Conductive MOF functionalized gel and preparation method thereof

Abstract

The invention discloses conductive MOF (Metal Organic Framework) functionalized gel and a preparation method thereof, can be applied to electroencephalogram signal conduction, and belongs to the field of medical instruments. According to the functionalized gel, a conductive MOF material is used as a proton transmission matrix and is further covalently grafted on a hydrophilic polymer to obtain an MOF modified polymer material, and the modified polymer is used as a conductive and gel matrix to prepare the gel material. According to the method, the dispersity and stability of the MOF in the gel can be improved, and the electrical signal conduction stability of the gel is improved. The conductive MOF functionalized gel material disclosed by the invention can be used as conductive gel and is used for electric signal conduction of electroencephalogram signal monitoring during anesthesia.

Description

Technical Field

[0001] The invention relates to a conductive MOF functionalized gel and a preparation method thereof, which can be applied in brain electric signal conduction and belongs to the field of medical devices. Background Art

[0002] Anesthesia plays an extremely important role in surgical operations. In addition to enabling patients to undergo surgical operations in a painless state, it is more important to protect the patient's life safety. Too shallow anesthesia or too deep anesthesia will lead to a series of problems and pose a threat to the patient's health. Therefore, accurate anesthesia depth monitoring is of great research significance. In clinical practice, the CBS dual-spectrum anesthesia depth multi-parameter monitor is usually used to monitor the patient's EEG signals to evaluate the depth of anesthesia, and the EEG signals are monitored by adhering monitoring electrodes to the skin. However, the EEG signal is weak, and the contact between the electrode and the skin is poor. The presence of the gap will produce a large impedance, resulting in a poor current signal. Therefore, when using it, it is necessary to apply conductive gel between the skin and the electrode to reduce the impedance between the electrode and the skin.

[0003] The conductive gels currently on the market still have the following problems when used for EEG signal transmission: first, the EEG signals are weak and the gel has poor conductivity, making it difficult for the electrodes to detect the EEG signals. The high impedance makes the electrodes' anti-interference ability poor, making them unsuitable for complex hospital environments and resulting in poor user experience. Second, the gel is easy to lose water, resulting in poor product stability and interference with test accuracy. To solve the impedance problem, the skin surface needs to be polished and degreased, which can easily cause skin infections. Furthermore, although the technology of foreign manufacturers is mature, it is highly confidential and requires a breakthrough in technical barriers.

[0004] Metal organic framework (MOF) is a new type of porous material with metal ions and carbon atoms. Using MOF as a precursor, carbon materials and metal oxide materials with controllable structure and morphology can be obtained. However, its own electrical conductivity is poor, and it can be made to have excellent electrical transmission performance through thermal excitation, photoexcitation, doping and electron injection. Adding MOF directly to hydrogel is a common method, but simple physical blending often leads to the problem of particle aggregation. MOF is difficult to disperse evenly in the material and has poor stability, which affects the conductive performance. In particular, when MOF is used in conductive gel for anesthesia, the gel needs to be able to be spread evenly to increase the fit between the skin and the electrode. The gel matrix is ​​weak in strength, and MOF needs to be evenly dispersed in the gel and be stable for a long time. Therefore, it is urgent to develop a conductive MOF functionalized hydrogel material for electrical signal conduction during anesthesia monitoring. Summary of the invention

[0005] The purpose of the present invention is to provide a conductive MOF functionalized gel and a preparation method thereof in view of the deficiencies of the prior art.

[0006] The present invention obtains a hydrophilic polymer modified with a conductive MOF by covalently grafting the conductive MOF material onto a hydrophilic polymer matrix, and then compounding the hydrophilic polymer with water, glycerol, etc. to obtain a conductive MOF functionalized gel. The MOF is evenly dispersed in the gel, and the gel has excellent stability and conductivity, and can be used for the conduction of electrical signals for EEG signal monitoring during anesthesia.

[0007] The hydrophilic polymer modified by the conductive MOF is obtained by reacting polysaccharide, polysaccharide derivative or anionic polymer and conductive MOF under the action of a condensation 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 disuccinimide suberate and a condensing agent auxiliary, and the condensing agent auxiliary is N-hydroxysuccinimide or N-hydroxysulfosuccinimide.

[0010] Preferably, the conductive MOF is prepared by the following steps: (1) 2,3,6,7,10,11-hexamethoxy-1,5,9-triaminotriphenyl (HMTATP), chloroform and a boron tribromide solution (dissolved in dichloromethane) are stirred at room temperature to obtain a primary reactant. Methanol is added to the primary reactant and stirred under a N2 atmosphere. After removing the solvent, methanol is added and mixed, and then added to a large amount of dichloromethane, filtered, and washed to obtain a ligand. (2) The synthesized ligand, dichloromethane and an appropriate amount of copper sulfate solution are mixed evenly, and reacted at a temperature of 40-80° C. for a certain period of time to obtain a crude product of MOF. (3) The crude product was washed with DMF, DCM and hexane, and then dried to obtain conductive MOF powder.

[0011] Preferably, the preparation method of the conductive MOF-modified hydrophilic polymer comprises: (1) 85-98 parts by weight of polysaccharide, polysaccharide derivative or anionic polymer is dissolved in water, 0.5-5 parts by weight of condensation agent is added and reacted for 10-60 minutes. Then, 1.5-10 parts by weight of conductive MOF (previously dispersed in water) is added and reacted at a stirring speed of 200-1000 rpm for 1-5 hours. (2) After the reaction is completed, the small molecule by-products are dialyzed using a dialysis bag (usually with a molecular weight cutoff of 3000 Da), and the conductive MOF-modified hydrophilic polymer is obtained after freeze-drying.

[0012] Preferably, the conductive MOF-modified hydrophilic polymer is mixed with purified water and glycerol to obtain 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.

[0013] Preferably, the viscosity of the conductive MOF functionalized gel is 3-15 Pa.S.

[0014] Preferably, the conductive MOF functionalized gel can be used as a conductive gel for conducting EEG signals during anesthesia monitoring.

[0015] Compared with the existing technology, the present invention has the following beneficial effects:

[0016] 1. In the present invention, conductive MOF is used as a conductive matrix in the gel. The MOF material has a very high specific surface area and porosity. In the present invention, the structure is controlled by metal ions and organic ligands to enable MOF to have excellent electron transmission ability.

[0017] 2. The present invention provides a gel material obtained by covalently grafting a conductive MOF material onto a hydrophilic polymer matrix and compounding it with water, glycerol, etc. Compared with directly incorporating MOF into the gel matrix, the covalent grafting method can enhance the interaction between MOF and the gel network and improve the stability of the electrical signal conduction of the conductive gel. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 This is a transmission electron microscope image of the conductive MOF prepared in Example 1. Figure 2 These are pictures of the conductive gel prepared in Example 2 and the conductive gel prepared in Comparative Example 1 after being left for 24 hours. Figure 3 The resistance changes of different areas of the conductive gel prepared in Example 3 and the conductive gel prepared in Comparative Example 2 after being placed for 24 hours. DETAILED DESCRIPTION

[0018] The technical solution of the present invention is described in detail below with reference to the accompanying drawings and specific embodiments.

[0019] The present application provides a conductive MOF functionalized gel and a preparation method thereof.

[0020] Embodiment 1: Weigh 0.68g of 2,3,6,7,10,11-hexamethoxy-1,5,9-triaminotriphenyl (HMTATP) in a 250mL round-bottom flask and add 30ml of anhydrous chloroform to dissolve. Then, add 30mL of 1.0M boron tribromide solution (dichloromethane as solvent) and stir at room temperature for 24h to obtain the primary reactant. Add 40mL of methanol to the primary reactant and stir for 3h under a nitrogen atmosphere. Remove the solvent under reduced pressure, add 200mL of methanol to mix, pour the mixture into 500mL of dichloromethane, and filter to obtain a white solid. After washing with dichloromethane 3 times, vacuum dry to obtain a light gray solid as the ligand. Add 1g of the ligand to a 1000mL flask and add 200mL of DMF solution. Then, add 1.1g of copper sulfate to obtain a suspension. Seal the mouth of the flask with a stopper and react at 65°C for 12h. After cooling, the suspension was washed three times with DMF, DCM and hexane respectively, and then vacuum dried to obtain MOF powder. Next, weigh 10g of sodium carboxymethyl cellulose in a 2000mL beaker, then add 0.5g of EDC and NHS (the molar amounts of the two are the same) and mix well. After reacting for 1h, slowly add 0.2g of MOF (previously mixed in 100mL of water) to the above mixture. Mix well under stirring at 700rmp. After reacting for 2h, put it into a dialysis bag and dialyze for 3 days. After freeze-drying, obtain a MOF-modified polymer. In 100mL of water, add 5g of MOF-modified polymer and 10g of glycerol, stir for 1h to obtain a uniform viscous liquid, which is a conductive MOF functionalized gel.

[0021] Example 2: The preparation of MOF is consistent with that of Example 1. In addition, weigh 5g of sodium polyacrylate into a 2000mL beaker, then add 0.3g of EDC and NHS (the molar amounts of the two are the same) and mix well. After reacting for 30 minutes, slowly add 0.1g of MOF (previously mixed in 50mL of water) to the above mixture. Mix well under stirring at 200rmp. After reacting for 5h, put it into a dialysis bag and dialyze for 3 days, and then freeze-dry to obtain a MOF-modified polymer. In 100mL of water, add 5g of MOF-modified sodium polyacrylate and 10g of glycerol, stir for 1h to obtain a uniform viscous liquid, which is a conductive MOF functionalized gel.

[0022] Example 3: The preparation of MOF is consistent with that of Example 1. In addition, weigh 5g of sodium alginate in a 2000mL beaker, then add 0.1g of EDC and NHS (the molar amounts of the two are the same) and mix well. After reacting for 20min, slowly add 0.1g of MOF (previously mixed in 100mL of water) to the above mixture. Mix well under stirring at 700rmp. After reacting for 4h, put it into a dialysis bag and dialyze for 3 days, and obtain a MOF-modified polymer after freeze-drying. In 100mL of water, add 5g of MOF-modified polymer and 10g of glycerol, stir for 1h to obtain a uniform viscous liquid, which is a conductive MOF functionalized gel.

[0023] Comparative Example 1: The preparation of MOF was consistent with that of Example 1. In 100 mL of water, 5 g of sodium polyacrylate, 0.1 g of MOF and 10 g of glycerol were added and stirred for 1 h to obtain a uniform viscous liquid, which was Comparative Example 1.

[0024] Comparative Example 2: In 100 mL of water, 5 g of sodium alginate, 0.1 g of MOF and 10 g of glycerol were added and stirred for 1 h to obtain a uniform viscous liquid, which is Comparative Example 2.

[0025] The following is a further description of the relevant tests in the invention:

[0026] Morphology test of MOF materials: The prepared MOF was evenly dispersed in an ethanol solution, an appropriate amount of the solution was dropped on a copper mesh, and after drying, the morphology of the MOF was tested using a transmission electron microscope.

[0027] Analyze the experimental results, such as Figure 1 As shown, a sheet-like MOF material was synthesized. After the MOF blended gel (Comparative Example 1) was placed for 24 hours, MOF aggregated and slightly precipitated in the gel matrix, while the MOF covalently modified gel sample (Example 2) was still able to stably exist after 24 hours. This covalent bonding method significantly improved the stability of the gel (e.g. Figure 2 In addition, Figure 3 As shown, the resistance of the blended gel (Comparative Example 2) also changes significantly due to the precipitation of MOF, which will lead to instability in the conduction of electrical signals during use and affect the shelf life of the product. However, the resistance of the covalently modified gel (Example 3) is stable.

[0028] The above experimental results show that the conductive gel based on MOF covalently modified polymer in the present invention has excellent conductivity and stability, and has significant beneficial effects.

Claims

1. A conductive MOF functionalized gel, characterized in that: The method is to covalently graft the conductive MOF material onto a hydrophilic polymer matrix to obtain a conductive MOF-modified hydrophilic polymer, and then compound it with water and glycerol to obtain a conductive MOF functionalized gel material.

2. The conductive MOF functionalized gel according to claim 1, characterized in that: The hydrophilic polymer modified by the conductive MOF is obtained by reacting polysaccharide, polysaccharide derivative or anionic polymer and conductive MOF under the action of a condensation agent.

3. The conductive MOF functionalized gel according to claim 2, characterized in that: 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.

4. The conductive MOF functionalized gel according to claim 2, characterized in that: The condensing agent is carbodiimide or disuccinimide suberate and a condensing agent auxiliary, and the condensing agent auxiliary is N-hydroxysuccinimide or N-hydroxysulfosuccinimide.

5. The conductive MOF functionalized gel according to claim 1, characterized in that: The conductive MOF is prepared by the following steps: (1) 2,3,6,7,10,11-hexamethoxy-1,5,9-triaminotriphenylphosphine (HMTATP), chloroform and a boron tribromide solution (dissolved in dichloromethane) are stirred at room temperature to obtain a primary reactant, methanol is added to the primary reactant and stirred under a N2 atmosphere, after removing the solvent, methanol is added and mixed, and the mixture is added to dichloromethane, filtered, washed, and then a ligand is obtained; (2) mixing the synthesized ligand, dichloromethane and copper sulfate solution evenly, and reacting them at a temperature of 40-80° C. to obtain a crude product of MOF; (3) The obtained crude product was washed with DMF, DCM and hexane, and then dried to obtain conductive MOF powder.

6. The conductive MOF functionalized gel according to claim 1, characterized in that: The preparation method of the conductive MOF-modified hydrophilic polymer comprises: (1) Preliminarily dispersing 1.5-10 parts by weight of a conductive MOF in water, dissolving 85-98 parts by weight of a polysaccharide, a polysaccharide derivative or an anionic polymer in water, adding 0.5-5 parts by weight of a condensation agent to react for 10-60 minutes, then adding the conductive MOF dispersion, and reacting at a stirring speed of 200-1000 rpm for 1-5 hours; (2) After the reaction is completed, the small molecule by-products are removed by dialysis, and the conductive MOF-modified hydrophilic polymer is obtained after freeze-drying.

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

8. 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.

9. The use of the conductive MOF functionalized gel according to any one of claims 1 to 8, characterized in that: Used as a conductive gel for conducting EEG signals during anesthesia monitoring.

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