Plasma activating solution as well as preparation method and application thereof

The plasma activation fluid formed by normal saline is solved by plasma treatment, which is difficult to effectively treat dermatitis after radiotherapy and repair skin damage in the prior art, and achieves the effect of promoting skin healing, slowing inflammatory response and reducing costs.

CN119868402APending Publication Date: 2025-04-25PEKING UNIVERSITY SHENZHEN HOSPITAL
View PDF 0 Cites 1 Cited by

Patent Information

Application Number
CN202510093746.X
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2025-01-21
Publication Date
2025-04-25

AI Technical Summary

Technical Problem

The prior art lacks effective drugs to prevent the progression of dermatitis after radiotherapy and repair skin lesions, and existing drugs such as epidermal growth factors have problems such as hyperstimulation, hyperplasia and high costs.

Method used

The normal saline is treated with plasma to form a plasma activation fluid. This fluid stimulates cell proliferation, migration and repair at the inflammatory site of the skin by promoting the transfer of active nitrogen, slows down the inflammatory response, promotes neovascularization, and thus accelerates wound healing.

Benefits of technology

Plasma activated fluid can effectively promote the healing of radioactive skin inflammation, repair radioactive damage, prevent scar generation, reduce the severity of skin inflammation after radiotherapy, and is not damaged to cells and animals, with good safety and low preparation cost.

✦ Generated by Eureka AI based on patent content.

Smart Images

  • Figure CN119868402A_ABST
    Figure CN119868402A_ABST
Patent Text Reader

Abstract

The invention discloses a plasma activating solution as well as a preparation method and application thereof, and relates to the field of medicines. The preparation method of the plasma activating solution comprises the following steps: generating plasma by using helium and oxygen; and treating normal saline by using the plasma to obtain the plasma activating solution. Plasma is adopted to treat normal saline, so that active species in the plasma are transferred into the normal saline, and the plasma activating solution is formed. The plasma activating fluid can promote healing of radiation dermatitis or mucosal inflammation, repair radioactive injury, prevent scar generation, reduce the severity of dermatitis or mucosal inflammation after radiotherapy (reduce inflammatory response, promote skin cell repair and angiogenesis) and slow down inflammatory response, and is free of damage to cells and animals and free of toxic and side effects. And the safety is very good. The method provided by the invention is simple in process and low in preparation cost, and can realize large-scale production of the plasma activating solution.
Need to check novelty before this filing date? Find Prior Art

Description

Technical Field

[0001] The present invention relates to the field of medicine, and in particular to a plasma activation liquid and a preparation method and application thereof. Background Art

[0002] Acute radiation-induced dermatitis is a common complication of radiotherapy, characterized by severe skin tissue damage, prolonged duration, difficulty healing, and difficulty in treatment. Failure to provide timely and effective treatment can lead to persistent, recurrent attacks after radiotherapy, long-term nonhealing, and ultimately cancerous development. It can also prevent patients from completing radiotherapy as planned. Unlike common skin inflammation, radiation-induced dermatitis and even skin ulcers are progressive, with the wound surface expanding and worsening as radiotherapy continues. The disease often progresses to chronic ulcers, lingering for years without healing, severely impacting life and treatment. Therefore, timely treatment of acute radiation-induced dermatitis and prevention of ulcer progression are crucial issues in the treatment of cancer.

[0003] Currently, there are no particularly effective drugs on the market to prevent the progression of post-radiotherapy dermatitis and repair skin damage. Epidermal growth factor (EGF) sprays are commonly used for this type of dermatitis. While these sprays can promote wound healing and repair to a certain extent, excessive EGF can lead to over-irritation or excessive proliferation of the skin, causing excessive wound healing, scarring, or uneven skin texture. Some people may also be sensitive to EGF, triggering allergic reactions such as redness, itching, or inflammation. Furthermore, the purification and preparation costs of EGF are relatively high, resulting in a low user rate.

[0004] Therefore, the existing technology still needs to be improved and developed. Summary of the Invention

[0005] Based on the above-mentioned deficiencies in the prior art, the purpose of the present invention is to provide a plasma activation liquid and a preparation method and application thereof, aiming to provide a low-cost drug for promoting the healing of radiation dermatitis.

[0006] The technical solutions of the present invention are as follows:

[0007] A first aspect of the present invention provides a method for preparing a plasma activation solution, wherein the method for preparing the plasma activation solution comprises the following steps:

[0008] Use helium and oxygen to generate plasma;

[0009] Physiological saline is treated with the plasma to obtain the plasma activated liquid.

[0010] Optionally, the preparation method of the plasma activation solution specifically includes the following steps:

[0011] An atmospheric pressure low-temperature plasma jet generating system and a container containing physiological saline are provided, wherein the atmospheric pressure low-temperature plasma jet generating system includes a plasma jet generating tube;

[0012] placing a container containing physiological saline at the lower part of the plasma jet generating tube;

[0013] A mixed gas of helium and oxygen is introduced into the plasma jet generating tube as a working gas, and the working parameters of the plasma jet generating tube are set. After the power is turned on, a plasma beam is generated and directed toward the physiological saline. After the plasma beam contacts the physiological saline, the plasma activated liquid is obtained.

[0014] Optionally, the distance between the lowermost end of the plasma jet generating tube and the surface of the physiological saline solution is 1 cm.

[0015] Optionally, the flow rate of the helium is 2 L / min, and the flow rate of the oxygen is 10 mL / min.

[0016] Optionally, the operating parameters of the plasma jet generating tube are as follows:

[0017] The discharge voltage is 4.5-4.7 kV, the discharge current frequency is 6.46 kHz, the discharge gap is 2-10 mm, and the discharge power is 0.467-0.550 W.

[0018] A second aspect of the present invention provides a plasma activation liquid, wherein the plasma activation liquid is prepared by the preparation method of the present invention as described above.

[0019] Optionally, the active species in the plasma activated liquid includes active nitrogen.

[0020] The third aspect of the present invention provides a use of the plasma activated liquid as described above in the preparation of a pharmaceutical preparation for treating radiation dermatitis or radiation mucositis.

[0021] Optionally, the pharmaceutical preparation is a liquid preparation or a gaseous preparation.

[0022] A fourth aspect of the present invention provides a pharmaceutical preparation for treating radiation dermatitis or radiation mucositis, wherein the pharmaceutical preparation for treating radiation dermatitis or radiation mucositis comprises the plasma-activated liquid of the present invention as described above, and a pharmaceutically acceptable carrier and / or a pharmaceutically acceptable additive.

[0023] Beneficial Effects: The present invention uses plasma to treat saline, transferring active species from the plasma into the saline to form a plasma-activated solution. This plasma-activated solution can promote the healing of radiation-induced skin or mucosal inflammation, repair radiation damage, prevent scarring, and reduce the severity of post-radiation skin or mucosal inflammation (reducing the inflammatory response, promoting skin cell repair and angiogenesis), slowing the inflammatory response while being harmless to cells and animals and exhibiting excellent safety. The method provided by the present invention is simple, has low production costs, and can achieve large-scale production of plasma-activated solutions. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 Schematic diagram of the structure of the atmospheric pressure low-temperature plasma jet generation system.

[0025] Figure 2 These are the test results of active particle components in plasma activation liquid.

[0026] Figure 3 This figure shows the results of plasma activation liquid promoting Hacat cell migration.

[0027] Figure 4 The diagram shows the results of plasma-activated liquid promoting tube formation of vascular endothelial cells.

[0028] Figure 5 The figure shows the test results of plasma activated liquid treatment on dermatitis in mice after radiotherapy.

[0029] Reference numerals in the accompanying drawings:

[0030] 1. DC high-voltage power supply; 2. Plasma jet generating tube; 21. Needle tip; 22. Current probe; 23. Nozzle; 24. Plasma jet; 3. Resistor. DETAILED DESCRIPTION

[0031] The present invention provides a plasma activation solution and its preparation method and application. To make the objectives, technical solutions, and effects of the present invention more clear and explicit, the present invention is further described below in detail. It should be understood that the specific embodiments described herein are only for the purpose of explaining the present invention and are not intended to limit the present invention.

[0032] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art of the present invention. The terms used in the specification of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention.

[0033] An embodiment of the present invention provides a method for preparing a plasma activation solution, wherein the method for preparing the plasma activation solution comprises the following steps:

[0034] Use helium and oxygen to generate plasma;

[0035] Physiological saline is treated with the plasma to obtain the plasma activated liquid.

[0036] The present invention uses plasma to treat physiological saline, transferring active species from the plasma into the saline to form a plasma-activated solution. This plasma-activated solution can promote the healing of radiation-induced skin or mucosal inflammation, repair radiation damage, prevent scarring, mitigate inflammatory responses, promote skin cell repair and angiogenesis, and reduce the severity of post-radiotherapy skin or mucosal inflammation. It is harmless to cells and animals and exhibits excellent safety. The method provided by the present invention is simple, has low production costs, and can achieve large-scale production of plasma-activated solutions.

[0037] Specifically, the plasma activated liquid described in the embodiments of the present invention can stimulate cell proliferation, migration and repair in the inflamed area of ​​the skin, and help promote the formation of new blood vessels in the inflamed area. The formation of new blood vessels is crucial for the delivery of oxygen and nutrients, thereby promoting the formation and repair of new tissues and accelerating wound healing.

[0038] The plasma activated liquid provided by the present invention has little irritation to the skin, can relieve the patient's pain, and is easy to use. It is used on tumor patients with skin ulcers and damage after radiotherapy. It not only relieves the patient's pain by promoting the healing process, but also avoids the patient's radiotherapy interruption and prolonged treatment due to the long wound healing process. In addition, the plasma activated liquid provided by the present invention is also very suitable for deep locations, more complex or narrow cavities such as oral mucositis, vaginitis, and proctitis caused by radiotherapy of some intracavitary tumors. For example, the plasma activated liquid can be used to prepare a medicinal spray or mouthwash, which can promote the healing of radiation dermatitis and radiation oral mucositis. In some embodiments, the preparation method of the plasma activated liquid specifically comprises the following steps:

[0039] S1. Providing an atmospheric pressure low-temperature plasma jet generating system and a container containing physiological saline, wherein the atmospheric pressure low-temperature plasma jet generating system includes a plasma jet generating tube;

[0040] S2. placing a container containing physiological saline at the bottom of the plasma jet generating tube;

[0041] S3. A mixed gas of helium and oxygen is introduced into the plasma jet generating tube as a working gas, and the working parameters of the plasma jet generating tube are set. After the power is turned on, a plasma beam is generated and directed toward the physiological saline. After the plasma beam contacts the physiological saline, the plasma activated liquid is obtained.

[0042] In step S2, in some embodiments, the distance between the lowermost end of the plasma jet generating tube and the surface of the physiological saline solution is 1 cm.

[0043] In step S3, after the airflow is stabilized, the power supply is turned on. The plasma beam is allowed to contact with the physiological saline solution for 15 minutes to obtain the plasma activated solution.

[0044] In some embodiments, the flow rate of the helium gas is 2 L / min, and the flow rate of the oxygen gas is 10 mL / min.

[0045] In some embodiments, the operating parameters of the plasma jet generator are as follows:

[0046] The discharge voltage is 4.5-4.7 kV; the discharge current frequency is 6.46 kHz; the discharge gap is 2-10 mm; and the discharge power is 0.467-0.550 W.

[0047] For example, the discharge voltage may be 4.5 kV, 4.6 kV, 4.7 kV, or any value in a numerical range consisting of two of the above values ​​as endpoints; the discharge gap may be 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, or any value in a numerical range consisting of two of the above values ​​as endpoints; the discharge power may be 0.467 W, 0.470 W, 0.475 W, 0.480 W, 0.485 W, 0.490 W, 0.500 W, 0.550 W, or any value in a numerical range consisting of two of the above values ​​as endpoints.

[0048] An embodiment of the present invention also provides a plasma-activated liquid, wherein the plasma-activated liquid is prepared by the preparation method described above in the embodiment of the present invention. The plasma-activated liquid in the embodiment of the present invention can stimulate cell proliferation, migration, and repair in inflamed skin areas, helping to promote the formation of new blood vessels in the inflamed area. New blood vessel formation is crucial for the delivery of oxygen and nutrients, thereby promoting the formation and repair of new tissue and accelerating wound healing. The plasma-activated liquid is suitable for treating radiation dermatitis or mucositis.

[0049] In some embodiments, the active species in the plasma-activated liquid include reactive nitrogen. Reactive nitrogen can stimulate cell proliferation, migration, and repair at the site of skin inflammation, helping to promote the formation of new blood vessels in the inflamed area. The formation of new blood vessels is crucial for the delivery of oxygen and nutrients, thereby promoting the formation and repair of new tissue and accelerating wound healing.

[0050] The present invention also provides a method for preparing a pharmaceutical preparation for treating radiation dermatitis (also known as radiotherapy dermatitis) or radiation mucositis (also known as radiotherapy mucositis). The plasma-activated liquid can promote the healing of radiation dermatitis or radiation mucositis (or mucosal ulcer wounds), or promote the healing of post-radiation dermatitis and acute ulcers, alleviate skin inflammation or mucosal inflammation, and repair radiation-induced skin damage.

[0051] In some embodiments, the pharmaceutical preparation is a liquid preparation (e.g., a mouthwash, etc.) or a gaseous preparation (e.g., a spray, etc.). Specifically, the plasma-activated liquid is prepared into a spray preparation and sprayed on the legs and feet of mice with radiation dermatitis. This can delay the progression of radiation dermatitis, reduce its severity, promote the healing of radiation-induced skin damage, and also reduce the rate of foot deformities in mice caused by radiotherapy, indicating that the plasma-activated liquid can significantly promote the healing of radiation dermatitis. In addition, in this embodiment, the plasma-activated liquid can reach radiation dermatitis and oral mucositis deep in the body by spraying or spreading, thereby promoting the healing of acute radiation dermatitis and mucositis.

[0052] An embodiment of the present invention further provides a pharmaceutical preparation for treating radiation dermatitis or radiation mucositis, wherein the pharmaceutical preparation for treating radiation dermatitis or radiation mucositis comprises the plasma-activated liquid described above in the embodiment of the present invention, and a pharmaceutically acceptable carrier and / or a pharmaceutically acceptable additive.

[0053] In some embodiments, the pharmaceutically acceptable carrier includes at least one of a glidant, a diluent, a wetting agent, and a solvent, but is not limited thereto.

[0054] In some embodiments, the pharmaceutically acceptable additive includes at least one of a preservative, a stabilizer, and an isotonic agent, but is not limited thereto.

[0055] The present invention will be further described below with reference to specific examples.

[0056] Unless otherwise specified, the materials and reagents used in the following examples are all commercially available products.

[0057] The physiological saline (NaCl mass fraction of 0.9%) used in the following examples was purchased from Sichuan Kelun Pharmaceutical Co., Ltd., with the product number H51021157. The atmospheric pressure plasma generation system (plasam jet, i.e., plasma jet device, see Y.Li, Yang Lv, M.Tang, EH Choi, J.Wang, G.Lv, Y.Zhu, S.Wang, Y.Liu, Low-temperature plasma-jet-activated medium inhibited tumorigenesis of lungadenocarcinoma in a 3D in vitro culture model. Plasma Processes Polym. 2021; 18:2100049.doi.org / 10.1002 / ppap.202100049.) was used. Figure 1 As shown, the plasma generation system mainly consists of four parts: a DC high-voltage power supply 1, a gas source, an ion jet generating tube 2 (i.e., a plasma reaction chamber), and a resistor 3 (500 MΩ). The ion jet generating tube 2 includes a needle tip 21, a current probe 22, and a nozzle 23. In the following embodiments, the working gases are high-purity helium (purity 99.999%) and high-purity oxygen (purity 99.999%).

[0058] Example 1

[0059] The preparation method of plasma activation solution comprises the following steps:

[0060] Using the above plasma generation system, high-purity helium (purity: 99.999%) and high-purity oxygen (purity: 99.999%) were used as working gases. First, the helium and oxygen valves were turned on and the gas flows were adjusted to 2 L / min and 10 mL / min, respectively. Then, a container containing 1.2 mL of normal saline was placed on the reaction table at the lower end of the plasma jet generating tube, so that the distance h between the lower end of the plasma jet generating tube and the normal saline liquid level was 1 cm (as shown in FIG1 ). Figure 1 As shown), set the working parameters of the plasma jet generating tube at the same time (discharge voltage is 4.5kV, discharge current frequency is 6.46kHz, discharge gap is 2mm, and discharge power is 0.55W); after the airflow is stable, turn on the power switch to generate a plasma jet 24 (as shown). Figure 1 After 15 minutes of reaction, the power supply is turned off to obtain a plasma activated solution (which can be referred to as PAS).

[0061] Example 2 Determination of the relative concentration of active particles (active species) in plasma activated liquid

[0062] The commercial ROS kit, superoxide anion free radical kit and RNS kit (all purchased from Beibo Biotechnology Co., Ltd.) were used to determine the reactive oxygen species (ROS) and superoxide anion free radical (O2 -· ) and reactive nitrogen (RNS) concentration levels, specifically comprising the following steps:

[0063] According to the instructions provided by the kit, 100 microliters of plasma activation solution were added to a 96-well plate as the experimental group, and 100 microliters of normal saline were added to a 96-well plate as the control group. The readings of the control and experimental groups were measured by a fluorescence microplate reader (excitation wavelength 488nm, emission wavelength 516nm). The results are as follows: Figure 2 As shown (ns indicates no significant difference, * indicates p < 0.05), the control group was used as a reference to calculate the O2 -· The plasma-activated liquid contained RNS at a concentration 1.2 times that of the control group, and at a concentration 1.4 times that of the control group. There was no significant difference in total ROS levels between the two groups. This suggests that RNS is the primary active species in the plasma-activated liquid. RNS can stimulate cell proliferation and migration within the wound site and promote angiogenesis in the wound area, which is crucial for oxygen and nutrient delivery, thereby promoting the formation and repair of new tissue and accelerating wound healing.

[0064] Example 3 Plasma Activated Liquid Promotes Migration of Immortalized Human Keratinocytes (Hacat)

[0065] During the wound healing process after acute skin injury, re-epithelialization, which occurs during the proliferation phase, is a key step in wound healing. During this process, keratinocytes migrate to the top of the underlying granulation tissue and connect with migrating keratinocytes from the opposing edge, closing the wound. This example uses a scratch assay with Hacat cells to study the cell migration and healing process, which specifically includes the following steps:

[0066] After Hacat cells were cultured to 80% density using DMEM medium, they were plated on the bottom of a 6-well plate at a cell plating density of 1×10 5Cells were plated in a 37°C CO2 incubator for 12 hours after adding 3 mL of complete DMEM to each well. The plates were then incubated for 12 hours at 37°C. The next day, when the cells had spread throughout the bottom of the 6-well plate, a scratch was made with a 1 mL pipette tip to simulate a wound or incision. The original culture medium was then discarded. 1 mL of serum-free DMEM was added to the control group, while 1 mL of plasma-activated solution was added to the treated group. After the medium was changed, the scratch width was observed under a microscope and photographed. The plates were then placed in an incubator for another 24 and 48 hours. The wound healing status (i.e., the cell migration area was recorded based on the photographic record) was photographed, and the cell migration rate was assessed based on the remaining scratch area. The healing percentage = [(initial scratch area - final scratch area) / initial scratch area] × 100%. The healing percentage was used to assess the cell migration rate.

[0067] The results are as follows Figure 3 As shown in the figure, the scratch healing rate of cells in the plasma activation liquid treatment group was faster than that of the control group, indicating that the cell migration rate was promoted. The plasma activation liquid significantly promoted cell migration, accelerating wound repair and promoting wound healing by promoting the migration of epidermal cells.

[0068] The present invention also establishes a post-radiotherapy cell damage model, which includes post-radiotherapy epidermal cells (NCM460 cells), primary human skin fibroblasts, and human oral mucosal epithelial cell models. When plasma activation liquid is applied to the above post-radiotherapy cells, the proliferation ability of epidermal cells and fibroblasts is improved, accompanied by a significant improvement in the migration ability of fibroblasts.

[0069] Example 4 Plasma activated liquid promotes tube formation of vascular endothelial cells

[0070] Endothelial cells provide oxygen and nutrients to the wound area by forming new blood vessels, helping to maintain tissue vitality and promote repair. They secrete various growth factors, such as vascular endothelial growth factor (VEGF), which promotes blood vessel regeneration and wound healing. The specific steps of this embodiment are as follows:

[0071] Primary human umbilical vein endothelial (HUVEC) cells were selected as the research object. 50 μL of matrigel (purchased from Merck) was placed on the bottom of a 96-well plate and placed in a 37°C incubator for 30 minutes. HUVEC cells were then plated in the plate at a density of 1×10 4 cells / well.

[0072] Next, different groups (control group, treatment group, radiotherapy group and PAS treatment group after radiotherapy) were set up, and the tube formation of cells in each group was observed under a microscope.

[0073] In the control group, 50 μL of normal saline was added to each well for 10 min, and then HUVEC culture medium was replaced and incubated in a 37°C carbon dioxide incubator.

[0074] For the treatment group, 50 μL of plasma activation solution was added to each well for 10 min, and then HUVEC specialized culture medium was replaced and incubated in a 37°C carbon dioxide incubator;

[0075] The radiotherapy group was treated with 6 Gy of radiotherapy, and 50 μL of normal saline was added to each well for 10 min, after which HUVEC culture medium was replaced and the cells were incubated in a 37°C carbon dioxide incubator.

[0076] After radiotherapy, the PAS treatment group was first treated with 6 Gy radiotherapy, and then 50 μL of plasma activation solution was added to each well for 10 minutes, and then the HUVEC special culture medium was replaced and placed in a 37°C carbon dioxide incubator for incubation.

[0077] The cells were observed every 2 hours. When the cells appeared to be arranged in tubular shapes, the experiment was terminated, the cell culture medium was aspirated, and the cells were washed once with PBS. Then, cell culture medium (100 μL) containing a 1:1000 diluted nuclear dye Hoechst33324 (purchased from Invitrogen, product number H3570) and 5 μM cytoplasmic dye Calciem AM (purchased from Yeasen, product number 40719ES50) and a working concentration of phalloidin dye was added to each well. After culturing in a 37°C carbon dioxide incubator for 20 minutes, the staining solution was discarded, each well was washed once with PBS, 100 μL of fresh culture medium was added, and the cells were detected using a fluorescence microscope (Leica).

[0078] The ability of endothelial cells to form tubular structures was quantitatively described by observing the tubular arrangement of cells under a microscope and recording the integrity of the tubular structure, as well as measuring parameters such as the length and diameter of the tubular structure. The results showed that the PAS-treated group had already formed tubular structures when observed 2 hours after radiotherapy. Figure 4 As shown, by the 4-hour observation period, the tube formation rate reached 90%, significantly higher than the 30% tube formation rate in the radiotherapy group. This indicates that plasma-activated fluid treatment can accelerate the formation of tubular structures in cells and that plasma-activated fluid has the potential to promote microvascular formation in endothelial cells.

[0079] Example 5 Plasma Activated Liquid Reduces Severity of Post-Radiotherapy Dermatitis and Promotes Healing of Radiation Dermatitis

[0080] Balb / c mice were used as a model to study the efficacy of plasma-activated liquid on dermatitis lesions after radiotherapy. The specific steps included the following:

[0081] (1) Establishment of mouse model

[0082] Healthy 6- to 8-week-old Balb / c mice were selected and radiotherapy was performed once on the bilateral hind legs and feet of the mice with a dose of 35 Gy using a small animal irradiator (RadSource RS2000) to simulate post-radiation dermatitis damage.

[0083] The mice were observed every other day. On the eighth day, skin lesions began to appear, and by the 12th day, all mice had skin lesions. At this point, the mice were randomly divided into three groups: a radiotherapy group (sprayed with saline), a plasma activation solution group (sprayed with plasma activation solution), and a positive control group (sprayed with epidermal growth factor), with a total of six mice in each group. Six healthy, untreated Balb / c mice aged 6 to 8 weeks were also selected as a control group.

[0084] (2) Spraying treatment

[0085] Control group: no spraying treatment;

[0086] Plasma activation liquid group: Use a sprayer to evenly spray the plasma activation liquid on the dermatitis lesions of the mice. Each spray is 50 μL. Each mouse is given 4 sprays on the feet and legs to ensure that all the lesions are covered by the plasma activation liquid. Spray once every other day for a total of 7 times.

[0087] Radiotherapy group: sprayed with the same amount of normal saline as the plasma activated liquid group;

[0088] Positive control group: sprayed with the same amount of epidermal growth factor as the plasma activation liquid group (purchased from Shenzhen Huashengyuan Gene Engineering Development Co., Ltd., product number S20010037)

[0089] (3) Damage assessment

[0090] Regularly observe the skin damage of the mice and record the severity of dermatitis, such as redness, swelling, peeling, ulceration, and moist exudation. Score the results based on the observations and create a skin lesion scoring curve. The scoring criteria are shown in Table 1.

[0091] Table 1. Scoring criteria

[0092]

[0093]

[0094] The results are as follows Figure 5 As shown, the dermatitis lesions in the plasma-activated liquid-treated mice were less severe than those in the positive control group. The mice's skin healed faster, and tissue repair was more pronounced. This indicates that plasma-activated liquid can accelerate the healing process of radiation-induced dermatitis.

[0095] In summary, the present invention provides a plasma-activated liquid and its preparation method and application. The invention uses plasma to treat physiological saline, so that the active species in the plasma are transferred to the physiological saline to form a plasma-activated liquid. The plasma-activated liquid can promote the healing of radiation-induced skin inflammation or mucosal inflammation, repair radiation damage, prevent scarring, reduce the severity of skin inflammation or mucosal inflammation after radiotherapy (reduce inflammatory response, promote skin cell repair and neovascularization), slow down the inflammatory response, and is harmless to cells and animals, with good safety. The method provided by the present invention is simple in process, low in preparation cost, and can achieve large-scale production of plasma-activated liquid.

[0096] It should be understood that the application of the present invention is not limited to the above examples. For those skilled in the art, improvements or changes can be made based on the above description. All these improvements and changes should fall within the scope of protection of the claims attached to the present invention.

Claims

1. A method for preparing a plasma activated liquid, characterized in that: The preparation method of the plasma activation solution comprises the following steps: Use helium and oxygen to generate plasma; Physiological saline is treated with the plasma to obtain the plasma activated liquid.

2. The preparation method according to claim 1, characterized in that: The preparation method of the plasma activation solution specifically comprises the following steps: An atmospheric pressure low-temperature plasma jet generating system and a container containing physiological saline are provided, wherein the atmospheric pressure low-temperature plasma jet generating system comprises a plasma jet generating tube; Placing a container containing physiological saline at the lower part of the plasma jet generating tube; A mixed gas of helium and oxygen is introduced into the plasma jet generating tube as working gas, and working parameters of the plasma jet generating tube are set at the same time. After the power is started, a plasma beam is generated and directed toward the physiological saline. After the plasma beam contacts the physiological saline, the plasma activated liquid is obtained.

3. The preparation method according to claim 2, characterized in that: The distance between the lowermost end of the plasma jet generating tube and the surface of the physiological saline solution is 1 cm.

4. The preparation method according to claim 2, characterized in that: The flow rate of the helium gas is 2 L / min, and the flow rate of the oxygen gas is 10 mL / min.

5. The preparation method according to claim 2, characterized in that: The operating parameters of the plasma jet generating tube are as follows: The discharge voltage is 4.5-4.7 kV, the discharge current frequency is 6.46 kHz, the discharge gap is 2-10 mm, and the discharge power is 0.467-0.550 W.

6. A plasma activation solution, characterized in that: The plasma activated liquid is prepared by the preparation method according to any one of claims 1 to 5.

7. The plasma activated liquid according to claim 6, characterized in that: The active species in the plasma activated liquid include active nitrogen.

8. Use of the plasma activated liquid according to any one of claims 6 to 7 in the preparation of a pharmaceutical preparation for treating radiation dermatitis or radiation mucositis.

9. The use according to claim 8, characterized in that: The pharmaceutical preparation is a liquid preparation or a gas preparation.

10. A pharmaceutical preparation for treating radiation dermatitis or radiation mucositis, characterized in that: The pharmaceutical preparation for treating radiation dermatitis or radiation mucositis comprises the plasma activated liquid according to any one of claims 6 to 7, and a pharmaceutically acceptable carrier and / or a pharmaceutically acceptable additive.

Citation Information

Cited By

  • Plasma activated nano-silver gel as well as preparation method and application thereof

    CN122124097A