Novel eutectoid gel for open wounds as well as preparation method and application of novel eutectoid gel
A novel deep eutectic gel is prepared by mixing SBMA with phenolic compounds and photopolymerization, addressing the limitations of traditional water gels by enhancing mechanical properties and providing antibacterial protection for open wounds through network transformation.
Patent Information
- Application Number
- CN202510559541.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-04-30
- Publication Date
- 2025-07-15
AI Technical Summary
Traditional hydrogels have problems such as high volatility, insufficient solvation ability, low tolerance to temperature fluctuations, limited functional versatility, and reduced use stability and durability in open wound applications. Research on regulating the eutectoid gel network structure to achieve multifunctional or functional transformation has not been reported.
By mixing methacryloylethylsulfobetaine with small molecule phenols, heating and stirring to form a clear and transparent solution, adding a photoinitiator and a crosslinking agent for photoinitiation polymerization, and then putting it in an aqueous solvent to convert the network structure to prepare an eutectoid gel with polymethacryloylethylsulfobetaine as the main component.
The prepared eutectoid gel releases small phenol molecules in a water environment to form a multifunctional gel, which has good antibacterial effect, can effectively protect open wounds, prevent bacterial invasion, and widens the application of eutectoid gel in the field of biomedical materials.
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Figure CN120305199A_ABST
Abstract
Description
Technical Field
[0001] The present invention belongs to the technical field of biomedical polymer materials, and particularly relates to a novel eutectoid gel for open wounds, a preparation method thereof, and an application thereof. Background Art
[0002] Traditional hydrogels use water as a solvent and have excellent mechanical properties, biocompatibility, and versatility, and have been widely used in various fields. However, these hydrogels also face some challenges, such as high volatility, insufficient solvation ability, low tolerance to temperature fluctuations, limited functional versatility, and reduced use stability and durability. Deep eutectic solvents (DESs) are usually composed of one or more hydrogen bond donors (HBDs) and hydrogen bond acceptors (HBAs), and have the characteristics of universal solubility and strong customizability compared with traditional water and organic reagents. In recent years, they have been used to replace traditional solvents to prepare eutectoid gels, and have been widely used in many fields such as electrochemistry, energy storage and conversion, sensors, and medical materials.
[0003] As a three-dimensional material, the network structure of gel materials (including hydrogels, organogels, composite gels, etc.) is crucial for performance. To adjust the microstructure of hydrogels to obtain ideal properties, various strategies have been proposed, such as adjusting the interaction between biopolymers and small molecules, controlling molecular crystallization in gels, setting heterogeneous preparation conditions, etc. However, there is no report on the research of realizing multifunction or functional transformation by adjusting the network structure of eutectoid gels. Summary of the Invention
[0004] In view of the above technical problems, the present invention provides a novel eutectoid gel for open wounds, a preparation method thereof, and an application thereof.
[0005] To achieve the above object, the technical solution adopted by the present invention is as follows: On the one hand, the present invention provides a preparation method of a novel eutectoid gel for open wounds, comprising the following steps:
[0006] (1) Mix sulfobetaine methacrylate (SBMA) with small molecule phenols, and heat and stir until a clear and transparent solution is formed to obtain a viscous liquid;
[0007] (2) Add a photoinitiator and a crosslinking agent to the viscous liquid prepared in step (1), stir evenly, and then carry out photoinitiated polymerization to form a eutectoid gel;
[0008] (3) Place the eutectoid gel in step (2) in an aqueous solvent. As time goes by, the network structure of the eutectoid gel undergoes transformation to obtain the novel eutectoid gel for open wounds. This gel is mainly composed of poly(sulfobetaine methacrylate) (PSBMA).
[0009] Further, the molar ratio of the methacryloylethyl sulfobetaine to the small molecule phenol in step (1) is 1:(2 - 4).
[0010] Further, the small molecule phenol in step (1) is selected from one of carvacrol, eugenol, 2-ethylphenol, and 3-ethylphenol. The above four phenolic small molecules are all phenol derivatives, and their molecular structures all contain a benzene ring, a phenolic hydroxyl group, and a hydrophobic substituent (such as isopropyl, propenyl, ethyl, etc.), and their melting points are all relatively low and are in a liquid state at room temperature.
[0011] Further, the heating temperature in step (1) is 50 - 80 °C.
[0012] Further, the molar ratio of the photoinitiator to the total number of double bonds in step (2) is (1 - 3):100, and the total number of double bonds is the total number of double bonds in the methacryloylethyl sulfobetaine and the crosslinking agent;
[0013] In step (2), the molar ratio of the crosslinking agent to the total number of double bonds is (1 - 10):100, and the total number of double bonds is the total number of double bonds in the methacryloylethyl sulfobetaine and the crosslinking agent.
[0014] Further, the photoinitiator in step (2) is selected from one of 2-hydroxy-2-methylphenylacetone and 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone;
[0015] The crosslinking agent in step (2) is selected from one of ethylene glycol dimethacrylate and polyethylene glycol diacrylate.
[0016] Further, the aqueous solvent includes water, PBS buffer solution, and physiological saline.
[0017] On the other hand, the present invention provides a novel eutectic gel for open wounds, which is prepared by the preparation method of the novel eutectic gel for open wounds described in any one of the above.
[0018] On the other hand, the present invention provides an application of the novel eutectic gel for open wounds described above in the preparation of a drug for treating open bacterial infection wounds.
[0019] On yet another aspect, the present invention provides a drug for treating open bacterial infection wounds, including the novel eutectic gel for open wounds described above.
[0020] The beneficial effects of the present invention are as follows:
[0021] The present invention provides a novel eutectic gel for open wounds, its preparation method and application. The specific preparation process is that after obtaining the eutectic gel mainly composed of SBMA, it is placed in an environment containing water. Through the combination of water molecules and SBMA, phenolic small molecules are released, and at the same time, a gel mainly composed of PSBMA is formed. This is a method to functionalize the eutectic gel, which is beneficial to expanding the application of the eutectic gel in the field of biomedical materials. Description of the Drawings
[0022] Figure 1 Macrophotograph of the DES prepared in Example 1 of the present invention at room temperature;
[0023] Figure 2 DSC curve of the DES prepared in Example 1 of the present invention;
[0024] Figure 3 FI-IR spectrum of the DES prepared in Example 1 of the present invention;
[0025] Figure 4 Macrophotograph of the eutectic gel prepared in Example 1 of the present invention at room temperature;
[0026] Figure 5 FI-IR spectrum of the eutectic gel prepared in Example 1 of the present invention;
[0027] Figure 6 Macrophotograph (left) and micrograph (right) of the initial state of the eutectic gel prepared in Example 1 of the present invention and after 48 hours in an aqueous environment;
[0028] Figure 7 Infrared spectrum change diagram of the aqueous environment during the network transformation of the eutectic gel in Example 1 of the present invention;
[0029] Figure 8 Raman spectrum of the initial state of the eutectic gel prepared in Example 1 of the present invention and after 48 hours in an aqueous environment;
[0030] Figure 9 Antibacterial effect diagram of the eutectic gel prepared in Example 1 of the present invention against Staphylococcus aureus and Escherichia coli;
[0031] Figure 10 Effect diagram of the protective effect of the eutectic gel prepared in Example 1 of the present invention in a simulated wound model;
[0032] Figure 11 Macrophotograph of the initial state of the eutectic gel prepared in Example 2 of the present invention and after 48 hours in a PBS environment;
[0033] Figure 12 This is a diagram showing the protective effect of the new eutectoid gel for open wounds prepared in Example 2 of the present invention in a simulated wound model. DETAILED DESCRIPTION
[0034] The following examples further illustrate the novel eutectoid gel for open wounds provided by the present invention and its preparation and application. It is necessary to point out that the following examples are only used to further illustrate the present invention and cannot be understood as limiting the scope of protection of the present invention. According to the above invention content, technicians in the relevant field make some non-essential improvements and adjustments to the present invention for specific implementation, which still falls within the scope of protection of the invention.
[0035] Example 1
[0036] Preparation of a novel eutectoid gel for open wounds:
[0037] (1) The synthesis of DES based on SBMA and carvacrol (CA) is as follows: 279.35 mg SBMA and 600.88 mg carvacrol were added to a 15 mL centrifuge tube, and a magnetic stirring rotor was added; the centrifuge tube was placed in a 60° C. oil bath and stirred until a clear and transparent solution was formed to obtain a viscous liquid.
[0038] (2) Add 3.45 mg of 2-hydroxy-2-methylphenylacetone and 9.91 mg of ethylene glycol dimethacrylate to the viscous liquid obtained in step (1), continue stirring for 10 minutes to obtain a uniform solution, transfer it to a polytetrafluoroethylene mold under light-proof conditions, and expose it to 365 nm ultraviolet light for 5 minutes to obtain a eutectoid gel.
[0039] (3) The freshly prepared eutectoid gel is placed in a beaker containing ultrapure water to change its network structure, thereby obtaining a new eutectoid gel for open wounds.
[0040] The state of the DES prepared in step (1) at room temperature was recorded using a smartphone. The macroscopic picture is as follows: Figure 1 As shown. Figure 1 It can be seen that DES has liquidity.
[0041] Freshly prepared DES was tested using a differential scanning calorimeter with a temperature range of -70 to 30°C and a heating rate of 5°C / min. The test procedure was cooling first and then heating. Figure 2 As shown, from Figure 2 It can be seen that DES exhibits glass transition behavior around -45°C without crystallization and melting behavior, which is similar to the DES that has been reported, indicating the successful preparation of DES.
[0042] The infrared spectra of DES and its raw materials (SBMA and CA) were determined using a Fourier transform infrared spectroscopy (FT-IR) instrument, and the results are as Figure 3 shown. As can be seen from Figure 3 , characteristic peaks of SBMA appear at 1725, 1181, and 1043 cm -1 , which are attributed to the stretching vibration of C=O and the asymmetric and symmetric stretching vibrations of S=O, respectively. After the formation of DES, they shift to 1719, 1177, and 1041 cm -1 . The hydroxyl group of CA peaks at 639 cm -1 , and after the formation of DES, it shifts to 643 cm -1 . The above changes indicate that the C=O and S=O groups of SBMA are hydrogen bond acceptors during the formation of DES, and their peaks show a red shift; the hydroxyl group of CA is a hydrogen bond donor during the formation of DES, and its peak shows a blue shift.
[0043] The state of the eutectoid gel prepared in step (2) at room temperature was recorded using a smartphone, and the macroscopic pictures are as Figure 4 shown. As can be seen from Figure 4 , the fluidity disappears after the successful preparation of the eutectoid gel.
[0044] The FT-IR spectrum of the freshly prepared eutectoid gel was determined using a Fourier transform infrared spectrometer, and the results are as Figure 5 shown. As can be seen from Figure 5 , compared with DES, the peaks on C=C and its C-H disappear and weaken respectively, indicating that the preparation of the eutectoid gel is completed through the polymerization of double bonds in DES.
[0045] The initial state of the eutectoid gel and the state of the eutectoid gel after being placed in water for 48 hours were recorded respectively. The macroscopic photos were recorded using a smartphone, and the microscopic structure was recorded using a cryogenic scanning electron microscope (Cryo-SEM), as Figure 6 shown. As can be seen from Figure 6 , the eutectoid gel in the initial state is colorless and transparent, and its cross-section is a dense and pore-free structure microscopically; after the network structure transformation, it is white and opaque, and its cross-section is a three-dimensional connected porous structure microscopically, indicating that the water environment induces the transformation of its network structure.
[0046] The infrared spectral changes of ultrapure water at the initial time and after the eutectoid gel was placed in water for 48 hours were monitored using an in-situ reaction detector, and the results are as Figure 7 shown. As can be seen from Figure 7 , with the extension of time, characteristic absorption peaks of benzene ring, O-H, and C-OH appear in the infrared spectrum respectively, indicating that CA in the eutectoid gel is released into the water environment during the network structure transformation.
[0047] The Raman spectra of the eutectic gel in its initial state and after 48 hours in an aqueous environment were detected using a Raman spectrometer, and the results are as follows Figure 8 shown. From Figure 8 it can be seen that the eutectic gel in its initial state shows characteristic peaks at 2930 and 1036 cm -1 , which are attributed to the quaternary ammonium group and the sulfonic acid group respectively; after the network structure transformation occurs, the above characteristic peaks shift to 2936 and 1040 cm -1 respectively, and a broad absorption peak of water molecules appears at 3419 cm -1 .
[0048] Combining Figure 6 , Figure 7 and Figure 8 , it can be known that the interaction between SBMA and water molecules triggers the transformation of the eutectic gel network structure. The water molecules disrupt the deep eutectic behavior of SBMA and CA, resulting in the release of CA from the eutectic gel. The strong interaction between SBMA and water molecules stems from the zwitterionic nature of SBMA. SBMA can bind water molecules through ion solvation to form a network structure mainly composed of PSBMA polymers and water molecules.
[0049] 100 μL of the bacterial suspension (10 8 CFU / mL) of Escherichia coli or Staphylococcus aureus was evenly spread on a sterile nutrient agar plate. Subsequently, the eutectic gel in its initial state sterilized by ozone was placed in the center of the agar plate and cultured in an incubator for 16 hours. The growth of bacteria on the plate was recorded with a smartphone, and the results are as Figure 9 shown. From Figure 9 it can be seen that a clear circular antibacterial zone appears on the plate, indicating that the eutectic gel has good antibacterial effects.
[0050] To evaluate the protective performance of the eutectic gel in its initial state on open wounds, a wound (6 mm) was created in the center of a square pigskin to simulate the wound protection process. The eutectic gel in its initial state was placed on the wound, and 20 μL of the bacterial suspension (10 8 CFU / mL) of Staphylococcus aureus was dropped onto the surface of the eutectic gel, and co-cultured for 24 hours to observe the situation of the eutectic gel protecting the wound, and the results are as Figure 10 shown. From Figure 10 it can be seen that almost no bacteria grow on the wound protected by the eutectic gel, indicating the good protective effect of the eutectic gel on the simulated wound.
[0051] Combining Figure 9 and Figure 10, it can be known that the eutectic gel not only has good antibacterial effects, but also can prevent bacteria from invading open wounds, indicating that the eutectic gel has great application potential in the treatment of bacterial-infected open wounds.
[0052] Example 2
[0053] Preparation of a novel eutectic gel for open wounds:
[0054] (1) Synthesis of a DES based on SBMA and carvacrol (CA) is as follows. In a 15 mL centrifuge tube, add 279.35 mg of SBMA and 600.88 mg of carvacrol, and add a magnetic stirring rotor. Place the above centrifuge tube in an oil bath at 60 °C and stir thoroughly until a clear and transparent solution is formed to obtain a viscous liquid.
[0055] (2) Add 3.53 mg of 2-hydroxy-2-methylpropiophenone and 14.87 mg of ethylene glycol dimethacrylate to the viscous liquid obtained in step (1), and continuously stir for 10 minutes to obtain a homogeneous solution. Transfer it to a polytetrafluoroethylene mold under light-shielded conditions and place it under 365 nm ultraviolet light for 5 minutes to obtain a eutectic gel.
[0056] (3) Place the freshly prepared eutectic gel in a beaker containing PBS buffer to change its network structure, and obtain a novel eutectic gel for open wounds.
[0057] Record the initial state of the eutectic gel and the state of the eutectic gel after being placed in PBS buffer for 48 hours respectively. Use a smartphone to record its macroscopic photos, as Figure 11 shown. From Figure 11 it can be seen that the eutectic gel in the initial state is colorless and transparent; it becomes white and opaque after the network structure transformation, indicating that the PBS environment induces the transformation of its network structure.
[0058] To evaluate the protection performance of the novel eutectic gel for open wounds on open wounds, a wound (6 mm) was created in the center of a square pigskin to simulate the wound protection process. Place the eutectic gel after being placed in PBS buffer for 48 hours on the wound, and drop 20 μL of a bacterial solution of Staphylococcus aureus (10 8 CFU / mL) onto the surface of the eutectic gel after the network structure transformation, and co-culture for 24 hours to observe the situation of the eutectic gel after the network structure transformation protecting the wound. The results are as Figure 12 shown. From Figure 12 it can be seen that there is almost no bacterial growth in the wound protected by the eutectic gel after the network structure transformation, indicating the good protection effect of the novel eutectic gel for open wounds on the simulated wound.
[0059] The above are only specific embodiments of the present invention, not all embodiments. Any equivalent transformation of the technical solution of the present invention made by those of ordinary skill in the art by reading the specification of the present invention shall be covered by the claims of the present invention.
Claims
1. A preparation method of a novel eutectic gel for open wounds, characterized in that, It includes the following steps: (1) Mix methacryloylethyl sulfobetaine with small molecule phenols, heat and stir until a clear and transparent solution is formed to obtain a viscous liquid; (2) Add a photoinitiator and a crosslinking agent to the viscous liquid prepared in step (1), stir evenly, and then carry out photoinitiated polymerization to form a co-precipitation gel; (3) Place the co-precipitation gel in step (2) in an aqueous solvent. As time goes by, the network structure of the co-precipitation gel is transformed to obtain the novel co-precipitation gel for open wounds.
2. The preparation method of the novel eutectic gel for open wounds according to claim 1, characterized in that, In step (1), the molar ratio of methacryloylethyl sulfobetaine to small molecule phenols is 1:(2 - 4).
3. The preparation method of the novel eutectoid gel for open wounds according to claim 1, characterized in that, In step (1), the small molecule phenols are selected from one of carvacrol, eugenol, 2-ethylphenol, and 3-ethylphenol.
4. The preparation method of the novel eutectic gel for open wounds according to claim 1, characterized in that, In step (1), the heating temperature is 50 - 80 °C.
5. The preparation method of the novel eutectoid gel for open wounds according to claim 1, characterized in that, In step (2), the molar ratio of the photoinitiator to the total number of double bonds is (1 - 3):100, and the total number of double bonds is the total number of double bonds in methacryloylethyl sulfobetaine and the crosslinking agent; In step (2), the molar ratio of the crosslinking agent to the total number of double bonds is (1 - 10):100, and the total number of double bonds is the total number of double bonds in methacryloylethyl sulfobetaine and the crosslinking agent.
6. The preparation method of the novel eutectoid gel for open wounds according to claim 1, characterized in that, In step (2), the photoinitiator is selected from one of 2-hydroxy-2-methylphenylacetone and 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone; In step (2), the crosslinking agent is selected from one of ethylene glycol dimethacrylate and polyethylene glycol diacrylate.
7. The preparation method of the novel eutectoid gel for open wounds according to claim 1, characterized in that, In step (3), the aqueous solvent includes water, PBS buffer solution, and normal saline.
8. A novel eutectic gel for open wounds, characterized in that, It is prepared by the preparation method of the novel co-precipitation gel for open wounds according to any one of claims 1 - 7.
9. Use of the novel co-precipitation gel for open wounds according to claim 8 in the preparation of a drug for treating open bacterial infection wounds.
10. A drug for treating open bacterial-infected wounds, characterized in that, It includes the novel co-precipitation gel for open wounds according to claim 8.