Strong-adhesion injectable self-healing hydrogel as well as preparation method and application thereof
Through the dual network structure and modified nanofiller lignin hydrogel, the problem of insufficient adhesion of injectable hydrogels is solved, and high adhesion, injectability and self-healing ability is achieved, which is suitable for medical trauma and drug release fields.
Patent Information
- Application Number
- CN202411818272.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-11
- Publication Date
- 2025-07-11
AI Technical Summary
While maintaining self-healing and injection capabilities, existing injectable hydrogels have insufficient adhesion and difficulty in effectively fitting into wounds or reusing them.
A hydrogel with a dual network structure is adopted to form a first network through dynamic cross-linking and hydrogen bonding, chemical cross-linking to form a second network, and a modified nanofiller lignin is added to prepare a natural polymer self-healing hydrogel with dynamic chemical bonds and high-strength hydrogen bonds.
The prepared hydrogel has excellent adhesion, injectability, ductility and self-healing ability, and has good swelling and water retention, which conforms to the concept of green chemistry, is harmless to the human body and environmentally friendly.
Smart Images
Figure CN120289729A_ABST
Abstract
Description
Technical Field
[0001] The present invention belongs to the technical field of polymer materials, and particularly relates to a strongly adhesive injectable self-healing hydrogel and a preparation method and application thereof. Background Art
[0002] Injectable self-healing hydrogels have broad application prospects in drug injection, wound treatment and other aspects due to their excellent plasticity and self-healing properties. However, while maintaining the above properties, the hydrogel must have good adhesiveness so that it can better adhere to the wound or be reused. Therefore, an ideal injectable dressing must have good adhesiveness while ensuring its self-healing and injection capabilities.
[0003] The adhesion performance of the hydrogel depends on the type of interfacial adhesion with the substrate and the cohesion of the hydrogel. In contrast, hydrogels with stronger hydrophilicity can exhibit better adhesion performance in most environments. The improvement of cohesion can be achieved by introducing reversible chemical bonds or adjusting physical cross-linking. However, the interaction between polymer chains will limit their movement to contact the substrate surface and weaken the bonding strength. Moreover, simply increasing the surface adhesion may also lead to cohesive failure of the adhesive, so it is necessary to adjust the network structure of the hydrogel to improve the adhesion. Currently, there is relatively little work on improving the adhesion performance of injectable hydrogels or the improvement strength is insufficient. Therefore, it has relatively good practical significance to develop a preparation method for strongly adhesive injectable self-healing hydrogels. Summary of the Invention
[0004] The purpose of this part is to outline some aspects of the embodiments of the present invention and briefly introduce some preferred embodiments. Some simplifications or omissions may be made in this part, as well as in the abstract and title of the present application, to avoid obscuring the purpose of this part, the abstract and the title, and such simplifications or omissions shall not be used to limit the scope of the present invention.
[0005] In view of the above and / or problems existing in the prior art, the present invention is proposed.
[0006] Therefore, the purpose of the present invention is to overcome the deficiencies in the prior art and provide a preparation method for a strongly adhesive injectable self-healing hydrogel.
[0007] To solve the above technical problems, the present invention provides the following technical solutions, including,
[0008] Sodium hydroxide is dissolved in water and then acrylic acid is added to obtain a 20-50% sodium acrylate solution; an initiator and a cross-linking agent are successively added to the sodium acrylate solution, and after stirring, a mixed solution A is obtained; a polyvinyl alcohol solution with a mass fraction of 8-12% is added to the mixed solution A, and after stirring and mixing, a mixed solution B is obtained;
[0009] Add a sulfonated lignin solution with a concentration of 0.01 - 0.05 g / mL and deionized water to the mixed solution B, and mix at a rotation speed of 350 - 450 rad / min; continue stirring, and slowly dropwise add a 2 - 5% boric acid aqueous solution. After the addition is complete, heat in an oil bath at 60 - 70 °C for 2 - 8 h, and at the same time adjust the rotation speed to 250 - 340 rad / min; after cooling to room temperature, perform freeze-thaw cycles with a frequency of freezing for 10 - 12 h and thawing at room temperature for 2 - 3 h, and cycle 4 - 6 times. After the last thawing is completed, the hydrogel preparation is completed;
[0010] Among them, the mass-volume ratio of the sulfonated lignin solution, the boric acid aqueous solution, and the polyvinyl alcohol solution is 1 - 2 mL∶2 - 10 mL∶2 - 10 g.
[0011] As a preferred embodiment of the preparation method of the strongly adhesive injectable self-healing hydrogel of the present invention, wherein: the molar ratio of sodium hydroxide to acrylic acid is 1∶1.
[0012] As a preferred embodiment of the preparation method of the strongly adhesive injectable self-healing hydrogel of the present invention, wherein: the addition amount of the initiator is 0.1 - 1% of acrylic acid; the initiator includes ammonium persulfate and sodium persulfate.
[0013] As a preferred embodiment of the preparation method of the strongly adhesive injectable self-healing hydrogel of the present invention, wherein: the mass ratio of the polyvinyl alcohol solution to the mixed solution A is 5∶6 - 10.
[0014] As a preferred embodiment of the preparation method of the strongly adhesive injectable self-healing hydrogel of the present invention, wherein: the addition amount of the cross-linking agent is 0.1 - 3% of acrylic acid; the cross-linking agent includes methylene bisacrylamide.
[0015] As a preferred embodiment of the preparation method of the strongly adhesive injectable self-healing hydrogel of the present invention, wherein: the sulfonated lignin solution is prepared by an acidolysis method, including,
[0016] Slowly dropwise add 3 - 5 g of concentrated sulfuric acid to a 10 - 20% lignin solution. After sufficient contact, heat in an oil bath at 90 - 120 °C for 2 - 5 h. After taking out, adjust the pH to 2 - 4, centrifuge, take out the solid, put it into a dialysis bag and dialyze for 7 days, and concentrate to adjust the solid content of the solution.
[0017] As a preferred embodiment of the preparation method of the strongly adhesive injectable self-healing hydrogel of the present invention, wherein: the molecular weight of the lignin is 10 4 ~10 6 .
[0018] As a preferred embodiment of the preparation method of the strongly adhesive injectable self-healing hydrogel of the present invention, wherein: the degree of polymerization of the polyvinyl alcohol is 100,000 to 300,000, and the degree of alcoholysis is 78% to 98%.
[0019] Another object of the present invention is to overcome the deficiencies in the prior art and provide a strongly adhesive injectable self-healing hydrogel, the hydrogel having a double network structure;
[0020] Among them, the first network is formed by dynamic crosslinking and hydrogen bonding, having good self-healing performance; the second network is formed by chemical crosslinking, having good mechanical strength.
[0021] The third object of the present invention is to overcome the deficiencies in the prior art and provide an application of a strongly adhesive injectable self-healing hydrogel in the fields of medical trauma and drug release.
[0022] Advantages of the present invention:
[0023] (1) Taking the double network hydrogel as a model, the present invention adds modified nano filler lignin to prepare a natural polymer self-healing hydrogel containing dynamic chemical bonds, high-strength hydrogen bonds and ionic interactions. The hydrogel prepared by this method has the healing ability without external stimulation and excellent adhesion performance.
[0024] (2) The strongly adhesive injectable self-healing hydrogel prepared by the present invention has excellent adhesion and injectability. In addition, it also has good ductility, self-healing ability, good swelling property and water retention property. The materials for preparing the strongly adhesive injectable self-healing hydrogel are all materials that can be directly sold in the market, are basically harmless to the human body and have no pollution to the environment, meeting the concepts of sustainable development and green chemistry.
[0025] (3) The present invention provides a preparation method and idea of a strongly adhesive injectable self-healing hydrogel for fields such as medical trauma and drug release to solve the problem of insufficient adhesion strength. Description of the Drawings
[0026] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following will briefly introduce the drawings required for the description of the embodiments. Obviously, the following drawings are only some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained based on these drawings. Among them:
[0027] Figure 1 It is a self-healing diagram of the hydrogel prepared in Example 2 of the present invention after shearing.
[0028] Figure 2 It is a real shot diagram of injecting the hydrogel prepared in Example 2 of the present invention.
[0029] Figure 3 The tensile diagram of the hydrogel prepared in Example 2 of the present invention.
[0030] Figure 4 The adhesion diagram of the hydrogel prepared in Example 2 of the present invention.
[0031] Figure 5 The scanning electron microscope image of the DL hydrogel prepared in Comparative Example 1 of the present invention.
[0032] Figure 6 The scanning electron microscope image of the SL hydrogel prepared in Example 2 of the present invention.
[0033] Figure 7 The water contact angle diagram of the hydrogels prepared in Comparative Example 1 (a) and Example 2 (b) of the present invention.
[0034] Figure 8 The lap joint strength diagram of the hydrogels prepared in Comparative Example 1 and Examples 1 - 3 of the present invention. Detailed implementation manners
[0035] To make the above - mentioned objects, features, and advantages of the present invention more obvious and understandable, the following describes the detailed implementation manners of the present invention in conjunction with the embodiments of the specification.
[0036] Many specific details are set forth in the following description to facilitate a thorough understanding of the present invention. However, the present invention may be implemented in other ways different from those described herein. Those skilled in the art can make similar extensions without departing from the connotation of the present invention. Therefore, the present invention is not limited by the specific embodiments disclosed below.
[0037] Secondly, the so - called "one embodiment" or "embodiment" herein refers to a specific feature, structure, or characteristic that can be included in at least one implementation manner of the present invention. The appearances of "in one embodiment" in different places in this specification do not all refer to the same embodiment, nor are they separate or selectively exclusive embodiments from other embodiments.
[0038] Unless otherwise specified, the raw materials used in the present invention are all ordinary commercially available products.
[0039] The substances and abbreviations in the present invention are as follows:
[0040] Polyvinyl alcohol (PVA), ammonium persulfate (APS), methylene bisacrylamide (BIS), sulfonated lignin (SL), delignified lignin (DL).
[0041] Unless otherwise specified, the percentages in the present invention all represent mass percentages.
[0042] The materials prepared in the embodiments of the present invention are tested for performance according to the following methods:
[0043] The lap joint strength was tested with reference to GB / T 6343-2009 "Test Method for Lap Joint Strength of Adhesives".
[0044] Self-healing test: A hydrogel was cut into two parts, one half was stained with methyl orange reagent, and then the two pieces of hydrogel were joined together to observe the self-healing situation.
[0045] Example 1
[0046] This example provides a preparation method of a hydrogel, specifically:
[0047] (1) Preparation of sulfonated lignin: Take 2.0 g of lignin with a molecular weight of 10 5 , add 10.5 mL of deionized water to prepare a lignin solution with a concentration of 16%. Slowly add 3.2 g of concentrated sulfuric acid, and after full contact, carry out an oil bath at 90 °C for 3 h. After taking it out, neutralize the excess sulfuric acid with NaOH solution, adjust the pH to 2, centrifuge, take out the solid and put it into a dialysis bag for dialysis for 7 days, and concentrate to adjust the solid content of the solution to 0.02 g / mL.
[0048] (2) Preparation of the solution of the strong adhesion hydrogel: Take 10 g of polyvinyl alcohol solid with a polymerization degree of 200,000 and a degree of alcoholysis of 98%, add 90 mL of deionized water, and at 90 °C, adjust the rotation speed to 300 rad / min, and stir for 6 h to prepare a polyvinyl alcohol solution with a concentration of 10%.
[0049] Take 1 g of boric acid, add 49 mL of deionized water to prepare a boric acid aqueous solution with a concentration of 2%.
[0050] Add 1.67 g of sodium hydroxide solid to 7.33 g of deionized water, stir until the sodium hydroxide solid is completely dissolved and the solution temperature returns to room temperature, then add 3 g of acrylic acid monomer, stir until completely reacted, and add deionized water to obtain a 30% sodium acrylate solution.
[0051] (3) Preparation of the strong adhesion injectable self-healing hydrogel: Add 0.015 g of initiator ammonium persulfate (APS) and 0.06 g of crosslinking agent N,N'-methylenebisacrylamide (BIS) to the above sodium acrylate solution in sequence, stir until completely dissolved to obtain a mixed solution A. Add 10 g of the prepared polyvinyl alcohol solution to the mixed solution A and stir evenly to obtain a mixed solution B.
[0052] Add 1 mL of the prepared sulfonated lignin solution and 5 mL of deionized water to the mixed solution B. Adjust the rotation speed to 400 rad / min, and slowly drip 3 mL of the prepared boric acid aqueous solution with a dropper while stirring until the boric acid aqueous solution is completely added to the above solution. Place the mixed liquid in a water bath at 60 °C and stir for 3 h, then adjust the stirring speed to 300 rad / min. Place the solution after the reaction in a -40 °C environment for freezing. After freezing for 10 h, take out the hydrogel and thaw it at room temperature for 2 h. Repeat this cycle 5 times to prepare a strongly adhesive injectable self-healing hydrogel.
[0053] Example 2
[0054] The difference between this example and Example 1 is that in step (3), the addition amount of the sulfonated lignin solution is adjusted to 2 mL, and the addition amount of deionized water is adjusted to 4 mL. The remaining preparation processes are the same as those in Example 1 to obtain the hydrogel.
[0055] Perform a self-healing test on the hydrogel prepared in this Example 2. The self-healing test results are as Figures 1 to 3 shown: Cut the hydrogel in half with scissors, stain one half, wipe off the excess pigment after staining, put the two pieces of hydrogel together, and it can be found that they can stick together and will not break under a certain external force. After one minute, it can be found that the pigment of the hydrogel penetrates into the other part of the unstained hydrogel, indicating that the hydrogel has a certain self-healing ability. Put the hydrogel into a syringe, and it can be found that it can be injected into any shape, indicating good injectability. Moreover, a small piece of hydrogel can be stretched to more than 5 times its original length, indicating good ductility.
[0056] Figure 4 This is the adhesion diagram of the hydrogel in this example. It can be seen that the hydrogel can adhere to substances with different substrates, indicating that the hydrogel has good adhesion.
[0057] Example 3
[0058] The difference between this example and Example 1 is that in step (3), the addition amount of the sulfonated lignin solution is adjusted to 3 mL, and the addition amount of deionized water is adjusted to 3 mL. The remaining preparation processes are the same as those in Example 1 to obtain the hydrogel.
[0059] Comparative Example 1
[0060] The difference between this comparative example and Example 1 is that in step (3), the addition amount of the sulfonated lignin solution is adjusted to 0, the addition amount of deionized water is adjusted to 6 mL, and 2 mL of unmodified lignin solution is used. The remaining preparation processes are the same as those in Example 1 to obtain the hydrogel.
[0061] Figure 5Scanning electron micrograph of the DL hydrogel prepared in Comparative Example 1 Figure 6 Scanning electron micrograph of the SL hydrogel prepared in Example 2. Comparing with Figure 5 it can be seen that the pore structure of the hydrogel prepared in the present invention is denser, and SL effectively improves the crosslinking density of the hydrogel. Figure 7 Water contact angle diagrams of the hydrogels prepared in Comparative Example 1 (a) and Example 2 (b). It can be seen that the water contact angle formed by the SL hydrogel is smaller, indicating better hydrophilicity and being more conducive to adhesion.
[0062] The materials prepared in the above examples were subjected to performance tests, and the comparison results with Example 1 are shown in Table 1.
[0063] Table 1 Lap shear strength of different hydrogels on different substrates
[0064]
[0065] The lap shear strength refers to the maximum shear stress that two materials can withstand under external pressure when connected by lap joint, and its magnitude can show the maximum adhesion size that the material can withstand under external force. Combining with the above table Figure 8 it can be seen that when comparing with the hydrogel added with DL in Comparative Example 1, when the hydrogel added with SL was subjected to lap tests with different substrates, the test results were significantly improved. This is because SL has better dispersibility in the hydrogel system, can effectively improve the cohesion of the hydrogel, and the sulfonate group makes the hydrogel have an obvious ionic effect when contacting with positively charged substances, thus further improving the adhesion. Therefore, after adding SL, the adhesion performance of the material has been significantly improved. By comparing Examples 1 to 3, it can be found that in Example 2, that is, when the addition amount of the SL solution is 2 mL and the addition amount of deionized water is 4 mL, the hydrogel exhibits the best lap shear strength.
[0066] Comparative Example 2
[0067] This comparative example provides a method for preparing a hydrogel, specifically as follows:
[0068] (1) Prepare an SL solution by sulfonating lignin with APS. Add the polypyrrole (PPy) / ethanol solution to the 0.15 wt% SL solution and stir vigorously for 20 min until PPy is uniformly dispersed. Then, add the APS solution 1.5 times the weight of PPy dropwise to the SL-PPy solution. Stir the resulting mixture in an ice bath at 4 °C for 48 h to polymerize PPy and composite it with SL. Obtain PPy / SL by centrifuging and washing the resulting mixture several times with water and ethanol.
[0069] (2) Add AM, APS, BIS, and TMEDA into a crusher placed in an ice bath. After stirring the reaction mixture for 10 min, synthesize the PPy / SL-PAM hydrogel with a PPy content of 0.3 g.
[0070] Comparative Example 3
[0071] The difference between this comparative example and Comparative Example 2 is that in step (2), the PPy content is adjusted to 0.6 g, and the remaining preparation processes are the same as those in Comparative Example 2 to obtain the hydrogel.
[0072] Perform performance tests on the materials obtained in the above comparative examples, and the comparison results with Example 2 are shown in Table 2.
[0073] Table 2 Lap Shear Strength of Different Hydrogels on Different Substrates
[0074]
[0075] As can be seen from the above table, the hydrogels prepared by the present invention have good adhesion to substances on different substrates.
[0076] In summary, the strongly adhesive injectable self-healing hydrogel prepared by the present invention has excellent adhesion and injectability. In addition, it also has good ductility and self-healing ability. While ensuring the improvement of the above properties, the hydrogel prepared by the present invention also has characteristics such as good swelling property and water retention property. The materials for preparing the strongly adhesive injectable self-healing hydrogel are all materials that can be directly sold in the market, are basically harmless to the human body, and have no pollution to the environment, meeting the concepts of sustainable development and green chemistry.
[0077] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit them. Although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that the technical solutions of the present invention can be modified or equivalently replaced without departing from the spirit and scope of the technical solutions of the present invention, and they should all be covered within the scope of the claims of the present invention.
Claims
1. A preparation method of a strongly adherent injectable self-healing hydrogel, characterized in that: including Sodium hydroxide is dissolved in water, and acrylic acid is added thereto to obtain a 20-50% sodium acrylate solution; an initiator and a crosslinking agent are successively added to the sodium acrylate solution, and after stirring, a mixed solution A is obtained; a polyvinyl alcohol solution with a mass fraction of 8-12% is added to the mixed solution A, and after stirring and mixing, a mixed solution B is obtained; A sulfonated lignin solution with a concentration of 0.01-0.05 g / mL and deionized water are added to the mixed solution B, and they are mixed at a rotation speed of 350-450 rad / min; continuous stirring is carried out, and a 2-5% boric acid aqueous solution is slowly added dropwise. After the addition is completed, it is heated in an oil bath at 60-70 °C for 2-8 h, and at the same time, the rotation speed is adjusted to 250-340 rad / min; after cooling to room temperature, freeze-thaw cycles are carried out, with a frequency of freezing for 10-12 h and thawing at room temperature for 2-3 h. Such cycles are carried out 4-6 times. After the last thawing is completed, the hydrogel preparation is completed; wherein, the mass volume ratio of the sulfonated lignin solution, the boric acid aqueous solution and the polyvinyl alcohol solution is 1-2 mL∶2-10 mL∶2-10 g.
2. The preparation method of the strongly adhesive injectable self-healing hydrogel according to claim 1, characterized in that: The molar ratio of the sodium hydroxide to the acrylic acid is 1∶1.
3. The preparation method of the strongly adherent injectable self-healing hydrogel according to claim 1, wherein: The addition amount of the initiator is 0.1-1% of the acrylic acid; the initiator includes ammonium persulfate and sodium persulfate.
4. The preparation method of the strongly adhesive injectable self-healing hydrogel according to claim 1, wherein: The mass ratio of the polyvinyl alcohol solution to the mixed solution A is 5∶6-10.
5. The preparation method of the strongly adhesive injectable self-healing hydrogel according to claim 1, characterized in that: The addition amount of the crosslinking agent is 0.1-3% of the acrylic acid; the crosslinking agent includes methylene bisacrylamide.
6. The preparation method of the strongly adhesive injectable self-healing hydrogel according to claim 1, characterized in that: The sulfonated lignin solution is prepared by an acidolysis method, including 3-5 g of concentrated sulfuric acid is slowly added dropwise to a 10-20% lignin solution. After sufficient contact, it is heated in an oil bath at 90-120 °C for 2-5 h. After taking it out, the pH is adjusted to 2-4, and after centrifugation, the solid is taken out and put into a dialysis bag for dialysis for 7 days, and the solid content of the solution is concentrated and adjusted.
7. The preparation method of the strongly adhesive injectable self-healing hydrogel according to claim 6, characterized in that: The molecular weight of the lignin is 10 4 ~10 6 .
8. The preparation method of the strongly adherent injectable self-healing hydrogel according to claim 6, characterized in that: The degree of polymerization of the polyvinyl alcohol is 100,000-300,000, and the degree of alcoholysis is 78-98%.
9. A strongly adhesive injectable self-healing hydrogel according to any one of claims 1 to 8, characterized in that: The hydrogel has a double network structure; wherein, the first network is formed by dynamic crosslinking and hydrogen bond action and has good self-healing performance; the second network is formed by chemical crosslinking and has good mechanical strength.
10. Application of the strongly adhesive injectable self-healing hydrogel according to claim 9 in the fields of medical trauma and drug release.