A method for preparing a plasma-activated hydrogel

Abstract

The application discloses a preparation method of plasma-activated hydrogel, which is based on a plasma device including a plasma pretreatment component, a plasma activation component and a monitoring control component, and comprises the following steps: adding the hydrogel into a pretreatment chamber, generating plasma by a first plasma generator and delivering the plasma to the pretreatment chamber to perform oxidative pretreatment on the hydrogel, adding an alkaline solution dropwise into the plasma-oxidized pretreated hydrogel to perform a neutralization reaction, and performing vacuum freeze drying on the neutralized hydrogel at-60 DEG C to-80 DEG C; and performing swelling and activation treatment on the freeze-dried hydrogel by the plasma activation component to obtain the plasma-activated hydrogel. The plasma-activated hydrogel prepared by the method can realize efficient loading of plasma active particles and improve the sterilization effect of the plasma-activated glue.

Description

TECHNICAL FIELD

[0001] The application relates to the technical field of hydrogel preparation, in particular to a preparation method of plasma-activated hydrogel. BACKGROUND

[0002] Cold atmospheric plasma (CAP) can generate reactive oxygen and nitrogen species (RONS) with high bioactivity by ionizing air, which has good application prospects in the biomedical field. In recent years, researchers have developed plasma-activated hydrogel (PAH) by loading RONS generated by plasma into hydrogel medium. PAH has good hydrophilic performance and mechanical properties, and its three-dimensional network structure can also limit the free movement of water molecules, reduce the mutual reaction of RONS and prolong the activity 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 and the like. However, many specific groups or structures of hydrogels (such as polysaccharide hydrogel, polyphenol hydrogel, amino acid / polypeptide hydrogel and the like) have strong antioxidant capacity, which will consume active particles during the preparation process, thereby reducing the effect of PAH. Although the antioxidant capacity of hydrogel can be reduced by chemical modification methods (such as sodium periodate oxidation, succinic anhydride acylation and the like), a large number of chemical reagents and complex elution processes are often required, and a large amount of waste liquid is generated, which has great limitations in actual application. SUMMARY

[0003] (I) Invention purposes

[0004] The purpose of the present application is to provide a preparation method of plasma-activated hydrogel, which removes the antioxidant groups in the hydrogel by plasma pretreatment of the hydrogel, does not require numerous chemical reagents and complex elution processes, and then performs acid-base neutralization treatment and freeze-drying. The present application realizes efficient loading of active particles in the acid-base neutralization hydrogel, and improves the sterilization effect of the plasma-activated glue.

[0005] (II) Technical solutions

[0006] To solve the above problems, the first aspect of the present application provides a preparation method of plasma-activated hydrogel, which is based on a plasma device, wherein the plasma device comprises a plasma pretreatment assembly, a plasma activation assembly and a monitoring control assembly, and the monitoring control assembly is electrically connected with the plasma pretreatment assembly and the plasma activation assembly respectively.

[0007] The plasma pretreatment assembly comprises a first gas feeding unit, a first plasma generator, a first power supply unit, and a pretreatment chamber, the first plasma generator is in electrical communication with the first power supply unit, one end of the first plasma generator is in communication with the first gas feeding unit, and the other end is in communication with the pretreatment chamber;

[0008] The method for preparing the plasma-activated hydrogel comprises the following steps:

[0009] S1, the hydrogel is added into the pretreatment chamber, the first plasma generator ionizes the working gas input by the first gas feeding unit, generates plasma and delivers it to the pretreatment chamber to oxidize and pretreat the hydrogel, and obtains a plasma-oxidized and pretreated hydrogel;

[0010] S2, an alkaline solution is added dropwise into the plasma-oxidized and pretreated hydrogel to perform a neutralization reaction, and a neutralized hydrogel is obtained, the pH value of the neutralized hydrogel is 6-8;

[0011] S3, the neutralized hydrogel is vacuum freeze-dried at-60℃ to-80℃, the vacuum degree is 0.1-10 Pa, and a freeze-dried hydrogel is obtained;

[0012] S4, the freeze-dried hydrogel is subjected to swelling and activation treatment by the plasma activation assembly, and a plasma-activated hydrogel is obtained.

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

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

[0015] Further, the aqueous medium comprises deionized water, ultrapure water, buffer, physiological saline and / or biological glue.

[0016] Further, the working gas comprises a mixture of air, oxygen and nitrogen, and the flow rate of the working gas is 0 L / min-5 L / min.

[0017] Further, the oxidation pretreatment of the hydrogel by the plasma comprises delivering the generated plasma to the pretreatment chamber and loading active particles into the hydrogel for oxidation pretreatment.

[0018] Further, the alkaline solution comprises a sodium hydroxide solution, a lithium hydroxide solution, a potassium hydroxide solution, a calcium hydroxide solution and / or a quaternary ammonium base solution.

[0019] Further, the plasma activation assembly comprises a second gas feeding unit, a second plasma generator, a second power supply unit and an activation chamber, the second plasma generator is electrically connected with the second power supply unit, one end of the second plasma generator is communicated with the second gas feeding unit, and the other end is communicated with the activation chamber.

[0020] Further, the plasma activation assembly comprises a second gas feeding unit, a second plasma generator, a second power supply unit and an activation chamber, the second plasma generator is electrically connected with the second power supply unit, one end of the second plasma generator is communicated with the second gas feeding unit, and the other end is communicated with the activation chamber.

[0021] Further, the plasma activation assembly comprises a second gas feeding unit, a second plasma generator, a second power supply unit and an activation chamber, the second plasma generator is electrically connected with the second power supply unit, one end of the second plasma generator is communicated with the second gas feeding unit, and the other end is communicated with the activation chamber.

[0022] Further, the plasma activation assembly comprises a second gas feeding unit, a second plasma generator, a second power supply unit and an activation chamber, the second plasma generator is electrically connected with the second power supply unit, one end of the second plasma generator is communicated with the second gas feeding unit, and the other end is communicated with the activation chamber.

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

[0024] (III) Beneficial effects

[0025] The above technical scheme of the present application has the following beneficial technical effects: the present application provides a preparation method of plasma-activated hydrogel, which is based on a plasma device, removes antioxidant groups in the hydrogel through plasma oxidation pretreatment of the hydrogel, adjusts the pH to a neutral level and removes generated aldehyde groups through acid-base neutralization treatment, realizes efficient loading of active particles in the acid-base neutralized hydrogel compared with the hydrogel without acid-base neutralization pretreatment, improves the sterilization effect of the plasma-activated glue, and the specific process of the present application is as follows: a first plasma generator generates plasma to oxidize the hydrogel in a pretreatment chamber to obtain plasma-oxidized pretreated hydrogel, the present application utilizes the oxidizability and natural decomposability of plasma active particles to solve the problems of traditional oxidation methods, such as the need for multiple chemical reagents, complex elution process and generation of a large amount of waste liquid. An alkaline solution is added dropwise to the plasma-oxidized pretreated hydrogel to perform a neutralization reaction to obtain neutralized hydrogel, and the pH value of the neutralized hydrogel is controlled to be 6-8 to avoid the irritant safety problem caused by the over-acid pH value of the hydrogel after plasma pretreatment, and the reaction between the hydroxyl ion and the aldehyde group in the medium of the hydrogel after plasma pretreatment generates hydroxyl and carboxylate to avoid the safety problem caused by the high concentration of aldehyde groups. Then, the neutralized hydrogel is vacuum freeze-dried at-60℃ to-80℃ to obtain freeze-dried hydrogel, and the method of vacuum freeze-drying removes the residual plasma active particles and reaction products in the acid-base neutralized pretreated hydrogel, solving the problem of difficult elution of the oxidation by-products in the hydrogel medium. Finally, the freeze-dried hydrogel is swelled and activated by the plasma activation assembly to obtain plasma-activated hydrogel. The present application uses plasma to oxidize and pretreat the hydrogel, which can remove antioxidant groups in the hydrogel, and then through acid-base neutralization treatment and freeze-drying, the hydrogen ion and aldehyde group in the hydrogel can be removed. The prepared re-swelled acid-base neutralized pretreated hydrogel itself has no sterilization effect, but compared with the hydrogel without pretreatment (plasma oxidation and acid-base neutralization), more long-lived and short-lived liquid active particles can be loaded under the same plasma activation conditions; these active particles can effectively induce bacterial inactivation, and play a key role in disinfection, anti-infection and skin disease treatment. BRIEF DESCRIPTION OF DRAWINGS

[0026] Figure 1 is a preparation method flowchart of the plasma-activated hydrogel of the present application;

[0027] Figure 2 is a structure schematic diagram of the plasma device of the present application;

[0028] Figure 3 is a specific flowchart of the preparation method of the plasma-activated hydrogel of the present application;

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

[0030] Figure 5 is a Fourier infrared spectrum detection result diagram of a specific embodiment of the present application;

[0031] Figure 6 is a long-lived active particle (NO2 - ) detection result diagram of a specific embodiment of the present application;

[0032] Figure 7 is a long-lived active particle (H2O2) particle detection result diagram of a specific embodiment of the present application;

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

[0034] Figure 9 is a staphylococcus aureus bactericidal effect comparison diagram of a specific embodiment of the present application. DETAILED DESCRIPTION

[0035] In order to make the purpose, technical scheme and advantages of the present application more clear and obvious, the present application will be further described in detail below in combination with specific embodiments and with reference to the drawings. It should be understood that these descriptions are only exemplary and are not intended to limit the scope of the present application. In addition, in the following description, the description of known structures and technologies is omitted to avoid unnecessary confusion of the concept of the present application.

[0036] As shown in Figure 1 , the present application provides a preparation method of plasma-activated hydrogel, which is based on a plasma device, the plasma device comprising a plasma pretreatment assembly, a plasma activation assembly and a monitoring control assembly, as shown in Figure 2 , the monitoring control assembly is electrically connected with the plasma pretreatment assembly and the plasma activation assembly respectively Figure 2 , the acid-base neutralization assembly and the vacuum freeze-drying assembly in can be freely selected and added). The monitoring control assembly sets the operation control parameters of the plasma pretreatment assembly and the plasma activation assembly.

[0037] The plasma pretreatment assembly comprises 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 with the first power supply unit to supply power for the first plasma generator; one end of the first plasma generator is in communication with the first gas supply unit, and the other end is in communication with the pretreatment chamber, 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 pretreatment chamber, and the pretreatment chamber contains a hydrogel. The plasma pretreatment assembly comprises corona discharge, spark discharge, sliding arc discharge, microwave discharge, or dielectric barrier discharge.

[0038] Further, the plasma activation assembly comprises 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 with the second power supply unit, one end of the second plasma generator is in communication with the second gas supply unit, and the other end is in communication with the activation chamber. The plasma activation assembly comprises jet discharge, corona discharge, spark discharge, sliding arc discharge, microwave discharge, or dielectric barrier discharge.

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

[0040] S1, the hydrogel is added into the pre-treatment chamber, the first plasma generator ionizes the working gas input by the first gas feeding unit to generate plasma and deliver to the pre-treatment chamber to oxidize the hydrogel and obtain the plasma oxidized pre-treated hydrogel (plasma oxidized hydrogel). The first gas feeding unit provides the plasma generator with a constant supply of working gas for ionization, and blows the ionized gas (active particles) into the hydrogel in the pre-treatment chamber to oxidize the hydrogel. The present application uses plasma to oxidize the hydrogel material to eliminate antioxidant groups and eliminate reducing chemical bonds or groups in the hydrogel. The hydrogel includes hydrogel powder and aqueous medium, and the mass fraction of the hydrogel powder in the hydrogel is 0.1% to 10%. When preparing the hydrogel or 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, physiological saline and / or biological glue. The working gas includes air (ambient air, cylinder air), a mixture of oxygen and nitrogen, and the flow rate of the working gas is 0L / min to 5L / min to ensure sufficient contact with the hydrogel. The plasma oxidizes the hydrogel by delivering the generated plasma to the pre-treatment chamber, loading active particles into the hydrogel for oxidation pre-treatment, and the active particles include at least one of O3, NO, NO2, N2O5, NO3, H2O2, ·OH and O2, for example: the generated active particles are loaded into the hydrogel through the gas outlet of the quartz tube (above the liquid level), the quartz tube (below the liquid level), the quartz porous aeration head (below the liquid level), the stainless steel aeration head (below the liquid level) and the like, in the form of free diffusion, air blowing, bubbling or micro-bubble. At the same time, the operation control parameters of each component are set and controlled by the monitoring and control assembly. 1 O2, for example: the generated active particles are loaded into the hydrogel through the gas outlet of the quartz tube (above the liquid level), the quartz tube (below the liquid level), the quartz porous aeration head (below the liquid level), the stainless steel aeration head (below the liquid level) and the like, in the form of free diffusion, air blowing, bubbling or micro-bubble. At the same time, the operation control parameters of each component are set and controlled by the monitoring and control assembly.

[0041] S2, the alkaline solution is added dropwise to the plasma oxidized pre-treated hydrogel for neutralization reaction to obtain the neutralized hydrogel, and the pH value of the neutralized hydrogel (acid-base neutralization pre-treated hydrogel) is 6 to 8. Specifically, the pH value of the hydrogel is monitored by a pH meter, and when the pH value is less than 6, the alkaline solution is continuously added, as shown in Figure 3 Figure 3 ​For the specific flow chart 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 problem of irritability caused by too low pH; on the other hand, the aldehyde group in the plasma pretreated hydrogel is eliminated and two active groups of hydroxyl and carboxylate groups are generated, which are biocompatible. 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 carboxyl / carboxylate group has an anti-symmetric 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 the mass of the polymer in the hydrogel accounting for 0.1%-10% of the total mass of the hydrogel). The alkaline solution includes a sodium hydroxide solution, a lithium hydroxide solution, a potassium hydroxide solution, a calcium hydroxide solution and / or a quaternary ammonium base solution. Compared with the hydrogel without acid-base neutralization, the acid-base neutralization pretreated hydrogel can reduce the loss of plasma active particles. The killing effect of the acid-base neutralization pretreated hydrogel on Staphylococcus aureus is less than 1 order of magnitude, and under the same conditions, compared with the plasma-activated hydrogel without pretreatment, the plasma-activated acid-base neutralization pretreated hydrogel can improve the killing effect on Staphylococcus aureus by more than 1 order of magnitude.

[0042] S3, vacuum freeze-drying the neutralized hydrogel at -60°C to -80°C to obtain a freeze-dried hydrogel;

[0043] S4, swelling and activating the freeze-dried hydrogel by the plasma activation assembly to obtain a plasma-activated hydrogel. This step includes two processing methods:

[0044] S41, after re-swelling the freeze-dried hydrogel in an aqueous medium, the second plasma generator ionizes the working gas input by the second gas feeding unit to generate plasma and deliver it to the activation cavity to activate the swelled freeze-dried hydrogel to obtain a plasma-activated hydrogel. The working gas and flow rate are the same as in step S1. The method of loading plasma (active particles) into the acid-base neutralization pretreated hydrogel includes free diffusion, air blowing, bubbling and micro-bubbling;

[0045] S42, or the aqueous medium is placed into the activation cavity, the second plasma generator ionizes the working gas input by the second gas feeding unit to generate plasma and deliver to the activation cavity to activate the aqueous medium, obtaining a plasma-activated aqueous medium, and then the freeze-dried hydrogel is placed into the plasma-activated aqueous medium to reswell, obtaining a plasma-activated hydrogel. The aqueous medium includes deionized water, ultrapure water, buffer, physiological saline and / or biological glue. Preferably, the biological glue material is uniformly mixed with medical purified water, buffer, physiological saline and the like, and then activated by the plasma activation assembly. The mass fraction of the biological glue material in the prepared aqueous medium is less than 10%, and the uniform mixture maintains good fluidity.

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

[0047] The vacuum freeze-drying assembly includes a freezing module and a vacuum drying module. The freezing module pre-freezes the acid-base neutralization preprocessed hydrogel at a temperature of -60°C to -80°C. The vacuum drying module is used to dry and dehydrate the acid-base neutralization preprocessed hydrogel to prepare a freeze-dried acid-base neutralization preprocessed hydrogel. The cold trap temperature is -60°C to -80°C, and the vacuum degree is 0.1 to 10 Pa.

[0048] The preparation of a plasma-activated hydrogel from hyaluronic acid is illustrated as follows:

[0049] First, hyaluronic acid (HA) is dissolved in deionized water and mixed to prepare a 1% mass fraction of hyaluronic acid gel. The hyaluronic acid gel is first treated by the plasma activation assembly to obtain plasma oxidized hyaluronic acid (POH). Then, using the acid-base neutralization assembly, alkaline solution is added dropwise to the plasma oxidized hyaluronic acid until the pH of the plasma oxidized hyaluronic acid is in the range of 6-8 to obtain acid-base neutralized pretreated hyaluronic acid (NPOH). Then, the acid-base neutralized pretreated hyaluronic acid is placed in a vacuum freeze-drying assembly and pre-frozen at -80°C for 12 hours, and then placed in a vacuum environment of 0.1 Pa for freeze-drying for 48 hours to obtain freeze-dried acid-base neutralized pretreated hyaluronic acid, at which time the residual active particles of the acid-base neutralized pretreated hyaluronic acid have been substantially removed. Next, the freeze-dried acid-base neutralized pretreated hyaluronic acid is re-swollen into a hydrogel state in an aqueous medium, with a mass fraction of 1%. Finally, the re-swollen acid-base neutralized pretreated hyaluronic acid is activated by the plasma activation assembly to prepare plasma-activated gel (PAH). The prepared re-swollen acid-base neutralized pretreated hyaluronic acid itself has no sterilization effect, but can load more active particles, and shows stronger sterilization effect compared to the acid-base neutralized pretreated hyaluronic acid.

[0050] As shown in Figure 4 , the chemical reaction of hyaluronic acid in acid-base neutralization pretreatment is illustrated. After the hyaluronic acid is pretreated by the plasma pretreatment assembly, due to the loading of plasma active particles, the adjacent dihydroxyl groups of the hyaluronic acid are destroyed, and two molecules of hydroxyl groups are oxidized to two molecules of aldehyde groups. The pH of the hyaluronic acid is reduced to obtain plasma pretreated hyaluronic acid. When a small amount of 0.1M NaOH solution is added, OH - preferentially reacts with H + . When a sufficient amount of 0.1M NaOH solution is added, OH - reacts with aldehyde groups to undergo organic disproportionation reaction, and two molecules of aldehyde groups generate one molecule of hydroxyl group and one molecule of carboxylate group to obtain acid-base neutralized pretreated hyaluronic acid.

[0051] As shown in Figure 5 , the Fourier infrared spectrum detection result diagram of the corresponding embodiment of the hyaluronic acid of the present application shows the change of the chemical groups of the hyaluronic acid in the acid-base neutralization pretreatment. The infrared characteristic absorption peak of the aldehyde group is at 1710-1730cm -1 , the infrared characteristic absorption peak of the hydroxyl group is at 3050-3570cm -1 , and the carboxylic acid / carboxylate group exists at 1560-1650cm -1 , and the anti-symmetric stretching vibration absorption peak is at 1360-1440cm -1 ; after being treated by the plasma pretreatment assembly, the plasma pretreated hyaluronic acid is at 1710-1730cm -1The absorption peak of aldehyde group appeared, which proved the formation of aldehyde group. After acid-base neutralization pretreatment, the absorption peak of the acid-base neutralization pretreated hyaluronic acid at 1710-1730 cm -1 disappeared, the absorption peak at 1560-1650 cm -1 and at 1360-1440 cm -1 was enhanced, which proved the disappearance of aldehyde group and the formation of carboxyl / carboxylate group. The shift of the absorption peak of hydroxyl group at 3050-3570 cm -1 also indicated the change of the content of hydroxyl group in the above process.

[0052] As shown in Figure 6 , it is a detection result diagram of long-lived active particles (NO2 - ) of the corresponding embodiment of the hyaluronic acid of the application, which studies the content of NO2 - in the hyaluronic acid and the acid-base neutralization pretreated hyaluronic acid before and after the treatment of the plasma activation assembly, and indicates that the acid-base neutralization pretreated hyaluronic acid can significantly enhance the loading of NO2 - .

[0053] As shown in Figure 7 , it is a detection result diagram of long-lived active particles (NO2 - ) of the corresponding embodiment of the hyaluronic acid of the application, which studies the content of H2O2 in the hyaluronic acid and the acid-base neutralization pretreated hyaluronic acid before and after the treatment of the plasma activation assembly, and indicates that the acid-base neutralization pretreated hyaluronic acid can significantly enhance the loading of H2O2.

[0054] As shown in Figure 8 , it is a detection result diagram of short-lived active particles (·OH) of the corresponding embodiment of the hyaluronic acid of the application, which studies the content of ·OH in the hyaluronic acid and the acid-base neutralization pretreated hyaluronic acid before and after the treatment of the plasma activation assembly, and indicates that the acid-base neutralization pretreated hyaluronic acid (neutralized hydrogel) can significantly enhance the loading of ·OH.

[0055] As shown in Figure 9 , it is a comparison diagram of the bactericidal effect of Staphylococcus aureus of the corresponding embodiment of the hyaluronic acid of the application, which studies the killing effect of Staphylococcus aureus of the hyaluronic acid and the acid-base neutralization pretreated hyaluronic acid before and after the treatment of the plasma activation assembly, and indicates that the plasma activated glue (PAH) prepared based on the acid-base neutralization pretreated hyaluronic acid can significantly improve the bactericidal effect.

[0056] The application provides a preparation method of plasma-activated hydrogel, and the plasma device in the method comprises: a plasma pretreatment assembly, an acid-base neutralization assembly, a vacuum freeze-drying assembly, a plasma activation assembly and a monitoring control assembly; the plasma pretreatment assembly performs pretreatment on the hydrogel to prepare a plasma oxidation pretreated hydrogel; the acid-base neutralization assembly adds an alkaline solution dropwise to the plasma oxidation hydrogel to perform acid-base neutralization treatment, so as to obtain an acid-base neutralization pretreated hydrogel; the vacuum freeze-drying assembly performs pre-freezing on the acid-base neutralization pretreated hydrogel, and performs freeze-drying in a vacuum environment; the plasma activation assembly performs activation treatment on the freeze-dried acid-base neutralization pretreated hydrogel containing a water medium or reswelled in a water medium, so as to obtain a plasma-activated hydrogel; the monitoring control assembly is electrically connected with the plasma pretreatment assembly, the acid-base neutralization assembly, the vacuum freeze-drying assembly and the plasma activation assembly respectively, and sets operation control parameters of the plasma pretreatment assembly, the acid-base neutralization assembly, the vacuum freeze-drying assembly and the plasma activation assembly.

[0057] (1) The application utilizes plasma to perform oxidation pretreatment on hydrogel materials to eliminate antioxidant groups, unlike traditional chemical oxidation methods, the application does not need numerous chemical reagents and complex elution processes, and the main oxidation mechanism is based on self-degradation of plasma active particles, and after freeze-drying, residual active particles can be basically eliminated, thereby providing a new idea for oxidation of hydrogel materials.

[0058] (2) The acid-base neutralization pretreatment assembly is used to perform acid-base neutralization treatment on the plasma pretreated hydrogel, on one hand, the pH of the plasma pretreated hydrogel is controlled to be 6-8, so as to avoid the problem of irritability caused by too low pH; on the other hand, aldehyde groups in the plasma pretreated hydrogel are eliminated, and two active groups of hydroxyl groups and carboxylate groups are generated, thereby having biological friendliness.

[0059] (3) The acid-base neutralization pretreated hydrogel in the application can load more long-life and short-life liquid-phase active particles, and the liquid-phase active particles can effectively induce bacterial oxidative stress to kill bacteria, thereby playing a key role in disinfection, anti-infection and skin disease treatment.

[0060] (4) Compared with traditional hydrogels, the acid-base neutralization pretreated hydrogel in the application has better loading efficiency, is more convenient to apply, has better biological activity, and is conducive to further popularization and application.

[0061] It should be understood that the foregoing detailed description of the application, rather than limiting the application, is intended to explain and describe the current implementation of the application. Therefore, any modification, equivalent replacement or improvement made without departing from the spirit and scope of the application should be included in the protection scope of the application. In addition, the appended claims of the application are intended to cover all changes and modifications falling within the scope and boundary of the appended claims, or the equivalent form of such scope and boundary.

Claims

1. A method for the preparation of a plasma-activated hydrogel, based on a plasma device, characterized in that, The plasma device comprises a plasma pretreatment assembly, a plasma activation assembly, and a monitoring control assembly electrically connected with the plasma pretreatment assembly and the plasma activation assembly respectively; The plasma pretreatment assembly comprises a first gas feeding unit, a first plasma generator, a first power supply unit, and a pretreatment chamber, the first plasma generator is electrically connected with the first power supply unit, one end of the first plasma generator is in communication with the first gas feeding unit, and the other end is in communication with the pretreatment chamber; The preparation method of the plasma-activated hydrogel comprises the following steps: S1, the hydrogel is added into the pretreatment chamber, the first plasma generator ionizes the working gas input by the first gas supply unit to generate plasma and deliver to the pretreatment chamber, so that the plasma performs oxidative pretreatment on the hydrogel to obtain plasma oxidative pretreatment hydrogel; wherein the working gas comprises a mixed gas of air, oxygen and nitrogen, the working gas flow rate is 0 L / min < flow rate ≤ 5 L / min, and the oxidative pretreatment of the plasma on the hydrogel comprises: delivering the generated plasma to the pretreatment chamber to load active particles into the hydrogel for oxidative pretreatment; the active particles comprise at least one of O3, NO, NO2, N2O5, NO3, H2O2, ·OH and O2. 1 O2. S2, adding an alkaline solution dropwise to the plasma-oxidized pretreated hydrogel to perform a neutralization reaction, to obtain a neutralized hydrogel, the pH value of the neutralized hydrogel is 6-8; S3, performing vacuum freeze drying on the neutralized hydrogel at-60℃ to-80℃, to obtain a freeze-dried hydrogel; S4, performing swelling and activation treatment on the freeze-dried hydrogel by the plasma activation assembly, to obtain a plasma-activated hydrogel.

2. The method of claim 1, wherein the plasma-activated hydrogel is prepared by the steps of: The hydrogel comprises a hydrogel powder and an aqueous medium, the mass fraction of the hydrogel powder in the hydrogel is 0.1%-10%.

3. The method of claim 2, wherein the plasma-activated hydrogel is prepared by the steps of: The hydrogel powder comprises hyaluronic acid, sodium hyaluronate, alginate, chitosan, cellulose, cellulose derivatives, pectin, starch, and / or dextran.

4. The method of claim 2, wherein the plasma-activated hydrogel is prepared by the steps of: The aqueous medium comprises deionized water, ultrapure water, a buffer solution, physiological saline, and / or biological glue.

5. The method for preparing plasma-activated hydrogel according to claim 1, characterized in that, The alkaline solution comprises a sodium hydroxide solution, a lithium hydroxide solution, a potassium hydroxide solution, a calcium hydroxide solution, and / or a quaternary ammonium base solution.

6. The method of claim 1, wherein the plasma-activated hydrogel is prepared by the steps of: The plasma activation assembly comprises a second gas feeding unit, a second plasma generator, a second power supply unit, and an activation chamber, the second plasma generator is electrically connected with the second power supply unit, one end of the second plasma generator is in communication with the second gas feeding unit, and the other end is in communication with the activation chamber.

7. The method of claim 6, wherein the plasma-activated hydrogel is prepared by the steps of: The swelling and activation treatment on the freeze-dried hydrogel by the plasma activation assembly in step S4 to obtain a plasma-activated hydrogel comprises: After the freeze-dried hydrogel is reswelled in the aqueous medium, the freeze-dried hydrogel is placed in the activation chamber, the second plasma generator ionizes the working gas input by the second gas feeding unit to generate plasma and deliver the plasma to the activation chamber, to activate the reswelled freeze-dried hydrogel, to obtain a plasma-activated hydrogel; Or the aqueous medium is placed in the activation chamber, the second plasma generator ionizes the working gas input by the second gas feeding unit to generate plasma and deliver the plasma to the activation chamber, to activate the aqueous medium, to obtain a plasma-activated aqueous medium, and then the freeze-dried hydrogel is placed in the plasma-activated aqueous medium to reswell, to obtain a plasma-activated hydrogel.

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