An antibacterial hydrogel dressing integrating constant temperature photothermal effect and controlled drug release function, and its preparation method and application

Abstract

The present application discloses an antibacterial hydrogel dressing with integrated constant temperature photothermal effect and controlled drug release function, as well as its preparation method and application, which belongs to the field of medical biomaterial technology. The antibacterial hydrogel dressing with integrated constant temperature photothermal effect and controlled drug release function provided by the present application includes: a dressing and an antibiotic drug compounded on the dressing; the dressing is woven from photothermal water gel fiber and thermosensitive hydrogel fiber; the photothermal water gel fiber is made of photothermal dye, proton donor and phase change material as the core layer and sodium alginate as the shell layer; the thermosensitive hydrogel fiber is made of N-isopropyl acrylamide, methylene bisacrylamide, phenyl-2,4,6-trimethylbenzoyl lithium phosphinate and sodium alginate. The hydrogel dressing prepared by the present application has an inherent temperature control mechanism, can release drugs on demand and in a concentrated manner, has excellent antibacterial effect, and has broad application prospects in the preparation of biomedical materials.

Description

Technical Field

[0001] The present application belongs to the technical field of medical biomaterials, and in particular relates to an antibacterial hydrogel dressing integrating a constant temperature photothermal effect and a controlled drug release function, as well as a preparation method and application thereof. Background Art

[0002] Photothermal (PTT) therapy is becoming increasingly important in combating multidrug-resistant (MDR) bacteria. The use of photosensitizers, which absorb light of specific wavelengths and rapidly release heat, damages bacterial cell membranes, leading to bacterial death. PTT can selectively target the site of infection, significantly reducing bacterial load within a short period of time and achieving rapid results. Currently, PTT is often used in combination with traditional antibiotics to further enhance its therapeutic effects, offering advantages such as enhanced antibacterial efficacy, shortened treatment time, and enhanced targeting.

[0003] However, existing materials have the following problems: First, they lack inherent temperature control mechanisms, which can easily damage or burn surrounding healthy tissue, hindering patient recovery; second, the combined drug delivery system can cause unstable and uneven drug release. Therefore, the development of new composite materials is needed to promote the development of biomedical materials. Summary of the Invention

[0004] The present application discloses an antibacterial hydrogel dressing that integrates a constant temperature photothermal effect and a controlled drug release function, as well as a preparation method and application thereof, aiming to solve the technical problems of existing antibacterial hydrogel dressings such as lack of inherent temperature control, unstable and uneven drug release.

[0005] In order to achieve the above objectives, the technical solution of this application is:

[0006] The first aspect of the present application provides an antibacterial hydrogel dressing integrating a constant temperature photothermal effect and a controlled drug release function, comprising: a dressing and an antibiotic drug compounded on the dressing;

[0007] The dressing is woven from photothermal hydrogel fibers and thermosensitive hydrogel fibers;

[0008] The photothermal water gel fiber is made of a photothermal dye, a proton donor and a phase change material as a core layer and sodium alginate as a shell layer;

[0009] The temperature-sensitive hydrogel fiber is made of N-isopropyl acrylamide, methylene bisacrylamide, lithium phenyl-2,4,6-trimethylbenzoyl phosphinate and sodium alginate.

[0010] In combination with the first aspect, preferably, the antibiotic drug is one or more of norfloxacin, ampicillin, and erythromycin.

[0011] In combination with the first aspect, preferably, the photothermal dye is spironolactone;

[0012] The proton donor is bisphenol A;

[0013] The phase change material is one or more of myristic acid, lauric acid, palmitic acid, and stearic acid.

[0014] In combination with the first aspect, preferably, the content of N-isopropylacrylamide is 5.6-22.6 wt %;

[0015] The content of the methylene bisacrylamide is 0.15-0.6 wt %.

[0016] In combination with the first aspect, preferably, the content of sodium alginate is 1-3 wt%;

[0017] The content of the lithium phenyl-2,4,6-trimethylbenzoylphosphinate is 0.01-0.1 wt %.

[0018] The second aspect of the present application provides a method for preparing the antibacterial hydrogel dressing integrating the constant temperature photothermal effect and the controlled drug release function as described in the first aspect, the preparation method comprising:

[0019] The photothermal dye, proton donor and phase change material are melt-mixed to form the core layer material, and sodium alginate solution is used as the shell layer material. Through a wet spinning process, a photothermal water gel fiber with a core-shell structure is obtained.

[0020] N-isopropylacrylamide, methylenebisacrylamide, lithium phenyl-2,4,6-trimethylbenzoylphosphinate and sodium alginate were mixed and subjected to a wet spinning process to obtain thermosensitive hydrogel fibers.

[0021] Weaving the photothermal hydrogel fibers and the thermosensitive hydrogel fibers to form a dressing;

[0022] The dressing is immersed in an antibiotic drug solution to obtain the antibacterial hydrogel dressing with integrated constant temperature photothermal effect and controlled drug release function.

[0023] In combination with the second aspect, preferably, the solution concentration of the antibiotic drug is 0.1-1 mg / mL.

[0024] In combination with the second aspect, preferably, the photothermal dye, proton donor and phase change material are melt-mixed to form the core layer material, and sodium alginate is used as the shell layer material. During the wet spinning process, the advancing speed of the core layer is 5-10 mm / hr, the advancing speed of the shell layer is 30-40 mm / hr, and the collection speed is 5-20 m / min.

[0025] In combination with the second aspect, preferably, the N-isopropylacrylamide, methylenebisacrylamide, lithium phenyl-2,4,6-trimethylbenzoylphosphinate and sodium alginate are mixed and subjected to a wet spinning process at a propulsion speed of 30-40 mm / hr and a collection speed of 5-20 m / min.

[0026] The third aspect of the present application provides the use of the antibacterial hydrogel dressing with integrated constant temperature photothermal effect and controlled drug release function described in the first aspect, or the antibacterial hydrogel dressing with integrated constant temperature photothermal effect and controlled drug release function prepared by the preparation method described in the second aspect in the preparation of biomedical materials.

[0027] Compared with the prior art, the advantages or beneficial effects of the embodiments of the present application include at least:

[0028] The antibacterial hydrogel dressing with integrated constant temperature photothermal effect and controlled drug release function provided by the present application is achieved by compounding antibiotic drugs on a dressing made of photothermal hydrogel fibers and thermosensitive hydrogel fibers; on the one hand, under the irradiation of near-infrared light, the photothermal fibers can generate heat to kill bacteria and heat the adjacent thermosensitive fibers at the same time, and the thermosensitive fibers heat up and shrink to release drugs on demand and in a concentrated manner; on the other hand, under the irradiation of near-infrared light, the photothermal fibers can generate heat to cause the phase change material to melt, the proton donor to detach, the photothermal dye to transform, no longer absorb near-infrared light, and the heat generation process to be shut down, so that the temperature of the hydrogel dressing reaches a dynamic equilibrium and will not cause thermal damage to the skin tissue; thirdly, through the photothermal effect and antibiotic drugs, the antibacterial effect is enhanced and the risk of drug resistance is reduced. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] To more clearly illustrate the technical solutions of the embodiments of this application, the following briefly introduces the drawings required for describing the embodiments. Obviously, the drawings described below are only some of the embodiments described in this application. For those skilled in the art, other drawings can be derived from these drawings without inventive effort.

[0030] Figure 1 Schematic diagram of the preparation process of the antibacterial hydrogel dressing with integrated constant temperature photothermal effect and controlled drug release function provided in an embodiment of the present application;

[0031] Figure 2 Provided in this application embodiment is A1-light thermal gel fiber F sp and A2-photothermal gel fiber F p Temperature rise under NIR irradiation;

[0032] Figure 3 The length change rate of the thermosensitive hydrogel fibers with different raw material contents provided in Example 3 of the present application in a 50°C water bath;

[0033] Figure 4 The temperature change of the antibacterial hydrogel dressing A4 provided in the embodiment of the present application, which integrates constant temperature photothermal effect and controlled drug release function, under NIR irradiation;

[0034] Figure 5 The embodiment of the present application provides A3-temperature sensitive hydrogel fiber F ts Temperature changes of the woven dressing under NIR irradiation;

[0035] Figure 6 The drug release of the antibacterial hydrogel dressing A4 provided in the embodiment of the present application, which integrates a constant temperature photothermal effect and a controlled drug release function;

[0036] Figure 7 A4-Antimicrobial effect characterization diagram of the antimicrobial hydrogel dressing with integrated constant temperature photothermal effect and controlled drug release function provided in the examples of this application;

[0037] Figure 8 This is a diagram showing the therapeutic effect of the antibacterial hydrogel dressing A4 provided in an embodiment of the present application, which integrates constant temperature photothermal effect and controlled drug release function, on a mouse infected wound model. DETAILED DESCRIPTION

[0038] The following will be combined with the accompanying drawings in the embodiments of this application to clearly and completely describe the technical solutions in the embodiments of this application. Obviously, the described embodiments are part of the embodiments of this application, not all of the embodiments. Based on the embodiments in this application, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of this application.

[0039] In the following description of this embodiment, the term "and / or" is used to describe the association relationship between associated objects, indicating that three possible relationships exist. For example, A and / or B can represent: A exists alone, B exists alone, and both A and B exist. A and B can be singular or plural. The character " / " generally indicates that the associated objects are in an "or" relationship.

[0040] In the following description of this embodiment, the term "at least one" refers to one or more, and "plurality" refers to two or more. "At least one of the following" or similar expressions refers to any combination of these items, including any combination of single items or plural items. For example, "at least one of a, b, or c", or "at least one of a, b, and c" can all represent: a, b, c, ab (i.e., a and b), ac, bc, or abc, where a, b, and c can be single or multiple.

[0041] Those skilled in the art should understand that in the following description of the embodiments of the present application, the order of serial numbers does not mean the order of execution, some or all of the steps can be executed in parallel or sequentially, and the execution order of each process should be determined by its function and internal logic, and should not constitute any limitation on the implementation process of the embodiments of the present application.

[0042] The terms used in the embodiments of the present application are only for the purpose of describing specific embodiments and are not intended to limit the present application. The singular forms "a", "an" and "the" used in the embodiments of the present application and the appended claims are also intended to include plural forms unless the context clearly indicates otherwise.

[0043] It will be understood by those skilled in the art that the numerical ranges in the examples of this application are to be understood as also specifically disclosing each intermediate value between the upper and lower limits of the ranges. Each smaller range between any stated value and the intermediate value in the stated range, as well as any other stated value or intermediate value in the stated range, is also encompassed by this application. The upper and lower limits of these smaller ranges may independently be included or excluded in the range.

[0044] Unless otherwise indicated, the technical / scientific terms used herein have the same meanings as those generally understood by those skilled in the art described in this application. Although this application describes only preferred methods and materials, any methods and materials similar or equivalent to those described herein may also be used in the embodiments or test examples of this application. All documents mentioned in this specification are generally incorporated by reference to disclose and describe the methods and / or materials related to the documents. In the event of any conflict with any incorporated document, the content of this application shall prevail.

[0045] It should be noted that all raw materials and reagents in the examples of the present application were purchased on the market or prepared according to conventional methods well known to those skilled in the art.

[0046] In a first aspect, an embodiment of the present application provides an antibacterial hydrogel dressing integrating a constant temperature photothermal effect and a controlled drug release function, comprising: a dressing and an antibiotic drug compounded on the dressing;

[0047] The dressing is woven from photothermal hydrogel fibers and thermosensitive hydrogel fibers;

[0048] The photothermal water gel fiber is made of a photothermal dye, a proton donor and a phase change material as a core layer and sodium alginate as a shell layer;

[0049] The raw materials for preparing the temperature-sensitive hydrogel fiber are N-isopropyl acrylamide, methylene bisacrylamide, lithium phenyl-2,4,6-trimethylbenzoyl phosphinate and sodium alginate.

[0050] Among them, on the one hand, under the irradiation of near-infrared light, the photothermal fiber can generate heat to kill bacteria and heat the adjacent thermosensitive fiber at the same time. The thermosensitive fiber heats up and contracts to release drugs on demand and in a concentrated manner; on the other hand, under the irradiation of near-infrared light, the photothermal fiber can generate heat to cause the phase change material to melt, the proton donor to detach, the photothermal dye to transform, no longer absorb near-infrared light, and the heat generation process to be shut down, so that the temperature of the hydrogel reaches a dynamic balance and will not cause thermal damage to the skin tissue; thirdly, through the photothermal effect and antibiotic drugs, the antibacterial effect is enhanced and the risk of drug resistance is reduced.

[0051] In the examples of the present application, the antibiotic is preferably one or more of norfloxacin, ampicillin, and erythromycin, preferably at a concentration of 0.1-1 mg / mL. These antibiotics all have a high-spectrum antibacterial activity and can synergize with the photothermal effect to impart excellent antibacterial activity to the hydrogel dressing, reducing the risk of drug resistance.

[0052] In an embodiment of the present application, the photothermal dye is preferably spironolactone; the proton donor is preferably bisphenol A; and the phase change material is preferably one or more of myristic acid, lauric acid, palmitic acid, and stearic acid. Among them, in the solid phase change material, spironolactone receives protons from bisphenol A to form a near-infrared light absorbing colored state. Under near-infrared light irradiation, the photothermal effect causes the system temperature to rise rapidly and causes the myristic acid to melt. In the liquid phase change material, the protons are detached, spironolactone is converted to a colorless state, no longer absorbs near-infrared light, and the heat generation process is turned off. Therefore, the system temperature of the dressing is in dynamic equilibrium near the melting point of myristic acid (≈50°C), and will not cause thermal damage to the skin tissue.

[0053] In the embodiment of the present application, the content of N-isopropylacrylamide is preferably 5.6-22.6 wt %; the content of methylenebisacrylamide is preferably 0.15-0.6 wt %; the content of lithium phenyl-2,4,6-trimethylbenzoylphosphinate is preferably 0.01-0.1 wt %; and the content of sodium alginate is preferably 1-3 wt %. In particular, N-isopropylacrylamide is a reactive monomer, methylenebisacrylamide is a cross-linking agent, lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) is an initiator, and sodium alginate is a fixative. When the content of N-isopropylacrylamide is less than 5.6 wt %, the pre-liquid cannot form a hydrogel fiber. When the content of N-isopropylacrylamide is greater than 22.6 wt %, the pre-liquid cannot be completely dissolved in water, and the resulting hydrogel fiber is uneven. By changing the proportion of thermosensitive hydrogel fiber components, its response to temperature is improved. When the content of monomer N-isopropyl acrylamide, crosslinker methylene bisacrylamide, and fixative sodium alginate are 22.6wt%, 0.15wt%, and 1wt%, respectively, the change rate of the thermosensitive fiber length at 50°C reaches 30%.

[0054] It should be noted that the present application uses photothermal fibers to generate heat under near-infrared light irradiation to heat the thermosensitive hydrogel fibers. Thermosensitive hydrogel fibers exhibit significant phase change behavior near the critical temperature (approximately 32°C), absorbing water and expanding to form a hydrated state at low temperatures, while dehydration and shrinkage occur at high temperatures. This characteristic causes them to exhibit reversible volume changes when the temperature changes. Due to its thermosensitivity, poly (N-isopropylacrylamide) can be used as a drug carrier to regulate the release rate of drugs through temperature changes. Compared with heating using the temperature of the human skin, light irradiation-induced heating based on photothermal materials is faster and more controllable.

[0055] In a second aspect, the present invention further provides a method for preparing the antibacterial hydrogel dressing having an integrated constant temperature photothermal effect and a controlled drug release function as described in the first aspect, the method comprising:

[0056] The photothermal dye, proton donor and phase change material are melt-mixed to form the core layer material, and sodium alginate solution is used as the shell layer material. Through a wet spinning process, a photothermal water gel fiber with a core-shell structure is obtained.

[0057] N-isopropylacrylamide, methylenebisacrylamide, lithium phenyl-2,4,6-trimethylbenzoylphosphinate and sodium alginate were mixed and subjected to a wet spinning process to obtain thermosensitive hydrogel fibers.

[0058] Weaving the photothermal hydrogel fibers and the thermosensitive hydrogel fibers to form a dressing;

[0059] The dressing is immersed in an antibiotic drug solution to obtain the antibacterial hydrogel dressing with integrated constant temperature photothermal effect and controlled drug release function.

[0060] In the embodiment of the present application, the photothermal dye, proton donor, and phase change material are melt-mixed to form the core layer material, and sodium alginate is used as the shell layer material. During the wet spinning process, the core layer advances at a speed of 5-10 mm / hr, the shell layer advances at a speed of 30-40 mm / hr, and the collection speed is 5-20 m / min. By controlling the process conditions of the shell and core layers during wet spinning, the flow rate of the shell layer spinning solution is greater than the flow rate of the core layer spinning solution, ensuring that the shell layer can completely encapsulate the core layer solution, forming a hydrogel fiber with a coaxial core-shell structure.

[0061] In the embodiments of the present application, the mixture of N-isopropylacrylamide, methylenebisacrylamide, lithium phenyl-2,4,6-trimethylbenzoylphosphinate, and sodium alginate is wet-spun at a speed of preferably 30-40 mm / hr and a collection speed of preferably 5-20 m / min. By controlling the wet-spinning process conditions, a uniform, stable, and water-temperature-sensitive gel fiber with excellent mechanical properties can be formed.

[0062] It should be noted that the present application does not impose any particular limitation on the weaving method used to weave the photothermal hydrogel fibers and the thermosensitive hydrogel fibers into a dressing, and can preferably be plain weave, twill weave, satin weave, and axial fiber weave. The present application does not impose any particular limitation on the weaving method used, and all methods are within the scope of protection of the present application.

[0063] The third aspect of this application provides the use of the antimicrobial hydrogel dressing with integrated constant-temperature photothermal effect and controlled drug release described in the first aspect, or the antimicrobial hydrogel dressing with integrated constant-temperature photothermal effect and controlled drug release prepared by the preparation method described in the second aspect, in the preparation of functional materials. Based on the inherent temperature control mechanism of the hydrogel dressing prepared above, which enables on-demand, centralized drug release and excellent antimicrobial efficacy, it has broad application prospects in the preparation of biomedical materials.

[0064] The technical solution of the present application will be further described below in conjunction with specific embodiments.

[0065] Example 1

[0066] This embodiment provides A1-photothermal water gel fiber F sp The preparation method specifically comprises:

[0067] 10 mg of spironolactone, 20 mg of bisphenol A, and 1 g of myristic acid were melted and mixed at 50°C to serve as the core material. A 0.04 g / mL aqueous solution of sodium alginate was prepared as the shell material. The two materials were injected into a 2 wt% calcium chloride solution in a coagulation bath through an 18 / 22 coaxial spinning needle at a propulsion speed of 10 mm / hr for the core and 40 mm / hr for the shell. The collection speed was 10 m / min, yielding A1-photothermal hydrogel fiber F with a constant temperature mechanism. sp .

[0068] Example 2

[0069] This embodiment provides A2-photothermal gel fiber F p The preparation method specifically comprises:

[0070] 10 mg of indocyanine green, 20 mg of bisphenol A, and 1 g of myristic acid were melted and mixed at 50°C to serve as the core material. A 0.04 g / mL aqueous solution of sodium alginate was prepared as the shell material. The two materials were injected into a 2 wt% calcium chloride solution in a coagulation bath through an 18 / 22 coaxial spinning needle. The propulsion speed was 10 mm / hr for the core layer and 40 mm / hr for the shell layer. The collection speed was 10 m / min. A2-photothermal hydrogel fiber F without a constant temperature mechanism was obtained. p .

[0071] In this embodiment, the type of photothermal dye, indocyanine green, is changed to obtain a photothermal hydrogel fiber F lacking a constant temperature mechanism. p .according to Figure 2 As shown, the spironolactone-based photothermal fiber F prepared in Example 1 sp , can be stably balanced at around 50°C under NIR irradiation; the photothermal fiber F based on indocyanine green prepared in Example 2 p , under NIR irradiation, the temperature will continue to rise to above 150℃ until it burns out.

[0072] Example 3

[0073] This embodiment provides A3-temperature sensitive hydrogel fiber F ts The preparation method specifically comprises:

[0074] 22.6 wt% monomer N-isopropyl acrylamide, 0.15 wt% crosslinker methylene bisacrylamide, 0.01 wt% initiator LAP, 1 wt% fixative sodium alginate were dissolved in deionized water and stirred until completely dissolved. The dissolved pre-liquid was injected into a 2 wt% calcium chloride solution in a coagulation bath at a propulsion speed of 40 mm / hr and a collection speed of 10 m / min. The pre-liquid was irradiated with 10 W UV for 20 min to obtain A3-thermosensitive hydrogel fiber F. ts .

[0075] The present invention obtains corresponding thermosensitive hydrogel fibers by changing the amount of monomer N-isopropylacrylamide added, that is, the monomer N-isopropylacrylamide is 5.6wt%, 11.2wt%, and 16.8wt%, respectively, and measures the change rate of fiber length. The obtained thermosensitive fibers are immersed in a 50℃ water bath for 1 minute, and the change rate of fiber length is measured to evaluate the degree of response to temperature. Figure 3 As shown in a), the change rate of fiber length increases with the increase of N-isopropylacrylamide content. When the content of N-isopropylacrylamide is 22.6wt%, the change rate of fiber length is about 30%.

[0076] The present invention obtains corresponding thermosensitive hydrogel fibers by changing the amount of crosslinking agent methylene bisacrylamide added, that is, the crosslinking agent methylene bisacrylamide is 0.3wt%, 0.45wt%, and 0.6wt%, respectively, and measures the change rate of fiber length. The obtained thermosensitive fibers are immersed in a 50℃ water bath for 1 minute, and the change rate of fiber length is measured to evaluate the degree of response to temperature. Figure 3 As shown in FIG. 2 , the change rate of the fiber length decreases with the increase of the methylene bisacrylamide content. When the content of methylene bisacrylamide is 0.15 wt %, the change rate of the fiber length is about 30%.

[0077] The present invention obtains corresponding thermosensitive hydrogel fibers by changing the amount of sodium alginate as a fixative, that is, 2wt% and 3wt% of the fixative sodium alginate respectively, and measures the change rate of the fiber length. The obtained thermosensitive fibers are immersed in a 50°C water bath for 1 minute, and the change rate of the fiber length is measured to evaluate the degree of response to temperature. Figure 3 As shown in Figure c), the change rate of fiber length decreases with the increase of sodium alginate content. When the sodium alginate content is 1 wt%, the change rate of fiber length is about 30%.

[0078] Example 4

[0079] This embodiment provides a method for preparing an antibacterial hydrogel dressing A4-integrated constant temperature photothermal effect and controlled drug release function, specifically comprising:

[0080] S101: The A1-photothermal gel fiber F prepared in Example 1 sp A3-thermosensitive hydrogel fiber F prepared in Example 3 ts The two hydrogel fibers are plain woven to form a dressing;

[0081] S102: The hydrogel dressing is loaded with antibiotic drugs by soaking the above dressing in 1 mg / mL norfloxacin solution to obtain A4-antibacterial hydrogel dressing with integrated constant temperature photothermal effect and controlled drug release function.

[0082] according to Figure 4 It can be seen that in order to verify the temperature change of the prepared hydrogel dressing under NIR irradiation, the A4-antibacterial hydrogel dressing with integrated constant temperature photothermal effect and controlled drug release function can be quickly heated up and stabilized at 50°C within two minutes under NIR irradiation.

[0083] according to Figure 5 It can be seen that only the A3-thermosensitive hydrogel fiber F prepared in Example 3 ts The temperature change of the woven dressing under NIR irradiation. sp Under these circumstances, the hydrogel dressing cannot heat up through the photothermal effect and always remains stable at room temperature.

[0084] In order to verify that the antibacterial hydrogel dressing A4-integrated constant temperature photothermal effect and controlled drug release function prepared in the embodiment of the present application has the ability to control drug release, the drug release of the hydrogel dressing provided in the embodiment of the present application was characterized, and the results are as follows. Figure 6 shown.

[0085] according to Figure 6 It can be seen that without NIR irradiation, the drug release rate of the hydrogel dressing is only about 20% at 5 minutes. sp Fiber generates heat to heat Fts Fiber, F ts The fibers undergo phase change and shrinkage, achieving concentrated release of the drug, with a release rate of up to 80% in 5 minutes.

[0086] In order to verify the antibacterial properties of the prepared hydrogel dressing, the four groups of samples in Examples 1-4 and a blank group were subjected to antibacterial experiments. The five groups of samples were: (I) blank control group; (II) A3-thermosensitive hydrogel fiber F ts Woven hydrogel dressing; (III) A3-thermosensitive hydrogel fiber F ts Drug-loaded hydrogel dressing prepared by weaving and soaking; (IV) A1-photothermal hydrogel fiber F sp and A3-thermosensitive hydrogel fiber F ts Two types of hydrogel fibers were woven into a hydrogel dressing; (V) A4-Antibacterial hydrogel dressing with integrated constant temperature photothermal effect and controlled drug release function. Each group of samples was mixed with 500 μL bacterial solution (OD 600 = 0.5) first incubated at room temperature for 10 min, then irradiated with NIR for 10 min. After irradiation, the whole plate was incubated at room temperature for 2 h. The bacterial solution was diluted 10 4 After culturing at 37℃ for 24 hours, spread the plate on a conventional plate and observe the number of colonies in each group. Figure 7 This is a characterization diagram of the antibacterial effect of each group of samples on methicillin-resistant Staphylococcus aureus.

[0087] according to Figure 7 It can be seen that Group I and Group II have almost no bactericidal ability; Group III is incubated at room temperature, the hydrogel does not change phase, the antibiotic release is limited, and the killing effect is limited; Group IV can kill some bacteria instantly by photothermal effect alone after NIR irradiation; Group V has almost complete release of antibiotics and combined with photothermal sterilization, and the killing effect is the most obvious.

[0088] In order to verify the application of the A4-integrated constant temperature photothermal effect and controlled drug release antibacterial hydrogel dressing prepared in the embodiment of this application in wound dressing materials, a mouse skin wound model was constructed for verification. Three groups of samples were used for antibacterial experiments, namely: (I) blank control group; (II) A2-photothermal hydrogel fiber F p and A3-thermosensitive hydrogel fiber F ts Drug-loaded hydrogel dressing prepared by weaving and soaking; (III) A4-Antibacterial hydrogel dressing integrating constant temperature photothermal effect and controlled drug release function. A circular wound with a diameter of 8 mm was created on the right back of the mouse, and then the wound was infected with MRSA (OD 600=0.5, 50 μL). The wound of each mouse was then bandaged with gauze, and the day of bacterial inoculation was designated as Day 0. 24 hours after inoculation, the infected mice were randomly divided into three groups, and different samples were added to the wound for different treatments. During the near-infrared irradiation process, the temperature was dynamically monitored using an infrared camera. In addition, the healing process of the infected site was recorded using a digital camera throughout the treatment window (10 days). Figure 8 The diagram shows the treatment effect of each group of samples.

[0089] according to Figure 8 It can be seen that, among them, a) is a real-time diagram of the temperature changes of the three groups of samples at different times; b) is a curve diagram of the temperature changes of the three groups of samples at different times; c) is a diagram of the healing process of the infected parts of the three groups of samples after 10 days. As shown in the figure, during the treatment of Group II, the photothermal fiber based on indocyanine green did not have a temperature control mechanism, the temperature rose significantly, and the uncontrolled heat generation caused damage to the skin, and there were obvious burn marks on the wound. However, the A4-antibacterial hydrogel dressing with integrated constant temperature photothermal effect and controlled drug release function (Group III) reached a dynamic equilibrium at about 50°C due to its inherent temperature control mechanism. The synergistic antibacterial effect of the intelligent photothermal effect and antibiotic drugs led to good wound recovery.

[0090] Therefore, the antibacterial hydrogel dressing provided by this application integrates a constant temperature photothermal effect and a controlled drug release function. The photothermal dye, proton donor, and phase change material are used as the core layer, and sodium alginate is used as the shell layer to make a photothermal hydrogel fiber with a core-shell structure; N-isopropyl acrylamide, methylene bisacrylamide, phenyl-2,4,6-trimethylbenzoyl lithium phosphinate, and sodium alginate are used to make a temperature-sensitive hydrogel fiber; the two fibers are woven into a dressing and compounded with antibiotic drugs to obtain a hydrogel dressing. The hydrogel dressing prepared by this application has an inherent temperature control mechanism, can release drugs on demand and in a concentrated manner, and has excellent antibacterial effects. It has broad application prospects in the preparation of biomedical materials.

[0091] The various embodiments in this specification are described in a progressive manner. The same or similar parts between the various embodiments can be referenced to each other, and each embodiment focuses on the differences from other embodiments.

[0092] The above embodiments are only used to illustrate the technical solutions of the present application, rather than to limit the present application. Although the present application has been described in detail with reference to the aforementioned embodiments, a person skilled in the art should understand that the technical solutions described in the aforementioned embodiments can still be modified, or some or all of the technical features therein can be replaced by equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the present application.

Claims

1. An antibacterial hydrogel dressing integrating constant temperature photothermal effect and controlled drug release function, characterized in that: include: A dressing and an antibiotic drug compounded on the dressing; The dressing is woven from photothermal hydrogel fibers and thermosensitive hydrogel fibers; The photothermal water gel fiber is made of a photothermal dye, a proton donor and a phase change material as a core layer and sodium alginate as a shell layer; The temperature-sensitive hydrogel fiber is made of N-isopropyl acrylamide, methylene bisacrylamide, lithium phenyl-2,4,6-trimethylbenzoyl phosphinate and sodium alginate; The photothermal dye is spironolactone; The proton donor is bisphenol A; The phase change material is one or more of myristic acid, lauric acid, palmitic acid, and stearic acid.

2. The antibacterial hydrogel dressing integrating constant temperature photothermal effect and controlled drug release function according to claim 1, characterized in that: The antibiotic drug is one or more of norfloxacin, ampicillin and erythromycin.

3. The antibacterial hydrogel dressing integrating constant temperature photothermal effect and controlled drug release function according to claim 1, characterized in that: The content of N-isopropylacrylamide is 5.6-22.6 wt %; The content of the methylene bisacrylamide is 0.15-0.6 wt %.

4. The antibacterial hydrogel dressing integrating constant temperature photothermal effect and controlled drug release function according to claim 1, characterized in that: The content of sodium alginate in the thermosensitive hydrogel fiber is 1-3 wt %; The content of the lithium phenyl-2,4,6-trimethylbenzoylphosphinate is 0.01-0.1 wt %.

5. A method for preparing an antibacterial hydrogel dressing integrating constant temperature photothermal effect and controlled drug release function according to any one of claims 1 to 4, characterized in that: The preparation method comprises: The photothermal dye, proton donor and phase change material are melt-mixed to form the core layer material, and sodium alginate solution is used as the shell layer material. Through a wet spinning process, a photothermal water gel fiber with a core-shell structure is obtained. N-isopropylacrylamide, methylenebisacrylamide, lithium phenyl-2,4,6-trimethylbenzoylphosphinate and sodium alginate were mixed and subjected to a wet spinning process to obtain thermosensitive hydrogel fibers. Weaving the photothermal hydrogel fibers and the thermosensitive hydrogel fibers to form a dressing; The dressing is immersed in an antibiotic drug solution to obtain the antibacterial hydrogel dressing with integrated constant temperature photothermal effect and controlled drug release function.

6. The method for preparing the antibacterial hydrogel dressing integrating constant temperature photothermal effect and controlled drug release function according to claim 5, characterized in that: The solution concentration of the antibiotic drug is 0.1-1 mg / mL.

7. The method for preparing the antibacterial hydrogel dressing integrating constant temperature photothermal effect and controlled drug release function according to claim 5, characterized in that: The photothermal dye, proton donor and phase change material are melt-mixed to form the core layer material, and sodium alginate is used as the shell layer material. During the wet spinning process, the core layer advances at a speed of 5-10 mm / hr, the shell layer advances at a speed of 30-40 mm / hr, and the collection speed is 5-20 m / min.

8. The method for preparing the antibacterial hydrogel dressing integrating constant temperature photothermal effect and controlled drug release function according to claim 5, characterized in that: The N-isopropylacrylamide, methylenebisacrylamide, lithium phenyl-2,4,6-trimethylbenzoylphosphinate and sodium alginate are mixed and subjected to a wet spinning process at a propulsion speed of 30-40 mm / hr and a collection speed of 5-20 m / min.

9. Use of an antibacterial hydrogel dressing with integrated constant temperature photothermal effect and controlled drug release function as described in any one of claims 1 to 4, or an antibacterial hydrogel dressing with integrated constant temperature photothermal effect and controlled drug release function prepared by the preparation method as described in any one of claims 5 to 8 in the preparation of biomedical materials.

Images