A novel water-soluble starch hydrogel, and a preparation method and application thereof

Abstract

The application discloses a novel water-soluble starch hydrogel and a preparation method and application thereof, and belongs to the technical field of functional composite materials.The water-soluble starch hydrogel prepared by the application is combined by cationized water-soluble starch and aldehyde-based water-soluble starch through Schiff base cross-linking.The water-soluble starch hydrogel has good adhesion, rheological property, biocompatibility and degradability, and can accelerate the healing of diabetic wounds compared with commercial dressings.

Description

Technical Field

[0001] The invention relates to a novel water-soluble starch hydrogel and a preparation method and application thereof, belonging to the technical field of functional composite materials. Background Art

[0002] Bacterial infection of diabetic wounds, long-term high levels of oxidative stress, and hyperglycemia lead to serious complications, which are the biggest challenges in wound healing research. Wound dressings are considered an important component and come in many different types, including gauze, films, foams, or hydrogels. Their purpose is to directly contact the wound, protect it from further damage or infection, and promote healing. Among these dressings, hydrogels are gaining increasing attention as an ideal candidate for treating and protecting wounds with long-term inflammation.

[0003] Current research proposes hydrogel systems that achieve multifunctionality by loading multiple exogenous additives, such as antimicrobial agents, bioactive substances, and growth factors, to synergize and promote wound repair. However, these systems face challenges such as drug resistance, high costs, and complex manufacturing processes. Furthermore, hydrogels derived from petrochemical polymers that are chemically cross-linked, while possessing excellent mechanical properties, are often accompanied by poor biodegradability, suboptimal biocompatibility, and some side effects such as cytotoxicity and chronic rejection.

[0004] The document "A multifunctional hydrogel based on nature polysaccharide fabricated by Schiff base reaction;DOI:10.1016 / j.eurpolymj.2023.112330" discloses the preparation of multifunctional hydrogels using carboxymethyl chitosan (CMCS) and oxidized hyaluronic acid (OHA); the document "Status and future scope of plant-based green hydrogels in biomedical engineering;DOI:10.1016 / j.apmt.2019.04.010" discloses the preparation of hydrogels using plant-based materials using Schiff base reaction; and patent CN118384315A discloses the preparation of composite hydrogels using dextran and sodium hyaluronate, which can be used for wound repair. The above technical solutions all require the use of two or more raw materials when preparing hydrogels. Although the prepared hydrogels have good strength, they are actually not conducive to wound healing and recovery, and the chemical reagents (such as cross-linking agents) introduced in the preparation process may produce degradation products during use, which raises safety issues. The preparation method of the water-soluble starch hydrogel provided by the present invention only involves simple physical mixing, does not use any exogenous additives in the preparation process, and is green, safe, and has no toxic side effects.

[0005] A renewable water-soluble starch with a compact, spherical and dendritic structure was discovered from sweet cereals. It contains a large number of hydroxyl groups on its surface and has unique functional properties such as excellent water retention, low intrinsic viscosity and good stability. Water-soluble starch can provide energy to skin cells by stimulating ATP production and cell metabolism, leading to increased production of hyaluronic acid and collagen. Water-soluble starch, which has the same structure as the skin, is the most effective energy source for skin cells and has multiple functions such as moisturizing, repairing, empowering, and anti-aging. In recent years, the unique hyperbranched dendritic nanostructure has made water-soluble starch an excellent carrier for lipophilic bioactive compounds. However, research on the preparation and application of water-soluble starch hydrogels has not yet appeared.

[0006] Therefore, developing a natural, renewable, and multifunctional hydrogel that uses only water-soluble starch as the hydrogel material without adding exogenous additives is of great significance for wound dressings. Summary of the Invention

[0007] To address these issues, the present invention utilizes water-soluble starch to prepare cationized water-soluble starch and formaldehyde-formyl water-soluble starch, respectively, and then prepares a water-soluble starch hydrogel based on this. The hydrogel prepared by the present invention has simple and natural components, effectively promotes wound healing, and exhibits good mechanical properties.

[0008] The first object of the present invention is to provide a method for preparing a water-soluble starch hydrogel, comprising the steps of:

[0009] (1) mixing water-soluble starch and water, adding ethylenediamine, reacting; then adding 2,3-epoxypropyltrimethylammonium chloride, reacting; after the reaction is completed, adding ethanol, precipitating, and drying to prepare cationic water-soluble starch;

[0010] The water-soluble starch and water are mixed, sodium periodate is added, and the mixture is reacted; after the reaction is completed, ethylene glycol is added, dialyzed, and dried to prepare the aldehyde-modified water-soluble starch;

[0011] (2) preparing an aqueous solution of cationized water-soluble starch and aldehyde-hydrated water-soluble starch, adding the cationized water-soluble starch aqueous solution to the aldehyde-hydrated water-soluble starch aqueous solution, and reacting the aqueous solution to obtain a water-soluble starch hydrogel.

[0012] In one embodiment, the water-soluble starch hydrogel is formed by combining cationic water-soluble starch and aldehyde-treated water-soluble starch through Schiff base cross-linking.

[0013] In one embodiment, the ratio of water-soluble starch, water, and ethylene glycol in step (1) is 1-10 g: 200-300 mL: 2-20 mL;

[0014] The molar ratio of 2,3-epoxypropyltrimethylammonium chloride to water-soluble starch is 1:1-20;

[0015] Optionally, the molar ratio of 2,3-epoxypropyltrimethylammonium chloride to water-soluble starch is 1:10-20;

[0016] Preferably, the molar ratio is 1:14-16.

[0017] In one embodiment, the ratio of water-soluble starch to water in step (1) is 1-10 g: 50-500 mL;

[0018] The molar ratio of water-soluble starch to sodium periodate is 1-4:1.

[0019] In one embodiment, in the water-soluble starch hydrogel of step (2), the mass ratio of the cationic water-soluble starch to the aldehyde-treated water-soluble starch is 1-10:1-5.

[0020] Optionally, the mass ratio of the cationic water-soluble starch to the aldehyde-hydrated water-soluble starch is 1 to 2:1; preferably, the mass ratio is 2:1.

[0021] In one embodiment, the preparation method of water-soluble starch comprises:

[0022] The su1 sweet grains are crushed and mixed with water, centrifuged, and a first supernatant is collected; the pH value of the first supernatant system is adjusted, centrifuged, and a second supernatant is collected; the second supernatant system is adjusted, centrifuged, and a third supernatant is collected, boiled, allowed to stand, and then centrifuged to collect a fourth supernatant; excess anhydrous ethanol is added to the fourth supernatant, followed by standing, filtration, and drying to obtain water-soluble starch.

[0023] In one embodiment, the preparation method of water-soluble starch comprises:

[0024] The su1 sweet grains are crushed and mixed with water, centrifuged, and a first supernatant is collected; the pH value of the first supernatant system is adjusted, centrifuged, and a second supernatant is collected; the second supernatant system is adjusted, centrifuged, and a third supernatant is collected, boiled, allowed to stand, and then centrifuged to collect a fourth supernatant; excess anhydrous ethanol is added to the fourth supernatant, followed by standing, filtration, and drying to obtain water-soluble starch.

[0025] In one embodiment, the preparation method of water-soluble starch comprises:

[0026] Take corn, add 5 times the mass volume of deionized water to it, soak it at 4°C overnight; beat it, and pass it through a 300-mesh sieve; add deionized water to the filter residue and beat it again, pass it through a 300-mesh sieve, collect the filtrate twice, and let the filtrate stand at 4°C to remove the precipitate;

[0027] The pH of the liquid was adjusted to 4.9 with acetic acid, and the mixture was allowed to stand at 4°C for 2 hours. The liquid was centrifuged and the supernatant was collected. The pH of the supernatant was adjusted to 7.0 with Na2CO3 solution, and the mixture was boiled in a boiling water bath for 30 minutes. The mixture was allowed to stand at 4°C for 2 hours, and the supernatant was collected after centrifugation.

[0028] Under stirring, anhydrous ethanol is added to the supernatant until the volume fraction of ethanol in the solution is 75%, and the solution is allowed to stand at 4°C for 2 hours; the mixed solution is filtered, and the filter cake is rinsed with anhydrous ethanol, and the filter cake is dissolved in water again to perform a secondary alcohol precipitation process, and then the filter cake is naturally spread out and dried to obtain water-soluble starch.

[0029] The second object of the present invention is to provide a water-soluble starch hydrogel prepared by any of the above methods.

[0030] In one embodiment, the liquid absorption swelling rate of the water-soluble starch hydrogel is 100% to 300%, the adhesion force reaches 400 to 2500 mN, and the hardness reaches 100 to 300 g.

[0031] A third object of the present application is to provide any of the above-mentioned methods or the above-mentioned hydrogel for use in the biomedical field.

[0032] In one embodiment, the use comprises preparing a wound repair material, a drug delivery material, a tissue filling material, a hemostatic material.

[0033] A fourth object of the present application is to provide a wound repair product comprising the above-mentioned water-soluble starch hydrogel.

[0034] In one embodiment, the product is a dressing for promoting the healing of chronic wounds in diabetes.

[0035] A fifth object of the present application is to provide a method for improving the wound repair effect of a hydrogel, the hydrogel being prepared using water-soluble starch, comprising the steps of:

[0036] (1) mixing water-soluble starch and water, adding ethylenediamine, and reacting; then adding 2,3-epoxypropyltrimethylammonium chloride, and reacting; after the reaction is completed, adding ethanol, and precipitating and drying to prepare cationized water-soluble starch;

[0037] mixing water-soluble starch and water, adding sodium periodate, and reacting; after the reaction is completed, adding ethylene glycol, and dialyzing and drying to prepare aldehyde-modified water-soluble starch;

[0038] (2) preparing an aqueous solution of the cationized water-soluble starch and the aldehyde-modified water-soluble starch, adding the aqueous solution of the cationized water-soluble starch to the aqueous solution of the aldehyde-modified water-soluble starch, and reacting to obtain a water-soluble starch hydrogel.

[0039] Advantages of the present application

[0040] The water-soluble starch hydrogel provided by the present application is combined by Schiff base cross-linking of cationized water-soluble starch and aldehyde-modified water-soluble starch; the water-soluble starch hydrogel prepared by the present application has a liquid absorption and swelling rate of 100-300%, a degradation rate of 26.54±1.36-39.90±1.96% in 11 hours, an adhesion force of 400-2500 mN, a hardness of 100-300 g, excellent antibacterial properties, and excellent wound healing effect.

[0041] Specifically,

[0042] (1) The water-soluble starch hydrogel of the present invention uses water-soluble starch as a raw material, so it is more natural, green and safe, so that the hydrogel does not contain exogenous additives such as metal compounds, growth factors, antibiotics or nanoparticles, and has inherent antibacterial, antioxidant and immunomodulatory properties, which synergistically promote the healing of chronic wounds. Water-soluble starch is a highly branched soluble α-D-glucan connected by α-1,4 and α-1,6 glycosidic bonds. Due to its short average chain length, high branching degree, and structural characteristics such as a dendritic branching pattern with tight outside and loose inside and a small particle size, it has a large number of hydroxyl groups in its molecular structure, which can undergo acylation, oxidation and carboxymethylation reactions, and can also form hydrogen bonds with water molecules, so it has excellent water retention. Water-soluble starch is the storage form of glucose in the human body and is also the main energy substance required for skin metabolism. Water-soluble starch, which has the same structure as the skin, is the most effective energy source for skin cells and has multiple functions such as moisturizing, repairing, empowering, anti-aging, immunomodulation and macrophage stimulation activity. The grafted quaternary ammonium salt groups have good antibacterial activity, while the added acetaldehyde groups enhance the antioxidant activity and adhesion of the hydrogel. The present invention provides a simple and effective method for preparing a multifunctional natural hydrogel dressing, which has great potential for promoting the healing of chronic diabetic wounds.

[0043] (2) The preparation method of the water-soluble starch hydrogel provided by the present invention is green, safe, and non-toxic. This method solves the problems faced by most current studies on hydrogels that use synergistic effects of multiple exogenous additives such as antimicrobial agents, bioactive substances, and growth factors, such as the development of drug resistance, high costs, and complex production processes.

[0044] (3) The water-soluble starch hydrogel provided by the present invention is formed by combining cationic water-soluble starch and aldehyde-soluble starch through Schiff base cross-linking, and has antibacterial and antioxidant properties, good adhesion and rheological properties, and biocompatibility for scavenging active oxygen and immunomodulation. The water-soluble starch hydrogel avoids the limitations of petrochemical polymer hydrogels, such as poor biodegradability, unsatisfactory biocompatibility, and some cytotoxicity and chronic rejection side effects. The results show that the water-soluble starch hydrogel of the present invention accelerates the healing process of diabetic wounds, and the wound healing rate is 1.76 times that of commercially available dressings. BRIEF DESCRIPTION OF THE DRAWINGS

[0045] Figure 1 This is a scanning electron microscope image of the water-soluble starch hydrogel prepared in Example 1 at 100 μm.

[0046] Figure 2 This is a scanning electron microscope image of the water-soluble starch hydrogel prepared in Example 2 at 100 μm.

[0047] Figure 3 This is a comparison chart of the infrared absorption spectra of the water-soluble starch hydrogels prepared in Example 1 and Example 2.

[0048] Figure 4 The liquid absorption and swelling rate curves of the water-soluble starch hydrogels prepared in Examples 1 and 2 are shown.

[0049] Figure 5 The degradation rate curves of the water-soluble starch hydrogels prepared in Example 1 and Example 2 are shown.

[0050] Figure 6 These are the adhesion force / displacement curves of the water-soluble starch hydrogels prepared in Examples 1 and 2.

[0051] Figure 7 The hardness of the water-soluble starch hydrogel prepared in Example 1 and Example 2 was measured.

[0052] Figure 8 The graphs show the change of storage modulus and loss modulus over time during the continuous jump strain change of the water-soluble starch hydrogels prepared in Example 1 and Example 2.

[0053] Figure 9 These are photos of the inhibition zones of the water-soluble starch hydrogels prepared in Examples 1 and 2 against Staphylococcus aureus and Escherichia coli.

[0054] Figure 10 These are representative photos of the water-soluble starch hydrogel prepared in Example 2 applied to the wounds of a diabetic mouse model on days 0, 3, 7, and 14.

[0055] Figure 11 This is the adhesion curve of the water-soluble starch hydrogel prepared in Comparative Example 1.

[0056] Figure 12 The wound healing effect of the water-soluble starch hydrogel prepared in Comparative Example 1 is shown. DETAILED DESCRIPTION

[0057] The following describes preferred embodiments of the present invention. It should be understood that the embodiments are for better explanation of the present invention and are not intended to limit the present invention.

[0058] The raw materials used in the embodiment are:

[0059] su1 sweet grains were purchased from Beijing Agricultural Science Institute;

[0060] 2,3-Epoxypropyltrimethylammonium chloride was purchased from Sigma-Aldrich.

[0061] Test method:

[0062] 1. Swelling rate and degradation rate detection method:

[0063] The swelling rate and degradation rate of the hydrogel are determined by soaking the sample in PBS solution and weighing it at predetermined time intervals. After the freshly prepared hydrogel is freeze-dried, the sample is accurately weighed (recorded as W0) and then soaked in PBS at 37°C, pH 7.4. At predetermined time intervals, the hydrogel is removed from the PBS solution. After gently absorbing excess surface moisture with moistened filter paper, the weight is recorded as Wp. This process is repeated until the hydrogel reaches water absorption equilibrium. The swelling rate calculation formula is as follows:

[0064] where Wp and W0 represent the weights of the initial freeze-dried hydrogel and the swollen hydrogel, respectively.

[0065] Accurately weigh the freshly prepared hydrogel sample (denoted as W f ) and then immersed in PBS at 37°C, pH 7.4. At predetermined time intervals, the hydrogel was removed from the PBS solution. The excess surface water was gently absorbed with a moistened filter paper and the weight was recorded as W. r The degradation rate calculation formula is as follows:

[0066] Among them, W f and W r represent the weight of the initial hydrogel and the remaining hydrogel, respectively.

[0067] 2. Adhesion force / displacement curve detection method:

[0068] The hydrogel was placed between two identical glass plates, with an application area of ​​1 cm 2 The thickness of the hydrogel was 1 mm and the pressure was applied for 5 minutes to obtain sufficient adhesion. The relationship between the adhesion force and displacement of the hydrogel was recorded using a universal material tensile testing machine to characterize its adhesion performance. All tests were carried out at a speed of 2 mm min -1 The stretching is carried out at a constant speed.

[0069] The relationship between the adhesion force and displacement of the hydrogel was recorded using a tensile tester to characterize the adhesion properties of the hydrogel.

[0070] 3. Hardness testing method:

[0071] The hardness of the hydrogel was analyzed using a TA.XTC-20 texture analyzer with a 36 mm cylindrical probe and a test speed of 0.05 mm / s.

[0072] 4. Storage modulus and loss modulus detection method:

[0073] The rheological properties of the hydrogels were investigated using an Anton Paar rheometer (MCR 302) through dynamic amplitude sweep, frequency sweep, viscosity measurement, and strain sweep experiments. Static shear rheology measurements were used to determine the apparent viscosity (η) of the hydrogel samples at 25°C as a function of shear rate (γ) increasing from 0.01 s⁻¹ to 100 s⁻¹. Cyclic strain sweep (thixotropy) experiments were used to observe the strain variations of the hydrogels between 1% and 1000% to assess their self-healing ability. Based on the strain sweep results, the linear viscoelastic range was set to 0.1%, and a small-amplitude oscillatory shear mode was employed. The temperature was maintained at 25°C to measure the changes in the storage modulus (G') and loss modulus (G") over a frequency range of 0.1 Hz to 100 Hz.

[0074] 5. Antibacterial effect detection method:

[0075] Place two sterile Oxford cups (Φ7.8×6×10mm) evenly in each sterile Petri dish with a diameter of 70mm. Then, pour about 15mL of melted LB solid medium into the Petri dish, wait for the medium to solidify, and remove the Oxford cup. Add 50μL of Escherichia coli (10 7 CFU / mL) and 50 μL of Staphylococcus aureus (10 6 CFU / mL) bacterial solution and spread evenly. Then, add 150 μL of sterile hydrogel extract at a concentration of 4 mg / mL to each well. Add buffer to the microwells as a control. Cover the culture dish with a parafilm sealant and pre-diffusion in a 4°C refrigerator for 2 hours, then incubate in a 37°C incubator for 24 hours. Photograph and record the zone of inhibition.

[0076] 6. Wound healing effect detection method:

[0077] Type 1 diabetes was induced in male Kunming mice by subcutaneous injection of 60 mg / kg of 1% streptozotocin (STZ) solution. One week after STZ injection, blood glucose levels were measured using a Sinovac blood glucose meter. Mice with blood glucose levels exceeding 11.1 mmol / L were selected to establish a wound infection model. For the full-thickness infected wound model, a 1 cm diameter wound was created on the back of each mouse using surgical scissors. The diabetic mice with wound infection were randomly divided into three treatment groups (n=6): control group; commercial wound dressing (Tegaderm) group; and hydrogel CPG2-Gel group (wound diameter 1 cm, sample load 0.2 g). Wound photographs were taken on days 0, 3, 7, 10, and 12. Wound area was measured and analyzed using ImageJ software.

[0078] Example 1: Preparation of water-soluble starch hydrogel

[0079] 1. The preparation method of water-soluble starch comprises the following steps:

[0080] A certain mass of corn was taken, 5 times its mass volume of deionized water was added to it, and the corn was soaked overnight at 4°C; the corn was pulped and passed through a 300-mesh sieve; deionized water was added to the residue and the corn was pulped again, and the corn was passed through a 300-mesh sieve; the filtrates were collected and allowed to stand at 4°C to remove the precipitate;

[0081] The pH of the liquid was adjusted to 4.9 with acetic acid, and the mixture was allowed to stand at 4°C for 2 hours. The liquid was centrifuged and the supernatant was collected. The pH of the supernatant was adjusted to 7.0 with Na2CO3 solution, and the mixture was boiled in a boiling water bath for 30 minutes. The mixture was allowed to stand at 4°C for 2 hours, and the supernatant was collected after centrifugation.

[0082] Under stirring, anhydrous ethanol is added to the supernatant until the volume fraction of ethanol in the solution is 75%, and the solution is allowed to stand at 4°C for 2 hours; the mixed solution is filtered, and the filter cake is rinsed with anhydrous ethanol, and the filter cake is dissolved in water again to perform a secondary alcohol precipitation process, and then the filter cake is naturally spread out and dried to obtain water-soluble starch.

[0083] 2. The preparation method of water-soluble starch hydrogel is as follows:

[0084] (1) Cationized and aldehyde-treated water-soluble starch

[0085] 5 g of water-soluble starch was mixed with 250 mL of deionized water, and 15 mL of ethylenediamine was added. The mixture was stirred at 50 ° C for 4 h, and then 2,3-epoxypropyltrimethylammonium chloride was added. The molar ratio of water-soluble starch to 2,3-epoxypropyltrimethylammonium chloride was 1:1. The mixture was stirred at 50 ° C for 2 h at a speed of 200 rpm. After the reaction was completed, it was diluted with 3 times ethanol and stored at 4 ° C to obtain a precipitate. The precipitate was dried in an oven to obtain a cationic water-soluble starch.

[0086] Water-soluble starch was dissolved in deionized water (0.05 g / mL), sodium periodate was added, and the molar ratio of water-soluble starch to sodium periodate was 2:1. The mixture was stirred at 30°C (200 rpm) for 2 h, and then 10% (v / v) ethylene glycol was added. The mixture was dialyzed for 2 days and freeze-dried to obtain hydroformylated water-soluble starch.

[0087] (2) Preparation of hydrogel

[0088] A 0.1 g / mL cationized water-soluble starch solution was prepared by using cationic water-soluble starch, and a 0.05 g / mL aldehyded water-soluble starch solution was prepared by using hydroformylation water-soluble starch;

[0089] 0.1 g / mL cationic water-soluble starch solution was added dropwise to 0.05 g / mL aldehyded water-soluble starch solution at a volume ratio of 1:1, and a cross-linking reaction was carried out at 30° C. for 10 minutes to obtain a water-soluble starch hydrogel.

[0090] Example 2: Preparation of water-soluble starch hydrogel

[0091] On the basis of Example 1, in step (1) of 2, the molar ratio of water-soluble starch to 2,3-epoxypropyltrimethylammonium chloride was changed to 1:15, and the remaining steps were consistent with Example 1 to prepare a water-soluble starch hydrogel.

[0092] Example 3: Performance testing of water-soluble starch hydrogel

[0093] 1. Testing of water-soluble starch properties

[0094] The water-soluble starch, cationic water-soluble starch, and formaldehyde-treated water-soluble starch prepared in Example 1 and the cationic water-soluble starch prepared in Example 2 were tested for weight-average molecular weight (MW), average particle size, z-average root mean square radius (RZ), molecular density (ρ), polydispersity (PDI), degree of substitution, and ζ potential (ζ). The results are shown in Table 1.

[0095] Table 1 Water-soluble starch property test

[0096]

[0097] The results showed that the degree of substitution of the cationic water-soluble starches in Examples 1 and 2 increased from 18.50±0.50% to 38.15±1.67%, and the particle size increased from 85.27±1.86nm to 219.73±13.74nm. As the degree of substitution increases, the number of quaternary ammonium groups introduced into the water-soluble starch molecules increases, leading to an increase in charge density. This higher charge density enhances the electrostatic repulsion between molecules, making the molecular chains more stretched, thus increasing the particle size.

[0098] At the same time, the ζ-potential of the cationic water-soluble starch of Examples 1 and 2 increased from 5.77±0.77 to 28.78±4.32mV. This is because the presence of quaternary ammonium cations (three methyl groups and one glycidyl group attached to the N atom, and a positive charge) in the 2,3-epoxypropyltrimethylammonium chloride molecule increases the ζ-potential of the water-soluble starch derivative. The charged nature of quaternary ammonium salts gives water-soluble starch a certain antibacterial ability, because the positive charge carried by quaternary ammonium salts can attract the negatively charged components on the surface of bacterial cell membranes. When quaternary ammonium salts accumulate on the cell membrane, they interfere with the normal structure and function of the cell membrane.

[0099] On this basis, the molecular weights of the cationic water-soluble starches and the water-soluble starches derivatized with aldehydes in Examples 1 and 2 were both reduced. This is because the derivatization reactions with 2,3-epoxypropyltrimethylammonium chloride and sodium periodate, respectively, resulted in the formation of new functional groups through the cleavage of glycosidic bonds. Glycosidic bonds are the chemical bonds connecting glucose units, and their cleavage shortens the chain length of the water-soluble starch molecules, resulting in a decrease in molecular weight.

[0100] 2. Testing of water-soluble starch properties

[0101] (1) Scanning electron microscopy

[0102] The water-soluble starch hydrogels prepared in Examples 1 and 2 were characterized using a scanning electron microscope. Figure 1 、 Figure 2 The results showed that the SEM image of the hydrogel showed a typical porous microstructure, but the structure of the water-soluble starch hydrogel of Example 2 was relatively dense.

[0103] (2) Infrared absorption spectrum

[0104] The water-soluble starch hydrogels prepared in Examples 1 and 2 were characterized using infrared absorption spectroscopy.

[0105] The results are as follows Figure 3 As shown, at 1645cm -1 There is a very obvious imine bond (C=N) stretching vibration absorption peak, which is the infrared characteristic absorption peak of Schiff base. The results show that cationic water-soluble starch and aldehyde-treated water-soluble starch form hydrogel through Schiff base cross-linking.

[0106] (3) Swelling properties

[0107] Swelling is a key property of an ideal wound dressing. It should absorb fluid and exudate from the wound surface and maintain adequate moisture in the wound area to facilitate wound recovery. An ideal wound dressing should have a fluid absorption swelling rate of 100% to 900%.

[0108] The water-soluble starch hydrogels prepared in Examples 1 and 2 were placed in a PBS buffer solution, and their swelling properties were characterized by measuring the mass of the hydrogels at different time points.

[0109] The results are as follows Figure 4 The results show that the mass of the water-soluble starch hydrogels prepared in Examples 1 and 2 gradually increased over time. After immersion for 6 hours, the hydrogels expanded to approximately 200% of their initial mass. Afterward, the swelling reached equilibrium and no further mass increase occurred. The high swelling capacity of the hydrogel in Example 2 is related to its porous structure and cross-linking bonds.

[0110] (4) Degradation rate

[0111] The water-soluble starch hydrogels prepared in Examples 1 and 2 were taken to detect the degradation rate of the hydrogels.

[0112] As shown in the results, the degradation rates of the water-soluble starch hydrogels prepared in Example 1 and Example 2 were 39.90 ± 1.96% and 26.54 ± 1.36% respectively after 11 h; the degradation rate of the hydrogel of Example 2 was lower, which was due to its stronger cross-linking effect and more stable hydrogel structure. Figure 5 (5) Adhesion

[0113] The water-soluble starch hydrogels prepared in Examples 1 and 2 were taken to detect the adhesion / displacement curve of the hydrogels, and the hydrogels were placed between two glass plates for lap shear test, and the relationship between the adhesion force and displacement was obtained by universal testing machine test.

[0114] As shown in the results, the maximum adhesion forces of the water-soluble starch hydrogels prepared in Example 1 and Example 2 under the same displacement conditions reached 433.68 mN and 2342.86 mN respectively; it can be seen that the adhesion performance of the hydrogel of Example 2 was better than that of Example 1.

[0115] Figure 6 (6) Hardness

[0116] A hydrogel dressing with moderate hardness can provide certain mechanical protection for the wound to prevent external physical irritation and bacterial invasion. At the same time, it can well adhere to the wound surface without causing additional pressure or friction damage to the wound, and promote wound healing.

[0117] The water-soluble starch hydrogels prepared in Examples 1 and 2 were taken to detect the hardness of the hydrogels.

[0118] As shown in the results, the hardness of the water-soluble starch hydrogels prepared in Example 1 and Example 2 also showed similar characteristics to the adhesion performance, and the hardness increased with the increase of the degree of substitution; among them, the hardness of the hydrogel of Example 2 was the largest, reaching 288.98 ± 2.14 g.

[0119] (7) Storage modulus and loss modulus Figure 7 The water-soluble starch hydrogels prepared in Examples 1 and 2 were taken to characterize the self-healing performance and viscoelastic behavior of the water-soluble starch hydrogels prepared in Examples 1 and 2 by rheological measurement.

[0120] As shown in the results, the storage modulus and loss modulus of the water-soluble starch hydrogels prepared in Example 1 and Example 2 were 0.01 Pa and 0.01 Pa respectively, and the storage modulus and loss modulus of the hydrogel of Example 2 were 0.01 Pa and 0.01 Pa respectively.

[0121]

[0122] Figure 8 ​​​As shown in the figure, according to the strain amplitude sweep test, 1% and 100% strains were selected for 5 cycle tests. When a large strain was applied, the storage modulus dropped significantly and was lower than the dissipation modulus, indicating that the network was broken. When the strain was switched to 1%, the network could recover, indicating that the storage modulus and dissipation modulus values ​​were immediately and completely restored to their original state. Even after four repeated cycles, the modulus curve did not change significantly, which shows that the water-soluble starch hydrogel of the present invention has excellent self-healing ability.

[0123] (8) Antibacterial effect

[0124] The water-soluble starch hydrogels prepared in Examples 1 and 2 were used to detect their antibacterial effects on Staphylococcus aureus and Escherichia coli using the inhibition zone method.

[0125] The results are as follows Figure 9 As shown, there are very clear inhibition zones on the bacterial plates after being treated with the water-soluble starch hydrogels prepared in Examples 1 and 2. As the degree of substitution increases, the diameter of the inhibition zone gradually increases.

[0126] The above results demonstrate that the water-soluble starch hydrogel of the present invention has a significant inhibitory effect on Staphylococcus aureus and Escherichia coli, and exhibits excellent antibacterial properties.

[0127] (9) Wound healing effect

[0128] The water-soluble starch hydrogels prepared in Examples 1 and 2 were used to test their wound healing effects on diabetic mice (0, 3, 7, and 14 days).

[0129] The results are as follows Figure 10 As shown, circular diabetic wounds were treated with the hydrogel from Example 2 and a commercially available Tegaderm dressing, and wound healing was monitored after 3, 7, and 14 days. Digital photographs of wound closure markings show gradual circular healing of the diabetic wounds in both the hydrogel from Example 2 and commercially available hydrogel groups, with the hydrogel from Example 2 demonstrating superior wound healing. Over the 14-day observation period, the hydrogel from Example 2 significantly accelerated wound healing.

[0130] Compared to the commercially available hydrogel group or the control group, the healing rate of the hydrogel in Example 2 was statistically further improved, reaching 70.77%, which is 1.76 times higher than the healing rate of the commercially available dressing. This shows that the water-soluble starch hydrogel prepared in Example 2 is an excellent hydrogel for promoting diabetic wound healing.

[0131] The hydrogel prepared in Example 2 has the following advantages compared to the pure starch-based hydrogel prepared from ordinary starch:

[0132] (1) Pure starch-based hydrogels prepared from ordinary starch have low strength and insufficient toughness, and usually require the addition of functional polymers to form a double network structure for modification; however, the water-soluble starch hydrogel prepared in Example 2 has higher strength and toughness, can more evenly disperse stress when subjected to external force, and has a stronger ability to resist deformation and rupture;

[0133] (2) The pure starch-based hydrogel prepared from ordinary starch has poor water absorption and water retention capabilities, which is not conducive to providing a more lasting moist environment for cell growth or wound healing. However, the branched structure and functional groups on the molecular surface of the water-soluble starch hydrogel prepared in Example 2 may give it a higher water absorption capacity and can better retain moisture for a certain period of time. In a dry environment, the water retention performance may be better, which can provide a more lasting moist environment for cell growth or wound healing.

[0134] (3) The structure of the starch molecules in the pure starch-based hydrogel prepared from ordinary starch may change under high or low temperature conditions, which may affect the performance of the hydrogel and make it less stable. However, the water-soluble starch hydrogel prepared in Example 2 can maintain good network structure integrity and original function when facing changes in temperature, pH value, etc.

[0135] (4) The size and crystallinity of starch particles in the pure starch-based hydrogel prepared from ordinary starch will affect the recognition of the immune system and trigger an inflammatory response. However, the molecular structure of the water-soluble starch in the water-soluble starch hydrogel prepared in Example 2 has certain similarities with the carbohydrate substances in the body. Its immunogenicity, on the one hand, is conducive to maintaining the stability of the local immune environment, and on the other hand, it has a certain anti-inflammatory effect, which can reduce the inflammatory response and promote tissue repair.

[0136] Comparative Example 1: Preparation of hydrogel using water-soluble starch and glutaraldehyde

[0137] Based on Example 2, 1 g of cationic water-soluble starch was dissolved in 10 mL of a 25% glutaraldehyde aqueous solution, and the mixture was stirred with a vortex mixer to obtain a water-soluble starch / glutaraldehyde hydrogel after thorough mixing.

[0138] Testing of properties of water-soluble starch glutaraldehyde hydrogel

[0139] (1) Adhesion

[0140] The water-soluble starch / glutaraldehyde hydrogel prepared in Comparative Example 1 was taken, and the adhesion force / displacement curve of the hydrogel was tested. The hydrogel was placed between two glass plates for a lap shear test, and the relationship between the adhesion force and the displacement was obtained by testing with a universal testing machine.

[0141] The results are as follows Figure 11As shown, the adhesion force of the water-soluble starch hydrogel prepared in Comparative Example 1 under the same displacement conditions reaches 3670 mN; it can be seen that the adhesion force of the hydrogel in Comparative Example 1 is greater than that in Examples 1 and 2.

[0142] (2) Wound healing effect

[0143] The water-soluble starch hydrogel prepared in Comparative Example 1 was used to test its healing effect on the wounds of diabetic mice (0, 3, 7, and 14 days). Figure 12 As shown, the water-soluble starch / glutaraldehyde hydrogel has too strong adhesion to the skin, penetrates into the skin and affects skin recovery, hindering dressing changes.

[0144] Although the present invention has been disclosed above in terms of preferred embodiments, it is not intended to limit the present invention. Anyone familiar with this technology can make various changes and modifications without departing from the spirit and scope of the present invention. Therefore, the scope of protection of the present invention should be based on the definition of the claims.

Claims

1. A method for preparing a water-soluble starch hydrogel, characterized in that: Including steps: (1) Mixing water-soluble starch and water, adding ethylenediamine, and reacting; then adding 2,3-epoxypropyltrimethylammonium chloride, and reacting; after the reaction, adding ethanol, precipitating, and drying to prepare cationic water-soluble starch; The water-soluble starch and water are mixed, sodium periodate is added, and the mixture is reacted; after the reaction is completed, ethylene glycol is added, dialyzed, and dried to prepare the aldehyde-modified water-soluble starch; (2) Aqueous solutions of cationized water-soluble starch and aldehyde-hydrated water-soluble starch are prepared separately, and the cationized water-soluble starch aqueous solution is added to the aldehyde-hydrated water-soluble starch aqueous solution to react and obtain a water-soluble starch hydrogel.

2. The method according to claim 1, wherein In step (1), in preparing the cationic water-soluble starch, the ratio of water-soluble starch, water, and ethylene glycol is 1-10 g: 200-300 mL: 2-20 mL; The molar ratio of 2,3-epoxypropyltrimethylammonium chloride to water-soluble starch is 1:1-20.

3. The method according to claim 1, wherein In step (1), in the preparation of the aldehyde-modified water-soluble starch, the ratio of the water-soluble starch to water is 1-10 g: 50-500 mL; The molar ratio of water-soluble starch to sodium periodate is 1-4:

1.

4. The method according to claim 1, wherein In the water-soluble starch hydrogel of step (2), the mass ratio of cationic water-soluble starch to aldehyde-soluble starch is 1-10:1-5.

5. The method according to claim 1, wherein The preparation method of water-soluble starch comprises: The su1 sweet grains are crushed and mixed with water, centrifuged, and a first supernatant is collected; the pH value of the first supernatant system is adjusted, centrifuged, and a second supernatant is collected; the second supernatant system is adjusted, centrifuged, and a third supernatant is collected, boiled, allowed to stand, and then centrifuged to collect a fourth supernatant; excess anhydrous ethanol is added to the fourth supernatant, followed by standing, filtration, and drying to obtain water-soluble starch.

6. The water-soluble starch hydrogel prepared by the method according to any one of claims 1 to 5.

7. Use of the hydrogel according to claim 6 in the biomedical field, characterized in that: The applications include preparing wound repair materials, drug delivery materials, tissue filling materials, and hemostatic materials.

8. A wound repair product, characterized in that: The product contains the water-soluble starch hydrogel according to claim 6.

9. A method for improving the wound repair effect of hydrogel, characterized in that: The method for preparing a hydrogel using water-soluble starch comprises the following steps: (1) Mixing water-soluble starch and water, adding ethylenediamine, and reacting; then adding 2,3-epoxypropyltrimethylammonium chloride, and reacting; after the reaction, adding ethanol, precipitating, and drying to prepare cationic water-soluble starch; The water-soluble starch and water are mixed, sodium periodate is added, and the mixture is reacted; after the reaction is completed, ethylene glycol is added, dialyzed, and dried to prepare the aldehyde-modified water-soluble starch; (2) An aqueous solution prepared by preparing cationic water-soluble starch and aldehyde-treated water-soluble starch is added to the aqueous solution of aldehyde-treated water-soluble starch to react and obtain a water-soluble starch hydrogel.

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