Shape memory frozen gels and frozen gel sponges and methods of making the same

Abstract

This invention discloses a shape memory cryogel and a cryogel sponge, as well as their preparation method, belonging to the field of medical technology. The cryogel incorporates a polymeric surfactant, polysaccharide, and an amino-containing polymeric compound during its preparation. Utilizing the property of the polymeric surfactant and polysaccharide to generate dense and stable bubbles, a cryogel with higher porosity and a denser network is prepared. The addition of vermiculite to the cryogel further enhances its hemostatic effect, enabling rapid hemostasis for wounds that cannot be pressed. The cryogel sponge prepared based on this cryogel possesses the same function.

Description

Technical Field

[0001] This invention belongs to the field of medical technology, specifically relating to a shape memory cryogel and a cryogel sponge and their preparation method. Background Technology

[0002] Penetrating, non-compressible wounds frequently occur in war, traumatic accidents, and surgery. Death following penetrating injuries is usually related to bleeding. Massive bleeding can cause hypothermia, coagulation disorders, infection, acidosis, and multiple organ failure, all of which contribute to its high mortality rate. Therefore, massive bleeding from penetrating injuries places immense pressure on both patients and healthcare personnel.

[0003] Cryogels are gels that cross-link at low temperatures to form a network structure. Compared to traditional hydrogels, they have a large porous structure, allowing liquid to freely enter and exit, making them highly promising for hemostasis in penetrating wounds. Cryogels exhibit water-triggered shape memory behavior; when water is squeezed out, they remain in a contracted state in the air. Upon reabsorption of water, they rapidly recover their shape. Shape memory cryogels demonstrate unique properties in hemostasis applications in narrow or penetrating wounds. They can be delivered to the wound site in a fixed shape through compression and recover their shape to fill the wound boundary upon contact with bleeding blood. In contrast, gelatin and hyaluronic acid cryogel systems, due to the rigid covalent network, have increased dissipation energy and lack inherent shape memory, making them unable to maintain a fixed shape and unsuitable for hemostasis in narrow wounds. On the other hand, many polymer sponges have been used as hemostatic agents to treat non-pressable bleeding and have shown some hemostatic ability. However, they lack shape memory and cannot be compressed into narrow wounds. Summary of the Invention

[0004] The purpose of this invention is to overcome the shortcomings of the prior art and provide a shape memory cryogel and a cryogel sponge and a method for preparing the same, so as to solve the problem that the cryogel system of gelatin and hyaluronic acid lacks shape memory function in the prior art.

[0005] To achieve the above objectives, the present invention employs the following technical solution:

[0006] A method for preparing a shape memory cryogel includes the following steps: mixing a polymeric surfactant solution, a polysaccharide solution, and an amino-containing polymeric compound solution evenly, adding a crosslinking agent to form a mixed system, and then performing freeze crosslinking to obtain a shape memory cryogel.

[0007] A further improvement of the present invention is that:

[0008] Preferably, the polymeric surfactant solution is prepared by dissolving a polymeric surfactant in water; the polymeric surfactant is any one or more of polyvinylpyrrolidone, polyvinyl alcohol, polyether F-127, polyethyleneimine, polymaleimide, polyacrylate, polyethylene oxide, propylene oxide, water-soluble phenolic resin, amino resin, and sorbitol ester.

[0009] The polysaccharide solution is prepared by dissolving polysaccharides in water; the polysaccharide is any one or more of hyaluronic acid, sodium alginate, carboxymethyl chitosan, malic acid, agaric acid, erythric acid, alginic acid, naringin, hawthorn glycoside, sea urchin flavin, and chitin.

[0010] The amino-containing polymer solution is obtained by dissolving an amino-containing polymer in water, and the amino-containing polymer is any one or more of gelatin, bovine serum albumin, polyacrylamide, chitosan, amino polylactic acid, amino hyaluronic acid, and collagen.

[0011] Preferably, the crosslinking agent is 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide;

[0012] The amount of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride added is 0.01% to 5% of the mass of the mixture, and the amount of N-hydroxysuccinimide added is 0.02% to 5% of the mass of the mixture.

[0013] Preferably, the mass fraction of amino-containing polymeric compounds in the mixed system is 0.1% to 25%; the mass fraction of polysaccharides in the mixed system is 0.1% to 25%; and the mass fraction of polymeric surfactants in the mixed system is 0.01% to 15%.

[0014] Preferably, the freezing crosslinking temperature is -80 to 80°C, and the crosslinking time is 1 to 120 hours.

[0015] Preferably, the two-dimensional vermiculite suspension is added after mixing the polymer surfactant solution, polysaccharide solution and amino-containing polymer compound solution.

[0016] A shape memory cryogel prepared by any of the above methods, wherein a polymeric surfactant, a polysaccharide, and an amino-containing polymeric compound form an interpenetrating network.

[0017] Preferably, two-dimensional vermiculite is distributed in the interpenetrating network.

[0018] A method for preparing a cryogel sponge involves placing the cryogel at -80°C to -20°C for 1 to 72 hours, freeze-drying the frozen product, and then preparing a cryogel sponge. The freeze-drying temperature is -80°C to -20°C, and the freeze-drying time is 1 hour to 120 hours.

[0019] A cryogel sponge prepared by the above preparation method.

[0020] A cryogel sponge prepared by the above preparation method.

[0021] Compared with the prior art, the present invention has the following beneficial effects:

[0022] This invention discloses a method for preparing shape memory cryogels based on polymeric surfactants, polysaccharides, and amino-containing polymeric compounds. The method involves thoroughly mixing a polymeric surfactant solution, a polysaccharide solution, and an amino-containing polymeric compound solution, then adding 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide as crosslinking agents. After crosslinking and thawing, the shape memory cryogel is obtained. Conventional amino-containing polymeric compound crosslinked gels are aerogels obtained by freeze-drying hydrogels and do not possess shape memory functionality. This invention utilizes the dense and stable bubbles generated by mixing polymeric surfactants and polysaccharides. These bubbles act as pore-forming agents, and combined with the physical crosslinking of hydrogen bonds between the polymeric surfactant surface and the system, a cryogel with higher porosity and a denser network is obtained. The high porosity and dense network reduce energy dissipation, thus exhibiting shape memory functionality. Furthermore, the resulting cryogel uses inexpensive and easily scalable high-molecular surfactants, polysaccharides, and amino-containing polymers as raw materials, which greatly enhances its commercial value and application potential. The shape memory cryogel prepared by this invention has the characteristic of rapid hemostasis for non-pressable wounds.

[0023] Furthermore, two-dimensional vermiculite can be added during the preparation of cryogels, yielding a cryogel loaded with two-dimensional vermiculite after thawing. Vermiculite, as a silicon-based mineral material, possesses the same negative charge as kaolinite and has negatively charged silanol groups on its surface. These groups can interact with the positively charged amino acids on the coagulation factor XII chain, activating the coagulation factor, the intrinsic coagulation pathway, and accelerating the coagulation cascade reaction, thereby improving the hemostatic effect of the cryogel material. Traditional silicon-based mineral materials, such as zeolite and kaolinite, are prone to causing thermal damage and thrombosis in tissues. In cases of emergency bleeding, the application of cryogels through pressure and packing can achieve timely hemostasis. Moreover, vermiculite is inexpensive, greatly enhancing its commercial value and application potential.

[0024] This invention also discloses a method for preparing a cryogel sponge, which is a product obtained by freeze-drying a cryogel. By using freeze-drying technology to remove moisture from the cryogel, the cryogel sponge allows the gel to be stored for a longer period, facilitating future use. Furthermore, it retains its shape memory function upon contact with liquid, meeting the needs of packing and applying pressure to emergency bleeding sites during surgery to achieve hemostasis. Attached Figure Description

[0025] Figure 1 A water-triggered shape memory image of a cryogel of polyvinylpyrrolidone, hyaluronic acid, and gelatin prepared in Example 1 of the present invention;

[0026] (a) The image shows a cryogel without surfactants, and (b) The image shows a cryogel with polyvinylpyrrolidone.

[0027] Figure 2 A water-triggered shape memory image of a cryogel of polyvinyl alcohol, hyaluronic acid and gelatin prepared in Example 4 of the present invention.

[0028] Figure 3 A water-triggered shape memory image of a cryogel of polyether P-F127, hyaluronic acid, and gelatin prepared in Example 5 of the present invention.

[0029] Figure 4 A water-triggered shape memory image of a cryogel of polyethylene glycol, hyaluronic acid, and gelatin prepared in Example 6 of the present invention.

[0030] Figure 5 A water-triggered shape memory image of a cryogel of polyvinylpyrrolidone, sodium alginate, and gelatin prepared in Example 7 of the present invention;

[0031] Among them, (a) shows the sodium alginate system; (b) shows the polyvinylpyrrolidone-sodium alginate system.

[0032] Figure 6 A water-triggered shape memory image of a cryogel of polyvinyl alcohol, sodium alginate, and gelatin prepared in Example 6 of the present invention.

[0033] Figure 7 A water-triggered shape memory image of a cryogel of polyether P-F127, sodium alginate, and gelatin prepared in Example 7 of the present invention.

[0034] Figure 8 A water-triggered shape memory image of a cryogel of polyethylene glycol, sodium alginate, and gelatin prepared in Example 8 of this invention;

[0035] Figure 9 This is a diagram illustrating the effect verification of Embodiment 9 of the present invention;

[0036] (a) Image showing liver hemorrhage in rats treated with medical gelatin sponge and vermiculite cryogel; (b) Image showing the amount of blood loss in rats treated with medical gelatin sponge and vermiculite cryogel; (c) Image showing the time to hemostasis in rats treated with medical gelatin sponge and vermiculite cryogel. Detailed Implementation

[0037] To enable those skilled in the art to understand the features and effects of the present invention, the terms and expressions used in the specification and claims are explained and defined in general below. Unless otherwise specified, all technical and scientific terms used herein have the ordinary meaning understood by those skilled in the art regarding the present invention, and in case of conflict, the definitions in this specification shall prevail.

[0038] In this article, unless otherwise specified, the terms “contains,” “includes,” “containing,” “has,” or similar terms cover the meanings of “composed of” and “mainly composed of”. For example, “A contains a” covers the meanings of “A contains a and others” and “A contains only a”.

[0039] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Furthermore, it should be understood that after reading the teachings of this invention, those skilled in the art can make various alterations or modifications to the invention, and these equivalent forms also fall within the scope defined by the appended claims.

[0040] The following examples use instruments and equipment conventional in the art. Experimental methods in the following examples, unless otherwise specified, are generally performed under conventional conditions or as recommended by the manufacturer. All raw materials used in the following examples are conventional commercially available products with specifications conventional in the art. In this specification and the following examples, unless otherwise specified, "%" refers to weight percentage, "parts" refers to parts by weight, and "ratio" refers to weight proportion.

[0041] The first aspect of this invention discloses a method for preparing shape memory cryogels, specifically a method for preparing shape memory cryogels based on polymeric surfactants, polysaccharides, and amino-containing polymeric compounds. The specific preparation process is as follows:

[0042] After thoroughly mixing a polymeric surfactant solution, a polysaccharide solution, and an amino-containing polymeric compound solution, a crosslinking agent is added to form a mixed system. This system is then subjected to freeze crosslinking to obtain a shape memory cryogel. During this process, the polymeric surfactant and polysaccharide mixture generates dense and stable bubbles. These bubbles act as pore-forming agents, and the polymeric surfactant also contributes to the physical crosslinking of the system. Upon thawing, a cryogel with higher porosity and a denser network is obtained.

[0043] The polymeric surfactant solution is prepared by dissolving a polymeric surfactant in water; the polysaccharide solution is prepared by dissolving a polysaccharide in water; and the amino-containing polymeric compound solution is prepared by dissolving an amino-containing polymeric compound in water.

[0044] The crosslinking agents are 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide.

[0045] In some embodiments of the present invention, the mass fraction of the amino-containing polymeric compound in the mixed system is 0.1% to 25%.

[0046] As a preferred embodiment, the mass fraction of amino-containing polymeric compounds in the mixed system is 1% to 15%.

[0047] In some embodiments of the present invention, the mass fraction of polysaccharides in the mixed system is 0.1% to 25%.

[0048] As a preferred embodiment, the mass fraction of polysaccharides in the mixture is 1% to 5%.

[0049] In some embodiments of the present invention, the mass fraction of the polymeric surfactant in the mixed system is 0.01% to 15%.

[0050] As a preferred embodiment, the mass fraction of the polymeric surfactant in the mixed system is 1% to 5%.

[0051] In some embodiments of the present invention, the polysaccharide is any one or more of hyaluronic acid, sodium alginate, carboxymethyl chitosan, malic acid, agaric acid, erythric acid, alginic acid, naringin, hawthorn glycoside, urticariin, and chitin.

[0052] In some embodiments of the present invention, the polymeric surfactant is an active agent with a molecular weight greater than 2000, and is any one or more of polyvinylpyrrolidone, polyvinyl alcohol, polyether F-127, polyethyleneimine, polymaleimide, polyacrylate, polyethylene oxide, propylene oxide, water-soluble phenolic resin, amino resin, and sorbitan ester; the polymeric surfactant can reduce surface tension and generate bubbles.

[0053] In some embodiments of the present invention, the amino-containing polymeric compound is any one or more of gelatin, bovine serum albumin, polyacrylamide, chitosan, amino polylactic acid, amino hyaluronic acid, and collagen.

[0054] In some embodiments of the present invention, the crosslinking temperature is -80 to 80°C and the crosslinking time is 1 to 120 h.

[0055] In some embodiments of the present invention, a method for preparing a shape memory cryogel is disclosed as follows: 5-1250 mg of an amino-containing polymer compound is dissolved in 2.5 mL of water to form an amino-containing polymer compound solution; 5-1250 mg of a polysaccharide is dissolved in 2 mL of water to form a polysaccharide solution. The amino-containing polymer compound solution and the polysaccharide solution are mixed evenly, and then 0.5-750 mg of a polymeric surfactant is added to form a mixed system. Then, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide are added as crosslinking agents, wherein the amount of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride added is 0.01%-0.5% of the mass of the mixed system, and the amount of N-hydroxysuccinimide added is 0.02%-5% of the mass of the mixed system. After mixing evenly, the mixture is frozen at -80 to -80°C for 1-120 h, and the cryogel is obtained after thawing.

[0056] As a preferred embodiment, the amount of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride added is 0.01% to 0.5% of the mass of the mixture, and the amount of N-hydroxysuccinimide added is 0.02% to 0.5% of the mass of the mixture.

[0057] In some embodiments of the present invention, two-dimensional vermiculite is loaded into the shape memory cryogel described above. After the amino-containing polymeric compound solution, polysaccharide solution and polymeric surfactant are thoroughly mixed, a two-dimensional vermiculite suspension is added, followed by the addition of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide as crosslinking agents. After mixing evenly, the mixture is frozen at -80 to 80°C for 1 to 120 hours. After thawing, a cryogel loaded with two-dimensional vermiculite material is obtained.

[0058] Preferably, the preparation process of the two-dimensional vermiculite is as follows: three-dimensional vermiculite is sequentially placed into NaCl solution and LiCl solution for ion intercalation, causing the three-dimensional structure to expand. Then, it is mixed with 30% hydrogen peroxide and refluxed at 110°C. The generated oxygen peels the expanded vermiculite into a two-dimensional sheet-like structure, ultimately preparing a two-dimensional vermiculite solution.

[0059] One embodiment of the present invention provides a method for preparing a shape memory cryogel loaded with two-dimensional vermiculite, comprising the following steps:

[0060] (1) Vermiculite stripping. The three-dimensional vermiculite was stripped using Na... + Solution and Li + The solution was subjected to ion intercalation, then mixed with 30% hydrogen peroxide, and refluxed at 110°C to obtain a two-dimensional vermiculite solution.

[0061] (2) Preparation of cryogel loaded with two-dimensional vermiculite. 5–1250 mg of gelatin was dissolved in 2.5 mL of water to form a gelatin solution; 5–1250 mg of polysaccharide was dissolved in 2 mL of water to form a polysaccharide solution. The gelatin solution and polysaccharide solution were mixed evenly, then 0.5–750 mg of a polymeric surfactant was added, followed by 1–10 mg of a suspension of two-dimensional vermiculite. Finally, 0.5–250 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 1–250 mg of N-hydroxysuccinimide were added as crosslinking agents. After mixing evenly, the mixture was frozen at -20 °C for 20 h. After thawing, the cryogel was obtained.

[0062] A second aspect of this invention discloses a shape memory cryogel prepared by the above method, based on a polymeric surfactant, polysaccharide, and amino-containing polymeric compound. This shape memory cryogel is a gel with an interpenetrating network structure formed by the combination of the polymeric surfactant, polysaccharide, and amino-containing polymeric compound. When applied, the cryogel can be compressed into a fixed shape while wet, filled into a wound, and restores its original shape by absorbing blood from the wound, thereby achieving hemostasis.

[0063] Furthermore, when two-dimensional vermiculite is added to the gel, the two-dimensional vermiculite is distributed in the interpenetrating network structure formed above.

[0064] The third aspect of this invention discloses a method for preparing a cryogel sponge. To improve the utilization rate of the cryogel and make it easier to preserve, it is prepared in the form of a sponge. The specific process is as follows: the hydrogel is placed in an environment of -80℃ to -20℃ and frozen for 1 to 72 hours; the frozen product is then freeze-dried in a freeze dryer for 1 hour to 120 hours at a freeze-drying temperature of -80℃ to -20℃ to prepare the cryogel sponge.

[0065] As a preferred method, the freezing temperature is -80℃. The frozen product is freeze-dried in a freeze dryer for 24h to 48h at a freeze-drying temperature of -80℃ to prepare a freeze gel sponge, which is then dried and stored at -80℃ to 4℃ for a long time.

[0066] A fourth aspect of the present invention discloses a cryogel sponge prepared by the above method.

[0067] The following is a further explanation with reference to specific embodiments:

[0068] Example 1

[0069] Taking polyvinylpyrrolidone, hyaluronic acid, and gelatin as examples, shape memory cryogel raw materials, including polymeric surfactants, polysaccharides, and amino-containing polymeric compounds, are used. At 37°C, 200 mg of gelatin is dissolved in 2.5 mL of deionized water, followed by the dissolution of 15 mg of hyaluronic acid and 60 mg of polyvinylpyrrolidone in deionized water. The hyaluronic acid and polyvinylpyrrolidone solutions are thoroughly mixed with the gelatin solution. Then, 18 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC) and 12 mg of N-hydroxysuccinimide (NHS) are added to the system, and after thorough mixing, the mixture is poured into a mold. The mixture is then reacted at -20°C for 16 hours. After thawing, unreacted monomers are removed by soaking in deionized water. Finally, the mixture is frozen and freeze-dried in a vacuum freeze dryer for 2 days to obtain the dried cryogel. Figure 1 As shown, cryogels using polyvinylpyrrolidone, hyaluronic acid, and gelatin as monomers exhibit good water-triggered shape memory properties.

[0070] Example 2

[0071] Taking polyvinylpyrrolidone, hyaluronic acid, and gelatin as examples, shape memory cryogel raw materials, including polymeric surfactants, polysaccharides, and amino-containing polymeric compounds, are used. At 37°C, 5 mg of gelatin is dissolved in 2.5 mL of deionized water, followed by 5 mg of hyaluronic acid and 0.5 mg of polyvinylpyrrolidone. The hyaluronic acid and polyvinylpyrrolidone solutions are thoroughly mixed with the gelatin solution. Then, 0.5 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC) and 1 mg of N-hydroxysuccinimide (NHS) are added to the system. After thorough mixing, the mixture is poured into a mold and reacted at -20°C for 16 hours. After thawing, unreacted monomers are removed by soaking in deionized water. Finally, the mixture is frozen and freeze-dried in a vacuum freeze dryer for 2 days to obtain the dried cryogel.

[0072] Example 3

[0073] Taking polyvinylpyrrolidone, hyaluronic acid, and gelatin as examples, shape memory cryogel raw materials, including polymeric surfactants, polysaccharides, and amino-containing polymeric compounds, were used. At 37°C, 1250 mg of gelatin was dissolved in 2.5 mL of deionized water, followed by 1250 mg of hyaluronic acid and 750 mg of polyvinylpyrrolidone. The hyaluronic acid and polyvinylpyrrolidone solutions were thoroughly mixed with the gelatin solution. Then, 250 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC) and 250 mg of N-hydroxysuccinimide (NHS) were added to the system and thoroughly mixed before being poured into a mold. The mixture was then reacted at -20°C for 16 hours. After thawing, unreacted monomers were removed by soaking in deionized water. Finally, the mixture was frozen and freeze-dried in a vacuum freeze dryer for 2 days to obtain the dried cryogel.

[0074] Example 4

[0075] Shape memory cryogel raw materials, including polymeric surfactants, polysaccharides, and amino-containing polymeric compounds, are exemplified by polyvinyl alcohol, hyaluronic acid, and gelatin. At 37°C, 200 mg of gelatin was dissolved in 2.5 mL of deionized water, followed by the dissolution of 15 mg of hyaluronic acid in deionized water. The dissolution of 50 mg of polyvinyl alcohol was carried out at 80°C. The hyaluronic acid and polyvinyl alcohol solutions were thoroughly mixed with the gelatin solution. Then, 18 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC) and 12 mg of N-hydroxysuccinimide (NHS) were added to the system, and after thorough mixing, the mixture was poured into a mold. The mixture was then reacted at -20°C for 16 hours. After thawing, unreacted monomers were removed by soaking in deionized water. Finally, the mixture was frozen and freeze-dried in a vacuum freeze dryer for 2 days to obtain the dried cryogel. Figure 2 As shown, cryogels with polyvinyl alcohol, hyaluronic acid and gelatin as monomers have good water-triggered shape memory properties.

[0076] Example 5

[0077] This study uses polyether P-F127, hyaluronic acid, and gelatin as examples of shape memory cryogel raw materials, including polymeric surfactants, polysaccharides, and amino-containing polymeric compounds. At 37°C, 200 mg of gelatin was dissolved in 2.5 mL of deionized water, followed by 15 mg of hyaluronic acid and 80 mg of polyether P-F127. The hyaluronic acid and polyether P-F127 solutions were thoroughly mixed with the gelatin solution. Then, 18 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC) and 12 mg of N-hydroxysuccinimide (NHS) were added to the system. After thorough mixing, the mixture was poured into a mold and reacted at -20°C for 16 hours. After thawing, unreacted monomers were removed by soaking in deionized water. Finally, the mixture was frozen and freeze-dried in a vacuum freeze dryer for 2 days to obtain the dried cryogel. Figure 3 As shown, the cryogel with polyether P-F127, hyaluronic acid and gelatin as monomers has good water-triggered shape memory properties.

[0078] Example 6

[0079] Taking polyethylene glycol, hyaluronic acid, and gelatin as examples, shape memory cryogel raw materials, including polymeric surfactants, polysaccharides, and amino-containing polymeric compounds, are used. At 37°C, 200 mg of gelatin is dissolved in 2.5 mL of deionized water, followed by 15 mg of hyaluronic acid and 40 mg of polyethylene glycol. The hyaluronic acid and polyethylene glycol solutions are thoroughly mixed with the gelatin solution. Then, 18 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC) and 12 mg of N-hydroxysuccinimide (NHS) are added to the system, and after thorough mixing, the mixture is poured into a mold. The mixture is then reacted at -20°C for 16 hours. After thawing, unreacted monomers are removed by soaking in deionized water. Finally, the mixture is frozen and freeze-dried in a vacuum freeze dryer for 2 days to obtain the dried cryogel. Figure 4 As shown, the cryogel with polyethylene glycol, hyaluronic acid and gelatin as monomers has good water-triggered shape memory properties.

[0080] Example 7

[0081] The shape memory cryogel raw materials, including polymeric surfactants, polysaccharides, and amino-containing polymeric compounds, are exemplified by polyvinylpyrrolidone, sodium alginate, and gelatin. At 37°C, 200 mg of gelatin was dissolved in 2.5 mL of deionized water, followed by the dissolution of 15 mg of sodium alginate and 60 mg of polyvinylpyrrolidone in deionized water. The sodium alginate and polyvinylpyrrolidone solutions were thoroughly mixed with the gelatin solution. Then, 18 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC) and 12 mg of N-hydroxysuccinimide (NHS) were added to the system, and after thorough mixing, the mixture was poured into a mold. The mixture was then reacted at -20°C for 16 hours. After thawing, unreacted monomers were removed by soaking in deionized water. Finally, the mixture was frozen and freeze-dried in a vacuum freeze dryer for 2 days to obtain the dried cryogel. Figure 5 As shown, cryogels using polyvinylpyrrolidone, sodium alginate, and gelatin as monomers exhibit good water-triggered shape memory properties.

[0082] Example 8

[0083] Shape memory cryogel raw materials, including polymeric surfactants, polysaccharides, and amino-containing polymeric compounds, are exemplified by polyvinyl alcohol, sodium alginate, and gelatin. At 37°C, 200 mg of gelatin was dissolved in 2.5 mL of deionized water, followed by the dissolution of 15 mg of sodium alginate in deionized water. The dissolution of 100 mg of polyvinyl alcohol was carried out at 80°C. The sodium alginate and polyvinyl alcohol solutions were thoroughly mixed with the gelatin solution. Then, 18 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC) and 12 mg of N-hydroxysuccinimide (NHS) were added to the system, and after thorough mixing, the mixture was poured into a mold. The mixture was then reacted at -20°C for 16 hours. After thawing, unreacted monomers were removed by soaking in deionized water. Finally, the mixture was frozen and freeze-dried in a vacuum freeze dryer for 2 days to obtain the dried cryogel. Figure 6 As shown, cryogels with polyvinyl alcohol, sodium alginate, and gelatin as monomers exhibit good water-triggered shape memory properties.

[0084] Example 9

[0085] Taking polyether P-F127, sodium alginate, and gelatin as examples, shape memory cryogel raw materials, including polymeric surfactants, polysaccharides, and amino-containing polymeric compounds, were used. At 37°C, 200 mg of gelatin was dissolved in 2.5 mL of deionized water, followed by the dissolution of 15 mg of sodium alginate and 150 mg of polyether P-F127 in deionized water. The sodium alginate and polyether P-F127 solutions were thoroughly mixed with the gelatin solution. Then, 18 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC) and 12 mg of N-hydroxysuccinimide (NHS) were added to the system, and after thorough mixing, the mixture was poured into a mold. The mixture was then reacted at -20°C for 16 hours. After thawing, unreacted monomers were removed by soaking in deionized water. Finally, the mixture was frozen and freeze-dried in a vacuum freeze dryer for 2 days to obtain the dried cryogel. Figure 7 As shown, the cryogel with polyether P-F127, sodium alginate and gelatin as monomers has good water-triggered shape memory properties.

[0086] Example 10

[0087] Taking polyethylene glycol, sodium alginate, and gelatin as examples, shape memory cryogel raw materials, including polymeric surfactants, polysaccharides, and amino-containing polymeric compounds, are used. At 37°C, 200 mg of gelatin is dissolved in 2.5 mL of deionized water, followed by 15 mg of hyaluronic acid and 150 mg of polyethylene glycol. The sodium alginate and polyethylene glycol solutions are then thoroughly mixed with the gelatin solution. Next, 18 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC) and 12 mg of N-hydroxysuccinimide (NHS) are added to the system, and after thorough mixing, the mixture is poured into a mold. The mixture is then reacted at -20°C for 16 hours. After thawing, unreacted monomers are removed by soaking in deionized water. Finally, the mixture is frozen and freeze-dried in a vacuum freeze dryer for 2 days to obtain the dried cryogel. Figure 8 As shown, the cryogel with polyethylene glycol, sodium alginate and gelatin as monomers has good water-triggered shape memory properties.

[0088] Example 11

[0089] The raw materials for the shape memory cryogel loaded with two-dimensional vermiculite are polyvinylpyrrolidone surfactant, hyaluronic acid polysaccharide, and gelatin containing amino-containing polymers. At 37°C, 200 mg of gelatin was dissolved in 2.5 mL of deionized water, followed by 15 mg of hyaluronic acid and 60 mg of polyvinylpyrrolidone. The hyaluronic acid, polyvinylpyrrolidone solution, and the exfoliated vermiculite solution were thoroughly mixed with the gelatin solution. Then, 18 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC) and 12 mg of N-hydroxysuccinimide (NHS) were added to the system, and after thorough mixing, the mixture was poured into a mold. The mixture was then reacted at -20°C for 16 h. After thawing, unreacted monomers were removed by soaking in deionized water. Finally, the mixture was frozen and freeze-dried in a vacuum freeze dryer for 2 days to obtain the dried cryogel loaded with two-dimensional vermiculite. By filling the liver wound (circular wound with a diameter of 12 mm) into the cryogel of injured SD rats, as... Figure 9 As shown, compared with the medical sponge group, the shape memory cryogel loaded with two-dimensional vermiculite has less blood loss and shorter hemostasis time.

[0090] Example 12

[0091] The raw materials for the shape memory cryogel loaded with two-dimensional vermiculite are polyvinyl alcohol surfactant, hyaluronic acid polysaccharide, and gelatin containing amino groups. At 37°C, 200 mg of gelatin was dissolved in 2.5 mL of deionized water, followed by 15 mg of hyaluronic acid and 50 mg of polyvinyl alcohol. The hyaluronic acid, polyvinyl alcohol solution, and the exfoliated vermiculite solution were thoroughly mixed with the gelatin solution. Then, 18 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC) and 12 mg of N-hydroxysuccinimide (NHS) were added to the system, and after thorough mixing, the mixture was poured into a mold. The mixture was then reacted at -20°C for 16 h. After thawing, unreacted monomers were removed by soaking in deionized water. Finally, the mixture was frozen and freeze-dried in a vacuum freeze dryer for 2 days to obtain the dried cryogel loaded with two-dimensional vermiculite.

[0092] Example 13

[0093] The raw materials for the shape memory cryogel loaded with two-dimensional vermiculite are polyether P-F127 surfactant, hyaluronic acid polysaccharide, and gelatin containing amino groups. At 37°C, 200 mg of gelatin was dissolved in 2.5 mL of deionized water, followed by 15 mg of hyaluronic acid and 80 mg of polyether P-F127. The hyaluronic acid, polyether P-F127 solution, and the exfoliated vermiculite solution were thoroughly mixed with the gelatin solution. Then, 18 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC) and 12 mg of N-hydroxysuccinimide (NHS) were added to the system, and after thorough mixing, the mixture was poured into a mold. The mixture was then reacted at -20°C for 16 h. After thawing, unreacted monomers were removed by soaking in deionized water. Finally, the mixture was frozen and freeze-dried in a vacuum freeze dryer for 2 days to obtain the dried cryogel loaded with two-dimensional vermiculite.

[0094] Example 14

[0095] The raw materials for the shape memory cryogel loaded with two-dimensional vermiculite are polyethylene glycol surfactant, hyaluronic acid polysaccharide, and gelatin containing amino groups. At 37°C, 200 mg of gelatin was dissolved in 2.5 mL of deionized water, followed by 15 mg of hyaluronic acid and 40 mg of polyethylene glycol. The hyaluronic acid, polyethylene glycol solution, and the exfoliated vermiculite solution were thoroughly mixed with the gelatin solution. Then, 18 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC) and 12 mg of N-hydroxysuccinimide (NHS) were added to the system, and after thorough mixing, the mixture was poured into a mold. The mixture was then reacted at -20°C for 16 h. After thawing, unreacted monomers were removed by soaking in deionized water. Finally, the mixture was frozen and freeze-dried in a vacuum freeze dryer for 2 days to obtain the dried cryogel loaded with two-dimensional vermiculite.

[0096] Example 15

[0097] The raw materials for the shape memory cryogel loaded with two-dimensional vermiculite are polyvinylpyrrolidone surfactant, sodium alginate polysaccharide, and gelatin containing amino groups. At 37°C, 200 mg of gelatin was dissolved in 2.5 mL of deionized water, followed by 15 mg of sodium alginate and 60 mg of polyvinylpyrrolidone. The sodium alginate, polyvinylpyrrolidone solution, and the exfoliated vermiculite solution were thoroughly mixed with the gelatin solution. Then, 18 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC) and 12 mg of N-hydroxysuccinimide (NHS) were added to the system, and after thorough mixing, the mixture was poured into a mold. The mixture was then reacted at -20°C for 16 h. After thawing, unreacted monomers were removed by soaking in deionized water. Finally, the mixture was frozen and freeze-dried in a vacuum freeze dryer for 2 days to obtain the dried cryogel loaded with two-dimensional vermiculite. By filling the liver wound (circular wound with a diameter of 12 mm) into the cryogel of injured SD rats, as... Figure 9 As shown, compared with the medical sponge group, the shape memory cryogel loaded with two-dimensional vermiculite has less blood loss and shorter hemostasis time.

[0098] Example 16

[0099] The raw materials for the shape memory cryogel loaded with two-dimensional vermiculite are polyvinyl alcohol surfactant, sodium alginate polysaccharide, and gelatin containing amino groups. At 37°C, 200 mg of gelatin was dissolved in 2.5 mL of deionized water, followed by 15 mg of sodium alginate and 100 mg of polyvinyl alcohol. The sodium alginate, polyvinyl alcohol solution, and the exfoliated vermiculite solution were thoroughly mixed with the gelatin solution. Then, 18 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC) and 12 mg of N-hydroxysuccinimide (NHS) were added to the system, and after thorough mixing, the mixture was poured into a mold. The mixture was then reacted at -20°C for 16 h. After thawing, unreacted monomers were removed by soaking in deionized water. Finally, the mixture was frozen and freeze-dried in a vacuum freeze dryer for 2 days to obtain the dried cryogel loaded with two-dimensional vermiculite.

[0100] Example 17

[0101] The raw materials for the shape memory cryogel loaded with two-dimensional vermiculite are polyether P-F127 surfactant, sodium alginate polysaccharide, and gelatin containing amino groups. At 37°C, 200 mg of gelatin was dissolved in 2.5 mL of deionized water, followed by the dissolution of 15 mg of sodium alginate and 150 mg of polyether P-F127 in deionized water. The sodium alginate, polyether P-F127 solution, and the exfoliated vermiculite solution were thoroughly mixed with the gelatin solution. Then, 18 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC) and 12 mg of N-hydroxysuccinimide (NHS) were added to the system, and after thorough mixing, the mixture was poured into a mold. The mixture was then reacted at -20°C for 16 h. After thawing, unreacted monomers were removed by soaking in deionized water. Finally, the mixture was frozen and freeze-dried in a vacuum freeze dryer for 2 days to obtain the dried cryogel loaded with two-dimensional vermiculite.

[0102] Example 18

[0103] The raw materials for the shape memory cryogel loaded with two-dimensional vermiculite are polyethylene glycol surfactant, sodium alginate polysaccharide, and gelatin containing amino groups. At 37°C, 200 mg of gelatin was dissolved in 2.5 mL of deionized water, followed by 15 mg of sodium alginate and 150 mg of polyethylene glycol. The sodium alginate, polyethylene glycol solution, and the exfoliated vermiculite solution were thoroughly mixed with the gelatin solution. Then, 18 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC) and 12 mg of N-hydroxysuccinimide (NHS) were added to the system, and after thorough mixing, the mixture was poured into a mold. The mixture was then reacted at -20°C for 16 h. After thawing, unreacted monomers were removed by soaking in deionized water. Finally, the mixture was frozen and freeze-dried in a vacuum freeze dryer for 2 days to obtain the dried cryogel loaded with two-dimensional vermiculite.

[0104] Example 19

[0105] Taking polyvinylpyrrolidone, hyaluronic acid, and gelatin as examples, shape memory cryogel raw materials, including polymeric surfactants, polysaccharides, and amino-containing polymeric compounds, are used. At 37°C, 50 mg of gelatin is dissolved in 2.5 mL of deionized water, followed by the dissolution of 10 mg of hyaluronic acid and 45 mg of polyvinylpyrrolidone in deionized water. The hyaluronic acid and polyvinylpyrrolidone solutions are thoroughly mixed with the gelatin solution. Then, 15 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC) and 10 mg of N-hydroxysuccinimide (NHS) are added to the system, and after thorough mixing, the mixture is poured into a mold. The mixture is then reacted at -80°C for 50 h. After thawing, unreacted monomers are removed by soaking in deionized water. Finally, the mixture is frozen and freeze-dried in a vacuum freeze dryer for 2 days to obtain the dried cryogel.

[0106] Example 20

[0107] Taking polyvinylpyrrolidone, hyaluronic acid, and gelatin as examples, shape memory cryogel raw materials, including polymeric surfactants, polysaccharides, and amino-containing polymeric compounds, were used. At 37°C, 750 mg of gelatin was dissolved in 2.5 mL of deionized water, followed by 50 mg of hyaluronic acid and 150 mg of polyvinylpyrrolidone. The hyaluronic acid and polyvinylpyrrolidone solutions were thoroughly mixed with the gelatin solution. Then, 25 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC) and 15 mg of N-hydroxysuccinimide (NHS) were added to the system and thoroughly mixed before being poured into a mold. The mixture was then reacted at -80°C for 1 hour. After thawing, unreacted monomers were removed by soaking in deionized water. Finally, the mixture was frozen and freeze-dried in a vacuum freeze dryer for 2 days to obtain the dried cryogel.

[0108] Example 21

[0109] Taking polyvinylpyrrolidone, hyaluronic acid, and gelatin as examples, shape memory cryogel raw materials, including polymeric surfactants, polysaccharides, and amino-containing polymeric compounds, were used. At 37°C, 750 mg of gelatin was dissolved in 2.5 mL of deionized water, followed by the dissolution of 50 mg of hyaluronic acid and 150 mg of polyvinylpyrrolidone in deionized water. The hyaluronic acid and polyvinylpyrrolidone solutions were thoroughly mixed with the gelatin solution. Then, 25 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC) and 15 mg of N-hydroxysuccinimide (NHS) were added to the system, and after thorough mixing, the mixture was poured into a mold. The mixture was then reacted at -20°C for 120 h. After thawing, unreacted monomers were removed by soaking in deionized water. Finally, the mixture was frozen and freeze-dried in a vacuum freeze dryer for 2 days to obtain the dried cryogel.

[0110] Example 22

[0111] The cryogel prepared in Example 1 was placed at -20°C and frozen for 10 hours. The frozen product was then freeze-dried at -20°C for 20 hours to obtain a cryogel sponge.

[0112] Example 23

[0113] The cryogel prepared in Example 1 was placed at -80°C and frozen for 1 hour. The frozen product was then freeze-dried at -80°C for 1 hour to obtain a cryogel sponge.

[0114] Example 24

[0115] The cryogel prepared in Example 1 was placed at -60°C for 72 hours and then freeze-dried at -60°C for 120 hours to obtain a cryogel sponge.

[0116] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing a shape memory cryogel, characterized in that, The process includes the following steps: mixing a polymer surfactant solution, a polysaccharide solution, and an amino-containing polymer compound solution evenly, adding a crosslinking agent to form a mixed system, and then performing freeze crosslinking to obtain a shape memory cryogel; The polymeric surfactant solution is prepared by dissolving a polymeric surfactant in water; the polymeric surfactant is any one or more of polyvinylpyrrolidone, polyvinyl alcohol, polyether F-127, polyethyleneimine, polymaleimide, polyacrylate, polyethylene oxide, propylene oxide, water-soluble phenolic resin, amino resin, and sorbitan ester; the polymeric surfactant and polysaccharide are mixed to produce dense and stable bubbles, which act as pore-forming agents; The polysaccharide solution is prepared by dissolving polysaccharides in water; the polysaccharide is any one or more of hyaluronic acid, sodium alginate, carboxymethyl chitosan, malic acid, agaric acid, erythric acid, alginic acid, naringin, hawthorn glycoside, sea urchin flavin, and chitin. The amino-containing polymer solution is obtained by dissolving an amino-containing polymer in water, and the amino-containing polymer is any one or more of gelatin, bovine serum albumin, polyacrylamide, chitosan, amino polylactic acid, amino hyaluronic acid, and collagen. After mixing the polymer surfactant solution, polysaccharide solution, and amino-containing polymer compound solution, a two-dimensional vermiculite suspension is added. The crosslinking agent is 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide; The amount of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride added is 0.01%~5% of the mass of the mixture, and the amount of N-hydroxysuccinimide added is 0.02%~5% of the mass of the mixture. The mass fraction of amino-containing polymers in the mixed system is 0.1% to 25%; the mass fraction of polysaccharides in the mixed system is 0.1% to 25%; and the mass fraction of polymeric surfactants in the mixed system is 0.01% to 15%.

2. The method for preparing a shape memory cryogel according to claim 1, characterized in that, The freezing crosslinking temperature is -80~80℃, and the crosslinking time is 1~120h.

3. A shape memory cryogel prepared by the preparation method according to claim 1 or 2, characterized in that, The high molecular surfactant, polysaccharide, and amino-containing high molecular compound form an interpenetrating network.

4. The shape memory cryogel according to claim 3, characterized in that, Two-dimensional vermiculite is distributed in the interpenetrating network.

5. A method for preparing a cryogel sponge, characterized in that, The cryogel described in claim 3 or 4 is placed in an environment of -80°C to -20°C and frozen for 1 to 72 hours. After freeze-drying the frozen product, a cryogel sponge is prepared. The freeze-drying temperature is -80°C to -20°C and the freeze-drying time is 1 hour to 120 hours.

6. A cryogel sponge prepared by the preparation method of claim 5.

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