Gel, gel for holding plasma, and applications

Abstract

The present invention provides a gel, a gel for holding plasma and its applications, relating to the field of plasma biomedical applications. The gel is prepared by adding 1,2 - hexanediol and p - hydroxyacetophenone into water, reacting for 10 min to 15 min, adding octanoyl hydroxamic acid and reacting for 10 min to 15 min, adding a thickening agent, and standing still to obtain the gel. After being treated with plasma, the gel in the present invention can effectively hold the active particles generated under atmospheric pressure. The obtained gel for holding plasma can keep the active particles active persistently, and due to its good temperature sensitivity, it can release the active particles in the pores when the external temperature rises, having a good sustained - release effect.

Description

Technical Field

[0001] The present invention relates to the field of plasma biomedical applications, and particularly to a gel, a gel for locking plasma, and applications thereof. Background Art

[0002] At normal temperature and pressure, a voltage is used to break down gas and discharge to generate atmospheric pressure cold plasma. The atmospheric pressure cold plasma contains active particles such as NO 3- , O 2- , NO 2- , H2O2, O3, free electrons and other active particles. These active particles have good promoting effects in aspects such as bacterial inactivation, blood coagulation and hemostasis, and stimulating cell regeneration, and play a leading role in various biochemical effects. Especially in the fields of medical treatment, beauty, etc., when plasma acts on the skin surface, it can effectively relieve the symptoms of skin diseases such as psoriasis and vitiligo. In addition, plasma can also have a certain alleviating effect on skin acne, pimples, inflammation and swelling.

[0003] However, if plasma is directly applied to the skin surface, there will be hazards such as the skin surface being burned by the heat of the electrode, high-voltage electric shock to the human body, or inhalation of high-concentration ozone. In order to reduce the hazards brought by the direct action of plasma on the skin surface, in the prior art, plasma is used to treat a copolymer and then coated on the skin surface to reduce the hazards brought by the direct action of plasma on the skin surface. Existing copolymers are usually prepared from polyethylene glycol, polyacrylic acid, and polyacrylate. However, the above copolymers cannot lock the active particles in plasma for a long time, and have a poor sustained-release effect when coated on the skin surface.

[0004] Therefore, there is a need to provide a gel that can effectively lock the active particles in plasma. Summary of the Invention

[0005] In order to solve the problems that existing copolymers cannot lock active particles for a long time and have a poor sustained-release effect when coated on the skin surface, the present invention provides a gel, a gel for locking plasma, and applications thereof.

[0006] To achieve the above object, the specific technical solutions of the present invention are as follows.

[0007] In a first aspect of the present invention, a gel is provided, and the gel is prepared by the following method:

[0008] At room temperature, 1,2 - hexanediol and p-hydroxyacetophenone are added to water, reacted for 10 min to 15 min, caprylohydroxamic acid is added, reacted for 10 min to 15 min, and a thickening agent is added, and then left standing until it becomes gel-like, wherein the standing time is 60 min to 65 min, to obtain the gel.

[0009] The mass percentage of the 1,2 - hexanediol in the gel is 0.25% - 0.35%; the mass percentage of the p - hydroxyacetophenone in the gel is 0.15% - 0.25%; the mass percentage of the octanoyl hydroxamic acid in the gel is 0.05% - 0.15%; the mass percentage of the thickener in the gel is 0.5% - 1.5%; the rest is water, with a total of 100%. The gel prepared by the present invention has an intertwined pore structure and is sensitive to temperature changes.

[0010] In another preferred embodiment, the thickener is acryloyldimethyltaurate / VP copolymer.

[0011] The second aspect of the present invention provides a gel for locking plasma, and the gel for locking plasma is prepared by the following method:

[0012] Place the gel provided in the first aspect of the present invention in a plasma generator. Under a closed environment, ionize the air through the plasma generator to generate active particles, and use the gel to lock the active particles to obtain the gel for locking plasma.

[0013] In another preferred embodiment, the active particles include NO 3- , O 2- , NO 2- , H2O2, O3 and free electrons.

[0014] In another preferred embodiment, the plasma generator includes a sheet - shaped metal electrode, a mesh - shaped metal electrode, and a composite barrier medium.

[0015] The sheet - shaped metal electrode and the mesh - shaped metal electrode are respectively arranged on both sides of the composite barrier medium; when a voltage is applied, plasma will be generated on one side of the mesh - shaped metal electrode.

[0016] In another preferred embodiment, the composite barrier medium uses boron nitride ceramic as the substrate, and at 342 °C, molten polytetrafluoroethylene is sprayed onto both surface sides of the boron nitride ceramic to obtain it. The composite barrier medium combines the electrical properties of polytetrafluoroethylene and the mechanical properties of ceramic, which can ensure that during use, while stably discharging, the electrode temperature rises slowly and will not be electrically broken down.

[0017] In another preferred embodiment, the spraying thickness of the polytetrafluoroethylene is 20 μm - 40 μm.

[0018] In another preferred embodiment, the sheet - shaped metal electrode and the mesh - shaped metal electrode respectively correspond to the two surface sides of the composite barrier medium sprayed with polytetrafluoroethylene.

[0019] The third aspect of the present invention provides an application of a plasma-locking gel in the preparation of anti-acne products, wherein the plasma-locking gel is provided by the second aspect of the present invention.

[0020] The fourth aspect of the present invention provides an application of a plasma-locking gel in the preparation of hemostatic products, wherein the plasma-locking gel is provided by the second aspect of the present invention.

[0021] Compared with the prior art, the present invention has the following beneficial effects:

[0022] 1. 1,2-Hexanediol and p-hydroxyacetophenone in the gel of the present invention can endow the obtained gel with good temperature sensitivity, and by adding octanoyl hydroxamic acid and a thickening agent, the obtained gel has an interwoven pore structure for long-term locking of active particles.

[0023] 2. The plasma-locking gel in the present invention long-term locks active particles through interwoven pores, and due to its good temperature sensitivity, it can release the active particles in the pores when the external temperature rises, and thus has a good sustained-release effect.

[0024] 3. The plasma-locking gel in the present invention can effectively lock active particles generated under atmospheric pressure, and the active particles can maintain their activity persistently in the gel, and it can adapt to the coating on a large area of the body surface and the coating on an irregular curved surface. Moreover, the gel components in the present invention are non-toxic and non-irritating. When coated on the skin, it can effectively improve the skin quality, relieve skin diseases, and avoid the side effects brought by taking antibiotics and hormonal drugs orally or topically; and it can be used for a long time or repeatedly, and the human body will not develop dependence and drug resistance.

[0025] 4. The plasma-locking gel of the present invention is processed by a plasma generator to lock active particles in the gel, and then coated on the skin surface, which can avoid the direct contact or close-range non-contact of the plasma generator with the body surface, thus avoiding the occurrence of skin burns and electric shocks, and having great safety. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 It is a schematic structural diagram of the composite barrier medium in Example 4 of the present invention.

[0027] Figure 2 It is a schematic structural diagram of the plasma generator in Example 4 of the present invention.

[0028] Figure 3 It is a schematic diagram of the preparation process of the plasma-locking gel in Example 4 of the present invention.

[0029] Figure 4Schematic diagram of the slow-release process of the plasma-locking gel coated on the skin surface in Example 4 of the present invention.

[0030] Figure 5 Structural diagram of the infrared spectra of the gel in Example 1 of the present invention and the plasma-locking gel in Example 4; wherein, A is the structural diagram of the infrared spectrum of the gel in Example 1 of the present invention, and B is the structural diagram of the infrared spectrum of the plasma-locking gel in Example 4.

[0031] Figure 6 Map of the oxygen element content taken by scanning electron microscopy of the gel in Example 1 of the present invention and the plasma-locking gel in Example 4; wherein, A is the map of the oxygen element content taken by scanning electron microscopy of the gel in Example 1 of the present invention, and B is the map of the oxygen element content taken by scanning electron microscopy of the plasma-locking gel in Example 4.

[0032] Figure 7 Map of the nitrogen element content taken by scanning electron microscopy of the gel in Example 1 of the present invention and the plasma-locking gel in Example 4; wherein, A is the map of the nitrogen element content taken by scanning electron microscopy of the gel in Example 1 of the present invention, and B is the map of the nitrogen element content taken by scanning electron microscopy of the plasma-locking gel in Example 4.

[0033] Figure 8 Effect diagrams of 0 day, 7 days and 14 days of gel pimples without coating the plasma-locking gel; wherein, A is the effect diagram of 0 day, B is the effect diagram of 7 days, and C is the effect diagram of 14 days.

[0034] Figure 9 Effect diagrams of 0 day, 7 days and 14 days of pimples coated with the plasma-locking gel in Example 4 of the present invention; wherein, A is the effect diagram of 0 day, B is the effect diagram of 7 days, and C is the effect diagram of 14 days.

[0035] Figure 10 Effect diagram of the plasma-locking gel in Example 4 of the present invention for hemostasis of the femoral artery of mice; wherein, A is the effect diagram without using the plasma-locking gel in Example 4 of the present invention; B is the effect diagram of using the plasma-locking gel in Example 4 of the present invention.

[0036] Wherein: 1. Polytetrafluoroethylene layer; 2. Boron nitride ceramic layer; 3. Sheet metal electrode; 4. Mesh metal electrode; 5. Plasma generator; 6. Open container; 7. Gel; 8. Skin section. Detailed implementation manners

[0037] In order to make the objectives, technical solutions and advantages of the present invention more clearly understood, the present invention will be further described in detail below in conjunction with embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0038] In the following embodiments, unless otherwise specified, the experimental methods are all conventional methods; the reagents and materials, unless otherwise specified, can all be purchased on the market.

[0039] In the following embodiments, both Escherichia coli and Staphylococcus aureus were purchased from the Chemical Reagent Information Management System Mall of Xi'an Jiaotong University. The mice were purchased from the Experimental Animal Center of Xi'an Jiaotong University. The mice were 7 weeks old and weighed 17 g ± 0.2 g.

[0040] Example 1

[0041] A method for preparing a gel, comprising the following steps:

[0042] S1. Heat ultrapure water to 85°C, keep it warm for 10 min, and then cool it to room temperature to obtain cooled ultrapure water.

[0043] S2. Add 1,2-hexanediol and p-hydroxyacetophenone to the cooled ultrapure water and stir. React for 10 min, add octanoyl hydroxamic acid and stir. React for 10 min, add acryloyldimethyltaurine ammonium / VP copolymer and stir. React for 10 min, and finally let it stand for 60 min to obtain the gel.

[0044] Among them, the mass percentage of 1,2-hexanediol in the gel is 0.3%, the mass percentage of p-hydroxyacetophenone in the gel is 0.2%, the mass percentage of octanoyl hydroxamic acid in the gel is 0.1%, and the mass percentage of acryloyldimethyltaurine ammonium / VP copolymer in the gel is 1%. The rest is water, totaling 100%.

[0045] Example 2

[0046] A method for preparing a gel, comprising the following steps:

[0047] S1. Heat ultrapure water to 85°C, keep it warm for 10 minutes, and then cool it to room temperature to obtain cooled ultrapure water.

[0048] S2. Add 1,2-hexanediol and p-hydroxyacetophenone to the cooled ultrapure water and stir. React for 15 min, add octanoyl hydroxamic acid and stir. React for 15 min, add acryloyldimethyltaurine ammonium / VP copolymer and stir. React for 15 min, and finally let it stand for 65 min to obtain the gel.

[0049] Among them, the mass percentage of 1,2 - hexanediol in the gel is 0.25%, the mass percentage of p - hydroxyacetophenone in the gel is 0.15%, the mass percentage of octanoyl hydroxamic acid in the gel is 0.05%, the mass percentage of acryloyldimethyltaurine ammonium / VP copolymer in the gel is 0.5%, and the rest is water, totaling 100%.

[0050] Example 3

[0051] A method for preparing a gel, comprising the following steps:

[0052] S1. Heat ultrapure water to 85 °C, keep it warm for 10 minutes, and then cool it to room temperature to obtain cooled ultrapure water.

[0053] S2. Add 1,2 - hexanediol and p - hydroxyacetophenone to the cooled ultrapure water and stir. React for 10 min, add octanoyl hydroxamic acid and stir. React for 10 min, add acryloyldimethyltaurine ammonium / VP copolymer and stir. React for 10 min, and finally let it stand for 60 min to obtain the gel.

[0054] Among them, the mass percentage of 1,2 - hexanediol in the gel is 0.35%, the mass percentage of p - hydroxyacetophenone in the gel is 0.25%, the mass percentage of octanoyl hydroxamic acid in the gel is 0.15%, the mass percentage of acryloyldimethyltaurine ammonium / VP copolymer in the gel is 1.5%, and the rest is water, totaling 100%.

[0055] Gels were prepared in the above Examples 1 to 3, and the effects were comparable. Hereinafter, the gel prepared in Example 1 will be taken as an example for illustration.

[0056] Example 4

[0057] A gel for holding plasma, which is prepared by placing the gel in Example 1 in a plasma generator. Among them, the specific structure of the plasma generator is as follows:

[0058] As Figure 1 and Figure 2 shown, the plasma generator 5 includes a sheet - shaped metal electrode 3, a mesh - shaped metal electrode 4, and a composite barrier medium.

[0059] The sheet metal electrode 3 and the mesh metal electrode 4 are respectively arranged on both sides of the composite barrier medium. In this embodiment, the thickness of the sheet metal electrode 3 is 2 mm, the thickness of the mesh metal electrode 4 is 0.5 mm, the mesh of the mesh metal electrode 4 is a regular hexagon, the side width of each regular hexagon mesh is 0.75 mm, and the distance between two opposite sides is 4 mm. In the embodiment of the present invention, the sizes of the sheet metal electrode 3 and the mesh metal electrode 4 are not specifically limited and can be set according to actual requirements. The sheet metal electrode 3 and the mesh metal electrode 4 are respectively connected to a pair of opposite sinusoidal high voltages. When a voltage is applied, plasma will be generated on one side of the mesh metal electrode.

[0060] The composite barrier medium includes a boron nitride ceramic layer 2 and a polytetrafluoroethylene layer 1. The polytetrafluoroethylene layer 1 is located on both sides of the boron nitride ceramic layer 2. The sheet metal electrode 3 is arranged on one of the polytetrafluoroethylene layers 1, and the mesh metal electrode 4 is arranged on the other polytetrafluoroethylene layer 1. In this embodiment, the working area of the plasma generator 5 is 12.56 cm 2 . In the embodiment of the present invention, the working area of the plasma generator 5 is not specifically limited and can be set according to actual requirements.

[0061] The specific preparation process of the composite barrier medium is as follows:

[0062] Using sheet boron nitride ceramic as the base material with a thickness of 1 mm, it is made into the designed shape according to the design requirements. In this embodiment, the shape of the sheet boron nitride ceramic matches the shapes of the sheet metal electrode 3 and the mesh metal electrode 4. The two side surfaces of the sheet boron nitride ceramic are processed by a high-speed sandblasting process to make its roughness reach Ra150 - 200. At 342 °C, molten polytetrafluoroethylene is evenly sprayed onto the two side surfaces of the base material in the form of micron-sized droplets, and the spraying thickness is 20 microns. After drying and condensation treatment, the composite barrier medium is obtained.

[0063] The preparation method of the above-mentioned gel for locking plasma includes the following steps:

[0064] S1. In a closed environment, place the gel in Example 1 in an open container 6 so that the distance between the liquid surface of the gel and the mesh metal electrode 4 is 5 mm.

[0065] S2. As Figure 3As shown, start the plasma generator 5. At 6.5 kV, when the plasma generator 5 operates in ambient air, it generates plasma. At the same time, the mesh metal electrode 4 gradually heats up to 42 ± 5 °C. When the temperature conducts to the liquid surface of the gel 7, the gel 7 on the liquid surface layer changes from viscous to thin, and the water evaporates and transpires upward in a gaseous form to the vicinity of the mesh metal electrode 4. At this time, after the water molecules are fully mixed with the plasma, they aggregate with each other into extremely tiny liquid droplets and then fall back to the liquid surface layer of the gel 7, forming a very small concentration difference between the liquid surface layer and the inside of the gel 7, thereby quickly adsorbing the liquid droplets, enabling the liquid droplets mixed with active particles to enter the inside of the gel 7 and being locked in the gaps of the micro-hole intertwined structure; after 5 minutes, a large number of active particles in the plasma will be locked in the gel, obtaining the gel with locked plasma.

[0066] Figure 4 It is a schematic diagram of the slow-release application process of the gel for locking active particles on the skin surface. As can be seen from the skin cross-section 8, after the gel with locked plasma is evenly coated, a thin film is formed on the skin surface. When the human body temperature conducts to the gel with locked plasma, the gel with locked plasma gradually changes from viscous to thin, and the water molecules mixed with active particles gradually precipitate from the gel with locked plasma. At this time, due to the concentration difference of cell fluid between the inside and outside of the epidermal cells, the water molecules combined with active particles can enter the cell interior. The active nitrogen particles in the active particles will enhance cell metabolism and stimulate cell proliferation, playing a positive role in promoting skin health; at the same time, a part of the water molecules combined with active particles adhere to the skin surface, and the active oxygen particles and nitrogen oxide particles in the active particles inactivate the bacteria on the skin surface and in the folds, playing a role in disinfecting the skin. Another part of the water molecules combined with active particles can penetrate through the pores to the subcutaneous layer, playing an anti-inflammatory and anti-inflammatory role on the subcutaneous cell tissue.

[0067] Figure 5 A in it is the gel in Example 1 of the present invention, that is, the gel without plasma treatment. Figure 5 B in it is the gel with locked plasma in Example 4, that is, the gel with locked plasma obtained after plasma treatment. From Figure 5 It can be seen that after plasma treatment, the structure of the gel with locked plasma in Example 4 becomes cross-linked and dense compared with the structure of the gel in Example 1.

[0068] Figure 6 A in it is the oxygen element content map taken by scanning electron microscopy of the gel in Example 1 of the present invention. Figure 6 B in it is the oxygen element content map taken by scanning electron microscopy of the gel with locked plasma in Example 4. From Figure 6It can be seen that after plasma treatment, the oxygen element content in the gel holding plasma in Example 4 is significantly higher than that in the gel in Example 1 of the present invention, indicating that through plasma treatment, oxygen elements are effectively locked into the gel.

[0069] Figure 7 In [A], it is the nitrogen element content diagram taken by scanning electron microscopy of the gel in Example 1 of the present invention. Figure 7 In [B], it is the nitrogen element content diagram taken by scanning electron microscopy of the gel holding plasma in Example 4. From Figure 7 It can be seen that after plasma treatment, the nitrogen element content in the gel holding plasma in Example 4 is significantly higher than that in the gel in Example 1 of the present invention, indicating that through plasma treatment, nitrogen elements are effectively locked into the gel.

[0070] To further prove the effect, the following comparative tests were carried out.

[0071] 1. Comparative test on acne removal effect.

[0072] Using the method in Example 4, the prepared gel holding plasma was applied to the surface of skin acne. After 30 to 60 minutes, when the applied gel holding plasma was dried, it was washed with clean water and used as the experimental group. According to the above operation, it was applied every day, and photos were taken and recorded on the 0th day, 7th day, and 14th day respectively. The results are as Figure 9 shown.

[0073] The unapplied one was used as the control group, and photos were taken and recorded on the 0th day, 7th day, and 14th day respectively. The results are as Figure 8 shown.

[0074] From Figure 8 and Figure 9 the results in, it can be seen that applying the gel holding plasma in Example 4 of the present invention can effectively reduce the area of acne and has a certain acne removal effect. This is mainly because during the plasma treatment process, when the gel undergoes a physical form transformation, it will effectively lock the active particles in the plasma in its internal microporous intertwined structure. Taking out the gel holding the active particles and applying it to the skin surface, the internal active particles can attach to the epidermis to nourish the skin.

[0075] 2. Comparative test on hemostatic effect.

[0076] Using the method in Example 4, the prepared gel holding plasma was applied to the bleeding wound of the femoral artery of a mouse for 30 to 60 minutes. After the applied gel holding plasma was dried, it was washed with clean water and used as the experimental group; the unapplied one was used as the control group for taking photos and recording. The results are as Figure 10 shown.

[0077] From Figure 10 It can be seen that the bleeding volume of the bleeding wound of the femoral artery of the mouse coated with the gel holding the plasma in Example 4 is significantly reduced, indicating that the gel holding the plasma in Example 4 of the present invention has a certain blood coagulation effect.

[0078] 3. Sterilization performance test.

[0079] The sterilization effects of the gel holding the plasma in Example 4 were measured on Escherichia coli and Staphylococcus aureus respectively, as the experimental group, and 3 parallel experiments were carried out for each group; the gel not using the gel holding the plasma in Example 4 was used as the positive control group, and the results are shown in Table 1.

[0080] Table 1 Sterilization test results

[0081]

[0082] It can be seen from the results in Table 1 that the gel holding the plasma in Example 4 of the present invention has a good sterilization effect on Escherichia coli and Staphylococcus aureus.

[0083] 4. Toxicity detection.

[0084] The gel holding the plasma in Example 4 of the present invention was respectively subjected to acute oral toxicity test, multiple complete skin irritation test and micronucleus test of polychromatic erythrocytes in mouse bone marrow according to the disinfection technical specifications, 2002 edition, Part 2, 2.3.1, 2.3.3, 2.3.8.4.

[0085] The results of the acute oral toxicity test showed that the test substance had an acute oral toxicity LD 50 >5000mg / kg.BW for SPF-grade KM, belonging to actually non-toxic, meeting the requirements of 2.3.13.1 of the disinfection technical specifications 2002 edition.

[0086] The results of the multiple complete skin irritation test showed that the test substance had no irritation in the multiple complete skin irritation test on New Zealand rabbits, meeting the requirements of 2.3.13.1 of the disinfection technical specifications 2002 edition.

[0087] The results of the micronucleus test of polychromatic erythrocytes in mouse bone marrow showed that the test substance was negative in the micronucleus test of polychromatic erythrocytes in mouse bone marrow, meeting the requirements of 2.3.13.2 of the disinfection technical specifications 2002 edition.

[0088] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A gel for holding plasma, characterized in that, The gel for holding plasma is used for sterilization and coagulation hemostasis; The gel for holding plasma is prepared by the following method: At room temperature, 1,2 - hexanediol and p - hydroxyacetophenone are added to water. The gel that holds the plasma is made temperature - sensitive by 1,2 - hexanediol and p - hydroxyacetophenone. React for 10 min, add octanoyl hydroxamic acid, react for 10 min, add a thickener, and let it stand until it becomes jelly - like. Among them, the standing time is 60 min to obtain the gel. Place the gel in a plasma generator, ionize the air through the plasma generator to generate active particles, and use the gel to hold the active particles to obtain the gel that holds the plasma; the active particles include NO 3- , O 2- , NO 2- , H2O2, O3 and free electrons; 1,2 - hexanediol accounts for 0.3% by mass of the gel; p - hydroxyacetophenone accounts for 0.2% by mass of the gel; octanoyl hydroxamic acid accounts for 0.1% by mass of the gel; the thickener accounts for 0.1% by mass of the gel; the rest is water, totaling 100%; The plasma generator includes a sheet metal electrode, a mesh metal electrode and a composite barrier medium; the sheet metal electrode is disposed on one side of the composite barrier medium; the mesh metal electrode is disposed on the other side of the composite barrier medium; the composite barrier medium uses boron nitride ceramics as the base material, and at 342 °C, molten polytetrafluoroethylene is sprayed onto both side surfaces of the boron nitride ceramics to obtain; the thickness of the polytetrafluoroethylene spray is 20 μm to 40 μm; the sheet metal electrode and the mesh metal electrode respectively correspond to the two side surfaces of the composite barrier medium sprayed with polytetrafluoroethylene; The thickener is acryloyldimethyltaurate / VP copolymer.

2. Use of the gel for holding plasma according to claim 1 in the preparation of a hemostatic product.

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