroencephalogram (EEG) signals during anesthesia monitoring.

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