A plasma-activated ice microneedle preparation device and method

Abstract

This invention discloses a device and method for preparing plasma-activated ice microneedles, comprising: a plasma activation component activating an aqueous medium or ice microneedles to obtain plasma-activated aqueous medium or plasma-activated ice microneedles; a vacuum component filling an aqueous medium or plasma-activated aqueous medium into a microneedle mold; a freezing component freezing the microneedle mold filled with the aqueous medium or plasma-activated aqueous medium to obtain ice microneedles or plasma-activated ice microneedles; and a monitoring and control component electrically connected to the plasma activation component, vacuum component, and freezing component, respectively, and setting the operating control parameters of the plasma activation component, vacuum component, and freezing component. The low-temperature environment of plasma-activated ice microneedles effectively slows down the decay rate of active particles in aqueous solution, prolongs the storage time of active particles and their biomedical effects, and enables precise and efficient transdermal delivery of active particles.

Description

Technical Field

[0001] This invention relates to the field of medical device technology, and in particular to a plasma-activated ice microneedle preparation device and method. Background Technology

[0002] As the largest organ in the human body, the skin serves as a protective barrier against external environmental threats. Various skin diseases, such as wound infections, non-infectious skin diseases, and skin cancer, cause serious skin damage that threatens human health. However, existing conventional treatments (such as surgery and medication) are insufficient to fully meet patients' needs. In recent years, atmospheric pressure cold plasma technology has seen rapid development in the biomedical field, particularly in the treatment of skin diseases, demonstrating broad application prospects. Currently, domestic and international researchers generally believe that reactive oxygen species (ROS) and reactive nitrogen species (RNS) generated by plasma play a crucial role in its biomedical effects. However, current research and applications typically involve direct plasma treatment of human tissue, but the short lifespan of reactive particles makes it difficult to penetrate the outermost layer of the skin (the stratum corneum, typically 10-40 μm), preventing the plasma from effectively reaching deeper lesions. In recent years, numerous studies have discovered that aqueous solutions or hydrogels can store reactive particles. This is because plasma-activated aqueous solutions or hydrogels generate a rich variety of liquid-phase ROS and RNS. Currently, plasma-activated aqueous solutions and hydrogels have been proven to have significant application potential in chronic wound healing, psoriasis treatment, vitiligo treatment, and cancer treatment. Although plasma-activated aqueous solutions or hydrogels can penetrate the skin barrier for deep delivery via injection, commonly used subcutaneous injections can only deliver active particles through a single channel, resulting in a limited range of action. Furthermore, the active particles in the liquid phase decay rapidly at room temperature, making it difficult to maintain their activity for extended periods. In addition, while cosmetic injection techniques such as mesotherapy can use multiple needles to inject plasma-activated aqueous solutions or hydrogels under negative pressure, it is difficult to perform customized and precise injections based on the affected area, and it generates medical waste such as used needles, leading to significant limitations. Summary of the Invention

[0003] The purpose of this invention is to provide a plasma-activated ice microneedle preparation device and method. By using ice microneedles that have undergone plasma activation treatment, active particles can be transported deep into the skin barrier. Moreover, the low temperature environment effectively slows down the decay rate of active particles. Compared with the rapid decay of active particles in plasma-activated water, this invention extends the storage time of active particles and their biomedical effects, achieving precise and efficient transdermal delivery of active particles.

[0004] To address the aforementioned technical problems, a first aspect of this invention provides a plasma-activated ice microneedle preparation apparatus, comprising: a plasma activation component, a vacuum component, a freezing component, and a monitoring and control component.

[0005] The plasma activation component activates the aqueous medium or ice microneedles to obtain plasma-activated aqueous medium or plasma-activated ice microneedles.

[0006] The vacuum assembly fills the microneedle mold with the aqueous medium or the plasma-activated aqueous medium after being treated by the plasma activation assembly.

[0007] The freezing component freezes the microneedle mold filled with the aqueous medium or the plasma-activated aqueous medium to obtain the ice microneedles or the plasma-activated ice microneedles.

[0008] The monitoring and control component is electrically connected to the plasma activation component, the vacuum component, and the freezing component, respectively, and sets the operating control parameters of the plasma activation component, the vacuum component, and the freezing component.

[0009] Furthermore, the plasma activation assembly includes: a plasma device and an activation chamber;

[0010] The plasma device activates the aqueous medium or the ice microneedles in the activation chamber, generating atmospheric pressure cold plasma active particles in the aqueous medium or the ice microneedles.

[0011] The plasma device includes a discharge structure employing dielectric barrier discharge, corona discharge, sliding arc discharge, microwave discharge, radio frequency discharge, or jet discharge.

[0012] The working gas of the plasma device includes: air, nitrogen, oxygen, argon and / or helium;

[0013] The plasma device is located in the activation chamber and directly activates the aqueous medium or the ice microneedles; or, the plasma device is located outside the activation chamber and indirectly activates the aqueous medium or the ice microneedles by introducing the generated active gas into the activation chamber.

[0014] Furthermore, the microneedle mold has several holes for preparing ice microneedles;

[0015] The length of the hole ranges from 500μm to 3000μm, its diameter or side length ranges from 100μm to 1000μm, and its center-to-center distance ranges from 100μm to 20000μm.

[0016] Furthermore, conveyor belts are provided between each pair of the plasma activation component, vacuum component, and freezing component;

[0017] The monitoring and control component is electrically connected to the conveyor belt and controls the operation of the conveyor belt.

[0018] Furthermore, the aqueous medium includes: medical purified water, buffer solution, physiological saline, or biogel.

[0019] Furthermore, the aqueous medium or plasma-activated aqueous medium contains bioactive substances, including cells, bacteria, polypeptides, proteins, cytokines, or small molecule drugs.

[0020] Furthermore, the ambient temperature at which the freezing component delivers the ice microneedles to the plasma activation component is below 0°C.

[0021] Furthermore, the freezing component freezes the microneedle mold filled with the aqueous medium or the plasma-activated aqueous medium at a temperature below 0°C for a freezing time greater than 10 minutes.

[0022] Accordingly, a second aspect of the present invention provides a method for preparing plasma-activated ice microneedles, which prepares ice microneedles using the aforementioned plasma-activated ice microneedle preparation apparatus, comprising the following steps:

[0023] The aqueous medium is activated by a plasma activation component to obtain a plasma-activated aqueous medium, which is then injected into a microneedle mold.

[0024] The microneedle mold containing the plasma-activated aqueous medium is filled using a vacuum assembly.

[0025] The microneedle mold, after vacuum filling, is frozen using a freezing component to obtain plasma-activated ice microneedles.

[0026] Accordingly, a third aspect of the present invention provides a method for preparing plasma-activated ice microneedles, which prepares ice microneedles using the aforementioned plasma-activated ice microneedle preparation apparatus, comprising the following steps:

[0027] An aqueous medium is injected into a microneedle mold, and the microneedle mold containing the aqueous medium is filled using a vacuum assembly.

[0028] The microneedle mold that has undergone vacuum filling is frozen using a freezing component to obtain ice microneedles;

[0029] The ice microneedles are activated by a plasma activation component to obtain plasma-activated ice microneedles.

[0030] The above-described technical solutions of the embodiments of the present invention have the following beneficial technical effects:

[0031] 1. This invention breaks through the skin barrier and can simultaneously release liquid-phase active particles into the body after penetrating the skin, and act on the surrounding lesion tissue through diffusion. Unlike traditional plasma-activated water therapy which uses subcutaneous injection, this invention delivers active particles to the lesion in a painless and minimally invasive manner, solving the problem of shallow effective treatment depth of plasma treatment.

[0032] 2. The microneedle mold parameters in this invention can be customized in advance according to the condition of the skin lesion site (such as area and depth), such as the length, number, spacing, and shape of the holes, so that the plasma-activated ice microneedles can accurately treat the lesion site without contacting capillaries and nerve endings.

[0033] 3. The low-temperature environment of plasma-activated ice microneedles in this invention effectively slows down the decay rate of active particles; compared with the rapid decay of active particles in plasma-activated water, this invention prolongs the storage time of active particles and their biomedical effects.

[0034] 4. The plasma-activated ice microneedles of this invention contain a large number of long-lived and some short-lived liquid-phase active particles; these active particles can effectively induce bacterial inactivation and apoptosis of abnormal cells such as cancer cells, playing a key role in the treatment of skin diseases.

[0035] 5. The plasma-activated ice microneedles in this invention can be prepared by plasma-activated water low-temperature molding or by direct plasma treatment of ice microneedles, which is conducive to further promotion and application.

[0036] 6. The plasma-activated ice microneedles in this invention are made of biocompatible materials and have a good storage effect on added bioactive substances such as cells, bacteria, polypeptides, proteins, cytokines, or small molecule drugs. Attached Figure Description

[0037] Figure 1a This is a schematic diagram of the plasma-activated ice microneedle preparation device in an embodiment of the present invention.

[0038] Figure 1b This is a schematic diagram of the plasma-activated ice microneedle preparation process in an embodiment of the present invention.

[0039] Figure 2 This is a flowchart of the plasma-activated ice microneedle preparation method in one embodiment of the present invention.

[0040] Figure 3 This is a flowchart of the second method for preparing plasma-activated ice microneedles in this embodiment of the invention.

[0041] Figure 4 This is a diagram illustrating the effect of plasma-activated ice microneedles based on AVC hydrogel used in selective anticancer research in an embodiment of the present invention.

[0042] Figure 5 This is a diagram illustrating the effect of plasma-activated ice microneedles based on physiological saline in selective anticancer research according to an embodiment of the present invention.

[0043] Figure 6a This is a schematic diagram comparing the changes in anticancer effects of plasma-activated ice microneedles (stored at -80°C) and plasma-activated physiological saline (stored at room temperature) with increasing storage time in embodiments of the present invention.

[0044] Figure 6b This is a schematic diagram comparing the changes in H2O2 active particle concentration with increasing storage time in plasma-activated ice microneedles based on physiological saline (stored at -80°C) and plasma-activated physiological saline (stored at room temperature) in embodiments of the present invention.

[0045] Figure 7a This is a schematic diagram comparing the changes in anticancer effects of plasma-activated ice microneedles (stored at -80°C) and plasma-activated AVC hydrogel (stored at room temperature) with increasing storage time in embodiments of the present invention.

[0046] Figure 7b This is a comparative schematic diagram showing the change of H2O2 active particle concentration with increasing storage time in plasma-activated ice microneedles based on AVC hydrogel (stored at -80℃) and plasma-activated AVC hydrogel (stored at room temperature) in embodiments of the present invention.

[0047] Figure 8 This is an image illustrating the effect of plasma-activated ice microneedles on inhibiting subcutaneous tumor growth in nude mice, as described in an embodiment of the present invention. Detailed Implementation

[0048] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to specific embodiments and the accompanying drawings. It should be understood that these descriptions are merely exemplary and not intended to limit the scope of the invention. Furthermore, descriptions of well-known structures and techniques are omitted in the following description to avoid unnecessarily obscuring the concept of the invention.

[0049] Please refer to Figure 1a and Figure 1bThe first aspect of this invention provides a plasma-activated ice microneedle preparation apparatus, comprising: a plasma activation component, a vacuum component, a freezing component, and a monitoring and control component. The plasma activation component activates an aqueous medium or ice microneedles to obtain plasma-activated aqueous medium or plasma-activated ice microneedles. The vacuum component fills an aqueous medium or a plasma-activated aqueous medium treated by the plasma activation component into a microneedle mold. The freezing component freezes the microneedle mold filled with the aqueous medium or plasma-activated aqueous medium to obtain ice microneedles or plasma-activated ice microneedles. The monitoring and control component is electrically connected to the plasma activation component, the vacuum component, and the freezing component, respectively, and sets the operating control parameters of the plasma activation component, the vacuum component, and the freezing component.

[0050] Specifically, the microneedle mold used in the above-mentioned preparation device can be customized in advance according to the condition of the skin lesion site (such as area and depth) to ensure that the plasma-activated ice microneedles can accurately treat the lesion site without contacting capillaries and nerve endings.

[0051] Specifically, the layout of the plasma activation component, vacuum component, freezing component, and monitoring and control component in the preparation device includes, but is not limited to, full integration, partial integration, and separate placement of components. The specific arrangement of each component can be configured according to environmental requirements.

[0052] The vacuum assembly performs vacuum treatment on the aqueous medium or plasma-activated aqueous medium filled into the microneedle mold for a duration of more than 30 seconds, which can achieve full filling of the aqueous medium or plasma-activated aqueous medium into the microneedle mold.

[0053] The plasma activation component includes a plasma device and an activation chamber. The plasma device activates the aqueous medium or ice microneedles in the activation chamber, generating atmospheric pressure cold plasma active particles in the aqueous medium or ice microneedles.

[0054] Specifically, plasma devices can be configured in two ways. One is to place the plasma device within the activation chamber, allowing it to directly activate the aqueous medium or ice microneedles. The other is to place the plasma device outside the activation chamber, introducing the active gas generated by the plasma device into the activation chamber to indirectly activate the aqueous medium or ice microneedles.

[0055] Optionally, the working gas of the plasma device includes air, nitrogen, oxygen, argon and / or helium.

[0056] Furthermore, the plasma assembly activates the aqueous medium or ice microneedles through dielectric barrier discharge, corona discharge, sliding arc discharge, or jet discharge, generating atmospheric pressure cold plasma active particles in the aqueous medium or ice microneedles.

[0057] Furthermore, the microneedle mold has several holes for preparing ice microneedles; the length of the holes ranges from 500μm to 3000μm, the diameter or side length ranges from 100μm to 1000μm, and the center-to-center distance ranges from 100μm to 20000μm.

[0058] Specifically, conveyor belts are installed between each pair of the plasma activation component, vacuum component, and freezing component; the monitoring and control component is electrically connected to the conveyor belts to control their operation. Furthermore, the ambient temperature for transferring ice microneedles from the freezing component to the plasma activation component is below 0°C. In addition, the transfer of items between these components can also be achieved manually by the operator.

[0059] Furthermore, the aqueous medium includes: medical purified water, buffer solution, physiological saline, or biogel.

[0060] Furthermore, before the freezing components undergo freezing treatment, bioactive substances are added to the aqueous medium or plasma-activated aqueous medium. These bioactive substances include cells, bacteria, peptides, proteins, and cytokines. In addition, small molecule drugs and other substances may also be added to the aqueous medium or plasma-activated aqueous medium.

[0061] Furthermore, the freezing component freezes the microneedle mold filled with an aqueous medium or a plasma-activated aqueous medium at a temperature below 0°C for a freezing time greater than 10 minutes.

[0062] Accordingly, please refer to Figure 2 The second aspect of this invention provides a method for preparing plasma-activated ice microneedles, which prepares ice microneedles using the aforementioned plasma-activated ice microneedle preparation apparatus, comprising the following steps:

[0063] S110, the aqueous medium is activated by a plasma activation component to obtain a plasma-activated aqueous medium, which is then injected into a microneedle mold.

[0064] S120 is a microneedle mold filled with plasma-activated aqueous medium using a vacuum assembly.

[0065] S130, based on the freezing component, freezes the microneedle mold after vacuum filling treatment to obtain plasma-activated ice microneedles.

[0066] Specifically, the above preparation method first activates the aqueous medium with a plasma activation component to obtain a plasma-activated aqueous medium; then, the plasma-activated aqueous medium is injected into a microneedle mold and treated by a vacuum component to fully fill it; then, excess plasma-activated aqueous medium is removed, and a layer of moist gauze is further covered on the mold; finally, after low-temperature treatment by a freezing component, it is peeled off to obtain plasma-activated ice microneedles.

[0067] Accordingly, please refer to Figure 3 The third aspect of this invention provides a method for preparing plasma-activated ice microneedles, which prepares ice microneedles using the aforementioned plasma-activated ice microneedle preparation apparatus, including the following steps:

[0068] S210, injecting an aqueous medium into a microneedle mold, and filling the microneedle mold containing the aqueous medium using a vacuum component.

[0069] S220 uses a freezing component to freeze a vacuum-filled microneedle mold to obtain ice microneedles.

[0070] S230, the ice microneedles are activated by the plasma activation component to obtain plasma-activated ice microneedles.

[0071] Specifically, the above preparation method first injects an aqueous medium into a microneedle mold and treats it with a vacuum component to ensure full filling; then removes the excess aqueous medium and further covers the mold with a layer of moist gauze; after low-temperature treatment by a freezing component, the mold is peeled off to obtain ice microneedles; finally, the ice microneedles are activated by a plasma activation component to obtain plasma-activated ice microneedles.

[0072] In the two preparation processes mentioned above, the preparation of plasma-activated ice microneedles includes the preparation of an aqueous medium, the preparation of a plasma-activated aqueous medium, and the preparation of plasma-activated ice microneedles.

[0073] The aqueous medium is a material with good flowability and biocompatibility, such as medical purified water, buffer solution, physiological saline, or bio-gels prepared from these materials. The plasma-activated aqueous medium is prepared by activating it using a plasma activation component. This plasma-activated aqueous medium is then injected into a microneedle mold and treated with a vacuum component to ensure full filling. Excess plasma-activated aqueous medium is removed, and a layer of moistened gauze is then placed over the mold. Finally, after cryogenic treatment using a freezing component, the microneedles are peeled off, yielding plasma-activated ice microneedles.

[0074] Preferably, the bio-adhesive material is uniformly mixed with medical purified water, buffer solution, physiological saline, etc., and then activated by a plasma activation component. The mass fraction of the bio-adhesive material in the prepared aqueous medium is less than 10%, and it maintains good flowability after being uniformly mixed with medical purified water, buffer solution, physiological saline, etc.

[0075] Preferably, the plasma generator in the plasma activation assembly is a plasma generation device based on atmospheric pressure cold plasma discharge.

[0076] Preferably, the conditions for low-temperature treatment based on the freezing component are freezing at 0°C for more than 10 minutes.

[0077] Preferably, the method of fully filling the microneedle mold with an aqueous medium or plasma-activated aqueous medium based on a vacuum component involves vacuum treatment for more than 30 seconds.

[0078] In another embodiment, the method for preparing plasma-activated ice microneedles includes the preparation of an aqueous medium, the preparation of ice microneedles, and the preparation of plasma-activated ice microneedles.

[0079] In this process, ice microneedles are produced by injecting an aqueous medium into a microneedle mold using a peristaltic pump, removing air bubbles through a vacuum filling chamber, and then cryogenically freezing and demolding. A plasma generator is used to activate the ice microneedles, resulting in plasma-activated ice microneedles. Preferably, the plasma activation component activates the ice microneedles, and the plasma generator is also placed at 0°C or below to prevent the ice microneedles from melting. Alternatively, the exhaust gas generated by the plasma generator is introduced into the semi-enclosed space of the temperature-controlled chamber containing the ice microneedles.

[0080] Preferably, the plasma-activated ice microneedles obtained by the above preparation method should be stored at a temperature below -20°C.

[0081] In one embodiment, when preparing the bio-gel aqueous medium, a magnetic stirrer can be used to mix the solvent and the bio-gel material, while simultaneously treating it with a plasma activation component.

[0082] In one embodiment, to avoid damage to the bio-adhesive properties due to excessively high plasma activation medium temperature, the reaction vessel is pre-cooled in a cold water bath or ice bath when using the plasma activation component.

[0083] In one embodiment, in a preferred embodiment of the plasma-activated medium, the plasma-activated aqueous medium is prepared by the plasma generator in the plasma activation component treating the aqueous medium, and the discharge mode of the generated plasma is atmospheric pressure cold plasma discharge, including dielectric barrier discharge, corona discharge, sliding arc discharge, jet discharge, etc.

[0084] In a preferred embodiment, the unactivated aqueous substance is selected from materials with good biocompatibility and flowability, such as medical purified water, buffer solution, physiological saline, or bio-glue.

[0085] In one embodiment, the aqueous medium is kept in a liquid state before cryogenic treatment, and bioactive substances such as cells, bacteria, peptides, proteins, cytokines, or small molecule drugs can be added to it in this state. The low-temperature environment of plasma-activated ice microneedles prolongs the activity of bioactive substances and small molecule drugs. After penetrating the skin barrier, the plasma-activated ice microneedles dissolve under the influence of body temperature, and active particles, bioactive substances, or small molecule drugs are released from the microneedles and act on the surrounding lesion area.

[0086] In one embodiment, plasma-activated ice microneedles are prepared using hydrogel. First, dimethyl tauryl acryloyl / VP copolymer (ice crystal forming agent AVC) is dissolved in deionized water and mixed to prepare a 5 wt% bio-gel solution. The bio-gel solution is then activated using a plasma activation component to obtain a plasma-activated bio-gel solution. Next, the plasma-activated bio-gel solution is injected into a microneedle mold and treated with a vacuum component to ensure full filling. Excess plasma-activated bio-gel solution is then removed, and a layer of moistened gauze is placed over the mold. Finally, after cryogenic treatment with a freezing component, the microneedles are peeled off to obtain the plasma-activated ice microneedles. The prepared plasma-activated ice microneedles possess the excellent sustained-release and mechanical properties of bio-gel, easily penetrating the skin barrier and prolonging the release duration and stability of active particles at the lesion site.

[0087] like Figure 4 As shown in the figure, according to one embodiment of the present invention, the effect of plasma-activated ice microneedles based on AVC on the viability of A375 cancer cells and normal HaCaT cells was studied, indicating that plasma-activated ice microneedles have a selective anti-cancer effect, which can significantly inhibit the viability of cancer cells without causing significant damage to normal cells.

[0088] like Figure 5 As shown in the figure, according to one embodiment of the present invention, the effect of plasma-activated ice microneedles based on physiological saline on the viability of A375 cancer cells and normal HaCaT cells was studied, indicating that plasma-activated ice microneedles have a selective anti-cancer effect, which can significantly inhibit the viability of cancer cells without causing significant damage to normal cells.

[0089] like Figure 6a and Figure 6b As shown, according to one embodiment of the present invention, plasma-activated saline and plasma-activated ice microneedles based on saline (stored at -80°C) were subjected to experiments, and the anticancer effects and changes in active particles H2O2 with prolonged storage time were investigated. Figure 6a and Figure 6bThis indicates that plasma-activated ice microneedles can prolong the lifespan of active particles, thereby extending their anti-cancer effect.

[0090] like Figure 7a and Figure 7b As shown, according to one embodiment of the present invention, the anticancer effects and changes in active particles H2O2 of plasma-activated AVC hydrogel and plasma-activated ice microneedles based on AVC hydrogel (stored at -80°C) were studied with prolonged storage time. Figure 7a and Figure 7b As shown in the figure, plasma-activated ice microneedles can prolong the lifespan of active particles, thereby extending their anti-cancer effect.

[0091] like Figure 8 As shown, according to one embodiment of the present invention, the inhibitory effect of plasma-activated ice microneedles based on physiological saline on subcutaneous tumor growth in nude mice was studied. The tumor size of the nude mice in the plasma-activated ice microneedle group was significantly smaller than that in the non-activated ice microneedle group and the control group, indicating that the plasma-activated ice microneedles have a strong ability to inhibit tumor growth and have potential medical value.

[0092] This invention aims to protect a plasma-activated ice microneedle preparation apparatus and method. The apparatus includes: a plasma activation component, a vacuum component, a freezing component, and a monitoring and control component. The plasma activation component activates an aqueous medium or ice microneedles to obtain plasma-activated aqueous medium or plasma-activated ice microneedles. The vacuum component fills a microneedle mold with an aqueous medium or plasma-activated aqueous medium treated by the plasma activation component. The freezing component freezes the microneedle mold filled with the aqueous medium or plasma-activated aqueous medium to obtain ice microneedles or plasma-activated ice microneedles. The monitoring and control component is electrically connected to the plasma activation component, the vacuum component, and the freezing component, respectively, and sets the operating control parameters of the plasma activation component, the vacuum component, and the freezing component. The above technical solution has the following effects:

[0093] 1. This invention breaks through the skin barrier and can simultaneously release liquid-phase active particles into the body after penetrating the skin, and act on the surrounding lesion tissue through diffusion. Unlike traditional plasma-activated water therapy which uses subcutaneous injection, this invention delivers active particles to the lesion in a painless and minimally invasive manner, solving the problem of shallow effective treatment depth of plasma treatment.

[0094] 2. The microneedle mold parameters in this invention can be customized in advance according to the condition of the skin lesion site (such as area and depth), such as the length, number, spacing, and shape of the holes, so that the plasma-activated ice microneedles can accurately treat the lesion site without contacting capillaries and nerve endings.

[0095] 3. The low-temperature environment of plasma-activated ice microneedles in this invention effectively slows down the decay rate of active particles; compared with the rapid decay of active particles in plasma-activated water, this invention prolongs the storage time of active particles and their biomedical effects.

[0096] 4. The plasma-activated ice microneedles of this invention contain a large number of long-lived and some short-lived liquid-phase active particles; these active particles can effectively induce bacterial inactivation and apoptosis of abnormal cells such as cancer cells, playing a key role in the treatment of skin diseases.

[0097] 5. The plasma-activated ice microneedles in this invention can be prepared by plasma-activated water low-temperature molding or by direct plasma treatment of ice microneedles, which is conducive to further promotion and application.

[0098] 6. The plasma-activated ice microneedles in this invention are made of biocompatible materials and have a good storage effect on added bioactive substances such as cells, bacteria, polypeptides, proteins, cytokines, or small molecule drugs.

[0099] It should be understood that the specific embodiments described above are merely illustrative or explanatory of the principles of the invention and do not constitute a limitation thereof. Therefore, any modifications, equivalent substitutions, improvements, etc., made without departing from the spirit and scope of the invention should be included within the protection scope of the invention. Furthermore, the appended claims are intended to cover all variations and modifications falling within the scope and boundaries of the appended claims, or equivalent forms of such scope and boundaries.

Claims

1. A plasma-activated ice microneedle preparation device, characterized in that, include: Plasma activation components, vacuum components, freezing components, and monitoring and control components; The plasma activation component activates the aqueous medium to obtain a plasma-activated aqueous medium. The vacuum assembly fills the microneedle mold with the plasma-activated aqueous medium, which has been treated by the plasma activation assembly; The freezing component freezes the microneedle mold filled with the plasma-activated aqueous medium to obtain the plasma-activated ice microneedles. The monitoring and control component is electrically connected to the plasma activation component, the vacuum component, and the freezing component, respectively, and sets the operating control parameters of the plasma activation component, the vacuum component, and the freezing component.

2. The plasma-activated ice microneedle preparation device according to claim 1, characterized in that, The plasma activation assembly includes: a plasma device and an activation chamber; The plasma device activates the aqueous medium in the activation chamber, generating atmospheric pressure cold plasma active particles in the aqueous medium. The plasma device includes a discharge structure employing dielectric barrier discharge, corona discharge, sliding arc discharge, microwave discharge, radio frequency discharge, or jet discharge. The working gas of the plasma device includes: air, nitrogen, oxygen, argon and / or helium; The plasma device is located in the activation chamber and directly activates the aqueous medium; or, the plasma device is located outside the activation chamber and indirectly activates the aqueous medium by introducing the generated active gas into the activation chamber.

3. The plasma-activated ice microneedle preparation apparatus according to claim 2, characterized in that, The microneedle mold has several holes for preparing ice microneedles; The length of the hole ranges from 500 μm to 3000 μm, its diameter or side length ranges from 100 μm to 1000 μm, and its center-to-center distance ranges from 100 μm to 20000 μm.

4. The plasma-activated ice microneedle preparation apparatus according to claim 3, characterized in that, Conveyor belts are provided between each pair of the plasma activation component, vacuum component, and freezing component; The monitoring and control component is electrically connected to the conveyor belt and controls the operation of the conveyor belt.

5. The plasma-activated ice microneedle preparation apparatus according to claim 4, characterized in that, The aqueous medium includes: medical purified water, buffer solution, physiological saline, or biogel.

6. The plasma-activated ice microneedle preparation apparatus according to claim 5, characterized in that, The aqueous medium or plasma-activated aqueous medium contains bioactive substances, including cells, bacteria, polypeptides, proteins, cytokines, or small molecule drugs.

7. The plasma-activated ice microneedle preparation apparatus according to claim 6, characterized in that, The freezing component freezes the microneedle mold filled with the plasma-activated aqueous medium at a temperature below 0°C for a time greater than 10 minutes.

8. A method for preparing plasma-activated ice microneedles, characterized in that, The preparation of ice microneedles using the plasma-activated ice microneedle preparation apparatus according to any one of claims 1-7 includes the following steps: The aqueous medium is activated by a plasma activation component to obtain a plasma-activated aqueous medium, which is then injected into a microneedle mold. The microneedle mold containing the plasma-activated aqueous medium is filled using a vacuum assembly. The microneedle mold, after vacuum filling, is frozen using a freezing component to obtain plasma-activated ice microneedles.

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