Preparation method of plasma activated hydrogel

Abstract

The invention discloses a preparation method of plasma activated hydrogel, the method is based on a plasma device, the plasma device comprises a plasma pretreatment assembly, a plasma activation assembly and a monitoring control assembly, the preparation method comprises the following steps: adding hydrogel into a pretreatment chamber, generating plasmas by a first plasma generator, conveying the plasmas to the pretreatment chamber to perform oxidation pretreatment on the hydrogel, dropwise adding an alkaline solution into the hydrogel subjected to the plasma oxidation pretreatment to perform neutralization reaction, and performing vacuum freeze drying on the neutralized hydrogel at the temperature of 60 DEG C below zero to 80 DEG C below zero; the freeze-dried hydrogel is subjected to swelling and activating treatment through a plasma activating assembly, and the plasma activated hydrogel is obtained. By adopting the method to prepare the plasma activated hydrogel, efficient loading of plasma active particles can be realized, and the sterilizing effect of the plasma activated hydrogel is improved.

Description

Technical Field

[0001] The present invention relates to the technical field of hydrogel preparation, and particularly to a preparation method of plasma-activated hydrogel. Background Art

[0002] Atmospheric pressure cold plasma (CAP) can generate reactive oxygen and reactive nitrogen species (RONS) with high biological activity by ionizing air, and has good application prospects in the biomedical field. In recent years, researchers have developed plasma-activated hydrogels (PAH) by loading RONS generated by plasma into hydrogel media. PAH has good hydrophilic properties and mechanical characteristics, and its three-dimensional network structure can also limit the free movement of water molecules, reduce the mutual reaction of RONS, and thus extend the active time. In addition, PAH can achieve local slow release of RONS through concentration gradient diffusion or self-degradation. At present, PAH has shown great application potential in the fields of skin disease treatment, in vivo cancer treatment, wound treatment, etc. However, many hydrogels (such as polysaccharide hydrogels, polyphenol hydrogels, amino acid / polypeptide hydrogels, etc.) have specific groups or structures with strong antioxidant capabilities, which will consume active particles during the preparation process, thereby reducing the effect of PAH. Although the antioxidant ability of hydrogels can be reduced by chemical modification methods (such as sodium periodate oxidation, succinic anhydride acylation, etc.), it often requires a large number of chemical reagents and complex elution processes, and generates a large amount of waste liquid, which has great limitations in practical applications. Summary of the Invention

[0003] (1) Object of the Invention

[0004] The object of the present invention is to provide a preparation method of plasma-activated hydrogel. This method pre-treats the hydrogel with plasma to remove the antioxidant groups in the hydrogel, without the need for a large number of chemical reagents and complex elution processes. Then, through acid-base neutralization treatment and freeze-drying, the present invention realizes the efficient loading of active particles in the acid-base neutralized hydrogel, and improves the bactericidal effect of the plasma-activated gel.

[0005] (2) Technical Solution

[0006] To solve the above problems, the first aspect of the present invention provides a preparation method of plasma-activated hydrogel. This method is based on a plasma device, and the plasma device includes a plasma pre-treatment component, a plasma activation component, and a monitoring and control component. The monitoring and control component is electrically connected to the plasma pre-treatment component and the plasma activation component respectively;

[0007] The plasma pretreatment assembly includes a first gas supply unit, a first plasma generator, a first power supply unit and a pretreatment chamber, wherein the first plasma generator is electrically connected to the first power supply unit, one end of the first plasma generator is connected to the first gas supply unit, and the other end is connected to the pretreatment chamber;

[0008] The preparation method of the plasma-activated hydrogel comprises the following steps:

[0009] S1, adding the hydrogel into the pretreatment chamber, and ionizing the working gas input by the first gas supply unit with the first plasma generator to generate plasma and supply the plasma to the pretreatment chamber to perform oxidation pretreatment on the hydrogel, thereby obtaining a plasma-oxidation pretreated hydrogel;

[0010] S2, adding an alkaline solution dropwise to the plasma oxidation pretreated hydrogel for neutralization reaction to obtain a neutralized hydrogel, wherein the pH value of the neutralized hydrogel is 6 to 8;

[0011] S3, vacuum freeze-drying the neutralized hydrogel at -60°C to -80°C with a vacuum degree of 0.1 to 10 Pa to obtain a freeze-dried hydrogel;

[0012] S4, performing swelling and activation treatment on the freeze-dried hydrogel by the plasma activation component to obtain a plasma-activated hydrogel.

[0013] Furthermore, the hydrogel comprises hydrogel powder and an aqueous medium, and the mass fraction of the hydrogel powder in the hydrogel is 0.1% to 10%.

[0014] Furthermore, the hydrogel powder includes hyaluronic acid, sodium hyaluronate, alginate, chitosan, cellulose, cellulose derivatives, pectin, starch and / or dextran.

[0015] Furthermore, the aqueous medium includes: deionized water, ultrapure water, buffer solution, physiological saline and / or biological glue.

[0016] Furthermore, the working gas includes a mixture of air, oxygen and nitrogen, and the flow rate of the working gas is 0 L / min to 5 L / min.

[0017] Furthermore, the plasma oxidative pretreatment of the hydrogel includes: transporting the generated plasma to a pretreatment chamber, and loading active particles into the hydrogel for oxidative pretreatment.

[0018] Furthermore, the alkaline solution includes sodium hydroxide solution, lithium hydroxide solution, potassium hydroxide solution, calcium hydroxide solution and / or quaternary ammonium solution.

[0019] Further, the plasma activation assembly includes a second gas supply unit, a second plasma generator, a second power supply unit, and an activation chamber. The second plasma generator is electrically connected to the second power supply unit. One end of the second plasma generator communicates with the second gas supply unit, and the other end communicates with the activation chamber.

[0020] Further, in step S4, the freeze-dried hydrogel is swollen and activated by the plasma activation assembly to obtain a plasma-activated hydrogel, which includes:

[0021] The freeze-dried hydrogel is re-swollen in an aqueous medium and then placed in the activation chamber. The second plasma generator ionizes the working gas input by the second gas supply unit to generate plasma and transports it to the activation chamber to activate the swollen freeze-dried hydrogel, thereby obtaining a plasma-activated hydrogel;

[0022] Alternatively, the aqueous medium is placed in the activation chamber. The second plasma generator ionizes the working gas input by the second gas supply unit to generate plasma and transports it to the activation chamber to activate the aqueous medium, thereby obtaining a plasma-activated aqueous medium. Then, the freeze-dried hydrogel is placed in the plasma-activated aqueous medium for re-swelling to obtain a plasma-activated hydrogel.

[0023] Further, in the plasma generated by the first plasma generator, the active particles include at least one of O3, NO, NO2, N2O5, NO3, H2O2, ·OH, and 1 O2.

[0024] (III) Beneficial effects

[0025] The above technical solution of the present invention has the following beneficial technical effects: The present invention provides a method for preparing a plasma-activated hydrogel. Based on a plasma device, the hydrogel is pretreated by plasma oxidation to remove antioxidant groups in the hydrogel. Through acid-base neutralization treatment, the pH is adjusted to a neutral level and the generated aldehyde groups are removed. Compared with the hydrogel without acid-base neutralization pretreatment, the present invention realizes the efficient loading of active particles in the acid-base neutralized hydrogel, improving the bactericidal effect of the plasma-activated gel. The specific process of the present invention is as follows: The first plasma generator generates plasma to oxidize the hydrogel in the pretreatment chamber to obtain a plasma-oxidized pretreated hydrogel. The present invention utilizes the oxidizing property and natural decomposability of plasma active particles to solve the problems of traditional oxidation methods that require multiple chemical reagents, a complex elution process, and the generation of a large amount of waste liquid. Then, an alkaline solution is added dropwise to the plasma-oxidized pretreated hydrogel for a neutralization reaction to obtain a neutralized hydrogel, and the pH value of the neutralized hydrogel is controlled to be 6-8 to avoid the irritating safety problem caused by the over-acidic pH value of the hydrogel after plasma pretreatment. At the same time, hydroxide ions react with aldehyde groups in the hydrogel medium after plasma pretreatment to generate hydroxyl groups and carboxylate ions, avoiding the safety problem caused by too high an aldehyde group concentration. Then, the neutralized hydrogel is vacuum freeze-dried at -60°C to -80°C to obtain a freeze-dried hydrogel. The method of vacuum freeze-drying is used to remove the residual plasma active particles and their reaction products in the acid-base neutralized pretreated hydrogel, solving the problem of difficult elution of oxidation by-products in the hydrogel medium. Finally, the freeze-dried hydrogel is swollen and activated by the plasma activation component to obtain a plasma-activated hydrogel. The present invention uses plasma to oxidize and pretreat the hydrogel, which can remove antioxidant groups in the hydrogel. Then, through acid-base neutralization treatment and freeze-drying, hydrogen ions and aldehyde groups in the hydrogel can be removed. The re-swollen acid-base neutralized pretreated hydrogel prepared has no bactericidal effect itself, but compared with the hydrogel without pretreatment (plasma oxidation and acid-base neutralization), it can load more long-lived and short-lived liquid-phase active particles under the same plasma activation conditions; these active particles can effectively induce bacterial inactivation and play a key role in disinfection and anti-infection and the treatment of skin diseases. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 is a flowchart of the method for preparing a plasma-activated hydrogel of the present invention;

[0027] Figure 2 is a schematic structural diagram of the plasma device of the present invention;

[0028] Figure 3 is a specific flowchart of the method for preparing a plasma-activated hydrogel of the present invention;

[0029] Figure 4 It is a schematic diagram of a chemical reaction in a specific embodiment of the present invention.

[0030] Figure 5 It is a Fourier transform infrared spectroscopy detection result diagram of a specific embodiment of the present invention;

[0031] Figure 6 It is a detection result diagram of long-lived active particles (NO2 - ) in a specific embodiment of the present invention;

[0032] Figure 7 It is a detection result diagram of long-lived active particles (H2O2) in a specific embodiment of the present invention;

[0033] Figure 8 It is a detection result diagram of short-lived active particles (·OH) in a specific embodiment of the present invention;

[0034] Figure 9 It is a comparison diagram of the bactericidal effect of Staphylococcus aureus in a specific embodiment of the present invention. Specific Embodiments

[0035] To make the objectives, technical solutions, and advantages of the present invention clearer and more understandable, the present invention will be further described in detail below in conjunction with specific embodiments and with reference to the accompanying drawings. It should be understood that these descriptions are merely exemplary and are not intended to limit the scope of the present invention. In addition, in the following descriptions, descriptions of well-known structures and technologies are omitted to avoid unnecessarily confusing the concepts of the present invention.

[0036] As Figure 1 shown, the present invention provides a method for preparing a plasma-activated hydrogel. This method is based on a plasma device, and the plasma device includes a plasma pretreatment component, a plasma activation component, and a monitoring and control component. As Figure 2 shown, the monitoring and control component is electrically connected to the plasma pretreatment component and the plasma activation component respectively ( Figure 2 The acid-base neutralization component and the vacuum freeze-drying component in can be freely selected and added). The monitoring and control component is used to set the operating control parameters of the plasma pretreatment component and the plasma activation component.

[0037] The plasma pretreatment assembly includes a first gas supply unit, a first plasma generator, a first power supply unit, and a pretreatment chamber. The first plasma generator is electrically connected to the first power supply unit to supply power to the first plasma generator. One end of the first plasma generator is communicated with the first gas supply unit, and the other end is communicated with the pretreatment chamber. The first gas supply unit provides a continuous working gas for the plasma generator to be ionized, and blows the ionized gas (active particles) into the pretreatment chamber, where the hydrogel is placed. The plasma pretreatment assembly devices include: corona discharge, spark discharge, sliding arc discharge, microwave discharge, or dielectric barrier discharge.

[0038] Further, the plasma activation assembly includes a second gas supply unit, a second plasma generator, a second power supply unit, and an activation chamber. The second plasma generator is electrically connected to the second power supply unit. One end of the second plasma generator is communicated with the second gas supply unit, and the other end is communicated with the activation chamber. The plasma activation assembly includes: jet discharge, corona discharge, spark discharge, sliding arc discharge, microwave discharge, or dielectric barrier discharge;

[0039] The method for preparing the plasma-activated hydrogel includes the following steps:

[0040] S1. Add the hydrogel into the pretreatment chamber. The first plasma generator ionizes the working gas input by the first gas supply unit to generate plasma and transports it to the pretreatment chamber to perform oxidative pretreatment on the hydrogel, obtaining a plasma-oxidized pretreated hydrogel (plasma-oxidized hydrogel). The first gas supply unit provides a continuous supply of working gas for the plasma generator to ionize, and blows the ionized gas (active particles) into the hydrogel in the pretreatment chamber to perform oxidative pretreatment on the hydrogel. In the present invention, plasma is used to perform oxidative pretreatment on the hydrogel material to eliminate antioxidant groups and reduce the reducing chemical bonds or groups in the hydrogel. The hydrogel includes hydrogel powder and an aqueous medium, and the mass fraction of the hydrogel powder in the hydrogel is 0.1% - 10%. When preparing the hydrogel or the aqueous medium, a magnetic stirrer can be used to mix the solvent with the hydrogel material or the aqueous medium solute. The hydrogel powder includes hyaluronic acid, sodium hyaluronate, alginate, chitosan, cellulose, cellulose derivatives, pectin, starch, and / or dextran. The aqueous medium includes: deionized water, ultrapure water, buffer solution, physiological saline, and / or biogel. The working gas includes air (ambient air, cylinder air), a mixture of oxygen and nitrogen, and the working gas flow rate is 0 L / min - 5 L / min to ensure sufficient contact with the hydrogel. The plasma performs oxidative pretreatment on the hydrogel by: transporting the generated plasma to the pretreatment chamber and loading active particles into the hydrogel for oxidative pretreatment. The active particles include at least one of O3, NO, NO2, N2O5, NO3, H2O2, ·OH, and 1 O2. For example, the generated active particles are loaded into the hydrogel in a free diffusion, gas blowing, bubbling, or microbubble manner through gas outlets such as a quartz tube (above the liquid surface), a quartz tube (below the liquid surface), a quartz porous aeration head (below the liquid surface), and a stainless steel aeration head (below the liquid surface). At the same time, the operation control parameters of each component are set and controlled through the monitoring and control component.

[0041] S2. Add an alkaline solution to the plasma-oxidized pretreated hydrogel to perform a neutralization reaction, obtaining a neutralized hydrogel. The pH value of the neutralized hydrogel (acid-base neutralized pretreated hydrogel) is 6 - 8. Specifically, use a pH meter to monitor the pH value of the hydrogel. When pH < 6, continue to add the alkaline solution, as Figure 3 shown, Figure 3As a specific flowchart of the preparation method, when pH≥6, step S3 is entered. The pH value is controlled to be 6-8. On the one hand, the pH of the plasma-pretreated hydrogel is controlled to be 6-8 to avoid the irritation problem of too low pH; on the other hand, the aldehyde groups in the plasma-pretreated hydrogel are eliminated, and two active groups, hydroxyl groups and carboxylate groups, are generated, which have biocompatibility. In the acid-base neutralization-pretreated hydrogel, the infrared characteristic absorption peak of the aldehyde group is at 1710-1730 cm -1 , the infrared characteristic absorption peak of the hydroxyl group is at 3050-3570 cm -1 , and the carboxylic acid / carboxylate group has an antisymmetric stretching vibration absorption peak at 1560-1650 cm -1 , and a symmetric vibration absorption peak at 1360-1440 cm -1 . The mass fraction of the acid-base neutralization-pretreated hydrogel is 0.1%-10% (referring to 0.1%-10% of the polymer mass in the hydrogel accounting for the total mass of the hydrogel). The alkaline solution includes sodium hydroxide solution, lithium hydroxide solution, potassium hydroxide solution, calcium hydroxide solution and / or quaternary ammonium base solution. The acid-base neutralization-pretreated hydrogel can reduce the loss of plasma active particles compared with the hydrogel without acid-base neutralization. The killing effect of the acid-base neutralization-pretreated hydrogel on Staphylococcus aureus is <1 order of magnitude. Under the same conditions, the plasma-activated acid-base neutralization-pretreated hydrogel can improve the killing effect on Staphylococcus aureus by more than 1 order of magnitude compared with the plasma-activated non-pretreated hydrogel.

[0042] S3. Vacuum freeze-dry the neutralized hydrogel at -60°C to -80°C to obtain a freeze-dried hydrogel;

[0043] S4. Swell and activate the freeze-dried hydrogel through the plasma activation component to obtain a plasma-activated hydrogel. This step includes two treatment methods:

[0044] S41. Re-swell the freeze-dried hydrogel in an aqueous medium and then put it into the activation chamber. The second plasma generator ionizes the working gas input by the second gas supply unit to generate plasma and transports it to the activation chamber to activate the re-swelled freeze-dried hydrogel to obtain a plasma-activated hydrogel. The flow rate of this working gas is the same as that in step S1. The methods for loading plasma (active particles) into the acid-base neutralization-pretreated hydrogel include free diffusion, gas blowing, bubbling and microbubbles;

[0045] S42, or put the aqueous medium into the activation chamber. The second plasma generator ionizes the working gas input by the second gas supply unit to generate plasma and transport it to the activation chamber to activate the aqueous medium, obtaining plasma-activated aqueous medium. Then, put the freeze-dried hydrogel into the plasma-activated aqueous medium to re-swell, obtaining plasma-activated hydrogel. The aqueous medium includes deionized water, ultrapure water, buffer solution, physiological saline, and / or bioadhesive. Preferably, the bioadhesive material is uniformly mixed with medical purified water, buffer solution, physiological saline, etc. and then activated by the plasma activation component. The mass fraction of the bioadhesive material in the prepared aqueous medium is less than 10%, and it maintains good fluidity after being uniformly mixed with medical purified water, buffer solution, physiological saline, etc.

[0046] In addition, in addition to the above operation process, an acid-base neutralization component and a vacuum freeze-drying component can also be set in the plasma device, which are respectively used in steps S2 and S3. The acid-base neutralization component and the vacuum freeze-drying component can be freely selected and added. When adding the two components, as Figure 2 shown, the acid-base neutralization component and the vacuum freeze-drying component are respectively electrically connected to the monitoring and control component to control the corresponding operation control parameters of each component. The acid-base neutralization component includes a solution dropper, a pH meter, and a neutralization tank; the solution dropper is used to drop the alkaline solution into the plasma-oxidized pretreated hydrogel; the pH meter is used to monitor the pH value of the plasma-oxidized hydrogel; the neutralization tank contains the plasma-oxidized hydrogel, the solution dropper is above the neutralization tank, and the pH meter is located in the neutralization tank. The neutralization tank is the place for acid-base neutralization of the plasma-oxidized hydrogel, and is used to prepare the acid-base neutralized pretreated hydrogel (neutralized hydrogel).

[0047] The vacuum freeze-drying component includes a freezing module and a vacuum drying module; the freezing module pre-freezes the acid-base neutralized pretreated hydrogel, and the pre-freezing temperature is -60°C to -80°C; the vacuum drying module is used to dry and dehydrate the acid-base neutralized pretreated hydrogel to prepare the freeze-dried acid-base neutralized pretreated hydrogel, where the cold trap temperature is -60°C to -80°C and the vacuum degree is 0.1 to 10 Pa.

[0048] Taking the preparation of plasma-activated hydrogel with hyaluronic acid as an example, it is described as follows:

[0049] First, dissolve hyaluronic acid (HA) and mix it evenly with deionized water to prepare a hyaluronic acid gel with a mass fraction of 1%. First, treat the hyaluronic acid gel with a plasma activation component to obtain plasma-oxidized hyaluronic acid (POH). Then, using an acid-base neutralization component, add an alkaline solution dropwise to the plasma-oxidized hyaluronic acid until the pH value of the plasma-oxidized hyaluronic acid is in the range of 6-8 to obtain acid-base neutralization pretreated hyaluronic acid (NPOH). Then place the acid-base neutralization pretreated hyaluronic acid in a vacuum freeze-drying component and pre-freeze it at -80°C for 12 h, and then place it in a vacuum environment of 0.1 Pa and freeze-dry it for 48 h to obtain freeze-dried acid-base neutralization pretreated hyaluronic acid. At this time, the residual active particles in the acid-base neutralization pretreated hyaluronic acid have basically been removed. Next, re-swell the freeze-dried acid-base neutralization pretreated hyaluronic acid into a hydrogel state in an aqueous medium, controlling the mass fraction to be 1%. Finally, use the plasma activation component to activate the re-swelled acid-base neutralization pretreated hyaluronic acid to prepare plasma-activated glue (PAH). The prepared re-swelled acid-base neutralization pretreated hyaluronic acid itself has no bactericidal effect, but can load more active particles, and shows a stronger bactericidal effect compared to the hyaluronic acid without acid-base neutralization pretreatment.

[0050] As Figure 4 illustrates the chemical reactions that occur during the acid-base neutralization pretreatment of hyaluronic acid. After the hyaluronic acid is pretreated by the plasma pretreatment component, due to the loading of plasma active particles, the adjacent dihydroxyl groups of hyaluronic acid are destroyed, and the two hydroxyl groups are oxidized into two aldehyde groups, and the pH of the hyaluronic acid decreases, resulting in plasma-pretreated hyaluronic acid. When a small amount of 0.1 M NaOH solution is added dropwise, OH - reacts preferentially with H + to undergo an acid-base neutralization reaction. When a sufficient amount of 0.1 M NaOH solution is added dropwise, OH - reacts with the aldehyde group to undergo an organic disproportionation reaction, and two aldehyde groups generate one hydroxyl group and one carboxylate group to obtain acid-base neutralization pretreated hyaluronic acid.

[0051] As Figure 5 shown is the Fourier transform infrared spectroscopy detection result diagram of the corresponding example of the hyaluronic acid of the present invention, indicating the change of chemical groups during the acid-base neutralization pretreatment of hyaluronic acid. The infrared characteristic absorption peak of the aldehyde group is at 1710-1730 cm -1 , the infrared characteristic absorption peak of the hydroxyl group is at 3050-3570 cm -1 , and the carboxylic acid / carboxylate group has an antisymmetric stretching vibration absorption peak at 1560-1650 cm -1 , and a symmetric vibration absorption peak at 1360-1440 cm -1 ; after being treated by the plasma pretreatment component, the plasma-pretreated hyaluronic acid is at 1710-1730 cm -1An absorption peak of the aldehyde group appeared, proving the formation of the aldehyde group. After acid-base neutralization pretreatment, the absorption peak of the acid-base neutralization pretreated hyaluronic acid disappeared at 1710 - 1730 cm -1 The absorption peak disappeared at 1560 - 1650 cm -1 and the absorption peaks at 1360 - 1440 cm -1 were enhanced, proving the disappearance of the aldehyde group and the formation of carboxylic acid / carboxylate groups. The shift and fluctuation of the absorption peak of the hydroxyl group at 3050 - 3570 cm -1 also indicated the change in the hydroxyl group content during the above process.

[0052] As Figure 6 shown is the detection result diagram of the long-lived active particles (NO2 - ) of the corresponding embodiment of the hyaluronic acid of the present invention. The content of NO2 - in the hyaluronic acid and the acid-base neutralization pretreated hyaluronic acid before and after being treated by the plasma activation component was studied, indicating that the acid-base neutralization pretreated hyaluronic acid can significantly enhance the loading of NO2 - .

[0053] As Figure 7 shown is the detection result diagram of the long-lived active particles (NO2 - ) of the corresponding embodiment of the hyaluronic acid of the present invention. The content of H2O2 in the hyaluronic acid and the acid-base neutralization pretreated hyaluronic acid before and after being treated by the plasma activation component was studied, indicating that the acid-base neutralization pretreated hyaluronic acid can significantly enhance the loading of H2O2.

[0054] As Figure 8 shown is the detection result diagram of the short-lived active particles (·OH) of the corresponding embodiment of the hyaluronic acid of the present invention. The content of ·OH in the hyaluronic acid and the acid-base neutralization pretreated hyaluronic acid before and after being treated by the plasma activation component was studied, indicating that the acid-base neutralization pretreated hyaluronic acid (neutralized hydrogel) can significantly enhance the loading of ·OH.

[0055] As Figure 9 shown is the comparison diagram of the bactericidal effect of Staphylococcus aureus of the corresponding embodiment of the hyaluronic acid of the present invention. The killing effect of the hyaluronic acid and the acid-base neutralization pretreated hyaluronic acid on Staphylococcus aureus before and after being treated by the plasma activation component was studied, indicating that the plasma-activated glue (PAH) prepared based on the acid-base neutralization pretreated hyaluronic acid can significantly improve the bactericidal effect.

[0056] The present invention provides a method for preparing a plasma-activated hydrogel. The plasma device in this method includes: a plasma pretreatment component, an acid-base neutralization component, a vacuum freeze-drying component, a plasma activation component, and a monitoring and control component; the plasma pretreatment component pre-treats the hydrogel to prepare a plasma-oxidized pre-treated hydrogel; the acid-base neutralization component drops an alkaline solution into the plasma-oxidized hydrogel for acid-base neutralization treatment to obtain an acid-base neutralized pre-treated hydrogel; the vacuum freeze-drying component pre-freezes the acid-base neutralized pre-treated hydrogel and performs freeze-drying in a vacuum environment; the plasma activation component activates the freeze-dried acid-base neutralized pre-treated hydrogel containing an aqueous medium or re-swollen in an aqueous medium to obtain a plasma-activated hydrogel; the monitoring and control component is electrically connected to the plasma pretreatment component, the acid-base neutralization component, the vacuum freeze-drying component, and the plasma activation component respectively, and sets the operation control parameters of the plasma pretreatment component, the acid-base neutralization component, the vacuum freeze-drying component, and the plasma activation component. The above technical solution has the following effects:

[0057] (1) The present invention uses plasma to perform oxidation pretreatment on the hydrogel material to eliminate antioxidant groups. Different from the traditional chemical oxidation method, the present invention does not require a large number of chemical reagents and a complex elution process. The main oxidation mechanism is based on self-degrading plasma active particles, and the residual active particles can be basically eliminated after freeze-drying, providing a new idea for the oxidation of hydrogel materials.

[0058] (2) The present invention uses the acid-base neutralization pretreatment component to perform acid-base neutralization treatment on the plasma-pretreated hydrogel. On the one hand, it controls the pH of the plasma-pretreated hydrogel to be between 6 and 8 to avoid the irritating problem of too low pH; on the other hand, it eliminates the aldehyde groups in the plasma-pretreated hydrogel and generates two active groups, namely hydroxyl groups and carboxylate groups, which have biocompatibility.

[0059] (3) The acid-base neutralized pre-treated hydrogel in the present invention can load more long-lived and short-lived liquid-phase active particles, and these liquid-phase active particles can effectively induce bacterial oxidative stress to kill bacteria, playing a key role in disinfection and anti-infection and skin disease treatment.

[0060] (4) The acid-base neutralized pre-treated hydrogel in the present invention has better loading efficiency, is more convenient to apply, and has better biological activity compared with traditional hydrogels, which is conducive to further popularization and application.

[0061] It should be understood that the above specific embodiments of the present invention are only for illustrative or explanatory purposes of the principles of the present invention and do not constitute a limitation on the present invention. Therefore, any modifications, equivalent replacements, improvements, etc. made without departing from the spirit and scope of the present invention shall be included within the protection scope of the present invention. In addition, the appended claims of the present invention are intended to cover all variations and modifications that fall within the scope and boundaries of the appended claims or equivalent forms of such scope and boundaries.

Claims

1. A method for preparing a plasma-activated hydrogel, which is based on a plasma device, characterized in that, The plasma device includes a plasma pretreatment component, a plasma activation component, and a monitoring and control component. The monitoring and control component is electrically connected to the plasma pretreatment component and the plasma activation component respectively; The plasma pretreatment component includes a first gas supply unit, a first plasma generator, a first power supply unit, and a pretreatment chamber. The first plasma generator is electrically connected to the first power supply unit. One end of the first plasma generator is communicated with the first gas supply unit, and the other end is communicated with the pretreatment chamber; The method for preparing the plasma-activated hydrogel includes the following steps: S1. Add the hydrogel into the pretreatment chamber. The first plasma generator ionizes the working gas input by the first gas supply unit to generate plasma and transport it to the pretreatment chamber, so that the plasma performs oxidative pretreatment on the hydrogel to obtain a plasma-oxidized pretreated hydrogel; S2. Drop an alkaline solution into the plasma-oxidized pretreated hydrogel for a neutralization reaction to obtain a neutralized hydrogel, and the pH value of the neutralized hydrogel is 6-8; S3. Vacuum freeze-dry the neutralized hydrogel at -60°C to -80°C to obtain a freeze-dried hydrogel; S4. Perform swelling and activation treatment on the freeze-dried hydrogel through the plasma activation component to obtain a plasma-activated hydrogel.

2. The preparation method of the plasma-activated hydrogel according to claim 1, wherein, The hydrogel includes hydrogel powder and an aqueous medium, and the mass fraction of the hydrogel powder in the hydrogel is 0.1% - 10%.

3. The preparation method of the plasma-activated hydrogel according to claim 2, wherein, The hydrogel powder includes hyaluronic acid, sodium hyaluronate, alginate, chitosan, cellulose, cellulose derivatives, pectin, starch, and / or dextran.

4. The preparation method of the plasma-activated hydrogel according to claim 2, wherein The aqueous medium includes: deionized water, ultrapure water, buffer solution, physiological saline, and / or biogel.

5. The preparation method of the plasma-activated hydrogel according to claim 1, characterized in that, The working gas includes a mixture of air, oxygen, and nitrogen, and the flow rate of the working gas is 0 L / min to 5 L / min.

6. The preparation method of the plasma-activated hydrogel according to claim 1, wherein, The oxidative pretreatment of the hydrogel by the plasma includes: transporting the generated plasma to the pretreatment chamber and loading active particles into the hydrogel for oxidative pretreatment.

7. The preparation method of the plasma-activated hydrogel according to claim 1, characterized in that, The alkaline solution includes sodium hydroxide solution, lithium hydroxide solution, potassium hydroxide solution, calcium hydroxide solution, and / or quaternary ammonium base solution.

8. The preparation method of the plasma-activated hydrogel according to claim 1, characterized in that, The plasma activation component includes a second gas supply unit, a second plasma generator, a second power supply unit, and an activation chamber. The second plasma generator is electrically connected to the second power supply unit. One end of the second plasma generator is communicated with the second gas supply unit, and the other end is communicated with the activation chamber.

9. The preparation method of the plasma-activated hydrogel according to claim 8, wherein, In step S4, the swelling and activation treatment of the freeze-dried hydrogel by the plasma activation component to obtain a plasma-activated hydrogel includes: Redissolve the freeze-dried hydrogel in an aqueous medium and then put it into the activation chamber. The second plasma generator ionizes the working gas input by the second gas supply unit to generate plasma and transport it to the activation chamber to activate the swollen freeze-dried hydrogel to obtain a plasma-activated hydrogel; Alternatively, an aqueous medium is placed into the activation chamber, and the second plasma generator ionizes the working gas input by the second gas supply unit to generate plasma and deliver it to the activation chamber to activate the aqueous medium, thereby obtaining a plasma-activated aqueous medium. Then, the freeze-dried hydrogel is placed into the plasma-activated aqueous medium to re-swell, resulting in a plasma-activated hydrogel.

10. The preparation method of the plasma-activated hydrogel according to claim 6, characterized in that, The active particles include at least one of O3, NO, NO2, N2O5, NO3, H2O2, ·OH, and 1 O2.

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