Clay mineral-based aerogel hemostatic material and preparation method thereof

Abstract

The invention relates to the technical field of hemostatic materials, in particular to a clay mineral-based aerogel hemostatic material and a preparation method thereof. The invention discloses a preparation method of a clay mineral-based aerogel hemostatic material. The preparation method comprises the following steps: S1, uniformly dispersing clay minerals and sodium alginate in deionized water respectively, and stirring to prepare slurry and sol for later use; s2, uniformly mixing the slurry and the sol, preparing a mixed sol, introducing the mixed sol into a mold, dropwise adding a proper amount of a metal salt solution, and standing to obtain a standing product; s3, freeze-drying the standing product to obtain the clay mineral-based aerogel hemostatic material. The composite material disclosed by the invention combines the adsorbability of clay and the biocompatibility of sodium alginate, has excellent biocompatibility and high safety, and shows excellent performance in the aspects of absorbing and concentrating tissue fluid, and the composite aerogel can quickly activate platelets and stimulate blood coagulation factors to efficiently coagulate blood, and has efficient hemostasis capability.

Description

Technical Field

[0001] The present invention relates to the technical field of hemostatic materials, and in particular to a clay mineral-based aerogel hemostatic material and a preparation method thereof. Background Art

[0002] At present, the hemostatic materials on the market mainly include zeolite powder, fibrin dressing, medical gelatin sponge, chitosan bandage, calcium alginate fiber pad, etc. These materials have certain limitations in the hemostatic effect. For example, when zeolite powder absorbs water, it is accompanied by an exothermic reaction, which may cause secondary trauma or even cause thrombosis. Aerogels show great potential in the field of hemostatic materials due to their porous and low-density characteristics. They can quickly absorb wound exudate, promote blood coagulation, and have good biocompatibility. For example, Chinese patent CN118806980A discloses an antibacterial modified sodium alginate aerogel hemostatic dressing and its preparation method, but its hemostatic effect mainly depends on the hygroscopicity of the aerogel itself, and its hemostatic effect is general. Summary of the invention

[0003] The purpose of the present invention is to provide a clay mineral-based aerogel hemostatic material and a preparation method thereof in view of the above-mentioned deficiencies in the prior art.

[0004] A method for preparing a clay mineral-based aerogel hemostatic material of the present invention comprises the following steps:

[0005] S1: Disperse clay minerals and sodium alginate uniformly in deionized water and stir to prepare slurry and sol for later use;

[0006] S2: uniformly mixing the slurry and the sol, preparing the mixed sol and introducing it into a mold, dropping an appropriate amount of a metal salt solution and letting it stand to obtain a standing product;

[0007] S3: freeze-drying the static product to obtain a clay mineral-based aerogel hemostatic material.

[0008] Furthermore, the clay mineral includes one or more of attapulgite, halloysite, sepiolite, montmorillonite, kaolinite, and laponite.

[0009] Furthermore, the clay minerals include fibrous clay and flaky clay.

[0010] Furthermore, the content ratio of the fiber-type clay to the flaky-type clay is 1:1-3.

[0011] Furthermore, the fibrous clay includes attapulgite, halloysite, and sepiolite; the flaky clay includes montmorillonite, kaolinite, and laponite.

[0012] Furthermore, in step S1, clay mineral and deionized water are configured into a 2-7 wt% slurry, and sodium alginate and deionized water are configured into a 2-7 wt% sol.

[0013] Furthermore, in step S2, in the mixed sol, the mass ratio of the clay mineral to the sodium alginate is 1:0.1-9.

[0014] Furthermore, in step S2, the metal salt is selected from one of calcium lactate, calcium chloride, magnesium chloride, zinc chloride, ferric chloride, zinc nitrate, and silver nitrate, wherein the mass ratio of sodium alginate to the metal salt is 1:0.03-0.1.

[0015] Furthermore, in step S2, the standing temperature is 30-50°C, and the standing time is 12-24 hours; in step S3, freeze drying is adopted, the freezing temperature is -20°C to -196°C, and the time is 24-36 hours.

[0016] A clay mineral-based aerogel hemostatic material prepared by the above-mentioned preparation method.

[0017] 1. The composite aerogel prepared by the present invention presents the dual advantages of excellent absorption and concentration of tissue fluid and rapid activation of platelets and stimulation of coagulation factors for efficient coagulation in the field of trauma hemostasis. This is due to the unique network structure of the aerogel and the clay mineral active components, which synergistically construct a unique mesoporous-microporous hierarchical porous system. This structural characteristic enables the material to quickly absorb liquid and form a dense hydrogel protective layer on the wound surface. It is worth noting that the surface of the clay mineral functional component synergistically activates platelets and efficiently stimulates coagulation factors, showing outstanding performance of rapid hemostasis in 30 seconds in a mouse liver hemostasis model. This structural-functional synergistic effect provides new ideas for the design of new hemostatic materials.

[0018] 2. The composite material of the present invention combines the adsorption of clay and the biocompatibility of sodium alginate, and has excellent biocompatibility and high safety. Its main components are natural minerals and natural polymers, which have a high affinity for human tissues. The hemolysis rate of the obtained composite aerogel is as low as less than 2%, which significantly reduces the irritation and inflammatory response of the wound. In addition, the unique three-dimensional network structure design of the aerogel effectively avoids the risk of thrombosis caused by the shedding of powder in traditional hemostatic powder and its composite gauze, further improving the safety of use.

[0019] 3. The composite aerogel in the present invention is cross-linked with functional metal salts. This design not only improves the overall structure of the aerogel to achieve stability, but also gives the material multiple functions such as hemostasis, antibacterial and healing promotion. The present invention integrates material science with the biomedical field, and innovatively develops clay-based composite aerogel functional dressings, bringing a breakthrough new solution to the biomedical field.

[0020] 4. The present invention preferably uses fibrous clay and flaky clay to prepare aerogels. Through the design of flaky-fiber mixed-dimensional structure, a macroporous structure (10-100 μm) is constructed. The skeleton in the composite aerogel is a "fiber-lamellar mixed-dimensional network" formed by one-dimensional fibrous clay (diameter 10-50 nm, aspect ratio>100) and flaky clay (thickness 0.05-2 μm), which synergistically constructs a unique mesoporous-microporous hierarchical porous system, that is, a three-dimensional interpenetrating network with hierarchical pores. Among them, the micron-scale pores (10-100) formed by cross-linking of fiber-lamellae quickly absorb tissue fluid through capillary action, achieving effective concentration of blood components; at the same time, the multidimensional network synergistically regulates the enrichment and activation of coagulation factors, significantly accelerating the coagulation cascade reaction. This mixed-dimensional structure gives the aerogel excellent mechanical properties, maintains structural integrity during blood penetration, and effectively solves the problem of secondary bleeding caused by structural collapse of traditional hemostatic materials. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 Macroscopic and microscopic SEM images of the clay mineral-based aerogel hemostatic material prepared in Example 1;

[0022] Figure 2 This is the SEM image of blood coagulation of clay mineral-based aerogel hemostatic material;

[0023] Figure 3 The in vitro coagulation rate graphs of kaolinite, diatomite, sodium alginate aerogel, kaolinite / sodium alginate composite aerogel, diatomite / sodium alginate composite aerogel, hemostatic gauze and wound dressing are shown;

[0024] Figure 4 Figure 2 shows the hemostasis model of the blank group, the composite aerogel of cellulose / sodium alginate and the commercial hemostatic gauze on the liver of mice;

[0025] Figure 5 It is the in vitro hemolysis rate of kaolinite, cellulose, sodium alginate aerogel, kaolinite / sodium alginate composite aerogel and cellulose / sodium alginate composite aerogel. DETAILED DESCRIPTION

[0026] The following are specific embodiments of the present invention and the accompanying drawings to further describe the technical solution of the present invention, but the present invention is not limited to these embodiments.

[0027] Example 1

[0028] Take 3g of attapulgite and 2g of kaolinite (mixed clay) and add deionized water to prepare a 5wt% slurry, and stir at a high speed of 10000rpm / min for 1h, then ultrasonicate for 30min to obtain a uniformly dispersed mixed clay slurry. At the same time, take 4g of sodium alginate and add deionized water to 100mL, stir at a uniform speed for 5h under a magnetic stirrer to prepare a 4wt% sodium alginate sol. Mix the above sol with the mixed clay slurry in a volume ratio of 2:3, stir at a uniform speed for 1h, and pour the mixed sol into a container. A 0.3wt% calcium lactate solution was prepared, and calcium lactate was added dropwise into the composite sol (wherein the amount of sodium alginate and calcium lactate was 1:0.05), stirred evenly, and allowed to stand for 6 hours at a constant temperature of 40°C to form a composite gel. Finally, the gel was frozen at -80°C and freeze-dried to obtain a mixed clay / sodium alginate composite aerogel, i.e., a clay mineral-based aerogel hemostatic material.

[0029] Example 2

[0030] Take 2g of sepiolite and 4g of kaolinite and add them to deionized water to prepare a 6wt% slurry, stir at a high speed of 10000rpm / min for 1h, and then ultrasonicate for 30min to obtain a uniformly dispersed mixed clay slurry. At the same time, take 6g of sodium alginate and add deionized water to 100mL, stir at a uniform speed for 5h under a magnetic stirrer to prepare a 6wt% sodium alginate sol. The above sol is mixed with the mixed clay slurry in a volume ratio of 4:1, and after stirring at a uniform speed for 1h, the mixed sol is poured into a container. Prepare a 0.3wt% zinc chloride solution, add the zinc ion solution dropwise to the composite sol (wherein the amount of sodium alginate and calcium lactate is 1:0.03), stir evenly, and stand for 6h at a constant temperature of 40°C to form a composite gel. Finally, the gel is frozen at -20°C and freeze-dried to prepare a mixed soil / sodium alginate composite aerogel, i.e., a clay mineral-based aerogel hemostatic material.

[0031] Example 3

[0032] Take 3g of attapulgite and 3g of montmorillonite and add them to deionized water to prepare a 6wt% slurry, and stir at a high speed of 10000rpm / min for 1h, then ultrasonicate for 30min to obtain a uniformly dispersed mixed clay slurry. At the same time, take 6g of sodium alginate and add deionized water to 100mL, stir at a uniform speed for 5h under a magnetic stirrer to prepare a 6wt% sodium alginate sol. The above sol is mixed with the mixed clay slurry in a volume ratio of 1:4, and after stirring at a uniform speed for 1h, the mixed sol is poured into a container. Prepare a 0.3wt% magnesium chloride solution, add the magnesium ion solution dropwise to the composite sol (wherein, the amount of sodium alginate and calcium lactate is 1:0.03), stir evenly, and stand for 7h at a constant temperature of 50°C to form a composite gel, and finally freeze the gel at -196°C and prepare a mixed soil / sodium alginate composite aerogel, i.e., a clay mineral-based aerogel hemostatic material by freeze drying.

[0033] Example 4

[0034] Take 1g of attapulgite and 3g of kaolinite and add them to deionized water to prepare a 4wt% slurry, and stir at a high speed of 10000rpm / min for 1h, then ultrasonicate for 30min to obtain a uniformly dispersed mixed clay slurry. At the same time, take 4g of sodium alginate and add deionized water to 100mL, stir at a uniform speed for 5h under a magnetic stirrer to prepare a 4wt% sodium alginate sol. The above sol is mixed with the mixed clay slurry in a volume ratio of 2:3, and after stirring at a uniform speed for 1h, the mixed sol is poured into a container. Prepare a 0.3wt% silver nitrate solution, add the magnesium ion solution dropwise to the composite sol (wherein the amount of sodium alginate and calcium lactate is 1:0.05), stir evenly, and stand for 6h at a constant temperature of 45°C to form a composite gel, and finally freeze the gel at -196°C and prepare a mixed soil / sodium alginate composite aerogel, i.e., a clay mineral-based aerogel hemostatic material by freeze drying.

[0035] Example 5

[0036] Take 4g of attapulgite and 2g of kaolinite and add them to deionized water to prepare a 6wt% slurry, stir at a high speed of 10000rpm / min for 1h, and then ultrasonicate for 30min to obtain a uniformly dispersed mixed clay slurry. At the same time, take 5g of sodium alginate and add deionized water to 100mL, stir at a uniform speed for 5h under a magnetic stirrer to prepare a 5wt% sodium alginate sol. The above sol is mixed with the mixed clay slurry in a volume ratio of 1:3, and after stirring at a uniform speed for 1h, the mixed sol is poured into a container. Prepare a 0.2wt% silver nitrate solution, add the magnesium ion solution dropwise to the composite sol (wherein the amount of sodium alginate and calcium lactate is 1:0.04), stir evenly, and stand for 12h at a constant temperature of 40°C to form a composite gel, and finally freeze the gel at -20°C and prepare a mixed soil / sodium alginate composite aerogel, i.e., a clay mineral-based aerogel hemostatic material, by freeze drying.

[0037] Example 6

[0038] Take 3g of sepiolite and 4g of montmorillonite and add them to deionized water to prepare a 7wt% slurry, stir at a high speed of 10000rpm / min for 1h, and then ultrasonicate for 30min to obtain a uniformly dispersed mixed clay slurry. At the same time, take 2g of sodium alginate and add deionized water to 100mL, stir at a uniform speed for 5h under a magnetic stirrer to prepare a 2wt% sodium alginate sol. The above sol is mixed with the mixed clay slurry in a volume ratio of 2:1, and after stirring at a uniform speed for 1h, the mixed sol is poured into a container. Prepare a 0.2wt% silver nitrate solution, add the magnesium ion solution dropwise to the composite sol (wherein the amount of sodium alginate and calcium lactate is 1:0.04), stir evenly, and stand for 12h at a constant temperature of 40°C to form a composite gel, and finally freeze the gel at -80°C and prepare a mixed soil / sodium alginate composite aerogel, i.e., a clay mineral-based aerogel hemostatic material, by freeze drying.

[0039] Example 7

[0040] 5g of kaolinite was added to deionized water to prepare a 5wt% slurry, and stirred at 10000rpm / min for 1h, followed by ultrasonication for 30min to obtain a uniformly dispersed mixed-dimensional clay slurry. At the same time, 4g of sodium alginate was added to 100mL of deionized water, and stirred at a constant speed for 5h under a magnetic stirrer to prepare a 4wt% sodium alginate sol.

[0041] The above sol and clay slurry were mixed in a volume ratio of 2:3, stirred at a constant speed for 1 hour, and then the mixed sol was poured into a container. A 0.3wt% calcium lactate solution was prepared, and calcium lactate was added dropwise to the composite sol (wherein the amount of sodium alginate and calcium lactate was 1:0.05), stirred evenly, and then allowed to stand for 6 hours at a constant temperature of 40°C to form a composite gel. Finally, the gel was frozen at -80°C and freeze-dried to obtain a kaolinite / sodium alginate composite aerogel, i.e., a clay mineral-based aerogel hemostatic material.

[0042] Comparative Example 1

[0043] 4 g of sodium alginate was added to 100 mL of deionized water and stirred at a constant speed for 5 h under a magnetic stirrer to prepare a 4 wt % sodium alginate sol.

[0044] Pour the sodium alginate sol into a container, prepare a 0.3wt% calcium lactate solution, add calcium lactate dropwise into the sodium alginate sol (wherein the amount of sodium alginate to calcium lactate is 1:0.05), stir evenly, and place at a constant temperature of 40°C for 6 hours to form a composite gel, and finally freeze the gel at -80°C and freeze-dry to obtain a sodium alginate aerogel.

[0045] Figure 1 The macroscopic and microscopic SEM images of the clay mineral-based aerogel hemostatic material prepared in Example 1. The composite aerogel is a solid material with a three-dimensional porous structure. Its unique porous structure has a larger capacity for rapid adsorption of tissue fluid or blood and a faster adsorption efficiency than hydrogel.

[0046] Figure 2 This is the SEM image of blood coagulation of clay mineral-based aerogel hemostatic material. In the SEM image at 200 times magnification ( Figure 2 a) shows that the composite aerogel quickly adsorbs red blood cells on its surface and in its pores to fix the red blood cells. The SEM image is further enlarged as shown in Figure 2 As shown in b, the composite aerogel can quickly activate platelets and stimulate coagulation factors for efficient coagulation.

[0047] Figure 3 The in vitro coagulation rate diagrams of kaolinite, hygroscopic soil (mixture of kaolinite and attapulgite in a mass ratio of 3:2), sodium alginate aerogel (prepared in comparative example 1), kaolinite / sodium alginate composite aerogel (prepared in example 7), hygroscopic soil / sodium alginate composite aerogel (prepared in example 1), hemostatic gauze and wound dressing are shown, and the coagulation indexes are 6.65%, 6.08%, 8.95%, 3.12%, 2.83%, 7.44% and 4.07% respectively. Among them, the coagulation index of hygroscopic soil / sodium alginate composite aerogel is the lowest at 2.83%, indicating that the composite aerogel has excellent coagulation properties and can achieve rapid blood coagulation.

[0048] Figure 4 The blank group, the composite aerogel / sodium alginate composite aerogel and the commercial hemostatic gauze were used in the liver hemostasis model experiment. The figure shows that compared with the blank group, the composite aerogel and the commercial hemostatic gauze can effectively stop the bleeding of liver damage. Compared with the commercial gauze, the composite aerogel has the least blood loss and further shortens the hemostasis time. In the mouse (6-8 weeks, female) liver hemostasis model, effective hemostasis is achieved within only 30 seconds.

[0049] Figure 5 The in vitro hemolysis rates of kaolinite, hygroscopic soil, sodium alginate aerogel, kaolinite / sodium alginate composite aerogel and hygroscopic soil / sodium alginate composite aerogel are 10.1%, 4.3%, 1.6%, 1.9% and 1.8% respectively. The hemolysis rate of the composite aerogel is as low as less than 2%, indicating that it has good biocompatibility.

[0050] The present invention successfully prepared a clay-based composite aerogel hemostatic dressing with both high-efficiency hemostasis and biosafety through structural and component regulation and design of mixed-dimensional clay and sodium alginate. It is expected to show broad application prospects in the fields of biomedicine as a functional wound dressing.

[0051] For matters not mentioned above, the prior art applies.

[0052] Although some specific embodiments of the present invention have been described in detail through examples, those skilled in the art should understand that the above examples are for illustration only and are not intended to limit the scope of the present invention. Those skilled in the art to which the present invention belongs may make various modifications or supplements to the specific embodiments described or replace them in a similar manner, but they will not deviate from the direction of the present invention or exceed the scope defined by the attached claims. Those skilled in the art should understand that any modifications, equivalent substitutions, improvements, etc. made to the above embodiments based on the technical essence of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing a clay mineral-based aerogel hemostatic material, characterized in that: The steps include: S1: Disperse clay minerals and sodium alginate uniformly in deionized water and stir to prepare slurry and sol for later use; S2: uniformly mixing the slurry and the sol, preparing the mixed sol and introducing it into a mold, dropping an appropriate amount of a metal salt solution and letting it stand to obtain a standing product; S3: freeze-drying the static product to obtain a clay mineral-based aerogel hemostatic material.

2. The preparation method according to claim 1, characterized in that: The clay minerals include one or more of attapulgite, halloysite, sepiolite, montmorillonite, kaolinite and laponite.

3. The preparation method according to claim 1, characterized in that: The clay minerals include fibrous clay and flaky clay.

4. The preparation method according to claim 1, characterized in that: The content ratio of the fiber-type clay to the flaky-type clay is 1:1-3.

5. The preparation method according to claim 1, characterized in that: The fiber-type clay includes attapulgite, halloysite, and sepiolite; the flaky clay includes montmorillonite, kaolinite, and laponite.

6. The preparation method according to claim 1, characterized in that: In step S1, clay mineral and deionized water are prepared into 2-7 wt% slurry, and sodium alginate and deionized water are prepared into 2-7 wt% sol.

7. The preparation method according to claim 1, characterized in that: In step S2, in the mixed sol, the mass ratio of the clay mineral to sodium alginate is 1:0.1-9.

8. The preparation method according to claim 1, characterized in that: In step S2, the metal salt is selected from one of calcium lactate, calcium chloride, magnesium chloride, zinc chloride, ferric chloride, zinc nitrate and silver nitrate, wherein the mass ratio of sodium alginate to the metal salt is 1:0.03-0.

1.

9. The preparation method according to claim 1, characterized in that: In step S2, the standing temperature is 30-50°C and the standing time is 12-24h; in step S3, freeze drying is adopted, the freezing temperature is -20°C to -196°C and the time is 24-36h.

10. A clay mineral-based aerogel hemostatic material prepared by the preparation method according to any one of claims 1 to 9.

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