A CVLS-GelMA-based hydrogel wound dressing and preparation method thereof

Abstract

The present invention relates to the technical field of medical dressings, and in particular to a CVLS-GelMA-based hydrogel wound dressing and a preparation method thereof. The wound dressing uses a photothermal molecule CVLS, a proton donor bisphenol A, a phase change material polyhydric fatty alcohol, a methacrylated hydrogel, a photoinitiator LAP, a cationic monomer, and an anionic surfactant as main raw materials. The wound dressing has a stable photothermal thermochromic effect, photothermal cyclicity, an adjustable intelligent temperature wall switch, antibacterial properties, and biocompatibility. It can realize near-infrared light response, an adjustable photothermal temperature wall, and intelligent protection of the skin from photothermal burns, and can protect the skin from burns during photothermal therapy.

Description

Technical Field

[0001] The present invention relates to materials in the field of medical supplies, and in particular to a wound dressing with infrared light response and a temperature wall for protecting the temperature of skin photothermal therapy, and in particular to a CVLS-GelMA-based hydrogel wound dressing and a preparation method thereof. Background Art

[0002] In various accidents, skin tissue is inevitably infected by various bacteria after being injured. In more serious cases, biofilms can form. The bacteria in biofilms are highly tolerant and resistant to drugs and the host's own immune system. Therefore, other external interventional treatments are often required during the treatment process.

[0003] Currently, commonly used methods include photothermal therapy and photodynamic therapy. Photothermal therapy has the advantages of high efficiency, easy control, and a wide range of applications. At the same time, due to the high temperature tolerance of bacterial biofilms, the temperature is usually controlled at 50-55°C. However, traditional photothermal materials, such as indocyanine green, MXene, and graphene oxide, do not have a "temperature wall" switch. During photothermal therapy, the temperature continues to rise as external infrared irradiation is applied until burns are caused to the skin tissue due to the delay in wound temperature detection. Therefore, a strict temperature control mechanism is required during wound healing and antibacterial processes. Currently available photothermal agents on the market require users to closely monitor wound temperature in real time. However, in clinical use, changes in both external conditions and the lesion environment will affect the final temperature.

[0004] Crystal Violet Lactone (CVL), chemical name 3,3-bis(4-dimethylaminophenyl)-6-dimethylaminophenyl peptide, molecular formula C 26 H 29 N3O2, whose structural formula is shown in Formula I. CVL is a dye with fast color development, high chroma and good oil solubility, and is often used in thermal labels or information encryption printing.

[0005] After a simple one-step ring-closure reaction, a spirocyclic compound responsive in the near-infrared I region is formed, hereinafter referred to as CVLS, whose structural formula is shown in Formula II. It has never been added to a hydrogel for use as a dressing before.

[0006]

[0007] While CVLS offers excellent near-infrared light response and thermochromic properties, its biggest drawback is its harsh operating environment. It exhibits stable photothermal and color-changing properties only when used in oily solvents with specific melting points (such as lauric acid and palmitic acid). When used in combination with water, the system loses its original properties due to the incompatibility between oil and water, and the color-changing properties are lost after several cycles.

[0008] Therefore, an effective method is needed to apply CVLS to hydrogel materials commonly used in traditional wound dressings, while controlling its original biotoxicity while maintaining its stable photothermal properties in the aqueous hydrogel environment. At the same time, by combining it with oil-phase solvents with different melting points, it can realize the photothermal treatment temperature wall function. Summary of the Invention

[0009] In response to the shortcomings of the existing technology, the present invention provides a CVLS-GelMA-based hydrogel wound dressing, a preparation method and application thereof. The hydrogel wound dressing has stable photothermal properties and a temperature wall, so it can protect the skin from burns during photothermal therapy.

[0010] To achieve this object, the present invention adopts the following technical solutions:

[0011] In a first aspect, the present invention provides a CVLS-GelMA-based hydrogel wound dressing having a temperature wall, and the raw materials for preparing the wound dressing include:

[0012] Photothermal molecule CVLS, proton donor bisphenol A (BPA), phase change material polyhydric fatty alcohol (PCM), methacrylated hydrogel (GelMA), photoinitiator LAP, cationic monomer and anionic surfactant.

[0013] In the present invention, the mass ratio of CVLS, bisphenol A and polyol is 1:(1-10):(10-400), for example, it can be 1:1:10, 1:1:20, 1:1:50, 1:1:80, 1:1:100, 1:1:150, 1:1:200, 1:1:250, 1:1:300, 1:1:350, 1:1:400, 1:5:10, 1:5:20, 1:5:50, 1:1: :5:80, 1:5:100, 1:5:150, 1:5:200, 1:5:250, 1:5:300, 1:5:350, 1:5:400, 1:10:10, 1:10:20, 1:10:50, 1:10:80, 1:10:100, 1:10:150, 1:10:200, 1:10:250, 1:10:300, 1:10:350 or 1:10:400, etc. Preferably, the ratio of the three thermochromic components CVLS, BPA, and PCM is preferably 1:2:20, 1:2:40, 1:2:80, 1:2:160, 1:2:240, 1:2:320, and 1:2:400. Within this ratio gradient, the temperature wall is maintained at a constant and stable value and biocompatibility is guaranteed.

[0014] The molecular formula of the photothermal molecule CVLS used in the present invention is: C26 H 27 N3O2; English name:

[0015] Spiro-[9H-fluorene-9,1'(3'H)-isobenzofuran]-3'-one,3,5',6-tris(dimethylamino)-(9CI,ACI).

[0016] The hydrogel dressing provided by the present invention is prepared by mixing water, CVLS, BPA, PCM, GelMA, cationic monomers, LAP, and anionic surfactants. The obtained hydrogel dressing itself has excellent near-infrared light responsiveness, and the temperature of the final temperature wall of the hydrogel dressing can be adjusted by adjusting the types of PCMs with different melting points in the components.

[0017] In the present invention, the temperature wall refers to the maximum temperature limit reached by the hydrogel dressing due to its own phase change under photothermal response.

[0018] As a preferred technical solution of the present invention, the mass fraction of the methacrylated hydrogel (GelMA) is 5 to 20 wt%, for example, it can be 5%, 8%, 10%, 12%, 15%, 16%, 18% or 20%.

[0019] Preferably, the mass fraction of the photoinitiator LAP is 0.01-0.1 wt%, for example, it can be 0.01%, 0.02%, 0.04%, 0.05%, 0.06%, 0.08% or 0.1%.

[0020] Preferably, the mass fraction of the cationic monomer is 1 to 10 wt%, for example, 1%, 2%, 4%, 5%, 6%, 8%, 9% or 10%.

[0021] Preferably, the mass fraction of the anionic surfactant is 0.5-3 wt%, for example, it can be 0.5%, 0.6%, 0.8%, 1%, 1.2%, 1.5%, 2%, 2.5% or 3%.

[0022] As a preferred technical solution of the present invention, the polyhydric fatty alcohol comprises any one of tetradecanol (MA), pentadecanol, hexadecanol (CA), heptadecanol or stearyl alcohol (SA).

[0023] It should be noted that, in the present invention, the temperature of the hydrogel dressing can be adjusted by adjusting the type and ratio of the polyol.

[0024] In the present invention, when the phase change material polyhydric fatty alcohol is pentadecanol, the maximum temperature of the obtained CVLS-GelMA-based hydrogel wound dressing, i.e., the temperature wall, is 40.2°C.

[0025] In the present invention, when the phase change material polyhydric fatty alcohol is hexadecanol, the maximum temperature of the obtained CVLS-GelMA-based hydrogel wound dressing, i.e., the temperature wall, is 45.5°C.

[0026] In the present invention, when the phase change material polyhydric fatty alcohol is heptadecanol, the maximum temperature of the obtained CVLS-GelMA-based hydrogel wound dressing, i.e., the temperature wall, is 48.3°C.

[0027] In the present invention, when the phase change material polyhydric fatty alcohol is octadecyl alcohol, the maximum temperature of the obtained CVLS-GelMA-based hydrogel wound dressing, i.e., the temperature wall, is 56.8°C.

[0028] Preferably, the cationic monomer comprises acryloyloxyethyltrimethylammonium chloride (AETAC) and / or methacryloyloxyethyltrimethylammonium chloride.

[0029] Preferably, the anionic surfactant includes any one of sodium lauryl sulfate, sodium lauryl sulfonate, pure sodium lauryl sulfate, potassium oleate or sodium oleate, or a combination of at least two thereof.

[0030] As a preferred technical solution of the present invention, the photothermal molecule CVLS is prepared by the following method:

[0031] Crystal violet lactone is mixed with an ionic liquid, heated with stirring, and then cooled. After adding cold water, the resulting suspension is treated with hydrogen peroxide; then, the mixture is extracted with dichloromethane, and the combined organic phase is washed with water, dried, and concentrated; the resulting concentrate is filtered and purified using a mixture of ethyl acetate and dichloromethane on a silica gel column to obtain a white product, which is then dried to obtain the CVLS.

[0032] As a preferred technical solution of the present invention, the ionic liquid is an ionic liquid obtained by heating a mixture of urea, AlCl3 and AlCl3·6H2O, and the heating temperature is 125-140°C, for example, it can be 125°C, 128°C, 130°C, 132°C, 135°C, 138°C or 140°C.

[0033] Preferably, the heating temperature after the crystal violet lactone and the ionic liquid are mixed is 140-150°C, for example, 140°C, 142°C, 144°C, 145°C, 146°C, 148°C or 150°C.

[0034] Preferably, the mixing ratio of ethyl acetate to dichloromethane in the ethyl acetate and dichloromethane mixture is 1:(1-3), for example, 1:1, 1:1.2, 1:1.5, 1:1.8, 1:2, 1:2.4, 1:2.5 or 1:3.

[0035] In a second aspect, the present invention provides a method for preparing the CVLS-GelMA-based hydrogel wound dressing as described in the first aspect, the preparation method comprising the following steps:

[0036] (1) preparing a thermochromic component mixed solution and an anionic surfactant aqueous solution; wherein the thermochromic component mixed solution is prepared by the following method: mixing the photothermal molecule CVLS, the proton donor bisphenol A, and the phase change material polyhydric fatty alcohol in proportion to obtain the thermochromic component mixed solution;

[0037] (2) Then, the thermochromic component mixture is mixed with an anionic surfactant aqueous solution and emulsified using a high-speed emulsifier to obtain a product suspension;

[0038] (3) preparing a composite hydrogel precursor solution containing methacrylated hydrogel GelMA, cationic monomer and LAP, mixing the solution with the obtained product suspension, completing electrostatic self-assembly of microspheres, and obtaining a composite hydrogel precursor solution. After adjusting the pH, the solution is irradiated with UV to form a gel, thereby obtaining the wound dressing.

[0039] As a preferred technical solution of the present invention, the photothermal molecule CVLS is prepared by the following method:

[0040] Crystal violet lactone is mixed with an ionic liquid, heated and stirred, and then cooled. After adding cold water, the resulting suspension is treated with hydrogen peroxide; then, the mixture is extracted with dichloromethane, and the combined organic phase is washed with water, dried, and concentrated; the resulting concentrate is filtered and purified using a mixture of ethyl acetate and dichloromethane on a silica gel column to obtain a white product, which is then dried to obtain the CVLS;

[0041] Preferably, the pH value of the obtained composite hydrogel precursor solution is adjusted to 4-6.

[0042] As a preferred technical solution of the present invention, the preparation method comprises the following steps:

[0043] (1) Preparation of photothermal molecule CVLS: Crystal violet lactone is mixed with an ionic liquid, heated and stirred, and then cooled. After adding cold water, the resulting suspension is treated with hydrogen peroxide; then, the mixture is extracted with dichloromethane, and the combined organic phase is washed with water, dried, and concentrated; the resulting concentrate is filtered and purified using a mixture of ethyl acetate and dichloromethane on a silica gel column to obtain a white product, which is then dried to obtain the photothermal molecule CVLS;

[0044] Then, the photothermal molecule CVLS, the proton donor bisphenol A, and the phase change material polyhydric fatty alcohol are mixed in proportion to obtain a thermochromic component mixture, and an anionic surfactant aqueous solution is prepared;

[0045] (2) mixing the thermochromic component mixture with an anionic surfactant aqueous solution and emulsifying the mixture using a high-speed emulsifier to obtain a product suspension;

[0046] (3) preparing a precursor solution containing methacrylated hydrogel GelMA, cationic monomer and LAP, mixing the solution with the obtained product suspension, completing electrostatic self-assembly of microspheres, and obtaining a composite hydrogel precursor solution; adjusting the pH value of the obtained composite hydrogel precursor solution to 4-6, and irradiating the solution with UV to form a gel to obtain the wound dressing.

[0047] Specifically, the preparation method of the wound dressing with a temperature wall described in the present invention is prepared according to the following steps:

[0048] (1) Preparation of CVLS

[0049] Urea was added to a crucible containing AlCl3 and AlCl3·6H2O, and heated and stirred to form an ionic liquid at a temperature of 125-140°C; CVL was added, and the mixture was stirred under heating at a temperature of 140-150°C for 24 hours. After cooling to ambient temperature, the solid mixture in the crucible was poured into cold water to obtain a gray-green suspension, which was treated with hydrogen peroxide and stirred for 1.5 hours;

[0050] The resulting suspension was extracted with dichloromethane; the combined organic phases were washed with water, dried over anhydrous MgSO4, and concentrated under reduced pressure;

[0051] The resulting product was purified by multiple filtrations through a silica gel column using a 1:1 to 1:3 ethyl acetate:dichloromethane solution to obtain a white product, which was then dried. If 2 g of CVL is used as the starting material for preparing CVLS, the mass of CVLS produced by this procedure is 80 to 120 mg.

[0052] (2) Preparation of thermochromic precursor emulsion

[0053] Prepare a 0.5-3 wt% aqueous solution of anionic surfactant and heat it to 70°C;

[0054] Three thermochromic components in different proportions were prepared and heated to 300°C for 2 minutes. After the three thermochromic components were reheated to 70°C, an anionic surfactant aqueous solution was quickly poured in and emulsified using a high-speed emulsifier for 10 minutes.

[0055] Then, the hot emulsion was quickly poured into an anionic surfactant aqueous solution at 5°C to obtain a product suspension;

[0056] (3) Preparation of wound dressing with temperature wall

[0057] Prepare a precursor solution containing 5-20 wt% of LAP, 1-10 wt% of GelMA, and 0.01-0.1 wt% of cationic monomer; heat to 70°C and slowly inject into the product suspension prepared in step (2) using a syringe pump to complete the electrostatic self-assembly of microspheres; adjust the pH value of the composite hydrogel precursor solution to 4-6 and then irradiate with UV to form a gel.

[0058] In a third aspect, the present invention provides a use of the wound dressing as described in the first aspect in the field of medical device preparation.

[0059] The numerical range described in the present invention includes not only the point values ​​listed above, but also any point values ​​between the above numerical ranges that are not listed. Due to space limitations and for the sake of simplicity, the present invention no longer exhaustively lists the specific point values ​​included in the range.

[0060] Compared with the prior art, the present invention has the following beneficial effects:

[0061] The raw materials for preparing the wound dressing provided by the present invention include the photothermal molecule CVLS, which is prepared from crystal violet lactone. Compared with CVL, CVLS has excellent response and thermochromic properties in the near-infrared I region; at the same time, in order to overcome the defect that CVLS itself cannot be used on infectious wounds, the present invention uses it in combination with polyhydric fatty alcohols and methacrylated hydrogels to overcome the original usage conditions and maintain its stable photothermal properties in an aqueous hydrogel environment.

[0062] Performance tests show that the wound dressing provided by the present invention fades to an off-white color at high temperatures, losing its near-infrared light absorption function, and returns to a dark green color at room temperature. It also exhibits stable thermochromic cycling, retaining its original color saturation after repeated heating and fading. The resulting wound dressing also exhibits photothermal responsiveness to temperature. When CA is used as the phase change material, its temperature wall remains stable at 45.5°C. Furthermore, experiments have shown that the temperature wall can be adjusted by replacing PCMs with different melting points. BRIEF DESCRIPTION OF THE DRAWINGS

[0063] Figure 1 These are thermochromic images of the thermochromic precursor emulsion prepared in Example 1 of the present invention; Figure I is at 65°C, and Figure II is at 25°C.

[0064] Figure 2 These are thermochromic cycle images of the hydrogel wound dressing prepared in Example 1; Figure I shows the first application of the wound dressing at 65°C, Figure II shows the recovery to room temperature (25°C), Figure III shows the tenth repeated heating to 65°C, and Figure IV shows the recovery to room temperature (25°C).

[0065] Figure 3Photos of hydrogel dressings prepared by the methods of Example 1 and Comparative Example 1 of the present invention; Figure I shows the sample of Comparative Example 1 using the non-anionic surfactant Span 80, and Figure II shows the sample of Example 1 using the anionic surfactant sodium lauryl sulfate.

[0066] Figure 4 The results of the photothermal performance test of the prepared samples are shown in Figure I, which is a photothermal responsiveness change curve of Example 6, and Figure II is a specific temperature detection diagram of the sample.

[0067] Figure 5 This is a test curve of temperature wall changes after replacing PCM. DETAILED DESCRIPTION

[0068] The technical solution of the present invention is further illustrated below with reference to the accompanying drawings and through specific implementation methods. However, the following examples are merely simplified examples of the present invention and do not represent or limit the scope of protection of the present invention. The scope of protection of the present invention shall be subject to the claims.

[0069] In the following examples, unless otherwise specified, all reagents and consumables used were purchased from conventional reagent manufacturers in the field; unless otherwise specified, all experimental methods and technical means used were conventional methods and means in the field.

[0070] Example 1

[0071] This embodiment is used to prepare a wound dressing, and the raw materials of the wound dressing include:

[0072] Components Mass fraction or mass percentage CVLS 1 part by mass (prepared from 2g CVL) BPA 2 parts by mass MA 10 parts by mass Sodium lauryl sulfate 1wt% GelMA 5wt% AETAC 2wt% LAP 0.01wt% water Make up the balance 100%

[0073] The preparation method is as follows:

[0074] (1) Preparation of CVLS

[0075] a) 5 g of urea was added to a crucible containing AlCl3 (12.0 g) and AlCl3·6H2O (0.05 g), and heated to 125°C with stirring to form an ionic liquid;

[0076] b) CVL (2.0 g) was added, and the mixture was stirred at 145° C. for 24 hours. After cooling to ambient temperature, the solid mixture in the crucible was poured into cold water (400 mL) to obtain a gray-green suspension, which was treated with hydrogen peroxide (30 wt %, 1.2 mL) and stirred for 1.5 hours;

[0077] c) extracting the suspension obtained in b) with dichloromethane; washing the combined organic phases with water, drying over anhydrous MgSO4, and concentrating under reduced pressure;

[0078] d) The obtained product was purified by multiple filtrations on a silica gel column using a gradient solution of ethyl acetate:dichloromethane in a mixing ratio of 1:2 to obtain a white product, which was then dried to obtain CVLS.

[0079] (2) Preparation of thermochromic precursor emulsion

[0080] a) preparing a 1 wt% aqueous solution of sodium lauryl sulfate and heating it to 70° C.;

[0081] b) Prepare three thermochromic components (CVLS: BPA: MA = 1:2:10) and heat to 300°C for 2 minutes;

[0082] c) reheating the components obtained in b) to 70° C., then quickly pouring the S1 solution into the mixture and emulsifying the mixture using a high-speed emulsifier at 3000 rpm for 10 min;

[0083] d) The hot emulsion obtained in c) was quickly poured into the solution in a) at 5°C to obtain a product suspension.

[0084] (3) Preparation of wound dressing with temperature wall

[0085] a) preparing a precursor solution of 5 wt% GelMA, 2 wt% AETAC, and 0.01 wt% LAP;

[0086] b) heating the S1 solution to 70° C. and slowly injecting it into the product suspension of step (2) using a syringe pump to complete the electrostatic self-assembly of the microspheres;

[0087] c) adjusting the pH value of the composite hydrogel precursor solution in b) to 5 and irradiating it with UV for 1 minute to form a gel.

[0088] Example 2

[0089] This embodiment is used to prepare a wound dressing, and the raw materials of the wound dressing include:

[0090]

[0091]

[0092] The preparation method used was consistent with that in Example 1.

[0093] Example 3

[0094] This embodiment is used to prepare a wound dressing, and the raw materials of the wound dressing include:

[0095] Components Mass fraction or mass percentage CVLS 1 part by mass (prepared from 2g CVL) BPA 2 parts by mass MA 400 parts by mass Sodium lauryl sulfate 1wt% GelMA 10wt% AETAC 5wt% LAP 0.01wt% water Make up the balance 100%

[0096] The preparation method used was consistent with that in Example 1.

[0097] Example 4

[0098] This embodiment is used to prepare a wound dressing, and the raw materials of the wound dressing include:

[0099]

[0100]

[0101] The preparation method used was consistent with that in Example 1.

[0102] Example 5

[0103] This embodiment is used to prepare a wound dressing, and the raw materials of the wound dressing include:

[0104] Components Mass fraction or mass percentage CVLS 1 part by mass (prepared from 2g CVL) BPA 2 parts by mass MA 10 parts by mass Sodium lauryl sulfate 1wt% GelMA 5wt% AETAC 2wt% LAP 0.01wt% water Make up the balance 100%

[0105] In this embodiment, the steps differ from those in Example 1 in that: after adjusting the pH value of the composite hydrogel precursor solution to 5, the solution is heated at 80° C. for 8 h and then irradiated with UV for 1 min to form a gel.

[0106] The preparation methods of the remaining steps are consistent with those in Example 1.

[0107] Example 6

[0108] This embodiment is used to prepare a wound dressing, and the raw materials of the wound dressing include:

[0109] Components Mass fraction or mass percentage CVLS 1 part by mass (prepared from 2g CVL) BPA 2 parts by mass CA 10 parts by mass Sodium lauryl sulfate 1wt% GelMA 5wt% AETAC 2wt% LAP 0.01wt% water Make up the balance 100%

[0110] The preparation method used was consistent with that in Example 1.

[0111] Example 7

[0112] This embodiment is used to prepare a wound dressing, and the raw materials of the wound dressing include:

[0113] Components Mass fraction or mass percentage CVLS 1 part by mass (prepared from 2g CVL) BPA 2 parts by mass SA 10 parts by mass Sodium lauryl sulfate 1wt% GelMA 5wt% AETAC 2wt% LAP 0.01wt% water Make up the balance 100%

[0114] The preparation method used was consistent with that in Example 1.

[0115] Comparative Example 1

[0116] This comparative example is used to prepare a wound dressing. The raw materials of the wound dressing use a nonionic surfactant, which specifically includes the following components:

[0117] Components Mass fraction or mass percentage CVLS 1 part by mass (prepared from 2g CVL) BPA 2 parts by mass MA 10 parts by mass Span 80 1wt% GelMA 5wt% AETAC 2wt% LAP 0.01wt% water Make up the balance 100%

[0118] The preparation method used was consistent with that in Example 1.

[0119] Characterization and performance testing:

[0120] 1. From Figure 1 As can be seen in the figure, the left picture is the optical photograph of the emulsion in Figure I at 65°C. After heating, the photothermal molecular system fades to grayish white and loses its near-infrared light absorption function.

[0121] Figure II is an optical photograph of the emulsion at room temperature of 25°C, and the entire emulsion system returns to dark green.

[0122] 2. Figure 2 Optical photographs of the final gelled hydrogel from Example 1 after the first heating at 65°C (Figure I), after returning to room temperature at 25°C (Figure II), after the tenth heating at 65°C (Figure III), and after returning to room temperature at 25°C (Figure IV) demonstrate that after gelling, the entire hydrogel not only maintains its original color saturation but also maintains stable thermochromic cyclicity.

[0123] 3. Figure 3 Figure 1 shows a hydrogel prepared using the non-anionic surfactant (Span 80) as the emulsifier in the emulsion preparation step of Comparative Example 1. The hydrogel exhibits a very light green color and is nearly transparent, with poor thermochromic effect. Similarly, using the non-anionic surfactant Tween 20 as the emulsifier yields similar results to Span 80. The right image shows the hydrogel dressing prepared in Example 1, which is dark green in color.

[0124] 4. Figure 4 Photothermal test of the sample prepared in Example 6. Before starting the test, start the 808nm near-infrared light instrument and then turn on the thermal imager for initial settings. At room temperature, add 200μL of hydrogel precursor solution to a 1.5mL centrifuge tube to prepare the hydrogel sample. The near-infrared light irradiation power is 1.5W / cm 2 The test was carried out three times using three groups of samples. Each group of samples showed stable photothermal responsiveness (Figure I), and the final temperature wall was stable at 45.5℃ (Figure II).

[0125] 5. Figure 5 It is shown that by replacing PCMs with different melting points, the temperature of the temperature wall can be adjusted, such as the temperature corresponding to CA (Example 6) is 45.5°C, and the temperature wall corresponding to SA (Example 7) is 56.8°C.

[0126] The applicant declares that the above is only a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Those skilled in the art should understand that any changes or substitutions that can be easily thought of by those skilled in the art within the technical scope disclosed by the present invention fall within the scope of protection and disclosure of the present invention.

Claims

1. A CVLS-GelMA-based hydrogel wound dressing, characterized in that: The raw materials for preparing the CVLS-GelMA-based hydrogel wound dressing include: Photothermal molecule CVLS, proton donor bisphenol A, phase change material polyhydric fatty alcohol, methacrylated hydrogel, photoinitiator LAP, cationic monomer and anionic surfactant; The mass ratio of the photothermal molecule CVLS, the proton-providing agent bisphenol A and the phase-change material polyol is 1:(1-10):(10-400); The mass fraction of the methacrylated hydrogel is 5-20 wt%; The mass fraction of the photoinitiator LAP is 0.01-0.1 wt%; The mass fraction of the cationic monomer is 1-10 wt%; The mass fraction of the anionic surfactant is 0.5-3 wt%.

2. The CVLS-GelMA-based hydrogel wound dressing according to claim 1, characterized in that The phase change material polyhydric fatty alcohol comprises any one of tetradecanol, pentadecanol, hexadecanol, heptadecanol or octadecanol; The cationic monomer includes acryloyloxyethyl trimethyl ammonium chloride and / or methacryloyloxyethyl trimethyl ammonium chloride; The anionic surfactant includes any one of sodium lauryl sulfate, sodium lauryl sulfonate, potassium oleate or sodium oleate, or a combination of at least two of them.

3. The CVLS-GelMA-based hydrogel wound dressing according to claim 1, characterized in that The photothermal molecule CVLS is prepared by the following method: Crystal violet lactone is mixed with an ionic liquid, heated with stirring, and then cooled. After adding cold water, the resulting suspension is treated with hydrogen peroxide; then, the mixture is extracted with dichloromethane, and the combined organic phase is washed with water, dried, and concentrated; the resulting concentrate is filtered and purified using a mixture of ethyl acetate and dichloromethane on a silica gel column to obtain a white product, which is then dried to obtain the CVLS.

4. The CVLS-GelMA-based hydrogel wound dressing according to claim 3, characterized in that The heating temperature after the crystal violet lactone and the ionic liquid are mixed is 140-150° C.; The ionic liquid is a mixture of urea, AlCl3 and AlCl3·6H2O, and the mixture is heated to obtain an ionic liquid at a temperature of 125-140°C. The mixing ratio of ethyl acetate to dichloromethane in the ethyl acetate and dichloromethane mixture is 1:(1-3).

5. The CVLS-GelMA-based hydrogel wound dressing according to claim 1, characterized in that The CVLS-GelMA-based hydrogel wound dressing has a maximum temperature limit due to its own phase change under photothermal response; When the phase change material polyhydric fatty alcohol is pentadecanol, the maximum temperature, i.e., the temperature wall, of the obtained CVLS-GelMA-based hydrogel wound dressing is 40.2°C; When the phase change material polyhydric fatty alcohol is hexadecanol, the maximum temperature, i.e., the temperature wall, of the obtained CVLS-GelMA-based hydrogel wound dressing is 45.5°C; When the phase change material polyhydric fatty alcohol is heptadecanol, the maximum temperature, i.e., the temperature wall, of the obtained CVLS-GelMA-based hydrogel wound dressing is 48.3°C; When the phase change material polyhydric fatty alcohol is octadecyl alcohol, the maximum temperature of the obtained CVLS-GelMA-based hydrogel wound dressing, i.e., the temperature wall, is 56.8°C.

6. A method for preparing the CVLS-GelMA-based hydrogel wound dressing according to any one of claims 1 to 5, characterized in that: The preparation method comprises the following steps: (1) Preparing a mixed solution of thermochromic components and an aqueous solution of anionic surfactant; The thermochromic component mixture is prepared by the following method: photothermal molecule CVLS, proton donor bisphenol A, and phase change material polyhydric fatty alcohol are mixed in proportion to obtain a thermochromic component mixture; (2) mixing the thermochromic component mixture with an anionic surfactant aqueous solution and emulsifying the mixture using a high-speed emulsifier to obtain a product suspension; (3) preparing a composite hydrogel precursor solution containing methacrylated hydrogel, cationic monomer and photoinitiator LAP, mixing it with the obtained product suspension, completing electrostatic self-assembly of microspheres, and obtaining a composite hydrogel precursor solution. After adjusting the pH, the solution was irradiated with UV to form a gel, thereby obtaining the CVLS-GelMA-based hydrogel wound dressing.

7. The preparation method according to claim 6, characterized in that The photothermal molecule CVLS is prepared by the following method: Crystal violet lactone is mixed with an ionic liquid, heated and stirred, and then cooled. After adding cold water, the resulting suspension is treated with hydrogen peroxide; then, the mixture is extracted with dichloromethane, and the combined organic phase is washed with water, dried, and concentrated; the resulting concentrate is filtered and purified using a mixture of ethyl acetate and dichloromethane on a silica gel column to obtain a white product, which is then dried to obtain the CVLS; The pH value of the obtained composite hydrogel precursor solution is adjusted to 4-6.

8. The preparation method according to claim 6, characterized in that The preparation method comprises the following steps: (1) Preparation of photothermal molecule CVLS: crystal violet lactone is mixed with an ionic liquid, heated and stirred, and then cooled. After adding cold water, the resulting suspension is treated with hydrogen peroxide; then, the mixture is extracted with dichloromethane, and the combined organic phase is washed with water, dried, and concentrated; the resulting concentrate is filtered and purified using a mixture of ethyl acetate and dichloromethane on a silica gel column to obtain a white product, which is then dried to obtain the photothermal molecule CVLS; Then, the photothermal molecule CVLS, the proton donor bisphenol A, and the phase change material polyhydric fatty alcohol are mixed in proportion to obtain a thermochromic component mixture, and an anionic surfactant aqueous solution is prepared; (2) mixing the thermochromic component mixture with an anionic surfactant aqueous solution and emulsifying the mixture using a high-speed emulsifier to obtain a product suspension; (3) preparing a precursor solution containing methacrylated hydrogel GelMA, cationic monomer and LAP, mixing it with the obtained product suspension, completing the electrostatic self-assembly of microspheres, and obtaining a composite hydrogel precursor solution; After adjusting the pH value of the obtained composite hydrogel precursor solution to 4-6, UV irradiation is used to form gel to obtain the wound dressing.

9. Use of the CVLS-GelMA-based hydrogel wound dressing according to any one of claims 1 to 5 in the field of medical device preparation.

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