Amylose hydrogel cross-linking agent as well as preparation method and application thereof

Abstract

The invention relates to an amylose hydrogel cross-linking agent as well as a preparation method and application thereof, and belongs to the technical field of hydrogel materials. The preparation method of the amylose hydrogel cross-linking agent comprises the following steps: mixing a starch aqueous solution with the amylose content of 52% with an oxidizing agent, placing the mixture in a dark environment, adjusting the pH value to 2-5 by using a dilute sulfuric acid solution, and then carrying out reaction, centrifugation, washing and drying to obtain the amylose hydrogel cross-linking agent. The entanglement degree between the hydrogel cross-linking agent and the gelatin molecular chain can be adjusted by controlling the amylose content. These promote the formation of a potentially stronger, more tough gel structure in the hydrogel. Based on the results, the hydrogel cross-linking agent based on amylose regulation and control can be suitable for any protein / polysaccharide with a multi-amino structure, so that the efficiency and the accuracy of a cross-linking reaction are improved, and a controllable cross-linking effect can be realized in wider application.

Description

Technical Field

[0001] This application relates to the field of hydrogel materials technology, and in particular to a linear starch hydrogel crosslinking agent, its preparation method, and its application. Background Technology

[0002] Hydrogels, due to their excellent water absorption, softness, and biocompatibility, have been widely used in various fields, such as pharmaceuticals, food packaging, and environmental remediation. However, existing crosslinking agents for hydrogels are mostly synthetic polymers, whose synthesis processes are complex, costly, and cause serious environmental pollution, and their performance control is not flexible enough. In particular, the limited availability and chemical properties of crosslinking agents pose certain challenges to optimizing the performance of hydrogels in practical applications.

[0003] While some progress has been made in utilizing natural polysaccharides as hydrogel crosslinking agents, their weak chemical reactivity limits the precision of crosslinking effects and performance regulation. Among published literature, Chinese patent CN117323977A discloses "A hydrogel adsorbent based on an interpenetrating network and its preparation method and application," specifically revealing an interpenetrating network formed by Schiff base reaction (chitosan-soluble starch hydrogel network) and photopolymerization reaction (acrylamide-N,N-methylenebisacrylamide network). Although this hydrogel, with its designed dual-network interpenetrating structure, simplifies the process with a "one-pot" method, its complex composition and low biodegradability, such as the involved acrylamide monomers and crosslinking agent N,N-methylenebisacrylamide, limit its application, particularly in fields requiring high biocompatibility like food. Chinese patent CN118662688A discloses "An antibacterial hydrogel based on Schiff base reaction and its preparation method and application," which specifically discloses that the hydrogel components include dialdehyde starch, vanillin, and polylysine. Although the prepared hydrogel has high biocompatibility, its properties are mainly adjusted by the molar ratio of amino to aldehyde groups, making precise control of its properties impossible.

[0004] Therefore, there is an urgent need to develop a novel natural crosslinking agent that is environmentally friendly and biodegradable, and can provide good tunability and optimization during the hydrogel crosslinking process. This crosslinking agent should not only be able to form stable crosslinks with a variety of materials under mild conditions, but also achieve precise performance control under different production conditions. Furthermore, the crosslinking agent should possess good process operability and feasibility for large-scale production to meet the needs of commercial applications. Developing such a natural crosslinking agent can not only optimize the physical properties of hydrogels, such as mechanical strength, thermal stability, and water absorption, but also ensure their advantages in environmental friendliness and sustainability, providing broader technical support for applications in biomedicine, environmental protection, and food packaging. Summary of the Invention

[0005] In view of this, this application provides a linear starch hydrogel crosslinking agent, its preparation method and application, which can effectively overcome the defects of the prior art.

[0006] The first aspect of this application provides a method for preparing a linear starch hydrogel crosslinking agent, comprising the following steps:

[0007] An aqueous solution of starch with a content of 52% amylose was mixed with an oxidant and placed in a dark environment. The pH was adjusted to 2-5 with dilute sulfuric acid solution, and then the reaction was carried out. After centrifugation, washing, and drying, an amylose hydrogel crosslinking agent was obtained. The reaction temperature is 34~45℃, and the reaction time is 3~5 hours; The centrifugation conditions are: centrifugation at 6000~8000 rpm for 15~20 min; the drying conditions are: drying at 40℃ for 12 h.

[0008] Preferably, the starch in the starch aqueous solution is corn starch or potato starch, and the mass fraction of the starch aqueous solution is 4-60%.

[0009] Preferably, the oxidant is a sodium periodate solution, the solvent of the sodium periodate solution is a 0.6 mol / L hydrochloric acid solution, and the concentration of the sodium periodate solution is 0.5~0.8 mol / L; the concentration of the dilute sulfuric acid solution is 0.1 mol / L.

[0010] Preferably, the mass ratio of the starch aqueous solution to the oxidant is 1:(1~1.5).

[0011] A second aspect of this application also provides a linear starch hydrogel crosslinking agent, which is prepared by the above method.

[0012] A third aspect of this application also provides the application of the above-mentioned linear starch hydrogel crosslinking agent in dialdehyde crosslinked hydrogels, comprising the following steps:

[0013] S1. Heat the gelatin solution at 55~80℃ until it is completely dissolved to obtain a gelatin solution, and store it at 35~55℃ for later use.

[0014] S2. Dissolve the above-mentioned amylose hydrogel crosslinking agent in water to prepare an appropriate concentration, stir in a boiling water bath until it becomes a paste, add 2 mol / L NaOH to adjust the pH to 9-10, and obtain the crosslinking agent solution;

[0015] S3. Under gentle stirring, the crosslinking agent solution is slowly added to the gelatin solution, and the reaction is carried out at a temperature of 35~45℃ for 2~5 hours to obtain a dialdehyde crosslinked hydrogel, which is then stored at a temperature of 4℃ for later use.

[0016] Preferably, in step S1, the concentration of the gelatin solution is 8-12%; in step S2, the concentration of the crosslinking agent solution is 8-12%.

[0017] Preferably, in step S3, the volume ratio of the crosslinking agent solution to the gelatin solution is (1~5):10.

[0018] Compared with the prior art, this application has the following advantages:

[0019] This application utilizes an aldehyde-rich amylose hydrogel crosslinking agent obtained through oxidative modification, which exhibits excellent crosslinking effects on gelatin / polysaccharide-based hydrogels. These biopolymer hydrogels demonstrate enhanced physical properties through synergistic crosslinking via physical interactions and reversible chemical bonds. The interaction and entanglement mechanisms between gelatin and hydrogel crosslinking agents with different amylose contents (long amylose chains and highly branched starch) differ. The gelatin-rich / dicalcium-amylose system exhibits higher gel hardness and toughness. In contrast, the system rich in gelatin / amylose hydrogel crosslinking agent shows higher strength. Therefore, the degree of entanglement between the hydrogel crosslinking agent and gelatin molecular chains can be tuned by controlling the amylose content. This promotes the formation of potentially stronger and more robust gel structures in the hydrogel. Based on these results, the amylose-regulated amylose hydrogel crosslinking agent of this application can be applied to proteins / polysaccharides with any polyamine structure, improving the efficiency and precision of the crosslinking reaction and enabling controllable crosslinking effects in a wider range of applications. Attached Figure Description

[0020] To more clearly illustrate the technical solutions in this application or the prior art, the drawings used in the description of this application or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this application. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0021] Figure 1 The microstructures of the hydrogels prepared in Examples 1-3 and Control Example 1;

[0022] Figure 2 Thermal property curves of the hydrogels prepared in Examples 1-3 and Comparative Example 1;

[0023] Figure 3 The T2 curves are the transverse relaxation time curves of the hydrogels prepared in Examples 1-3 and Control Example 1.

[0024] Figure 4 Photographs of the hydrogels prepared in Examples 1-3 and Control Example 1. Detailed Implementation

[0025] To make the objectives, technical solutions, and advantages of this application clearer, the technical solutions of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this application, not all embodiments. Based on the embodiments of this application, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this application.

[0026] Unless otherwise specified, the experimental methods used in the embodiments of this application are all conventional methods.

[0027] In the following examples and comparative examples, unless otherwise specified, all raw materials can be prepared by commercial purchase or conventional methods.

[0028] It should be understood that the terminology used in the embodiments of this application is merely for describing particular implementations and is not intended to limit this application. Furthermore, regarding the numerical ranges in the embodiments of this application, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Any stated value or intermediate value within a stated range, as well as each smaller range between any other stated value or intermediate value within said range, are also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0029] The preparation methods of the materials and solutions required in this application embodiment are as follows:

[0030] The hydrogels in the examples and comparative examples were composed of fish gelatin, high branched corn starch (4% amylose content, w / w) / ordinary corn starch (23% amylose content, w / w) / high amylose corn starch (52% amylose content, w / w), wherein the volume ratio between the hydrogel crosslinking agent and the gelatin was 5:10.

[0031] Example 1: The preparation process of the hydrogel is as follows:

[0032] A 4% (w / w) aqueous solution of highly branched corn starch was mixed with a 0.6 mol / L sodium periodate solution (dissolved in hydrochloric acid) at a mass ratio of 1:1.5 and reacted at 35°C for 3 hours. The mixture was then centrifuged at 8000 rpm for 15 min and washed with distilled water until a white starch powder was obtained (a small amount of acetone was added to prevent starch agglomeration). Finally, the precipitate was freeze-dried (at 40°C for 12 h) to obtain a 4% (w / w) amylose hydrogel crosslinking agent. The aldehyde content of the obtained hydrogel crosslinking agent (4% amylose) was determined to be 90.56%.

[0033] An 8% (w / w) gelatin solution was heated to 70°C until completely dissolved and then stored at 40°C for later use. An 8% (w / w) hydrogel crosslinking agent was stirred in a boiling water bath until a paste was formed, and the pH was adjusted to 10 with 2 mol / L NaOH. Subsequently, the hydrogel crosslinking agent solution was slowly added to the gelatin solution with gentle stirring. The volume ratio of the hydrogel crosslinking agent solution to the gelatin solution was 5:10. The mixture was reacted at 40°C for 2 hours to obtain the hydrogel.

[0034] Example 2

[0035] The hydrogel and its preparation method provided in this embodiment can be referred to in Embodiment 1, except that the starch used is ordinary corn starch, and the aldehyde content of the crosslinking agent of the obtained hydrogel is measured to be 86.54%.

[0036] Example 3

[0037] The hydrogel and its preparation method provided in this embodiment can be referred to in Example 1, except that the starch used is high amylose corn starch, and the aldehyde content of the crosslinking agent of the obtained hydrogel is measured to be 85.87%.

[0038] Compare with Example 1 The hydrogel and its preparation method provided in this comparative example can be referred to Example 1, except that no hydrogel crosslinking agent is used, and the hydrogel is prepared only with a gelatin solution of 8% by mass.

[0039] Test case

[0040] 1. Methods for testing the textural properties of hydrogels

[0041] The textural properties of the hydrogel were determined using a P / 36R probe of a texture analyzer. The parameters were set as follows: initial speed 2 mm / s, post-test speed 2 mm / s, and strain 60%. The hardness, elasticity, cohesiveness, adhesion, and chewiness of the gel were obtained using the texture analyzer software. The test results are shown in Table 1.

[0042] Table 1. Analysis of the textural properties of hydrogels

[0043] As shown in Table 1, hydrogels with added hydrogel crosslinking agents exhibit higher hardness and elasticity. This indicates that the hydrogel crosslinking agent helps the hydrogel form a more compact structure and enhances its ability to withstand secondary deformation.

[0044] 2. Methods for testing the microstructure of hydrogels

[0045] The microstructure of the hydrogel was observed using scanning electron microscopy. The sample was first frozen in liquid nitrogen and then freeze-dried for 48 hours. The dried sample was then cut along a cross-section and sputter-coated with gold. The pore structure of the hydrogel was observed at 100x magnification, and the test results are as follows. Figure 1 .

[0046] Depend on Figure 1 It is evident that the average pore size of Comparative Example 1 is larger (145.50 μm), with a thinner pore wall structure and a coarser gel. This indicates that the hydrogel formed solely by interwoven gelatin chains is merely a weak self-supporting system. The unevenly dispersed water molecules lead to larger ice crystals and an irregular network. In contrast, the hydrogels in the examples exhibit a more uniform internal structure, smaller pore size, and thicker pore wall structure, due to the introduced hydrogel crosslinking agent enhancing the network structure of the composite hydrogel. This increased gel strength hinders crystal growth, which in turn facilitates the formation of a high-strength, self-supporting, complex mesoporous structure during freeze-drying. The mechanical properties of the gel material are primarily attributed to the performance of the pore wall structure, as the pore walls act as a continuous phase in the composite gel structure, effectively absorbing stress during loading. Therefore, the thicker pore structure of the hydrogel can improve its mechanical properties, making it more suitable for potential applications such as cell culture scaffolds and drug delivery carriers.

[0047] 3. Test methods for the thermal properties of hydrogels

[0048] The thermal stability of the hydrogel samples was measured using a thermogravimetric analyzer. The measurement range was 30–500 °C; the heating rate was 10 °C / min at a nitrogen flow rate of 50 mL / min. The test results are as follows: Figure 2 .

[0049] Depend on Figure 2As can be seen from A and 2B, the weight loss process of the hydrogel can be divided into three stages: (1) 30~100℃: This stage corresponds to the evaporation of residual water; (2) 120~300℃: The sample degrades rapidly, and the weight drops sharply, possibly due to the partial thermal degradation of the hydrogel crosslinking agent; (3) 310~500℃: The weight loss in this stage is attributed to the further degradation of the biopolymer, leading to the formation of carbonaceous residues. It was observed that Control Example 1 showed the highest weight loss, and the largest weight loss stage occurred at a lower temperature compared to the Examples. This indicates that the crosslinking of the hydrogel crosslinking agent with gelatin results in the composite hydrogel exhibiting higher thermal stability than pure gelatin hydrogel. In addition, the maximum thermal degradation temperatures of Examples 1, 2 and 3 were 342.21℃, 350.27℃ and 352.87℃, respectively. Obviously, increasing the amylose content enhances the thermal stability of the composite hydrogel. This may be related to the network structure of the gel. The long amylose structure increases the degree of crosslinking of the hydrogel, further promoting the formation of the crosslinking network and enhancing the thermal stability of the hydrogel.

[0050] 4. Methods for testing the water distribution of hydrogels

[0051] Water distribution and migration in hydrogels were determined using low-field nuclear magnetic resonance (NMR). The hydrogel (10 mm in diameter; 15 mm in height) was placed in an NMR tube. The parameters were set as follows: instrument temperature 32℃, main frequency 20 MHz, pulse lengths of 90 and 180 pulses (P1 and P2) of 7.00 and 15.04 μs respectively, sampling point number 400044, and echo time 1 ms. The test results are shown below. Figure 3 .

[0052] Figure 3 Results A and 3B show that, compared to Control Example 1, the proportion of non-flowing water in the hydrogel with added hydrogel crosslinking agent is significantly increased, indicating a denser network structure that traps many water molecules within the gel. This affects the composition and migration of water molecules, resulting in a more uniform distribution and stronger water retention capacity. Compared to Example 1, Example 3 exhibits a higher T21 peak area ratio, indicating stronger binding of water molecules in this system. The entanglement of long amylose chains is much greater than that of highly branched starch chains, which enhances the network structure of the hydrogel. Therefore, due to the association of amylose chains, amylose typically acts as a structural builder and migration reducer in gel systems. Thus, the hydrogel with added amylose hydrogel crosslinking agent has a more stable gel network and can maintain the desired water content. This is crucial for applications where hydrogel stability and hydration performance are important.

[0053] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of this application, and are not intended to limit them. Although this application has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features therein. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of this application.

Claims

1. A method for preparing a linear starch hydrogel crosslinking agent, characterized in that, Includes the following steps: An aqueous solution of starch with a content of 52% amylose was mixed with an oxidant and placed in a dark environment. The pH was adjusted to 2-5 with dilute sulfuric acid solution, and then the reaction was carried out. After centrifugation, washing, and drying, an amylose hydrogel crosslinking agent was obtained. The reaction temperature is 34~45℃, and the reaction time is 3~5 hours; Centrifugation conditions: centrifuge at 6000~8000 rpm for 15~20 min; drying conditions: dry at 40℃ for 12 h.

2. The method for preparing the amylose hydrogel crosslinking agent according to claim 1, characterized in that, The starch in the starch aqueous solution is corn starch or potato starch, and the mass fraction of the starch aqueous solution is 4-60%.

3. The method for preparing the amylose hydrogel crosslinking agent according to claim 1, characterized in that, The oxidant is a sodium periodate solution, the solvent of which is a 0.6 mol / L hydrochloric acid solution, and the concentration of the sodium periodate solution is 0.5~0.8 mol / L; the concentration of the dilute sulfuric acid solution is 0.1 mol / L.

4. The method for preparing the amylose hydrogel crosslinking agent according to claim 1, characterized in that, The mass ratio of the starch aqueous solution to the oxidant is 1:(1~1.5).

5. A linear starch hydrogel crosslinking agent, characterized in that, A linear starch hydrogel crosslinking agent prepared by the method according to any one of claims 1 to 4.

6. The application of the amylose hydrogel crosslinking agent according to claim 5 in dialdehyde crosslinked hydrogels, characterized in that, Includes the following steps: S1. Heat the gelatin solution at 55~80℃ until it is completely dissolved to obtain a gelatin solution, and store it at 35~55℃ for later use. S2. Dissolve the amylose hydrogel crosslinking agent of claim 5 in water to prepare an appropriate concentration, stir in a boiling water bath until it becomes a paste, add NaOH to adjust the pH to 9-10, and obtain a crosslinking agent solution. S3. Under gentle stirring, the crosslinking agent solution is slowly added to the gelatin solution, and the reaction is carried out at a temperature of 35~45℃ for 2~5 hours to obtain a dialdehyde crosslinked hydrogel, which is then stored at a temperature of 4℃ for later use.

7. The application of the amylose hydrogel crosslinking agent according to claim 6 in dialdehyde crosslinked hydrogels, characterized in that, In step S1, the concentration of the gelatin solution is 8-12%; in step S2, the concentration of the crosslinking agent solution is 8-12%.

8. The application of the amylose hydrogel crosslinking agent according to claim 6 in dialdehyde crosslinked hydrogels, characterized in that, In step S3, the volume ratio of the crosslinking agent solution to the gelatin solution is (1~5):10.

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