A medical conductive hydrogel with dry and wet two-phase conduction and a preparation method thereof

Abstract

The application discloses a medical conductive hydrogel with dry and wet two-phase conduction and a preparation method thereof. A dispersing agent TNWDIS is added into pure water, and after sufficient stirring and dissolving, ground graphite nano powder is added, and then is stirred by a magnetic stirrer; ultrasonic is performed by using an ultrasonic cell disruptor, and an ice water bath is used for cooling and defoaming during the process, so as to obtain a graphite nano powder dispersion liquid; glycerol and 1,2 propylene glycol are added into the graphite nano powder dispersion liquid while stirring, and then a certain amount of NaCl and KCl are added; after dissolving, hyaluronic acid is sieved and added, and a magnetic stirrer is used for stirring during the process; after standing for a period of time, a semi-coagulation gel is formed in the solution, and the dry and wet two-phase conductive hydrogel is obtained. The formula and process of the application are simple, the raw materials are non-toxic, and the application is safe on human skin; ion conduction and electron conduction are combined, and the conductive performance can be maintained after the gel is dried, and the conductivity has a significant advantage compared with similar products on the market.

Description

Technical Field

[0001] This invention relates to the fields of medical materials technology and medical preparation technology, and in particular to a medical conductive hydrogel with conductivity in both dry and wet phases and its preparation method. Background Technology

[0002] Medical conductive hydrogels are hydrogel materials that can conduct electricity and possess electrical signal conduction properties. They can be used in applications such as electrochemical sensing, biomedicine, battery technology, and flexible electronic devices.

[0003] Existing medical conductive hydrogels mainly involve adding ionic salts or other conductive substances to polymer gel materials to provide ion channels or conductive particles, thereby enhancing the ion conduction performance of the gel.

[0004] Ionic conductivity is a conductive process caused by the directional movement of positive and negative ions in an electrolyte solution or in a molten state.

[0005] Electron conductivity is a conductive phenomenon caused by the directional movement of free electrons in an electric field in a metal or semiconductor.

[0006] Hyaluronic acid is an acidic mucopolysaccharide, a high-molecular-weight polymer composed of D-glucuronic acid and N-acetylglucosamine. The hyaluronic acid molecule contains a large number of carboxyl and hydroxyl groups, which form numerous hydrogen bonds in aqueous solution, explaining its strong water-retention properties.

[0007] Hyaluronic acid has excellent water-retention properties, is non-toxic, and is a major component of connective tissues such as intercellular matrix and synovial fluid in joints. Its superior water retention allows it to maintain ionic conductivity for extended periods, making it a high-quality material for manufacturing medical conductive hydrogels.

[0008] Graphite nanopowder has good electrical conductivity, thermal conductivity and adhesion, and can be used to formulate conductive coatings or improve the wear resistance, compressive strength or conductivity of materials.

[0009] Commercial EEG conductive gels experience a significant reduction in conductivity after drying due to moisture evaporation, thus affecting the acquisition of bioelectrical signals over extended periods. Therefore, prolonging the duration of stable conductivity in the conductive gel is a crucial foundation for long-term EEG monitoring. Summary of the Invention

[0010] The purpose of this invention is to address the problem of the durability of conductivity in existing ion-conductive gels by providing a medical conductive hydrogel with conductivity in both dry and wet phases and its preparation method.

[0011] To address the aforementioned technical problems, the present invention provides the following technical solution:

[0012] This invention provides a method for preparing a medical conductive hydrogel with conductivity in both dry and wet phases, the specific steps of which are as follows:

[0013] Step 1: Add the dispersant TNWDIS to pure water, stir until fully dissolved, then add the ground graphite nanoparticles, stir with a magnetic stirrer, and then sonicate using an ultrasonic cell disruptor. During this process, cool and defoam with an ice water bath to obtain a graphite nanoparticle dispersion.

[0014] Step 2: Add glycerol and 1,2-propanediol to the graphite nanopowder dispersion while stirring, then add a certain amount of NaCl and KCl. After dissolving, add hyaluronic acid through a sieve. Stir continuously with a magnetic stirrer. After standing for a period of time, the solution can form a semi-solid colloid, thus obtaining a dry and wet two-phase conductive hydrogel.

[0015] In a preferred embodiment of the present invention, the graphite nanopowder in step 1 has a diameter of 50-300 μm; in step 2, the concentration of graphite nanopowder in the obtained conductive hydrogel is 2-10% (w / v), wherein the concentration of added hyaluronic acid is 2-6% (w / v), the concentration of glycerol is 6-20% (v / v), the concentration of 1,2-propylene glycol is 6-20% (v / v), the concentration of NaCl is 0-30% (w / v), and the concentration of KCl is 0-30% (w / v).

[0016] As a preferred embodiment of the present invention, in step 1, the ultrasonic dispersion power is set to 400-800w and the ultrasonic duration is 1-5 hours; in step 2, the solution is magnetically stirred for 5 minutes to 2 hours, the stirring speed is 120-500rpm, and the standing time is at least 1 hour.

[0017] A medical conductive hydrogel with conductivity in both dry and wet phases was prepared by the above method.

[0018] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0019] 1. The formula and process of this invention are simple, the raw materials are non-toxic, and it is safe to use on human skin.

[0020] 2: This invention combines ionic conductivity and electronic conductivity, and can maintain conductivity even after the gel is dried. Compared with similar products on the market, it has a significant advantage in conductivity.

[0021] 3. The medical conductive gel prepared by this invention has strong adhesion, which increases the convenience and stability of fixing the electrode position. Attached Figure Description

[0022] The accompanying drawings are provided to further illustrate the invention and form part of the specification. They are used in conjunction with embodiments of the invention to explain the invention and do not constitute a limitation thereof. In the drawings:

[0023] Figure 1 This is a flowchart of the manufacturing process of the dry and wet two-phase medical conductive gel of the present invention.

[0024] Figure 2 This is a comparison chart of the maximum adhesion force of the dry and wet two-phase conductive gel of Example 1 with similar products on the market;

[0025] Figure 3 These are scanning electron microscope images of the wet and dry two-phase conductive gel after lyophilization in Example 2;

[0026] Figure 4 This is a comparison chart of the conductivity of the dry and wet two-phase conductive gel of Example 2 with similar products on the market at different time points;

[0027] Figure 5 This is a graph showing the change in water content of each conductive gel at 37°C in Example 3;

[0028] Figure 6 This is a diagram showing the fibroblast proliferation effect of Example 4;

[0029] Figure 7 This is a graph showing the proportion of dead cells after flow cytometry cell sorting in Example 4; Detailed Implementation

[0030] The preferred embodiments of the present invention will be described below with reference to the accompanying drawings. It should be understood that the preferred embodiments described herein are for illustration and explanation only and are not intended to limit the present invention.

[0031] Example 1

[0032] As shown in 1 and 2, this embodiment provides a method for preparing a medical conductive hydrogel with both dry and wet phase conductivity. The specific steps are as follows:

[0033] Dispersant TNWDIS (1% v / v) was added to pure water and stirred until fully dissolved. Then, ground graphite nanoparticles were added and stirred with a magnetic stirrer for 15 minutes. The mixture was then sonicated at 630W for 2.5 hours using an ultrasonic cell disruptor, with cooling and defoaming performed in an ice-water bath to obtain a graphite nanoparticle dispersion. Glycerol (5% v / v) and 1,2-propylene glycol (2.5% v / v) were added to the graphite nanoparticle dispersion at specific concentrations while stirring. Then, a certain amount of NaCl (12% w / v) and KCl (12% w / v) were added. After dissolution, hyaluronic acid (5% w / v) was added through a sieve, with continuous stirring using a magnetic stirrer. After standing for 24 hours, the solution formed a semi-solid colloid, yielding the desired ion-conducting gel (the graphite content in the samples was 10, 20, 30, 40, 50, 60, and 100 mg / ml, respectively).

[0034] The medical conductive gel prepared in this embodiment exhibits a maximum adhesive force on the same plane during adhesive mechanical testing. Figure 2 This product is significantly superior to similar products on the market. In this embodiment, there was no significant difference in the maximum adhesion force among the medical conductive gel groups containing different proportions of graphite nanopowder (10, 20, 30, 40, 50, 60, 100 mg / ml), and all of them were significantly greater than the maximum adhesion force of similar products on the market (Greentech EEG Conductive Gel).

[0035] Example 2

[0036] As shown in 3 and 4, this embodiment provides a method for preparing a medical conductive hydrogel with both dry and wet phase conductivity. The specific steps are as follows:

[0037] TNWDIS dispersant was added to pure water and stirred until fully dissolved. Then, ground graphite nanoparticles were added and stirred with a magnetic stirrer for 15 minutes. The mixture was then sonicated at 630W for 2.5 hours using an ultrasonic cell disruptor, with cooling and defoaming performed in an ice-water bath to obtain a graphite nanoparticle dispersion. Glycerol (5% v / v) and 1,2-propylene glycol (2.5% v / v) were added to the graphite nanoparticle dispersion at a specific concentration while stirring. Then, a certain amount of NaCl (12% w / v) and KCl (12% w / v) were added. After dissolution, hyaluronic acid (5% w / v) was added through a sieve, with continuous stirring using a magnetic stirrer. After standing for 24 hours, the solution formed a semi-solid colloid, yielding the desired ion-conducting hydrogel (the graphite content in the samples was 0 and 50 mg / ml, respectively).

[0038] The medical conductive gel prepared in this embodiment exhibits a loose, reticular sponge structure under 50x scanning electron microscopy (e.g., Figure 3 As shown), within 70 hours, the conductivity of the dry-wet two-phase conductive gel containing graphite nanoparticles in this embodiment (as shown) Figure 4In the middle, with graphite(50), the dotted line) is higher than that of similar products in a certain market ( Figure 4 In the middle, commercial gel (triangular dot broken line); in addition, the results verified that graphite nanopowder significantly improved the conductivity of the conductive gel, and the conductivity of the gel without graphite nanopowder was ( Figure 4 In the middle, without graphite (a polygonal line with square dots) and the conductivity of similar products in a certain market ( Figure 4 In the middle, commercial gel (triangular point polyline) is similar.

[0039] Example 3

[0040] As shown in Figure 5, this embodiment provides a method for preparing a medical conductive hydrogel with both dry and wet phase conductivity. The specific steps are as follows:

[0041] TNWDIS dispersant was added to pure water and stirred until fully dissolved. Then, ground graphite nanoparticles were added and stirred with a magnetic stirrer for 15 minutes. The mixture was then sonicated at 630W for 2.5 hours using an ultrasonic cell disruptor, with cooling and defoaming performed in an ice-water bath to obtain a graphite nanoparticle dispersion. Glycerol (5% v / v) and 1,2-propylene glycol (2.5% v / v) were added to the graphite nanoparticle dispersion at specific concentrations while stirring. Then, a certain amount of NaCl (12% w / v) and KCl (12% w / v) were added. After dissolution, hyaluronic acid (5% w / v) was added through a sieve, with continuous stirring using a magnetic stirrer. After standing for 24 hours, the solution formed a semi-solid colloid, yielding the desired ion-conducting hydrogel (the graphite content in the samples was 0, 10 mg / ml, and 50 mg / ml, respectively).

[0042] The medical conductive gel prepared in this embodiment, under an ambient temperature simulating human body temperature of 37 degrees Celsius, exhibited a higher water content (0, 10, 50) within 45 hours than a similar product on the market (Greentech). Figure 5 As shown in the figure, all conductive gels were dried in about 20 hours.

[0043] Example 4

[0044] As shown in 3 and 4, this embodiment provides a method for preparing a medical conductive hydrogel with both dry and wet phase conductivity. The specific steps are as follows:

[0045] TNWDIS dispersant was added to pure water and stirred until fully dissolved. Then, ground graphite nanoparticles were added and stirred with a magnetic stirrer for 15 minutes. The mixture was then sonicated at 630W for 2.5 hours using an ultrasonic cell disruptor, with cooling and defoaming performed in an ice-water bath to obtain a graphite nanoparticle dispersion. Glycerol (5% v / v) and 1,2-propylene glycol (2.5% v / v) were added to the graphite nanoparticle dispersion at specific concentrations while stirring. After dissolution, hyaluronic acid (5% w / v) was added through a sieve, with continuous stirring using a magnetic stirrer. After standing for 24 hours, the solution formed a semi-solid colloid, yielding the desired ion-conducting hydrogel (the graphite content in the samples was 0, 10 mg / ml, 30 mg / ml, and 50 mg / ml, respectively).

[0046] In this embodiment, the medical conductive gel was immersed in cell culture medium for 2 hours, and the cell culture medium was then used for fibroblast cell culture. Cell proliferation in this cell culture medium was significantly increased within 5 days, and there was no significant difference in cell proliferation between different conductive hydrogel groups and the control group without samples (e.g., Figure 6 (As shown); after staining and flow cytometry sorting of dead cells on day 3, the proportion of dead cells was less than 3% (e.g. Figure 7 (as shown); Figure 6 The control group was a negative staining control group, and the T-control group was a no-sample control group with a dead cell rate of 1.19%. In the gel sample group with a graphite content of 0, the dead cell rate was 1.92%; in the gel sample group with a graphite content of 10, the dead cell rate was 1.48%; in the gel sample group with a graphite content of 30, the dead cell rate was 2.24%; and in the gel sample group with a graphite content of 50, the dead cell rate was 2.12%.

[0047] Finally, it should be noted that the above descriptions are merely preferred embodiments of the present invention and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. 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 medical conductive hydrogel with conductivity in both dry and wet phases, characterized in that: The specific steps are as follows: Step 1: Add the dispersant TNWDIS to pure water, stir until fully dissolved, then add the ground graphite nanoparticles, stir with a magnetic stirrer, and then sonicate using an ultrasonic cell disruptor. During this process, cool and defoam with an ice water bath to obtain a graphite nanoparticle dispersion. Step 2: Add glycerol and 1,2-propanediol to the graphite nanopowder dispersion while stirring, then add a certain amount of NaCl and KCl. After dissolving, add hyaluronic acid through a sieve. Stir continuously with a magnetic stirrer. After standing for a period of time, the solution can form a semi-solid colloid, thus obtaining a dry and wet two-phase conductive hydrogel.

2. The method for preparing a medical conductive hydrogel with both dry and wet phase conductivity according to claim 1, characterized in that, In step 1, the diameter of the graphite nanoparticles is 50-300 μm; in step 2, the concentration of graphite nanoparticles in the obtained conductive hydrogel is 2-10% w / v, the concentration of added hyaluronic acid is 2-6% w / v, the concentration of glycerol is 6-20% v / v, and the concentration of 1,2-propylene glycol is 6-20% v / v.

3. The method for preparing a medical conductive hydrogel with both dry and wet phase conductivity according to claim 1, characterized in that, In step 1, the ultrasonic dispersion power is set to 400-800w, and the ultrasonic duration is 1-5 hours; in step 2, the solution is magnetically stirred for 5 minutes to 2 hours, the stirring speed is 120-500rpm, and the standing time is at least 1 hour.

4. A medical conductive hydrogel with conductivity in both dry and wet phases, characterized in that, It is prepared by the method described in any one of claims 1-3.

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