A visual double network hydrogel and its preparation method and application

Abstract

The present invention provides a visualized double network hydrogel and its preparation method and application, which relate to the technical field of biomedical materials. In the method, a modified anionic polyelectrolyte, carboxymethyl chitosan and a crosslinking agent are mixed and dissolved in deionized water, and then an initiator is added to obtain a prepolymer solution, wherein the crosslinking agent and the modified anionic polyelectrolyte / carboxymethyl chitosan undergo a crosslinking reaction to form a reactant with a covalent crosslinking network, and after acetic acid fumigation, the amino groups in the carboxymethyl chitosan chain segments are protonated, and then rely on electrostatic interaction forces to combine with the carboxyl groups in the modified anionic polyelectrolyte chain segments to form a polyelectrolyte network, and finally obtain a hydrogel with a double network structure. The mechanical properties of the hydrogel prepared by the present invention are greatly improved, and it has a high light transmittance. When used as a dressing, the healing of the wound can be observed through the dressing without uncovering the dressing.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedical materials, and in particular to a visualized double-network hydrogel and a preparation method and application thereof. Background Art

[0002] In the prior art, there are two main types of wound dressings:

[0003] 1. Traditional dressings, such as dry gauze and oil gauze; however, these traditional dressings only cover the injury and absorb wound exudate, and the protection they provide is limited;

[0004] 2. New dressings, such as foam dressings, hydrogel dressings and silver ion dressings; in addition to the functions of traditional dressings, this new dressing can also prevent bacterial invasion to reduce wound infection. It also allows gas exchange and maintains a moist environment, which is beneficial to protecting new granulation tissue and promoting wound healing.

[0005] The most representative hydrogel dressing is polysaccharide-based polyelectrolyte hydrogel, which is a polyelectrolyte network composed of natural polysaccharides (or artificial synthesis). Due to the presence of a large number of active functional groups on its sugar chain, such as amino, amide, carboxyl and hydroxyl groups, and the existence of electrostatic interactions, it has good biocompatibility, liquid absorption and environmental sensitivity. As an excellent carrier for drug release, hydrogel has good permeability to low molecular weight drug solutes, which also gives it the function of a drug delivery system. Therefore, polysaccharide-based polyelectrolyte hydrogel is widely used in the field of wound repair as a wound dressing.

[0006] However, since polysaccharide-based polyelectrolyte hydrogels are formed by electrostatic interactions between different functional groups of different components, and electrostatic interactions cause uneven distribution of components in the hydrogel, their mechanical properties and light transmittance are poor, making them easy to break, and when used as dressings, it is difficult to visually observe the healing of the wound through the dressing.

[0007] There is currently no effective technical solution to the above problems. Summary of the invention

[0008] The purpose of the present invention is to provide a visualized double-network hydrogel and its preparation method and application, which greatly improves the mechanical properties of traditional hydrogel dressings and also has high light transmittance. When used as a dressing, the healing of the wound can be observed directly through the dressing.

[0009] In a first aspect, the present invention provides a method for preparing a visualized double network hydrogel, comprising the following steps:

[0010] S1. The modified anionic polyelectrolyte, carboxymethyl chitosan and crosslinking agent are mixed and dissolved in deionized water, and then an initiator is added to obtain a prepolymer solution;

[0011] S2. The prepolymer solution is vacuumed to remove residual air in the solution;

[0012] S3. The prepolymer solution after vacuum treatment is sealed and placed under a preset temperature condition to react for a first preset time to obtain a reactant;

[0013] S4. placing the reactants in an acetic acid atmosphere for fumigation for a second preset time to obtain a hydrogel dressing.

[0014] The method for preparing a visualized double-network hydrogel of the present invention introduces a covalent cross-linking network on the basis of a polyelectrolyte network to form a double-network structure, which changes the microstructure of the hydrogel and greatly improves the mechanical properties of the dressing, so that the dressing has high compressive strength, high elastic modulus and high elongation at break; the change in the microstructure also gives it high light transmittance. When used as a dressing, the healing of the wound can be observed without removing the dressing, thereby avoiding secondary damage to the wound surface.

[0015] Furthermore, the specific steps in step S1 include:

[0016] S11. The modified anionic polyelectrolyte 0.5-5 parts and the carboxymethyl chitosan 0.5-5 parts and 100 parts of the deionized water are mixed to prepare a first mixed solution;

[0017] S12. adding the crosslinking agent to the first mixed solution, mixing to obtain a second mixed solution;

[0018] S13. Add 0.1-0.3 parts of the initiator to the second mixed solution, and mix to obtain the prepolymer solution.

[0019] The obtained hydrogel has good mechanical properties (high compressive strength, high elastic modulus and high elongation at break, etc.) and light transmittance.

[0020] Furthermore, the cross-linking agent is any one of polyethylene glycol diacrylate, polyethylene glycol dimethacrylate, multi-arm polyethylene glycol acrylate, methacrylated amylopectin, methacrylated cellulose, dialdehyde polyethylene glycol, bisthiol polyethylene glycol, dialdehyde cellulose, dialdehyde-β-cyclodextrin, and dialdehyde dextran.

[0021] Furthermore, the specific steps in step S12 include:

[0022] S12A. Add 0.1-1 part of polyethylene glycol diacrylate with a relative molecular weight of 200-4000 Da to the first mixed solution, and mix to obtain the second mixed solution.

[0023] Furthermore, the specific steps in step S12 include:

[0024] S12B. Add 0.1-1 parts of polyethylene glycol dimethacrylate having a relative molecular weight of 550-10000 Da to the first mixed solution, and mix to obtain the second mixed solution.

[0025] Further, the multi-arm polyethylene glycol acrylate includes four-arm polyethylene glycol acrylate;

[0026] The specific steps in step S12 include:

[0027] S12C. Add -0.1-1 parts of four-arm polyethylene glycol acrylate with a relative molecular weight of 2000-10000 Da to the first mixed solution, and mix to obtain the second mixed solution.

[0028] Comparative experimental results show that the covalent cross-linked network can reduce the risk of excessive swelling of hydrogels.

[0029] Furthermore, the specific steps in step S12 include:

[0030] S12D. Add 0.1-1 part of dialdehyde polyethylene glycol with a relative molecular weight of 400-20000 Da to the first mixed solution, and mix to obtain the second mixed solution.

[0031] Furthermore, the specific steps in step S12 include:

[0032] S12E. Add 0.1-1 part of bis-thiol polyethylene glycol with a relative molecular weight of 400-20000 Da to the first mixed solution, and mix to obtain the second mixed solution.

[0033] In a second aspect, the present invention further provides a visualized double network hydrogel, which is prepared by any of the above-mentioned visualized double network hydrogel preparation methods.

[0034] This visualized double-network hydrogel has good mechanical properties and high light transmittance. When used as a dressing, the user can observe the healing of the wound without removing the dressing.

[0035] In a third aspect, the present invention also provides the use of the above-mentioned visualized double-network hydrogel in a dressing.

[0036] From the above, it can be seen that the method for preparing a visualized double-network hydrogel provided by the present invention introduces a covalent cross-linking network on the basis of a polyelectrolyte network to form a double-network structure, which changes the microstructure of the hydrogel, thereby greatly improving the mechanical properties of the hydrogel; at the same time, due to the change in the microstructure, it also has a high light transmittance. When the hydrogel is used as a dressing, the user can observe the healing of the wound without removing the dressing, thereby avoiding secondary damage to the wound surface; in addition, the double-network structure can effectively prevent the hydrogel from excessively absorbing liquid and swelling during use, thereby greatly extending the service life of the dressing.

[0037] Other features and advantages of the present invention will be described in the following description, and partly become apparent from the description, or be understood by implementing the embodiments of the present invention. The purpose and other advantages of the present invention can be realized and obtained by the structures particularly pointed out in the written description and the drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] Figure 1 A flow chart of a method for preparing a visualized double-network hydrogel provided in an embodiment of the present invention.

[0039] Figure 2 A schematic diagram of the microstructure regulation of a visualized double-network hydrogel provided in an embodiment of the present invention.

[0040] Figure 3 It is the scanning spectrum of the hydrogel prepared in Comparative Example 1 and Examples 1-6 of the present invention.

[0041] Figure 4 It is a comparison chart of the light transmittance of the hydrogels prepared in Comparative Example 1 and Examples 1-6 of the present invention.

[0042] Figure 5 It is a comparison chart of the water absorption rate of the hydrogels prepared in Comparative Example 1 and Examples 1-6 of the present invention.

[0043] Figure 6 This is a first comparison diagram of the mechanical properties of the hydrogels prepared in Comparative Example 1 and Examples 1-6 of the present invention.

[0044] Figure 7 This is a second comparison diagram of the mechanical properties of the hydrogels prepared in Comparative Example 1 and Examples 1-6 of the present invention.

[0045] Figure 8 The figure is a comparison chart of the drug sustained-release performance of the hydrogel dressings prepared in Comparative Example 1 and Examples 1-6 of the present invention. DETAILED DESCRIPTION

[0046] The technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. The components of the embodiments of the present invention generally described and shown in the drawings here can be arranged and designed in various different configurations. Therefore, the following detailed description of the embodiments of the present invention provided in the drawings is not intended to limit the scope of the claimed invention, but merely represents the selected embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without making creative work belong to the scope of protection of the present invention.

[0047] It should be noted that similar reference numerals and letters represent similar items in the following drawings, so once an item is defined in one drawing, it does not need to be further defined and explained in the subsequent drawings. At the same time, in the description of the present invention, the terms "first", "second", etc. are only used to distinguish the description and cannot be understood as indicating or implying relative importance.

[0048] Please refer to Figure 1 , Figure 1 The figure is a flow chart of a method for preparing a visual double network hydrogel. The method for preparing a visual double network hydrogel comprises the following steps:

[0049] S1. The modified anionic polyelectrolyte, carboxymethyl chitosan and crosslinking agent are mixed and dissolved in deionized water, and then an initiator is added to obtain a prepolymer solution;

[0050] S2. The prepolymer solution is vacuumed to remove residual air in the solution;

[0051] S3. The prepolymer solution after vacuum treatment is sealed and placed under a preset temperature (for example, 60° C., but not limited thereto, the embodiments below are all listed at 60° C.) for a first preset time to obtain a reactant;

[0052] S4. placing the reactants in an acetic acid atmosphere for fumigation for a second preset time to obtain a hydrogel dressing.

[0053] In the prior art, modified anionic polyelectrolytes and carboxymethyl chitosan react under certain conditions to form a polyelectrolyte network. However, this polyelectrolyte network is formed by the electrostatic interaction between different functional groups of different components and has a disordered and uneven three-dimensional network structure. Therefore, its mechanical properties and light transmittance are relatively poor.

[0054] In this regard, in this embodiment, a cross-linking agent is added to carry out a cross-linking reaction with a modified anionic polyelectrolyte (or carboxymethyl chitosan) so that part of the polysaccharide chain segments are fixed to obtain a hydrogel (i.e., the reactant) having a covalent cross-linked network. Thereafter, the reactant is placed in an acetic acid atmosphere so that the amino groups in the carboxymethyl chitosan chain segments are protonated and then rely on electrostatic interaction forces to combine with the carboxyl groups in the modified anionic polyelectrolyte chain segments to form a polyelectrolyte network, thereby obtaining a visualized double-network hydrogel (when used as a dressing, this dressing will be referred to as a hydrogel dressing hereinafter).

[0055] This embodiment introduces a covalent cross-linked network on the basis of the original polyelectrolyte network. Since the modified anionic polyelectrolyte chain segments (or carboxymethyl chitosan chain segments) are fixed in advance, the subsequently formed polyelectrolyte network is evenly distributed in the gel, thereby increasing the light transmittance of the hydrogel dressing; at the same time, the introduction of the covalent cross-linked network enables the hydrogel to have a double network structure, greatly improving the mechanical properties of the hydrogel, reducing the risk of excessive swelling of the hydrogel, and thus reducing the number of times the hydrogel dressing is replaced (existing hydrogel dressings cannot be used normally due to excessive swelling, and often have to be replaced with new hydrogel dressings).

[0056] Reference Figure 2 , attached Figure 2 The invention discloses the microstructure of a hydrogel obtained by mixing a modified anionic polyelectrolyte with carboxymethyl chitosan in a prior art manner, reacting to obtain a first mixed solution, and then fumigating the solution in an acetic acid atmosphere; at the same time, the invention also discloses the change process of the microstructure during the preparation of the visualized double network hydrogel of the invention.

[0057] Attached Figure 2 The circular marks in the figure are the chemical bonds related to the electrostatic interaction between different functional groups of different components in the polyelectrolyte network; the triangular marks are the chemical bonds related to the fixation of the modified anionic polyelectrolyte segments (or carboxymethyl chitosan segments) in the covalently cross-linked network.

[0058] Furthermore, the modified anionic polyelectrolyte is any one of modified sodium alginate, modified carrageenan, and modified hyaluronate (but not limited thereto, and also includes other hydrophilic polyanionic biomacromolecules). Specifically, it can be obtained by adding methacrylic anhydride to alginate, sodium hyaluronate, carrageenan, sodium carboxymethyl cellulose, sodium carboxymethyl starch, and carboxymethyl tuckahoe polysaccharide for modification, which is a prior art and will not be described in detail here.

[0059] Furthermore, the crosslinking agent is any one of polyethylene glycol diacrylate, polyethylene glycol dimethacrylate, multi-arm polyethylene glycol acrylate, methacrylated pullulan, methacrylated cellulose, dialdehyde polyethylene glycol, bisthiol polyethylene glycol, dialdehyde cellulose, dialdehyde-β-cyclodextrin, and dialdehyde dextran.

[0060] Among them, multi-arm polyethylene glycol acrylates are, for example, four-arm polyethylene glycol acrylates, six-arm polyethylene glycol acrylates, etc.; methacrylated amylopectin and methacrylated cellulose are modified biomacromolecules; and dialdehyde cellulose, dialdehyde-β-cyclodextrin, and dialdehyde dextran are dialdehyde polysaccharides.

[0061] Furthermore, the initiator is any one of ammonium persulfate, potassium persulfate, and sodium persulfate. In actual preparation, TEMED (tetramethylethylenediamine) can be added as a catalyst to catalyze the initiator to generate free radicals, thereby accelerating the polymerization of the reactants.

[0062] Furthermore, the first preset time is 6 hours and the second preset time is 12 hours, but not limited thereto.

[0063] In some embodiments, the specific steps in step S1 include:

[0064] S11. The modified anionic polyelectrolyte 0.5-5 parts and the carboxymethyl chitosan 0.5-5 parts and 100 parts of the deionized water are mixed to prepare a first mixed solution;

[0065] S12. adding the crosslinking agent to the first mixed solution, mixing to obtain a second mixed solution;

[0066] S13. Add 0.1-0.3 parts of the initiator to the second mixed solution, and mix to obtain the prepolymer solution.

[0067] In this embodiment, the first mixed solution prepared by mixing modified anionic polyelectrolyte and carboxymethyl chitosan will not initiate a reaction to form a polyelectrolyte network if the reaction conditions are not met. However, in order to ensure the quality of the subsequently formed polyelectrolyte network, the mixing ratio of the two needs to be adjusted in advance.

[0068] Afterwards, a proper amount of a crosslinking agent and an initiator are added to obtain a prepolymer solution, and then a reaction is initiated by controlling the reaction conditions to obtain a hydrogel dressing;

[0069] Specifically, after the vacuum treatment, the prepolymer solution is placed at 60° C. to initiate a cross-linking reaction and form a reactant; the reactant is then placed in an acetic acid atmosphere for fumigation to initiate a polymerization reaction and form a visualized double-network hydrogel.

[0070] Comparative Example 1 (Existing Technology):

[0071] Reference Figure 3 , Attachment Figure 4 , Attachment Figure 5 , Attachment Figure 6 and attached Figure 7 , 5 parts of modified anionic polyelectrolyte and 5 parts of carboxymethyl chitosan were mixed with 100 parts of deionized water to prepare a first mixed solution, which was then placed in an acetic acid atmosphere for fumigation. The resulting hydrogel had poor mechanical properties, low transmittance (the transmittance at 600nm was only 23.74%), and a water absorption rate of 64.36 times (water absorption rate is related to liquid swelling).

[0072] It should be noted that the hydrogel prepared in Comparative Example 1 is Figure 3 The local schematic diagram with the label a corresponds to the attached Figure 4 The curve marked with CM corresponds to the attached Figure 5 The column labeled CM corresponds to the attached Figure 6 The curve marked with CM corresponds to the attached Figure 7 The column labeled CM corresponds to the attached Figure 8 The curve marked with CM corresponds to the above.

[0073] It should also be noted that the mechanical properties of the hydrogel can be adjusted according to the Figure 6 (stress-strain data) and attached Figure 7 The values ​​of (compressive strength data, elastic modulus data and elongation at break data) are used for evaluation.

[0074] Embodiment 1:

[0075] Reference Figure 3 , Attachment Figure 4 , Attachment Figure 5 , Attachment Figure 6 and attached Figure 7 , 5 parts of modified anionic polyelectrolyte and 5 parts of carboxymethyl chitosan are mixed with 100 parts of deionized water to prepare a first mixed solution, and then 1 part of polyethylene glycol diacrylate with a relative molecular weight of 200-4000 Da is added and mixed to obtain a second mixed solution, and step S13 is performed and the reaction conditions are controlled according to step S3 to induce a cross-linking reaction, and then it is placed in an acetic acid atmosphere for fumigation according to step 4. The obtained visualized double network hydrogel has a slightly improved mechanical property and a higher transmittance than that of comparative example 1 (the transmittance at 600 nm reaches 93.39%).

[0076] It should be noted that the visualized double network hydrogel prepared in Example 1 is Figure 3 The local schematic diagram with the label b corresponds to the attached Figure 4 The curve labeled CMP1 corresponds to the Figure 5 The column labeled CMP1 corresponds to the attached Figure 6The curve labeled CMP1 corresponds to the Figure 7 The column labeled CMP1 corresponds to the attached Figure 8 The curve labeled CMP1 corresponds to this.

[0077] Embodiment 2:

[0078] Reference Figure 3 , Attachment Figure 4 , Attachment Figure 5 , Attachment Figure 6 and attached Figure 7 , 5 parts of modified anionic polyelectrolyte and 5 parts of carboxymethyl chitosan are mixed with 100 parts of deionized water to prepare a first mixed solution, and then 1 part of polyethylene glycol dimethacrylate with a relative molecular weight of 550-10000 Da is added and mixed to obtain a second mixed solution, and step S13 is performed and the reaction conditions are controlled according to step S3 to induce a cross-linking reaction, and then it is placed in an acetic acid atmosphere for fumigation according to step 4. The obtained visualized double network hydrogel has greatly improved mechanical properties and improved light transmittance compared with comparative example 1.

[0079] It should be noted that the visualized double network hydrogel prepared in Example 2 is Figure 3 The local schematic diagram with the label c corresponds to the attached Figure 4 The curve labeled CMP2 corresponds to the attached Figure 5 The column labeled CMP2 corresponds to the attached Figure 6 The curve labeled CMP2 corresponds to the attached Figure 7 The column labeled CMP2 corresponds to the attached Figure 8 The curve labeled CMP2 corresponds to this.

[0080] Embodiment 3:

[0081] Reference Figure 3 , Attachment Figure 4 , Attachment Figure 5 , Attachment Figure 6 and attached Figure 7 , 5 parts of modified anionic polyelectrolyte and 5 parts of carboxymethyl chitosan are mixed with 100 parts of deionized water to prepare a first mixed solution, and then 1 part of polyethylene glycol diacrylate with a relative molecular weight of 200-4000 Da is added and mixed to obtain a second mixed solution, and step S13 is performed and the reaction conditions are controlled according to step S3 to only induce the cross-linking reaction. The obtained reactant (the hydrogel with a covalent cross-linked network obtained by the cross-linking reaction is itself a hydrogel, but does not have a double network structure) has greatly improved mechanical properties (compressive strength is increased to 3 times) and improved light transmittance compared with comparative example 1.

[0082] This example demonstrates that the introduced covalent cross-linked network can improve the mechanical properties and light transmittance of the hydrogel.

[0083] It should be noted that the hydrogel prepared in Example 3 is Figure 3 The local schematic diagram marked with d in the figure corresponds to the attached Figure 4 The curves marked with *CMP correspond to the attached Figure 5 The columns marked with *CMP correspond to the attached Figure 6 The curves marked with *CMP correspond to the attached Figure 7 The columns marked with *CMP correspond to the attached Figure 8 The curves marked with *CMP correspond to the above.

[0084] Embodiment 4:

[0085] Reference Figure 3 , Attachment Figure 4 , Attachment Figure 5 , Attachment Figure 6 and attached Figure 7 , 5 parts of modified anionic polyelectrolyte and 5 parts of carboxymethyl chitosan are mixed with 100 parts of deionized water to prepare a first mixed solution, and then 1 part of four-arm polyethylene glycol acrylate with a relative molecular weight of 2000-10000Da is added to obtain a second mixed solution, and step S13 is performed and the reaction conditions are controlled according to step S3 to induce a cross-linking reaction, and then it is placed in an acetic acid atmosphere for fumigation according to step 4. The obtained visualized double network hydrogel has greatly improved mechanical properties compared with comparative example 1 (compressive strength is increased to 8.15 times, elastic modulus is increased to 19.70 times, and elongation at break is increased to 7.56 times), light transmittance is improved, and water absorption is 30.11 times (effectively controlling liquid absorption and swelling behavior).

[0086] This example demonstrates that the introduced covalent cross-linked network can reduce the risk of excessive swelling of the hydrogel.

[0087] It should be noted that the visualized double network hydrogel prepared in Example 4 is Figure 3 The local schematic diagram marked with number e corresponds to the attached Figure 4 The curve labeled CMP3 corresponds to the attached Figure 5 The column labeled CMP3 corresponds to the attached Figure 6 The curve labeled CMP3 corresponds to the attached Figure 7 The column labeled CMP3 corresponds to the attached Figure 8 The curve labeled CMP3 corresponds to this.

[0088] Embodiment 5:

[0089] Reference Figure 3 , Attachment Figure 4 , Attachment Figure 5 , Attachment Figure 6 and attached Figure 7 , 5 parts of modified anionic polyelectrolyte and 5 parts of carboxymethyl chitosan are mixed with 100 parts of deionized water to prepare a first mixed solution, and then 1 part of dialdehyde polyethylene glycol with a relative molecular weight of 400-20000 Da is added and mixed to obtain a second mixed solution, and step S13 is executed and the reaction conditions are controlled according to step S3 to induce a cross-linking reaction, and then it is placed in an acetic acid atmosphere for fumigation according to step 4. The obtained visualized double network hydrogel has greatly improved mechanical properties and improved light transmittance compared with comparative example 1.

[0090] It should be noted that the visualized double network hydrogel prepared in Example 5 is Figure 3 The local schematic diagram with the label f ​​corresponds to the attached Figure 4 The curve labeled CMP4 corresponds to the attached Figure 5 The column labeled CMP4 corresponds to the attached Figure 6 The curve labeled CMP4 corresponds to the attached Figure 7 The column labeled CMP4 corresponds to the attached Figure 8 The curve labeled CMP4 corresponds to this.

[0091] Embodiment 6:

[0092] Reference Figure 3 , Attachment Figure 4 , Attachment Figure 5 , Attachment Figure 6 and attached Figure 7 , 5 parts of modified anionic polyelectrolyte and 5 parts of carboxymethyl chitosan are mixed with 100 parts of deionized water to prepare a first mixed solution, and then 1 part of bis-thiol polyethylene glycol with a relative molecular weight of 400-20000 Da is added and mixed to obtain a second mixed solution, and after executing step S13 and controlling the reaction conditions according to step S3 to induce a cross-linking reaction, it is placed in an acetic acid atmosphere for fumigation according to step 4. The obtained visualized double network hydrogel has greatly improved mechanical properties compared with comparative example 1, but its transmittance is slightly decreased compared with example 4 (the transmittance at 600nm reaches 87.15%).

[0093] It should be noted that the visualized double network hydrogel prepared in Example 6 is Figure 3 The local schematic diagram with the label g corresponds to the attached Figure 4 The curve labeled CMP5 corresponds to the attached Figure 5 The column labeled CMP5 corresponds to the attached Figure 6 The curve labeled CMP5 corresponds to the attached Figure 7 The column labeled CMP5 corresponds to the attached Figure 8 The curve labeled CMP5 corresponds to the curve.

[0094] The present invention also provides a visualized double network hydrogel, which is prepared by the visualized double network hydrogel preparation method in the above embodiment.

[0095] This visualized double-network hydrogel has good mechanical properties and high light transmittance. When used as a dressing, the user can observe the healing of the wound without removing the dressing, overcoming the disadvantage of using traditional dressings, which requires removing the dressing to observe the healing of the wound, thus causing secondary damage to the wound surface.

[0096] The present invention also provides application of the above-mentioned visualized double-network hydrogel in dressings.

[0097] In practical applications, a specific drug can be added to the second mixed solution when executing step S13, so as to prepare a hydrogel dressing that can act on the wound. The hydrogel dressing can play a role in drug loading and sustained release. When attached to the wound, the hydrogel dressing itself can play a role in isolating and protecting the wound, and the drug is continuously released and acts on the wound, which can promote wound repair. In step S13, the following steps are performed:

[0098] S131. Add 0.05 parts of berberine hydrochloride to the second mixed solution, and mix to obtain a third mixed solution;

[0099] S132. Add an initiator to the third mixed solution and mix to obtain a prepolymer solution.

[0100] In order to prove that the hydrogel dressing has drug loading and sustained-release effects, berberine hydrochloride was added as a specific drug during the preparation process of the hydrogel.

[0101] Specific examples include:

[0102] Reference Figure 8 In Comparative Example 1, 0.05 parts of berberine hydrochloride was added, and the hydrogel dressing had no drug sustained release effect (the drug was completely released in 1 hour); the prepared hydrogel dressing was Figure 8 The columns marked with CM correspond to the above.

[0103] Reference Figure 8 , 0.05 parts of berberine hydrochloride were added to Example 1, and the hydrogel dressing had an obvious drug sustained release effect (the drug release amount in 2 hours was less than 80%); the prepared hydrogel dressing and the attached Figure 8 The curve labeled CMP1 corresponds to this.

[0104] Reference Figure 8 In Example 2, 0.05 parts of berberine hydrochloride was added, and the hydrogel dressing had an obvious drug sustained release effect (the drug release amount in 2 hours was less than 80%). Figure 8 The curve labeled CMP2 corresponds to this.

[0105] Reference Figure 8 In Example 3, 0.05 parts of berberine hydrochloride was added, and the hydrogel dressing had an obvious drug sustained release effect (the drug release amount in 2 hours was less than 60%). Figure 8 The curves marked with *CMP correspond to the above.

[0106] Reference Figure 8 In Example 4, 0.05 parts of berberine hydrochloride was added, and the hydrogel dressing had an obvious drug sustained release effect (the drug release amount in 2 hours was less than 60%). Figure 8 The curve labeled CMP3 corresponds to this.

[0107] Reference Figure 8 In Example 5, 0.05 parts of berberine hydrochloride was added, and the hydrogel dressing had an obvious drug sustained release effect (the drug release amount in 2 hours was less than 40%). Figure 8 The curve labeled CMP4 corresponds to this.

[0108] Reference Figure 8 In Example 6, 0.05 parts of berberine hydrochloride was added, and the hydrogel dressing had an obvious drug sustained release effect (the drug release amount in 2 hours was less than 20%). Figure 8 The curve labeled CMP5 corresponds to the curve.

[0109] In this document, relational terms such as first and second, etc. are used merely to distinguish one entity or operation from another entity or operation, but do not necessarily require or imply any such actual relationship or order between these entities or operations.

[0110] The above description is only an embodiment of the present invention and is not intended to limit the protection scope of the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A method for preparing a visualized double network hydrogel, characterized in that: The following steps are involved: S1. The modified anionic polyelectrolyte, carboxymethyl chitosan and crosslinking agent are mixed and dissolved in deionized water, and then an initiator is added to obtain a prepolymer solution; S2. The prepolymer solution is vacuumed to remove residual air in the solution; S3. The prepolymer solution after vacuum treatment is sealed and placed under a preset temperature condition to react for a first preset time to obtain a reactant; S4. The reactant is placed in an acetic acid atmosphere and fumigated for a second preset time to obtain a hydrogel; The modified anionic polyelectrolyte is any one of modified sodium alginate, modified carrageenan, and modified hyaluronate; wherein the modified sodium alginate is obtained by modifying alginate by adding methacrylic anhydride, the modified carrageenan is obtained by modifying carrageenan by adding methacrylic anhydride, and the modified hyaluronate is obtained by modifying sodium hyaluronate by adding methacrylic anhydride; The cross-linking agent is any one of polyethylene glycol diacrylate, polyethylene glycol dimethacrylate, multi-arm polyethylene glycol acrylate, methacrylated pullulan, methacrylated cellulose, dialdehyde polyethylene glycol, bisthiol polyethylene glycol, dialdehyde cellulose, dialdehyde-β-cyclodextrin, and dialdehyde dextran; Among them, the multi-arm polyethylene glycol acrylate is four-arm polyethylene glycol acrylate or six-arm polyethylene glycol acrylate; methacrylated amylopectin and methacrylated cellulose are modified biomacromolecules; and dialdehyde cellulose, dialdehyde-β-cyclodextrin and dialdehyde dextran are dialdehyde polysaccharides.

2. The method for preparing a visualized double network hydrogel according to claim 1, characterized in that: The specific steps in step S1 include: S11. The modified anionic polyelectrolyte 0.5-5 parts and the carboxymethyl chitosan 0.5-5 parts and 100 parts of the deionized water are mixed to prepare a first mixed solution; S12. adding the crosslinking agent to the first mixed solution, mixing to obtain a second mixed solution; S13. Add 0.1-0.3 parts of the initiator to the second mixed solution, and mix to obtain the prepolymer solution.

3. The method for preparing a visualized double network hydrogel according to claim 2, characterized in that: The specific steps in step S12 include: 0.1-1 part of polyethylene glycol diacrylate with a relative molecular weight of 200-4000 Da is added to the first mixed solution, and the mixture is mixed to obtain the second mixed solution.

4. The method for preparing a visualized double network hydrogel according to claim 2, characterized in that: The specific steps in step S12 include: 0.1-1 part of polyethylene glycol dimethacrylate with a relative molecular weight of 550-10000 Da is added to the first mixed solution, and the mixture is mixed to obtain the second mixed solution.

5. The method for preparing a visualized double network hydrogel according to claim 2, characterized in that: The multi-arm polyethylene glycol acrylate includes four-arm polyethylene glycol acrylate; The specific steps in step S12 include: 0.1-1 parts of four-arm polyethylene glycol acrylate with a relative molecular weight of 2000-10000 Da are added to the first mixed solution, and the mixture is mixed to obtain the second mixed solution.

6. The method for preparing a visualized double network hydrogel according to claim 2, characterized in that: The specific steps in step S12 include: 0.1-1 part of dialdehyde polyethylene glycol with a relative molecular weight of 400-20000 Da is added to the first mixed solution, and the mixture is mixed to obtain the second mixed solution.

7. The method for preparing a visualized double network hydrogel according to claim 2, characterized in that: The specific steps in step S12 include: 0.1-1 part of bis-thiol polyethylene glycol with a relative molecular weight of 400-20000 Da is added to the first mixed solution, and the mixture is mixed to obtain the second mixed solution.

8. A visualized double network hydrogel, characterized in that: The visualized double network hydrogel is prepared by the method for preparing the visualized double network hydrogel as described in any one of claims 1 to 7.

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