Starch-based magnesium diboride mixture, preparation method and application thereof, starch-based magnesium diboride gel and application thereof
By forming a dual-network cross-linked structure in the stomach using a starch-based magnesium diboride mixture, the problem of mucosal protectant adhesion in the gastric environment is solved, achieving efficient tissue adhesion and wound closure, and is suitable for the repair of gastric ulcers and skin trauma.
Patent Information
- Application Number
- CN202510953377.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-07-10
- Publication Date
- 2025-11-28
AI Technical Summary
Existing mucosal protectants are prone to detachment in the gastric environment, failing to effectively adhere to and repair gastric ulcer wounds, and their gel structure is unstable in highly acidic environments.
A starch-based magnesium diboride mixture is used to generate boron-rich hydroxyl nanosheets through MgB2 hydrolysis, forming a double network cross-linked structure to enhance gel stability. It also binds to the gastric mucosa through boron ester bonds to form a gastric acid-responsive in-situ gel.
It significantly enhances tissue adhesion and wound closure in the pathological environment of the stomach, improves the repair effect of gastrointestinal wounds, and also has antioxidant capacity, making it suitable for the repair of skin wounds.
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Figure CN121015952A_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the field of materials, in particular to a starch-based magnesium diboride mixture, a preparation method and application thereof, and a starch-based magnesium diboride gel and application thereof. BACKGROUND
[0002] Gastric ulcer is a common digestive system disease, and when it is serious, it can be accompanied by symptoms such as bleeding, perforation and pyloric obstruction. Due to the unique strong acid environment (pH < 2) of the stomach and the dynamic mechanical load brought by gastric peristalsis, the ulcer area is easily subjected to persistent deep stimulation. This persistent stimulation will hinder the convergence activity of the cells at the wound edge, thereby interfering with the closure process of the ulcer.
[0003] Clinically commonly used mucosal protective agents (such as CBP and bismuth potassium citrate) mainly form a coordination bond with bismuth ions and gastric mucosa functional groups (carboxyl, amino, sulfhydryl), and a protective layer of pectin and citric acid components through hydrogen bonds. However, under the complex mechanical effects of gastric emptying and peristalsis, such protective agents are prone to fall off from the gastric wall tissue. Starch-based gel dressings have the characteristics of shear thickening and can adhere to the wound and form a barrier in a dynamic environment; the rich hydroxyl groups in starch molecules not only construct a hydrogel network through internal hydrogen bonds, but also act as hydrogen bond donors / acceptors to combine with carboxyl, amino and other groups of the gastric mucosa, giving the material excellent adhesion and showing good application potential. However, under gastric physiological conditions, starch-based materials face two challenges:
[0004] (1) High concentration H + Destroys the hydrogen bond network through ion-dipole interaction and changes the charge state of the hydroxyl group, resulting in unstable gel structure;
[0005] (2) Excessive ROS oxidizes the hydroxyl group, weakening the binding ability of the material to the mucosa and significantly reducing its adhesion performance. SUMMARY
[0006] Therefore, the purpose of the present application is to provide a starch-based magnesium diboride mixture, a preparation method and application thereof, and a starch-based magnesium diboride gel and application thereof, aiming to solve the problems in the background art and improve gastric wound repair.
[0007] The present application provides a starch-based magnesium diboride mixture, which comprises soluble starch and magnesium diboride (MgB2), and the mass ratio of soluble starch to magnesium diboride is 1:0.005-0.020.
[0008] The hydroxyl groups in the starch molecules not only construct the hydrogel network through internal hydrogen bonds, but also combine with the carboxyl groups, amino groups and other groups of the gastric mucosa as hydrogen bond donors / acceptors, thereby endowing the material with excellent adhesion. MgB2 is used as a hydrogen bond stabilizer, and is blended with soluble starch to form a starch-based magnesium diboride mixture. The mixture can construct a gastric acid-responsive in-situ gel MBSG in the stomach. The core mechanism of the present application is that the hydrolysis of MgB2 generates boron-rich hydroxyl nanosheets (BNS), and the boron monohydroxyl groups form borate ester bonds with the hydroxyl groups of the starch, thereby forming a double-network crosslinked structure with the original hydrogen bonds, and greatly improving the stability of the gel. At the same time, the hydrolysis process consumes a large amount of H + , effectively inhibits the ion-dipole competition of H + with the hydroxyl groups, accelerates the hydrolysis under acidic conditions, and strengthens the hydrogen bond binding force between the starch and the mucosa. The mixture based on the double-network stabilization strategy exhibits excellent tissue adhesion and wound closure ability in the pathological environment of the stomach, and improves the gastrointestinal wound repair ability.
[0009] Further, the surface of the magnesium diboride is modified with polyvinylpyrrolidone (PVP), and the mass ratio of MgB2 to PVP in the modified nanoparticles is 15:1 to 20:1. The PVP-modified magnesium diboride has better water dispersibility and biological safety.
[0010] The present application also provides a preparation method of the starch-based magnesium diboride mixture, which comprises the following steps:
[0011] (1) grinding MgB2 powder to obtain MgB2 nanoparticles;
[0012] (2) mixing soluble starch and MgB2 nanoparticles at a mass ratio of 1:0.005 to 0.020 to obtain a starch-based magnesium diboride mixture. Preferably, the soluble starch and MgB2 nanoparticles are mixed at a mass ratio of 1:0.005 to 0.02.
[0013] Further, after step (1), the following steps are further included:
[0014] (1.1) blending MgB2 nanoparticles with PVP in an ethanol phase, i.e. dispersing MgB2 nanoparticles in a 95% ethanol solution containing PVP, and then performing ultrasonic treatment at 30 to 80 DEG C for 3 to 8 hours, followed by centrifugation, washing, and freeze-drying to obtain PVP-modified MgB2 nanoparticles. The mass ratio of MgB2 to PVP in the modified nanoparticles is 15:1 to 20:1.
[0015] Further, after ultrasonic treatment, the suspension is collected by differential centrifugation to remove excess free PVP and large particles, and then the final product is freeze-dried at -4℃ under a vacuum of ≤5 Pa for 15-24 h after being washed with ethanol (optionally 3 or 4 times, without limitation) to obtain PVP-modified magnesium diboride, i.e., MgB2-PVP nanoparticles (MB NPs).
[0016] Further, the specific process of grinding the MgB2 powder in step (1) includes:
[0017] The MgB2 powder and zirconia balls are placed in a zirconia ball mill tank, and the ball-to-material mass ratio is controlled to be 30:1-100:1.
[0018] The ball mill tank is subjected to vacuum treatment and filled with inert gas (such as argon) to prevent oxidation of the reaction mixture.
[0019] The rotation speed of the ball mill is set to 300-500 rpm, and the rotation direction is alternated, with the direction being switched after each 20 min of operation, and the total time being 3-15 h.
[0020] The starch-based magnesium diboride mixture is also applied in the preparation of a drug for gastric ulcer, wherein the mixture forms an adhesive starch-based magnesium diboride gel (MBSG) in gastric juice.
[0021] The starch-based magnesium diboride gel provided by the present application comprises a water solution and the starch-based magnesium diboride mixture as described above, and the volume of the water solution to the mass of the soluble starch is 0.8-1.5 ml:1 g.
[0022] Further, the pH of the water solution is ≤3, and under acidic conditions, MgB2 accelerates hydrolysis and strengthens the hydrogen bond between starch and mucosa. The deionized water solution can be used to form the starch-based magnesium diboride gel, and the pH is neutral (not greater than 7). The lower the pH, the faster the MBSG forms.
[0023] The starch-based magnesium diboride gel is also applied in skin wound dressings.
[0024] The present application has the following beneficial effects: MgB2 hydrolysis generates boron-rich hydroxyl nanosheets (BNS), which form borate ester bonds with starch hydroxyl groups, and the original hydrogen bonds form a double-network crosslinked structure, greatly improving the stability of the gel; at the same time, the hydrolysis process consumes a large amount of H + , effectively inhibiting H +Competition with ionic dipoles for hydroxyl groups accelerates hydrolysis under acidic conditions, strengthening the hydrogen bonding between starch and the mucosa. This dressing, based on a dual-network stabilization strategy, exhibits excellent tissue adhesion and wound closure capabilities in the pathological environment of the stomach, improving the repair capacity of gastrointestinal wounds. Furthermore, this starch-based magnesium diboride mixture, when mixed with an aqueous solution, is also suitable for the repair of external skin injuries. The components and preparation method of this invention are simple and have broad application prospects. Attached Figure Description
[0025] Figure 1 The X-ray diffraction patterns of MgB2 and MB NPs of the present invention are shown.
[0026] Figure 2 This is a particle size distribution diagram of MB NPs.
[0027] Figure 3 These are scanning electron microscope images and elemental distribution maps of MBSG.
[0028] Figure 4 MBSG is shown to have antioxidant capabilities.
[0029] Figure 5 This demonstrates the adhesion ability of MBSG.
[0030] Figure 6 MBSG is shown to have the function of healing gastric ulcers. Detailed Implementation
[0031] The term "range" disclosed herein takes the form of a lower limit and an upper limit. It can be one or more lower limits and one or more upper limits, respectively. A given range is defined by selecting a lower limit and an upper limit. The selected lower and upper limits define the boundaries of the particular range. All ranges that can be defined in this way are inclusive and composable; that is, any lower limit can be combined with any upper limit to form a range. For example, if ranges of 60-120 and 80-110 are listed for specific parameters, it is understood that ranges of 60-110 and 80-120 are also expected. Furthermore, if minimum range values 1 and 2 are listed, and if maximum range values 3, 4, and 5 are listed, then the following ranges are all expected: 1-3, 1-4, 1-5, 2-3, 2-4, and 2-5. In this invention, unless otherwise specified, all embodiments and preferred embodiments mentioned herein can be combined to form new technical solutions.
[0032] In this invention, unless otherwise specified, all the technical features and preferred features mentioned herein can be combined to form new technical solutions.
[0033] In the present application, all the steps mentioned herein can be performed sequentially or randomly, but preferably sequentially, if not otherwise specified.
[0034] The method for preparing the starch-based magnesium diboride mixture of the present application specifically comprises:
[0035] (1) Put MgB2 powder and zirconia balls into a zirconia ball mill tank, control the mass ratio of balls to material to be 30:1-100:1; vacuumize the ball mill tank and fill it with inert gas; set the rotation speed of the ball mill to be 300-500 rpm, run alternately in forward and reverse directions, switch the direction after each 20 min of running, and the total time is 3-15 h to obtain MgB2 nanoparticles;
[0036] (1.1) Blend MgB2 nanoparticles and an appropriate amount of PVP in ethanol phase, ultrasonically treat at 30-80℃ for 3-8 h, centrifuge the mixture after ultrasonic treatment at a rotation speed of 13000 rpm for 10 min, remove the supernatant, wash and redisperse the bottom precipitate with ethanol to make the precipitate evenly dispersed in ethanol again. Repeat the above centrifugation, supernatant removal, ethanol washing and dispersion operation 2-3 times, and retain the bottom precipitate. Place the precipitate in a freeze dryer, freeze dry at -4℃ and a vacuum degree of ≤5 Pa for 15-24 h to obtain PVP-modified MgB2 nanoparticles, and the mass ratio of MgB2 to PVP in the modified nanoparticles is 15:1-20:1. In this step, the mass ratio of MgB2 to PVP in the modified nanoparticles can be changed by changing the ratio of MgB2 nanoparticles to PVP, and those skilled in the art can determine it through a limited number of experiments, which will not be described here.
[0037] (2) Mix soluble starch and PVP-modified MgB2 nanoparticles (MgB2-PVP nanoparticles, MB NPs) at a mass ratio of 1:0.005-0.020 to obtain a starch-based magnesium diboride mixture.
[0038] Prepare the MgB2 nanoparticles and MB NPs of Examples 1-6 according to the above method.
[0039] Prepare a starch-based magnesium diboride gel (MBSG)
[0040] After mixing soluble starch and MB NPs to obtain a starch-based magnesium diboride mixture, mix the mixture with an aqueous solution to obtain MBSG. The mass ratio of the aqueous solution, starch and MB NPs is 0.8-1.5 mL: 1 g: 5-20 mg.
[0041] MBSG of Examples 1-6 was prepared according to the above method. The simulated gastric juice was prepared by taking 16.4 mL of dilute hydrochloric acid, adding about 800 mL of water, and mixing with 10 g of pepsin, then diluting with water to 1000 mL, and adjusting the pH to 2.3. The above mixture can accelerate the reaction in an acidic solution (simulated gastric juice or mouse gastric juice), and MBSG can be formed in a shorter time (10 min).
[0042] The following table shows the relationship between the substances and quantities in Examples 1-6 and Comparative Examples 1-3.
[0043]
[0044] MgB2nanoparticles and MB NPs used in Examples 1-6 were prepared by the above method. The X-ray diffraction patterns of MgB2nanoparticles and MB NPs of Examples 1-6, and the particle size distribution data of MB NPs were basically the same, with no significant difference, so only one set of data graphs is shown. Figure 1 The X-ray diffraction pattern of MgB2and MB NPs is shown. The diffraction peaks in the pattern are sharp in shape and have a small half-peak width, indicating good crystallinity, confirming the successful synthesis of MB NPs. Figure 2 The particle size distribution of MB NPs is shown. The synthesized MB NPs have a particle size of about 100 nm, a small PDI value, and uniform particle size distribution.
[0045] Examples 1-6 can all produce MBSG that meets the requirements. There is no significant difference in the scanning electron microscope photos and element distribution graphs, so only one set of data graphs is shown. The experimental results are shown in Figure 3 The above MBSG was frozen in liquid nitrogen for 2 h, and then scanned by electron microscopy to obtain scanning electron microscope photos and element distribution. As can be seen from the graph, MB NPs are uniformly distributed in the gel, indicating the successful synthesis of MBSG.
[0046] The antioxidant capacity of MBSG of Examples 1-6 was tested
[0047] First, MBSG was added to a buffer with a pH of 2.3 to prepare MBSG solutions of different concentrations. Second, the MBSG solution was mixed with ABTS·+stock solution (2 mM), and the absorbance at 734 nm was measured after 5 min to evaluate the ROS scavenging capacity.
[0048] The experimental results are shown in Figure 4As shown, the antioxidant capacity of MBSG was detected by spectrophotometry using riboflavin. As can be seen from the figure, the MBSG gels obtained in water, simulated gastric juice or mouse gastric juice all have good ROS scavenging capacity. And by comparing Example 2 and Example 5, and comparing Example 3 and Example 6, it can be known that under the same proportion of components, the ROS scavenging capacity of MBSG gel in simulated gastric juice or mouse gastric juice is better than that in water. And in Example 6, the ROS scavenging efficiency of MBSG is close to 100%.
[0049] Adhesion property test of MBSG of Examples 1-6
[0050] The adhesion properties of MBSG of Examples 1-6, Comparative Examples 1-3 and CBP (a kind of clinical gastric mucosa protective agent drug, colloidal bismuth pectin) were measured by lap shear test. The specific process is as follows:
[0051] 1) MBSG of Examples 1-6, Comparative Example 1, MB NPs of Comparative Examples 2-3 were taken.
[0052] 2) Preparation of CBP: Pectin, bismuth and CBP formed by reaction with simulated gastric juice were prepared, with a mass concentration of 1 mg / g.
[0053] 3) The pig stomach tissue was cut into rectangular pieces with a size of 4 cm x 1 cm x 2 mm.
[0054] 4) In the lap shear test, MBSG, MB NPs or CBP were applied to the surface of the tissue, with an application area of 50 mm x 50 mm.
[0055] 5) A glass sheet was used to apply a weight of 20 N on the tissue for about 30 seconds.
[0056] 6) A universal mechanical tester (CMT1103, China) was used to record the shear strength required to separate the two pieces of tissue at a load unit of 50 N and a fixed tensile speed of 60 mm / min.
[0057] 7) The experiment was repeated three times independently, and the data was expressed as mean ± S.D.
[0058] The experimental results are as follows: Figure 5As shown, CBP represents the CBP formed by the clinical gastric mucosal protectant drug in simulated gastric juice. This gel contains only starch components, specifically soluble starch (purchased directly from Shanghai Guoyao, CAS number: 9005-84-9). The figure shows that MBSG exhibits significantly improved adhesion compared to CBP and MB NPs (Comparative Examples 2 and 3). Comparisons between Examples 2 and 5, and Examples 3 and 6, indicate that MBSG's adhesion in simulated or mouse gastric juice is stronger than its adhesion in water. Comparisons between Examples 5 and 2, and Examples 6 and 3, show that Example 5's adhesion is significantly better than Comparative Example 2, and Example 6's adhesion is significantly better than Comparative Example 3. This demonstrates that MgB2 can effectively form borate ester bonds with the hydroxyl groups of soluble starch, synergizing with existing hydrogen bonds to form a double-network cross-linked structure, thus improving adhesion. MBSG's adhesion in simulated gastric juice, mouse gastric juice, and water is superior to that of the clinical drug CBP in simulated gastric juice.
[0059] MBSG treatment of gastric ulcers in mice
[0060] Before the test, ICR mice were fasted for 12 hours. After fasting, each mouse was administered 8 μL g of [unspecified substance] via gavage. -1 The mice were euthanized the following day, and their stomachs were dissected. After ligation of the pylorus and cardia, a 4% paraformaldehyde solution was injected into the stomach, and the mixture was fixed at room temperature for 15 minutes. After fixation, the stomach was cut along the greater curvature, the ulcer index was calculated, and photographs were taken for further observation. Pathological sections were then prepared for subsequent analysis.
[0061] Mice with acute gastric ulcers were randomly divided into 8 groups (n=9 per group, including a blank control group, Examples 1-4, and Comparative Examples 1-3). In the blank control group, each mouse was administered 100 μL of deionized water by gavage daily; in the experimental groups, mice were administered 0.1 g of a starch-based magnesium diboride mixture by gavage once daily (the starch-based magnesium diboride mixtures in Examples 5 and 6 were the same as those in Examples 2 and 3, so the starch-based magnesium diboride mixtures in Examples 1-4 were selected). Three mice from each group were euthanized on days 1, 3, and 7 of the experiment, and their stomachs were dissected to calculate the ulcer area.
[0062] Experimental results are as follows Figure 6As shown, after mice were treated according to Examples 1-4 (corresponding to 1-4 in the figure) and Comparative Examples 1-3 (corresponding to C1-C3 in the figure), the UI (gastric ulcer index) of Examples 1-4 was significantly lower than that of the blank control group (corresponding to Blank in the figure), indicating that MBSG has a good therapeutic effect on gastric ulcers. The UI of Example 2 was lower than that of Comparative Example 2, and the UI of Example 3 was lower than that of Comparative Example 3, indicating that the UI (gastric ulcer index) of MBSG decreased faster than that of MB NPs when applied to mice, and could relieve symptoms more quickly. This shows that the starch-based magnesium diboride mixture formed by mixing soluble starch and MB NPs has a good therapeutic effect on ulcers when applied to mice to form MBSG.
[0063] In this in vivo experiment, morphological studies of the mouse gastric flap confirmed that in mice with a gastric ulcer model, the MBSG formed by the starch-based magnesium diboride mixture in gastric juice could effectively adhere to the ulcer wound and significantly reduce the gastric ulcer index within one day. Blood samples were collected from the orbital venous plexus, and serum malondialdehyde (MDA) and superoxide dismutase (SOD) levels were measured. MBSG reduced the damage factors by approximately 70% and significantly accelerated wound healing.
[0064] The above-disclosed embodiments are merely preferred embodiments of the present invention and should not be construed as limiting the scope of the present invention. Therefore, any equivalent variations made in accordance with the claims of the present invention are still within the scope of the present invention.
Claims
1. A starch-based magnesium diboride mixture, characterized in that, It includes soluble starch and magnesium diboride (MgB2), with a mass ratio of soluble starch to magnesium diboride of 1:0.005 to 0.
020.
2. The starch-based magnesium diboride mixture as described in claim 1, characterized in that, Magnesium diboride is surface-modified with polyvinylpyrrolidone (PVP), and the mass ratio of MgB2 to PVP in the modified nanoparticles is 15:1 to 20:
1.
3. A method for preparing the starch-based magnesium diboride mixture according to claim 1 or 2, characterized in that, Includes the following steps: (1) Grind MgB2 powder to obtain MgB2 nanoparticles; (2) Soluble starch and MgB2 nanoparticles are mixed at a mass ratio of 1:0.005 to 0.020 to obtain a starch-based magnesium diboride mixture.
4. The method for preparing the starch-based magnesium diboride mixture as described in claim 3, characterized in that, Step (1) is followed by: (1.1) MgB2 nanoparticles were mixed with PVP in an ethanol phase and ultrasonically treated at 30-80℃ for 3-8 hours. Then, the mixture was centrifuged, washed, and freeze-dried to obtain PVP-modified MgB2 nanoparticles. The mass ratio of MgB2 to PVP in the modified nanoparticles was 15:1 to 20:
1.
5. The method for preparing the starch-based magnesium diboride mixture as described in claim 4, characterized in that, After ultrasonic treatment, the suspension was collected by differential centrifugation, washed with ethanol, and then freeze-dried at -4℃ and vacuum degree ≤5Pa for 15-24h.
6. The method for preparing the starch-based magnesium diboride mixture as described in claim 4, characterized in that, In step (1), the specific process of grinding the MgB2 powder includes: MgB2 powder and zirconia balls were placed in a zirconia ball mill jar, and the ball-to-material mass ratio was controlled to be 30:1 to 100:
1. The ball mill jar is evacuated and then filled with inert gas. The ball mill speed is set to 300-500 rpm, and it runs alternately in forward and reverse directions. After each 20-minute run, the direction is switched, and the total duration is 3-15 hours.
7. The use of the starch-based magnesium diborate mixture according to claim 1 or 2 in the preparation of a gastric ulcer drug, wherein, The mixture forms an adhesive starch-based magnesium diboride gel (MBSG) in gastric juice.
8. A starch-based magnesium diboride gel, characterized in that, The mixture includes an aqueous solution and a starch-based magnesium diboride mixture as described in any one of claims 1-2, wherein the volume ratio of the aqueous solution to the mass of the soluble starch is 0.8-1.5 ml:1 g.
9. The starch-based magnesium diboride gel as described in claim 8, characterized in that, The pH of the aqueous solution is ≤3.
10. The use of the starch-based magnesium diboride gel according to claim 8 or 9 in skin wound dressings.