Self-regulating photocurable cooling hydrogel, its manufacturing method and applications

Abstract

This invention belongs to the field of hydrogel materials technology, and specifically provides self-modulating photocurable cooling hydrogels, their manufacturing methods, and applications. [Solution] The self-regulating photocurable cooling hydrogel consists of 10-17 parts of a cooling matrix and acrylamide- 13 It contains 8-33 parts of C31, 27-42 parts of glycerin, 5 parts of TPGDA, 0.05-0.15 parts of crosslinking agent, and 0.1-0.3 parts of photoinitiator. By constructing a cooperative system between the antifreeze protein and the konjac glucomannan backbone, the objectives of gelation of isotope-labeled monomers and self-regulation of cooling sensation are achieved, and it can be used in the manufacture of drug-carrying gel dressings, cooling gel dressings, and in situ injection gel products. The photocuring crosslinking technology is advantageous for rapid formation of gel dressings and improves the stability of the active ingredient.

Description

[Technical Field]

[0001] This invention belongs to the field of hydrogel materials, and more specifically, relates to a self-regulating photocurable cooling hydrogel, its manufacturing method, and its applications. [Background technology]

[0002] In biomedical and other applied fields, cooling hydrogel dressings have become important medical materials for alleviating burning pain from wounds and suppressing inflammatory responses due to their high water content, thermal buffering ability, and flexible application. Conventional technology incorporates cooling agents such as menthol and borneol to give dressings both physical cooling and drug delivery functions, and is particularly applied to exudative wounds such as burns and acute soft tissue injuries. However, with the increasing demand for precision medicine, the inherent defects of conventional cooling gels are becoming increasingly apparent. On the one hand, if the wound surface is in a high-temperature and highly exudative state in the initial stages, the rapid release of cooling agents can worsen the pain due to cold stimulation. If the temperature drops during the healing phase, the cooling sensation will quickly disappear, and it will not be possible to suppress the burning sensation caused by residual inflammation. On the other hand, low-molecular-weight cooling agents and drugs are prone to migration and leakage to the wound surface, which not only shortens the period of effective action but also has the potential to penetrate newly formed epithelial tissue and cause toxic reactions. Furthermore, the formulation of functional components is difficult; for example, the compatibility between temperature-responsive materials and physiologically active components is poor. In sustained-release technologies such as microcapsule embedding, the introduction of synthetic polymer wall materials increases the risk of biotoxicity, and the complex process drives up production costs. More importantly, the molecular metabolic tracing function necessary for postoperative repair and disease research is often difficult to achieve due to structural instability in the thermosetting process of isotopically labeled molecules and insufficient mechanical strength of the UV-curing network. These contradictions force current cooling dressings to compromise between temperature adaptability, long-term sustained drug release, and biosafety, severely limiting their application to chronic wounds and precision medicine.

[0003] Therefore, in order to overcome the current technical challenges of cooling gel materials, there is an urgent need to develop novel hydrogel dressings that can provide a sustained cooling sensation, have high isotopic stability, and good biocompatibility. [Overview of the Initiative]

[0004] In response to the above situation, the present invention provides a self-regulating photocurable cooling hydrogel, a method for producing the same, and its applications. Through a biomimetic strategy, antifreeze proteins and hinokitiol are formed into a cooling matrix with allosteric dissociation properties, a gel backbone network is constructed, isotope-labeled monomers and a UV curing system are optimized, precise crosslinking of the photosensitive network is achieved, and it can be used as a dressing for hydrogel carriers for drug delivery or thermoregulation.

[0005] To achieve the above objectives, the present invention employs the following technical means.

[0006] This invention involves a cooling matrix of 10-17 parts, acrylamide- 13 The present invention provides a self-adjusting photocurable cooling hydrogel containing 8-33 parts of C31, 27-42 parts of glycerin, 5 parts of TPGDA (tripropylene glycol diacrylate), 0.05-0.15 parts of a crosslinking agent, and 0.1-0.3 parts of a photoinitiator.

[0007] Furthermore, the crosslinking agent is selected from one of the following: MBA (N,N'-methylenebisacrylamide), PEG400 (polyethylene glycol 400), and HAMA (methacryloyl hyaluronic acid).

[0008] Furthermore, the photoinitiator is selected from one of the following: TPO-L (2,4,6-trimethylbenzoylphenylphosphinate ethyl) or Irgacure 2959 (2-hydroxy-4'-(2-hydroxyethoxy)-2-methylacetophenone).

[0009] Furthermore, the cooling matrix contains an antifreeze protein, N-ethyl-p-menthane-3-carboxamide, konjac glucomannan, hinokitiol, NHS (N-hydroxysuccinimide), CaCl2 (calcium chloride), and β-mannanase.

[0010] Furthermore, the mass ratio of the antifreeze protein, N-ethyl-p-menthane-3-carboxamide, konjac glucomannan, hinokitiol, NHS, CaCl2, and β-mannanase is 15:1:22.5:4.7:0.3:0.5:0.15.

[0011] The method for manufacturing the aforementioned cooling matrix is ​​as follows: Step S1 involves weighing out konjac glucomannan, dissolving it in deionized water, adding β-mannanase and reacting for 30 minutes, then inactivating the enzyme at 90°C, adding hinokitiol and NHS and reacting further, reacting at 50°C for 3 hours under a nitrogen gas atmosphere, dialyzing, and obtaining a graft solution. Step S2 involves weighing out the antifreeze protein, dissolving it in deionized water to obtain an antifreeze protein solution, weighing out N-ethyl-p-menthane-3-carboxamide, dissolving it in anhydrous ethanol, and then adding it to the antifreeze protein solution while stirring at a rate of 2 mL / min at 80 rpm at 4°C. After it is completely added, the mixture is stirred for 4 hours to obtain the inclusion solution. The process includes step S3, in which the graft solution and inclusion solution are uniformly mixed, CaCl2 is added, and the mixture is homogenized at 12,000 rpm for 10 minutes to obtain a cooling matrix.

[0012] Specifically, this invention relates to: 18-33 parts acrylamide 13 Step 1 involves weighing out C3, dissolving it in deionized water, adding 27-42 parts of glycerin, and stirring at 400 rpm for 15 minutes to obtain the aqueous phase. Step 2 involves measuring out 5 parts TPGDA and 0.1 to 0.3 parts photoinitiator, mixing them while shielding from light, stirring at 200 rpm until transparent to obtain an oil phase, uniformly mixing the oil phase and aqueous phase, then adding 10 to 17 parts cooling matrix and 0.05 to 0.15 parts crosslinking agent to obtain a pregel. The present invention further provides a method for producing a self-modulating photocurable cooling hydrogel, comprising step 3, adjusting the pH of the pregel to 4.0-5.5 with a citrate buffer solution of pH 4.0, drying it in a vacuum drying chamber at 60°C until the water content reaches 18-22%, and obtaining a self-modulating photocurable cooling hydrogel.

[0013] Regarding the application of the self-regulating photo-curable cooling hydrogel, the photo-curable cooling hydrogel as described above can be used in drug-loaded gel dressings, cooling gel pads, cooling gel packs, cooling gel injection products, and in-situ injection gels.

[0014] Furthermore, regarding the use of the self-regulating photo-curable cooling hydrogel in the manufacture of the cooling gel pad, the specific manufacturing method is as follows. Adopt the manufacturing method using a suction mold, take molds with different pattern shapes that have been washed and dried, inject the manufactured cooling hydrogel into them, and under ultraviolet irradiation with a wavelength of 365 nm and 25 mW / cm 2 for 60 seconds to cure, press and form, process the plastic film on the surface, and obtain the cooling gel pad.

[0015] Furthermore, the cooling gel pad can be used in sports goods, office supplies, and automotive supplies.

[0016] Furthermore, the cooling gel pad can be used in the production of cushions, pet mats, yoga mats, mattresses, clothing, gloves, and head protection cover products.

[0017] Furthermore, regarding the use of the self-regulating photo-curable cooling hydrogel in the manufacture of the cooling gel pack, the specific manufacturing method is as follows. Fill the manufactured cooling hydrogel into a well-sealed pack, and under ultraviolet irradiation with a wavelength of 365 nm and 25 mW / cm 2 for 60 seconds to cure, and obtain the cooling gel pack.

[0018] Furthermore, regarding the use of the self-regulating photo-curable cooling hydrogel in the manufacture of the cooling gel injection product, the specific manufacturing method is as follows. Inject the manufactured cooling hydrogel into latex or sponge, and under ultraviolet irradiation with a wavelength of 365 nm and 25 mW / cm 2 for 60 seconds to cure and form, and obtain the cooling gel injection product.

[0019] Furthermore, the cooling gel injection product can be used in the production of pillows and lumbar support products.

[0020] Furthermore, regarding the use of the self-regulating photocurable cooling hydrogel in the production of drug-loaded gel dressings, the specific production method is as follows. After dispersing the drug in a solvent, a drug solution is obtained. The drug solution, Tween 80, and the cooling hydrogel are uniformly mixed at a mass ratio of 1:0.02:15 to obtain a drug-loaded gel. The drug-loaded gel is uniformly applied to a mold with a dressing, and cured for 60 seconds under ultraviolet irradiation with a wavelength of 365 nm and a power density of 25 mW / cm 2 and then press-molded to obtain a drug-loaded gel dressing.

[0021] Furthermore, the drug is selected from any one of indomethacin, mupiroxacin, rhEGF (recombinant human epidermal growth factor), and lidocaine.

[0022] Furthermore, regarding the use of the self-regulating photocurable cooling hydrogel in the production of in-situ injection gels, the cooling hydrogel is injected into the lesion site and cured with ultraviolet light of 365 nm, and then used as a tracer for in-vivo metabolism.

[0023] The effects obtained in the present invention are as follows. The self-regulating photocurable cooling hydrogel produced in the present invention is based on a cool-sensation matrix and a water / glycerin / TPGDA ternary medium system, constructs a temperature-controlled photocurable hydrogel, and is an isotope-labeled monomer acrylamide- 13This technology combines C3 with UV curing to improve the mechanical properties of acrylamide hydrogels. Specifically, the antifreeze protein, acting as a natural temperature-sensitive carrier, enables the regulated release of N-ethyl-p-menthane-3-carboxamide. The konjac glucomannan skeleton, induced by enzymatic decomposition, achieves optimized swelling and shrinkage characteristics through molecular chain modification. The synergistic effect of temperature-triggered mechanical stress and the sustained release of hinokitiol balances the intensity and duration of the cooling sensation, ensuring rapid curing while maintaining the gel's elastic recovery properties. The stepwise manufacturing process—enzymatic decomposition, grafting, and encapsulation—preserves the active sites of biomacromolecules while achieving highly efficient loading of functional factors. pH adjustment and vacuum drying techniques simultaneously balance defoaming efficiency with gel network integrity, offering new concepts for the functional development of photocurable hydrogels.

[0024] Furthermore, the excellent cooling and temperature control capabilities, biocompatibility, and mechanical properties of the self-regulating photocurable cooling hydrogel manufactured according to the present invention are advantageous for improving the adaptability of patients with fever, hyperthermia, skin wounds, or inflammation, making it suitable for the biomedical field, and particularly suitable as a skin cooling dressing, or as a hydrogel dressing for wound repair, antibacterial / anti-inflammatory, and analgesic drugs. [Brief explanation of the drawing]

[0025] [Figure 1] These are temperature-time curves after photocuring of the cooled hydrogels produced in Examples 2, 4, and 6 and Comparative Examples 1-3. [Figure 2] These are the results of the mechanical performance tests of the cooled hydrogels produced in Examples 2, 4, and 6 and Comparative Examples 1 to 3 after photocuring. [Figure 3] This is an evaluation of the injectability of the cooled hydrogel produced in Example 2. [Figure 4] These are the results of characterization using a scanning electron microscope after photocuring of the cooled hydrogel produced in Example 4. [Figure 5] This is an external view of the cooling gel dressing manufactured in Example 7.

Best Mode for Carrying Out the Invention

[0026] The technical means in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments in the present invention, all other embodiments obtained by those skilled in the art without creative labor all belong to the protection scope of the present invention.

[0027] Unless otherwise defined, all technical terms and scientific terms used in this specification have the same meaning as those well-known to those skilled in the art. Also, any methods and materials similar or equivalent to those described are applicable to the present invention. The preferred implementation methods and materials described in this specification are used only for illustration and cannot limit the content of this application.

[0028] In the following examples, unless otherwise specified, all are normal methods. The materials used in the following examples are all newly purchased materials available on the market unless otherwise specified, and the above parts are all in parts by weight. Among them, the purity of the acrylamide - 13 C3 isotope is ≧99%. In the TPGDA used, the polyethylene glycol chain n = 3, the free acrylic acid content <500 ppm, and the chromaticity <50. The substitution degree of the HAMA used is 1.2, and the HA-based molecular weight MW is 100 kDa. The antifreeze protein used is derived from the leaves of the plant, Sagittaria sagittifolia, and the enzyme activity of the β-mannanase used is ≧50000 U / g. The citrate buffer solution with pH 4.0 used is prepared from citric acid, sodium citrate, and distilled water, and the concentration is 0.1 M. The CaCl2 used is in the form of dihydrate.

[0029] In the following examples and comparative examples, in the above photocuring process, it was cured for 60 seconds under ultraviolet irradiation with a wavelength of 365 nm and 25 mW / cm 2 2.

[0030] In the following examples and comparative examples, the cooling matrix contains 60 parts of antifreeze protein, 4 parts of N-ethyl-p-menthane-3-carboxamide, 90 parts of konjac glucomannan, 18.8 parts of hinokitiol, 1.2 parts of NHS, 22 parts of CaCl, and 0.6 parts of β-mannanase. The method for producing the cooling matrix is ​​as follows. S1: 90 parts of konjac glucomannan were weighed out and dissolved in 120 parts of deionized water. 0.6 parts of activated β-mannanase were added, and the mixture was reacted for 30 minutes. The enzyme was then inactivated at 90°C for 15 minutes. 18.8 parts of hinokitiol and 1.2 parts of NHS were added, and the mixture was reacted at 50°C for 3 hours under a nitrogen atmosphere. The mixture was then dialyzed for 1 hour using a 500 Da dialysis bag to obtain the graft solution. S2: 60 parts of antifreeze protein were weighed out and dissolved in 104 parts of deionized water to obtain an antifreeze protein solution. 4 parts of N-ethyl-p-menthane-3-carboxamide were weighed out and dissolved in 8 parts of anhydrous ethanol. This solution was then added to the antifreeze protein solution at 4°C and 80 rpm while stirring at a rate of 2 mL / min. After complete addition, the mixture was stirred for 4 hours to obtain the inclusion solution. S3: After uniformly mixing the graft solution and inclusion solution, 2 parts of CaCl2 were added and homogenized at 12000 rpm for 10 minutes to obtain a cooling matrix. Measurements showed an average particle size of 235.9 nm and a PDI of 0.183.

[0031] Example 1: This example uses 10 parts of a cooling matrix and acrylamide- 13 A self-adjusting photocurable cooling hydrogel is provided, containing 18 parts of C3, 42 parts of glycerin, 5 parts of TPGDA, 0.05 parts of MBA, and 0.1 parts of TPO-L.

[0032] This embodiment further provides a method for producing a self-modulating photocurable cooling hydrogel, which specifically includes the following steps. Step 1: 18 parts acrylamide - 13 C3 was weighed out, dissolved in 25 parts of deionized water, 42 parts of glycerin were added, and the mixture was stirred at 400 rpm for 15 minutes to obtain an aqueous phase. The viscosity of the aqueous phase was measured to be 113.2 mPa·s. Step 2: Weigh out 5 parts TPGDA and 0.1 parts TPO-L, mix them while shielding from light, and stir at 200 rpm until clear to obtain the oil phase. Slowly stir the oil phase and aqueous phase together to mix uniformly and emulsify. Then add 10 parts cooling matrix and 0.05 parts MBA to obtain the pregel. Step 3: The pH of the pregel was adjusted to 4.72 with citrate buffer at pH 4.0, and dried in a vacuum drying chamber at 60°C until the water content reached 19.4% to obtain a self-regulating photocurable cooled hydrogel.

[0033] Example 2: This example uses 13 parts of a cooling matrix and acrylamide- 13 A self-adjusting photocurable cooling hydrogel is provided, containing 6 parts C326, 34 parts glycerin, 5 parts TPGDA, 0.1 parts MBA, and 0.2 parts TPO-L.

[0034] This embodiment further provides a method for producing a self-modulating photocurable cooling hydrogel, which specifically includes the following steps. Step 1: 26 parts of acrylamide - 13 C3 was weighed out, dissolved in 22 parts of deionized water, 34 parts of glycerin were added, and the mixture was stirred at 400 rpm for 15 minutes to obtain an aqueous phase. The viscosity of the aqueous phase was measured to be 134.8 mPa·s. Step 2: 5 parts TPGDA and 0.2 parts TPO-L were weighed out, mixed while shielded from light, and stirred at 200 rpm until clear to obtain the oil phase. The oil phase and aqueous phase were slowly stirred and uniformly mixed and emulsified, and then 13 parts cooling matrix and 0.1 parts MBA were added to obtain the pregel. Step 3: The pH of the pregel was adjusted to 4.54 with citrate buffer at pH 4.0, and dried in a vacuum drying chamber at 60°C until the water content reached 20.5% to obtain a self-regulating photocurable cooled hydrogel.

[0035] Example 3: This example uses 17 parts of a cooling matrix and acrylamide- 13A self-adjusting photocurable cooling hydrogel is provided, containing 3 parts C33, 27 parts glycerin, 5 parts TPGDA, 0.15 parts PEG4000, and 0.3 parts TPO-L.

[0036] This embodiment further provides a method for producing a self-modulating photocurable cooling hydrogel, which specifically includes the following steps. Step 1: 33 parts of acrylamide - 13 C3 was weighed out, dissolved in 18 parts deionized water, 27 parts glycerin was added, and the mixture was stirred at 400 rpm for 15 minutes to obtain an aqueous phase. The viscosity of the aqueous phase was measured to be 192.4 mPa·s. Step 2: Weigh out 5 parts TPGDA and 0.3 parts TPO-L, mix them while shielding from light, and stir at 200 rpm until clear to obtain the oil phase. Slowly stir the oil phase and aqueous phase together to mix uniformly and emulsify. Then add 17 parts cooling matrix and 0.15 parts PEG400 to obtain the pregel. Step 3: The pH of the pregel was adjusted to 4.54 with citrate buffer at pH 4.0, and dried in a vacuum drying chamber at 60°C until the water content reached 19.8% to obtain a self-regulating photocurable cooled hydrogel.

[0037] Example 4: This example uses 10 parts of a cooling matrix and acrylamide- 13 A self-adjusting photocurable cooling hydrogel is provided, containing 20 parts of C320, 40 parts of glycerin, 5 parts of TPGDA, 0.08 parts of PEG4000, and 0.2 parts of Irgacure 2959.

[0038] This embodiment further provides a method for producing a self-modulating photocurable cooling hydrogel, which specifically includes the following steps. Step 1: 20 parts acrylamide - 13 C3 was weighed out, dissolved in 25 parts of deionized water, 40 parts of glycerin were added, and the mixture was stirred at 400 rpm for 15 minutes to obtain an aqueous phase. The viscosity of the aqueous phase was measured to be 120.8 mPa·s. Step 2: Weigh out 5 parts TPGDA and 0.2 parts Irgacure 2959, mix them in the dark, and stir at 200 rpm until clear to obtain the oil phase. Slowly stir the oil phase and aqueous phase together to mix uniformly and emulsify. Then add 10 parts cooling matrix and 0.08 parts PEG400 to obtain the pregel. Step 3: The pH of the pregel was adjusted to 4.71 with citrate buffer at pH 4.0, and dried in a vacuum drying chamber at 60°C until the water content reached 21.4% to obtain a self-regulating photocurable cooled hydrogel.

[0039] Example 5: This example uses 10 parts of a cooling matrix and acrylamide- 13 A self-adjusting photocurable cooling hydrogel is provided, containing 20 parts of C320, 40 parts of glycerin, 5 parts of TPGDA, 0.08 parts of HAMA, and 0.2 parts of Irgacure 2959.

[0040] This embodiment further provides a method for producing a self-modulating photocurable cooling hydrogel, which specifically includes the following steps. Step 1: 20 parts acrylamide - 13 C3 was weighed out, dissolved in 25 parts of deionized water, 40 parts of glycerin were added, and the mixture was stirred at 400 rpm for 15 minutes to obtain an aqueous phase. The viscosity of the aqueous phase was measured to be 127.2 mPa·s. Step 2: Weigh out 5 parts TPGDA and 0.2 parts Irgacure 2959, mix them in the dark, and stir at 200 rpm until clear to obtain the oil phase. Slowly stir the oil phase and aqueous phase together to mix uniformly and emulsify. Then add 10 parts cooling matrix and 0.08 parts HAMA to obtain the pregel. Step 3: The pH of the pregel was adjusted to 4.66 with citrate buffer at pH 4.0, and dried in a vacuum drying chamber at 60°C until the water content reached 20.2% to obtain a self-regulating photocurable cooled hydrogel.

[0041] Example 6: This example uses 15 parts of a cooling matrix and acrylamide- 13A self-adjusting photocurable cooling hydrogel is provided, containing 325 parts of C3, 35 parts of glycerin, 5 parts of TPGDA, 0.08 parts of HAMA, and 0.2 parts of Irgacure 2959.

[0042] This embodiment further provides a method for producing a self-modulating photocurable cooling hydrogel, which specifically includes the following steps. Step 1: 25 parts acrylamide - 13 C3 was weighed out, dissolved in 20 parts of deionized water, 35 parts of glycerin were added, and the mixture was stirred at 400 rpm for 15 minutes to obtain an aqueous phase. The viscosity of the aqueous phase was measured to be 144.8 mPa·s. Step 2: Weigh out 5 parts TPGDA and 0.2 parts Irgacure 2959, mix them in the dark, and stir at 200 rpm until clear to obtain the oil phase. Slowly stir the oil phase and aqueous phase together to mix uniformly and emulsify. Then add 10 parts cooling matrix and 0.08 parts HAMA to obtain the pregel. Step 3: The pH of the pregel was adjusted to 4.81 with citrate buffer at pH 4.0, and dried in a vacuum drying chamber at 60°C until the water content reached 19.9% ​​to obtain a self-regulating photocurable cooled hydrogel.

[0043] Example 7: Use of hydrogel in cooling gel dressing A cooled hydrogel was prepared according to the material mixing ratio and manufacturing method in Example 4, using an adsorption mold production method. The mold was cleaned and dried, the prepared cooled hydrogel was poured into it, and then covered with a substrate. A wavelength of 365 nm and a power of 25 mW / cm² were used. 2 The material was cured under UV irradiation for 60 seconds, then press-molded to obtain a cooled gel pad. The contact surface between the base material and the hydrogel contained an adhesive.

[0044] Example 8: Use of hydrogel in in situ injection gel A cooling hydrogel was prepared according to the material mixing ratio and manufacturing method in Example 2, and injected into the lesion site of a subcutaneous tumor model mouse at 365 nm and 25 mW / cm². 2By in-situ photocuring molding for 60 seconds, the acrylamide in the cooled hydrogel was processed. 13 Metabolic tracing was performed using the C3 isotope.

[0045] Example 9: Use of hydrogel in drug-carrying gel dressings 0.64 parts of mopiroxacin were weighed out and dispersed in 1.36 parts of ethanol to obtain a drug solution. The drug solution, 0.04 parts of Tween 80, and 30 parts of the cooled hydrogel prepared in Example 3 were uniformly mixed and homogenized to obtain a drug-carrying gel. The drug-carrying gel was uniformly applied to a mold with a base material and exposed to light at a wavelength of 365 nm and a power of 25 mW / cm². 2 The gel dressing was cured under ultraviolet irradiation for 60 seconds, then press-molded to obtain a drug-carrying gel dressing.

[0046] The difference between Comparative Example 1 and Example 2 is that the hydrogel is produced by substituting glycerin with an equal mass of deionized water; the rest of the process is the same as in Example 1.

[0047] The difference between Comparative Example 2 and Example 2 is that a cooling matrix was not prepared, and the hydrogel was manufactured using an equal mass and equal concentration of N-ethyl-p-menthane-3-carboxamide solution.

[0048] Comparative Example 3 was a 30% acrylamide hydrogel containing 3 mg / mL of menthol.

[0049] Evaluation of temperature sensitivity threshold A DHR 3 rheometer was connected to a temperature control system to perform temperature scans, and the temperature dependence of the rheological properties of the hydrogels produced in Examples 1-6 and Comparative Examples 1-3 was evaluated. Temperature scans were performed at 25-40°C with a heating rate of 2°C / min. The point at which the storage modulus G dropped sharply was measured, the temperature point at which G decreased by 10% was recorded, and ΔG (difference between 25-32°C) was calculated. The results are shown in Table 1.

[0050] Evaluation of cooling effect After photocuring the cooled hydrogels produced in Examples 2, 4, 6 and Comparative Examples 1-3, the initial temperature was adjusted to 20°C, and the samples were incubated on the same 40°C constant temperature mat. The initial temperature and the temperature of the hydrogels after 5 minutes, 10 minutes, 30 minutes, 1 hour, 2 hours, and 4 hours of incubation were recorded using a temperature sensor, and the results are shown in Figure 1.

[0051] Evaluation of mechanical performance and injectability Figure 2 shows the results of measuring the compressive modulus and tensile strength of the cooled hydrogels produced in Examples 2, 4, and 6 and Comparative Examples 1-3 after photocuring using a texture analyzer. Figure 3 shows the results of evaluating the gel injectability after drawing 10 mL of the cooled hydrogel produced in Example 2 into a syringe.

[0052] Observation of microscopic morphology The cooled hydrogel produced in Example 4 was photocured, fixed to a sample plate using a conductive adhesive, gold plated using a sputtering apparatus, and the morphology of the self-regulating photocurable cooled hydrogel was evaluated using a scanning electron microscope. The results are shown in Figure 4.

[0053] Applications of dressings Figure 5 shows the results of evaluating and recording the appearance of the cooling gel dressing manufactured in Example 7.

[0054] Table 1 Evaluation of temperature sensitivity [Table 1]

[0055] The results in Table 1 show that the hydrogels produced in Examples 1-6 and Comparative Example 1 all have a certain temperature response threshold after photocuring. In particular, the hydrogels produced in Examples 3 and 4 had the lowest temperature threshold, while the hydrogels produced in Comparative Examples 2 and 3 lacked temperature responsiveness and storage modulus, making buffered heating impossible.

[0056] The results from the temperature-time curves in Figure 1 show that, compared to the hydrogels produced in Comparative Examples 1-3, the hydrogels produced in Examples 2, 4, and 6 showed slower heating up to 30 minutes after photocuring, the temperature stabilized at a threshold plateau for approximately 1.5 hours after 30 minutes, and continued to heat up after approximately 2 hours, clearly demonstrating that the addition of the cooling matrix is ​​important for the cooling effect of the hydrogel.

[0057] The results of the mechanical performance of the hydrogels in Figure 2 show that the hydrogels produced in Examples 2, 4, and 6 exhibited significantly higher compressive modulus and tensile strength after photocuring than all of the comparative examples. Among these, Examples 4 and 6 showed superior mechanical performance, demonstrating a certain level of structural stability and mechanical strength.

[0058] The gel injection experiment shown in Figure 3 demonstrates that the cooled hydrogel produced in Example 2 is suitable for injection and can be used for injection into tissues such as tumors, bones, and organs, as well as for in-situ hardening, enabling in-vivo metabolic tracing and in-vivo dressing molding.

[0059] The scanning electron microscope results in Figure 4 show that the cooled hydrogel produced in Example 4 has a large gel skeleton after photocuring, which is advantageous for enhancing mechanical properties. Furthermore, the large skeleton and small gel pores are advantageous for the sustained release of the cooling matrix, enabling long-term temperature control.

[0060] The external view of the cooled gel dressing in Figure 5 demonstrates good curability, moldability, and external application.

[0061] Although embodiments of the present invention have been shown and described, it will be obvious to those skilled in the art that various modifications, alterations, substitutions, and variations can be made to these embodiments without departing from the principles and spirit of the present invention. The scope of the present invention is defined by the appended claims and equivalents.

[0062] Although the present invention and its embodiments have been described above, this description is not limiting, and the accompanying drawings represent only one embodiment of the present invention, and actual applications are not limited thereto. In other words, any similar embodiments and examples of the technical means designed by a person skilled in the art, without departing from the spirit of the invention and without creativity, should all fall within the scope of the present invention.

Claims

1. A method for producing a self-regulating photocurable cooling hydrogel, Step 1 involves taking acrylamide-13C3, dissolving it, and then adding glycerin to obtain the aqueous phase. Step 2 involves mixing TPGDA and a photoinitiator to obtain an oil phase, then uniformly mixing the oil phase and the aqueous phase, and finally adding a cooling matrix and a crosslinking agent to obtain a pregel. The process includes step 3, which involves adjusting the pH of the pregel and drying it to obtain a self-regulating photocurable cooling hydrogel. The method for manufacturing the aforementioned cooling matrix is ​​as follows: Step S1 involves dissolving konjac glucomannan, then adding β-mannanase, hinokitiol, and NHS to obtain a graft solution. Step S2 involves dissolving the antifreeze protein to obtain an antifreeze protein solution, then dissolving N-ethyl-p-menthane-3-carboxamide and adding it to the antifreeze protein solution to obtain an inclusion complex. Graft solution, inclusion solution and CaCl ２ A method for producing a self-adjusting photocurable cooling hydrogel, characterized by comprising step S3 of mixing and homogenizing to obtain a cooling matrix.

2. The aforementioned antifreeze protein, N-ethyl-p-menthane-3-carboxamide, konjac glucomannan, hinokitiol, NHS, CaCl ２ A method for producing a self-regulating photocurable cooling hydrogel according to claim 1, characterized in that the mass ratio of the and β-mannanase is 15:1:22.5:4.7:0.3:0.5:0.

15.

3. The crosslinking agent is selected from one of MBA, PEG400, and HAMA. The method for producing a self-regulating photocurable cooling hydrogel according to claim 1, characterized in that the photoinitiator is selected from one of TPO-L and Irgacure 2959.

4. A method for producing a self-regulating photocurable cooling hydrogel according to claim 1, characterized in that the cooling hydrogel is used in the manufacture of drug-carrying gel dressings, cooling gel pads, cooling gel packs, cooling gel injection products, and gels for in situ injection.

5. The method for producing the cooling gel pad is characterized by comprising curing a cooling hydrogel with ultraviolet light in an adsorption mold, press molding it, and obtaining a cooling gel pad, as described in claim 4.

6. The drug-carrying gel dressing comprises a drug, tween 80, and a cooling hydrogel. A specific method for producing the drug-carrying gel dressing is a method for producing a self-regulating photocurable cooling hydrogel according to claim 4, characterized in that the method includes dispersing the drug to obtain a drug solution, uniformly mixing the drug solution, tween 80, and cooling hydrogel, then curing with ultraviolet light in a mold and press molding to obtain a drug-carrying gel dressing.

7. The wavelength of the UV curing process is 365 nm, and the light intensity is 25 mW / cm². ２ A method for producing a self-regulating photocurable cooled hydrogel according to claim 6, characterized in that...

Images