Preparation of a self-gelling hemostatic powder based on multiple non-covalent interactions

Abstract

This invention discloses a method for preparing a self-gelling hemostatic powder based on multiple non-covalent interactions. (Meth)acrylate isocyanate ethyl ester reacts with glycine to obtain a urea-modified (meth)acrylate monomer. Then, chitosan is grafted with 2,3-epoxypropyltrimethylammonium chloride to obtain quaternized chitosan. The urea-modified (meth)acrylate monomer is blended with quaternized chitosan or ε-polylysine, and a gel is prepared by free radical-initiated double-bond polymerization. The resulting gel is freeze-dried and ground to obtain the self-gelling hemostatic powder. Utilizing the multiple non-covalent interactions in the self-gelling hemostatic powder, it exhibits rapid gelation and hemostasis, while also demonstrating excellent antibacterial properties and wound-healing effects. The prepared self-gelling hemostatic powder has potential applications in wound dressings, medical hemostasis, and other biological fields.

Description

Technical Field

[0001] This invention belongs to the field of gel materials, and more specifically, relates to a method for preparing a self-gelling hemostatic powder based on multiple non-covalent interactions. Background Technology

[0002] In recent years, severe trauma has become a major challenge in global public health, and the management of post-traumatic hemorrhage continues to test healthcare systems worldwide. Traditional hemostasis methods are widely used but have significant drawbacks. For example, while medical gauze and hemostatic bandages can temporarily control bleeding, gauze works by compressing blood vessels in the wound, which may lead to excessive blood absorption and increase the risk of blood loss; while hemostatic bandages can block blood flow, prolonged use may cause serious damage to surrounding tissues, even leading to limb necrosis; commercially available hemostatic powders only absorb blood and cannot tightly seal wounds, increasing the risk of massive bleeding. Gels, due to their excellent biocompatibility, sufficient mechanical strength, strong water absorption capacity, and versatility, have become ideal hemostatic materials. Self-gelling hemostatic powder is a material produced by freeze-drying a gel and then finely grinding it. It combines the advantages of gel and powder materials, rapidly absorbing blood to form a gel that adheres to wounds of various depths and shapes to create a strong seal.

[0003] This invention first obtains urea-modified (meth)acrylic acid monomers by reacting (meth)acrylic acid isocyanate with glycine. Then, 2,3-epoxypropyltrimethylammonium chloride is grafted onto chitosan to obtain quaternized chitosan. The urea-modified (meth)acrylic acid monomers are then blended with quaternized chitosan or ε-polylysine, and finally, a gel is prepared via free radical-initiated double-bond polymerization. After freeze-drying and grinding, a self-gelling hemostatic powder is obtained. This powder, through multiple non-covalent interactions, achieves rapid gelation and quick hemostasis. The self-gelling hemostatic powder exhibits excellent adhesion, antibacterial properties, and promotes wound healing and rapid hemostasis. This makes it a promising candidate for applications in wound dressings, medical hemostasis, and other biological fields. Summary of the Invention

[0004] The purpose of this invention is to provide a method for preparing a self-gelling hemostatic powder based on multiple non-covalent interactions. By replacing the cross-linking effect of small molecule cross-linking agents with the intermolecular hydrogen bonding forces and the electrostatic interactions of positive and negative charges between amino and carboxyl groups, the gel can be formed without the addition of any cross-linking agent. Furthermore, the self-gelling hemostatic powder obtained after freeze-drying and grinding exhibits excellent adhesion properties, antibacterial properties, and the ability to promote wound healing and rapid hemostasis. This self-gelling hemostatic powder overcomes the adhesion limitations of traditional hemostatic powder materials and can achieve rapid and effective hemostasis for irregularly shaped, non-pressable internal organs and high-pressure arterial bleeding.

[0005] The technical objective of this invention is achieved through the following technical solution.

[0006] A method for preparing a self-gelling hemostatic powder based on multiple non-covalent interactions is characterized by the following steps: Urea-modified (meth)acrylic acid monomer is dissolved in water, dimethyl sulfoxide, or a mixture of both to prepare a solution with a molar concentration of 1-7 mol / L. Then, 0-20% (w / v) of quaternized chitosan or ε-polylysine is added, followed by 0.1-2% (w / v) of a photoinitiator or thermal initiator equivalent to the mass fraction of the urea-modified (meth)acrylic acid monomer. After mixing and deoxygenation, the mixture is injected into a sealed mold, and monomer polymerization is initiated by photoinitiation or thermal initiation. After a certain reaction time, the prepared gel is demolded and soaked in water for at least one day to remove unreacted monomers. Subsequently, the gel is freeze-dried and ground to obtain the self-gelling hemostatic powder.

[0007] The above-mentioned 2-hydroxy-2-methyl-1-phenyl-1-propanone (photoinitiator 1173), 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone (photoinitiator 2959), lithium phenyl (2,4,6-trimethylbenzoyl)phosphinic acid (photoinitiator LAP), or ammonium persulfate are selected as photoinitiators or thermal initiators.

[0008] When 2-hydroxy-2-methyl-1-phenyl-1-propanone (photoinitiator 1173) or 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone (photoinitiator 2959) is selected as the initiator for crosslinking, the monomer polymerization is initiated in a UV crosslinking apparatus for a reaction time of 10-180 minutes. When lithium phenyl (2,4,6-trimethylbenzoyl)phosphines (photoinitiator LAP) is selected as the photoinitiator, the monomer polymerization is initiated in a blue light crosslinking apparatus for a reaction time of 10-180 minutes. When ammonium persulfate is selected as the thermal initiator, the monomer polymerization is initiated by heating in an oven at a temperature of 60-80°C for a polymerization time of 12 hours.

[0009] The above-mentioned urea-modified (meth)acrylic acid monomer synthesis method is as follows:

[0010] (Meth)acrylate isocyanate ethyl ester and amino-containing glycine are reacted to generate urea-modified (meth)acrylate monomer. First, glycine and sodium hydroxide are dissolved in water at a molar ratio of 1:(1~1.5), and the mixture is reacted at low temperature (0~10℃) for 15~45 minutes to obtain an aqueous solution of sodium glycinate. Then, (meth)acrylate isocyanate ethyl ester is dissolved in tetrahydrofuran at 1~1.5 equivalents of glycine, and then added to the sodium glycinate aqueous solution. The reaction is continued at room temperature for 1~6 hours. The resulting solution is extracted with ethyl acetate, and the pH of the extracted aqueous solution is adjusted to 1-3 with hydrochloric acid to obtain an acidic aqueous solution. The acidic aqueous solution is then extracted again with ethyl acetate, and the resulting ethyl acetate solution is dried with anhydrous magnesium sulfate and filtered. The filtered solution is then precipitated in n-hexane to obtain a white precipitate, which is dried in a vacuum drying oven to obtain the urea-modified (meth)acrylate monomer. Its structural formula is as follows:

[0011]

[0012] Where R is CH3 or H.

[0013] The above-mentioned method for synthesizing quaternized chitosan is as follows:

[0014] Chitosan with a mass concentration of 1-6% was dissolved in an aqueous solution of acetic acid with a mass concentration of 0.5-1%. The solution was continuously stirred at 45-60°C for 30-60 minutes. 2,3-epoxypropyltrimethylammonium chloride was added by weight according to a molar ratio of amino groups on chitosan to 2,3-epoxypropyltrimethylammonium chloride of 1:(1-5) to react with the chitosan. After reacting for 15-18 hours with stirring at 45-60°C, the product was centrifuged at room temperature. The supernatant was precipitated with acetone to obtain a solid crude product. The crude product was then dried in a vacuum drying oven to obtain quaternized chitosan. The structural formula of the quaternized chitosan is shown below:

[0015]

[0016] Where R is Or H; m is the degree of polymerization of quaternized chitosan, with a value of 600-2000.

[0017] The ε-polylysine structure is shown below:

[0018]

[0019] Where n is the degree of polymerization of ε-polylysine, with a value of 10-100.

[0020] Compared with existing technologies, this invention first generates a urea-modified (meth)acrylic acid monomer by reacting (meth)acrylic acid isocyanate and glycine containing amino groups. Then, quaternized chitosan is synthesized by reacting chitosan with 2,3-epoxypropyltrimethylammonium chloride. The urea-modified (meth)acrylic acid monomer is further blended with quaternized chitosan or ε-polylysine, and then a gel is obtained through free radical polymerization without the addition of any crosslinking agent. The gel is freeze-dried and ground to obtain a self-gelling hemostatic powder. This powder, due to its multiple non-covalent interactions, exhibits excellent cohesive energy and adhesive properties, enabling rapid gelation. This makes the self-gelling hemostatic powder a promising candidate for applications in biological fields such as antibacterial, wound healing, and rapid hemostasis.

[0021] The advantages of this invention are: (1) The raw materials are readily available and the synthesis and preparation methods are simple; (2) The self-gelling hemostatic powder can quickly form a gel in a liquid environment through multiple non-covalent cross-linking, thereby achieving rapid hemostasis; (3) The self-gelling hemostatic powder has good antibacterial properties and can promote wound healing. Attached Figure Description

[0022] Figure 1 This is the NMR spectrum of the urea-modified methacrylic acid monomer prepared in this invention.

[0023] Figure 2 This is the NMR spectrum of the quaternized chitosan prepared by this invention.

[0024] Figure 3 This is the NMR spectrum of the urea-modified acrylic monomer prepared in this invention.

[0025] Figure 4 This is a diagram showing the gelation process of the self-gelling hemostatic powder prepared according to the present invention with water.

[0026] Figure 5 This is a curve showing the shear and tensile strength of the self-gelling hemostatic powder prepared in this invention adhering to pig skin tissue with water.

[0027] Figure 6 This is a stress-strain curve of the self-gelling hemostatic powder prepared by this invention after being gelled with water.

[0028] Figure 7 This invention describes the hemostatic effect of the self-gelling hemostatic powder prepared in this invention in a rat liver bleeding model. Detailed Implementation

[0029] The technical solution of the present invention will be further described below with reference to specific embodiments, but this is not intended to limit the scope of the present invention.

[0030] Nuclear magnetic resonance (NMR) spectroscopy (H1N) was performed using a deuterated water solvent at room temperature. The H1NN spectroscopy results confirmed the successful synthesis of all monomers. The adhesion properties of the prepared self-gelling hemostatic powder to porcine skin tissue after adding water and its mechanical properties after gelation were tested using a universal testing machine. The hemostatic effect of the self-gelling hemostatic powder was tested using a rat liver hemorrhage model.

[0031] Example 1

[0032] (1) The preparation method of urea-modified methacrylic acid monomer is as follows:

[0033] Glycine (5.00 g) and sodium hydroxide (2.67 g) were weighed out in a 1:1 molar ratio and dissolved in 40 mL of ultrapure water. The mixture was reacted at low temperature for 15 minutes to obtain an aqueous solution of sodium glycinate. Isocyanate of methacrylate was weighed out as one equivalent (10.33 g) of glycine and dissolved in 5 mL of tetrahydrofuran. This solution was then added to the sodium glycinate aqueous solution, and the reaction was continued at room temperature for 1 hour. The resulting solution was extracted with ethyl acetate, and the pH of the extracted aqueous solution was adjusted to 1 with hydrochloric acid to obtain an acidic aqueous solution. The acidic aqueous solution was then extracted again with ethyl acetate, and the resulting ethyl acetate solution was dried with anhydrous magnesium sulfate and filtered. The filtered solution was then precipitated in n-hexane to obtain a white precipitate, which was dried in a vacuum drying oven to obtain a urea-modified (meth)acrylic acid monomer. Its structural formula is as follows:

[0034]

[0035] The hydrogen NMR spectrum is attached. Figure 1 As shown, the urea-modified methacrylic acid monomer was successfully synthesized.

[0036] (2) The preparation method of quaternized chitosan is as follows:

[0037] 0.30 g of chitosan (1% by mass) was added to 30 mL of ultrapure water. Then, 143 μL of glacial acetic acid (0.5% by mass) was added to the suspension and stirred continuously at 45 °C for 30 minutes to dissolve. Following a 1:1 molar ratio of amino groups on the chitosan to 2,3-epoxypropyltrimethylammonium chloride, 0.24 g of 2,3-epoxypropyltrimethylammonium chloride was weighed and added to react with the chitosan. After reacting for 15 hours at 45 °C with stirring, the product was centrifuged at room temperature. The supernatant was precipitated with acetone to obtain a solid crude product. The crude product was then dried in a vacuum drying oven to obtain quaternized chitosan. Its structural formula is as follows:

[0038]

[0039] Where R is Or H; m is the degree of polymerization of quaternized chitosan, with a value of 600.

[0040] The hydrogen NMR spectrum is attached. Figure 2 As shown, this demonstrates the successful synthesis of quaternized chitosan.

[0041] (3) The preparation method of self-gelling hemostatic powder is as follows:

[0042] The prepared urea-modified methacrylic acid monomer was weighed and dissolved in ultrapure water to prepare a solution with a molar concentration of 3 mol / L. 3% (w / v) of quaternized chitosan was weighed and added to the above solution, followed by 0.1% (w / v) of 1173 photoinitiator (urea-modified methacrylic acid monomer). The solution was cured under ultraviolet light for 30 minutes, then demolded to obtain a gel. The gel was soaked in ultrapure water for 3 days until swelling equilibrium was reached. The hydrated gel was then freeze-dried and ground to obtain a self-gelling hemostatic powder.

[0043] As attached Figure 4 As shown, the self-gelling hemostatic powder, after being rehydrated, forms a gel that can be picked up with tweezers. Further testing using a universal testing machine was conducted to determine the adhesion strength of the self-gelling hemostatic powder to two pieces of pigskin. The amount of powder added was 40 mg, and the adhesion area was 1 cm². 2 Add 80 μL of water, as shown in the attached image. Figure 5 As shown, the shear adhesion strength of the self-gelling hemostatic powder can reach 55 kPa. This is attributed to the hydrogen bonding and electrostatic interaction between the self-gelling hemostatic powder and the pigskin tissue, which tightly adheres the two pieces of pigskin together. The compressive strength of the self-gelling hemostatic powder was further tested by adding water to a cylindrical mold at a solid content of 33 wt% to form a gel, as shown in the attached figure. Figure 6 As shown, the compressive fracture stress of the self-gelling hemostatic powder after gelation at 90% strain can reach 3.9 MPa. The hemostatic effect of the self-gelling hemostatic powder was tested using a rat liver hemorrhage model, as shown in the attached figure. Figure 7 As shown, compared with the blank control group, the application of self-gelling hemostatic powder significantly reduced the hemostatic effect on the liver of rats and significantly reduced the amount of bleeding. The blood loss in the control group was 725 mg, while the blood loss in the self-gelling hemostatic powder group was only 52 mg.

[0044] Example 2

[0045] (1) The preparation method of urea-modified acrylic monomer is as follows:

[0046] Glycine (5.00 g) and sodium hydroxide (3.46 g) were weighed out at a molar ratio of 1:1.3 and dissolved in 40 mL of ultrapure water. The mixture was reacted at low temperature for 30 minutes to obtain an aqueous solution of sodium glycinate. Isocyanate ethyl acrylate was weighed out as 1.3 equivalents (12.22 g) of glycine and dissolved in 5 mL of tetrahydrofuran. This solution was then added to the sodium glycinate aqueous solution, and the reaction was continued at room temperature for 3 hours. The resulting solution was extracted with ethyl acetate, and the pH of the extracted aqueous solution was adjusted to 2 with hydrochloric acid to obtain an acidic aqueous solution. The acidic aqueous solution was then extracted again with ethyl acetate, and the resulting ethyl acetate solution was dried with anhydrous magnesium sulfate and filtered. The filtered solution was then precipitated in n-hexane to obtain a white precipitate, which was dried in a vacuum drying oven to obtain a urea-modified acrylic monomer. Its structural formula is as follows:

[0047]

[0048] The hydrogen NMR spectrum is attached. Figure 3 As shown, the urea-modified acrylic monomer was successfully synthesized.

[0049] (2) The preparation method of quaternized chitosan is as follows:

[0050] 0.90 g of chitosan (3% by mass) was added to 30 mL of ultrapure water. Then, 229 μL of glacial acetic acid (0.8% by mass) was added to the suspension and stirred continuously at 55 °C for 30 minutes to dissolve. Following a feed ratio of 1:3 (amino group on chitosan to 2,3-epoxypropyltrimethylammonium chloride), 1.33 g of 2,3-epoxypropyltrimethylammonium chloride was weighed and added to react with the chitosan. After reacting for 16 hours at 50 °C with stirring, the product was centrifuged at room temperature. The supernatant was precipitated with acetone to obtain a solid crude product. The crude product was then dried in a vacuum drying oven to obtain quaternized chitosan. Its structural formula is as follows:

[0051]

[0052] Where R is Or H; m is the degree of polymerization of quaternized chitosan, with a value of 1200.

[0053] (3) The preparation method of self-gelling hemostatic powder is as follows:

[0054] The prepared urea-modified acrylic monomer was dissolved in an equal volume mixture of ultrapure water and dimethyl sulfoxide to prepare a solution with a molar concentration of 4 mol / L. 4% (w / v) of quaternized chitosan was added to the solution, followed by 0.5% (w / v) of 2959 photoinitiator containing the urea-modified acrylic monomer. The solution was cured under ultraviolet light for 40 minutes, then demolded to obtain a gel. The gel was soaked in ultrapure water for 3 days until swelling equilibrium was reached. The equilibrated gel was then freeze-dried and ground to obtain a self-gelling hemostatic powder.

[0055] The adhesion strength of the self-gelling hemostatic powder to two pieces of pigskin was further tested using a universal testing machine. The amount of powder added was 40 mg, and the adhesion area was 1 cm². 2 With the addition of 80 μL of water, the shear adhesion strength of the self-gelling hemostatic powder reached 50 kPa. This is attributed to the hydrogen bonding and electrostatic interaction between the self-gelling hemostatic powder and the pigskin tissue, which tightly adheres the two pieces of pigskin together. The compressive strength of the self-gelling hemostatic powder was further tested by adding water to a cylindrical mold at a solid content of 50 wt% to form a gel. The compressive fracture stress at 90% strain after gelation reached 2.5 MPa. The hemostatic effect of the self-gelling hemostatic powder was tested using a rat liver hemorrhage model. Compared with the blank control group, the rats treated with the self-gelling hemostatic powder showed significantly better hemostasis and a substantial reduction in bleeding. The blood loss in the control group was 825 mg, while the blood loss in the self-gelling hemostatic powder group was only 65 mg.

[0056] Example 3

[0057] (1) The preparation method of urea-modified methacrylic acid monomer is as follows:

[0058] Glycine (5.00 g) and sodium hydroxide (3.73 g) were weighed out at a molar ratio of 1:1.4 and dissolved in 40 mL of ultrapure water. The mixture was reacted at low temperature for 40 minutes to obtain an aqueous solution of sodium glycinate. Isocyanoethyl methacrylate was weighed out at 1.4 equivalents (14.47 g) of glycine and dissolved in 5 mL of tetrahydrofuran. This mixture was then added to the sodium glycinate aqueous solution, and the reaction was continued at room temperature for 4 hours. The resulting solution was extracted with ethyl acetate, and the pH of the extracted aqueous solution was adjusted to 2.5 with hydrochloric acid to obtain an acidic aqueous solution. The acidic aqueous solution was then extracted again with ethyl acetate, and the resulting ethyl acetate solution was dried with anhydrous magnesium sulfate and filtered. The filtered solution was then precipitated in n-hexane to obtain a white precipitate, which was dried in a vacuum drying oven to obtain a urea-modified methacrylic acid monomer. Its structural formula is as follows:

[0059]

[0060] The hydrogen NMR spectrum is attached. Figure 1 As shown, the urea-modified methacrylic acid monomer was successfully synthesized.

[0061] (2) The structural formula of ε-polylysine is as follows:

[0062]

[0063] Where n is the degree of polymerization of ε-polylysine, with a value of 10-100.

[0064] (3) The preparation method of self-gelling hemostatic powder is as follows:

[0065] The prepared urea-modified methacrylic acid monomer was dissolved in an equal volume mixture of ultrapure water and dimethyl sulfoxide to prepare a solution with a molar concentration of 6 mol / L. 10% (w / v) of ε-polylysine was added to the above solution, followed by 1% (w / v) of ammonium persulfate as a thermal initiator. The solution was cured at 60°C for 12 hours, then demolded to obtain a gel. The gel was soaked in ultrapure water for 3 days until swelling equilibrium was reached. The equilibrated gel was then freeze-dried and ground to obtain a self-gelling hemostatic powder.

[0066] The adhesion strength of the self-gelling hemostatic powder to two pieces of pigskin was further tested using a universal testing machine. The amount of powder added was 40 mg, and the adhesion area was 1 cm². 2 With the addition of 80 μL of water, the shear adhesion strength of the self-gelling hemostatic powder reached 45 kPa. This is attributed to the hydrogen bonding and electrostatic interaction between the self-gelling hemostatic powder and the porcine skin tissue, which tightly adheres the two pieces of porcine skin together. The compressive strength of the self-gelling hemostatic powder was further tested by adding water to a cylindrical mold at a solid content of 60 wt% to form a gel. The compressive fracture stress at 90% strain after gelation reached 2.8 MPa. The hemostatic effect of the self-gelling hemostatic powder was tested using a rat liver hemorrhage model. Compared with the blank control group, the rats treated with the self-gelling hemostatic powder showed significantly better hemostasis and a substantial reduction in bleeding. The blood loss in the control group was 736 mg, while the blood loss in the self-gelling hemostatic powder group was only 45 mg.

[0067] Example 4

[0068] (1) The preparation method of urea-modified methacrylic acid monomer is as follows:

[0069] Glycine (5.00 g) and sodium hydroxide (4 g) were weighed out at a molar ratio of 1:1.5 and dissolved in 40 mL of ultrapure water. The mixture was reacted at low temperature for 45 minutes to obtain an aqueous solution of sodium glycinate. Isocyanoethyl methacrylate was weighed out as 1.5 equivalents (15.50 g) of glycine and dissolved in 5 mL of tetrahydrofuran. This solution was then added to the sodium glycinate aqueous solution, and the reaction was continued at room temperature for 6 hours. The resulting solution was extracted with ethyl acetate, and the pH of the extracted aqueous solution was adjusted to 3 with hydrochloric acid to obtain an acidic aqueous solution. The acidic aqueous solution was then extracted again with ethyl acetate, and the resulting ethyl acetate solution was dried with anhydrous magnesium sulfate and filtered. The filtered solution was then precipitated in n-hexane to obtain a white precipitate, which was dried in a vacuum drying oven to obtain a urea-modified methacrylic acid monomer. Its structural formula is as follows:

[0070]

[0071] The hydrogen NMR spectrum is attached. Figure 1 As shown, the urea-modified methacrylic acid monomer was successfully synthesized.

[0072] (2) The preparation method of quaternized chitosan (QCS) is as follows:

[0073] 1.8 g of chitosan (6% by mass) was added to 30 mL of ultrapure water. Then, 286 μL of 1% glacial acetic acid was added to the suspension and the mixture was continuously stirred at 60 °C for 60 minutes to dissolve. Following a molar ratio of 1:5 between the amino groups on the chitosan and 2,3-epoxypropyltrimethylammonium chloride, 7.20 g of 2,3-epoxypropyltrimethylammonium chloride was added to react with the chitosan. After reacting for 18 hours at 60 °C with stirring, the product was centrifuged at room temperature. The supernatant was precipitated with acetone to obtain a solid crude product. The crude product was then dried in a vacuum drying oven to obtain quaternized chitosan. Its structural formula is as follows:

[0074]

[0075] Where R is Or H; m is the degree of polymerization of quaternized chitosan, with a value of 2000.

[0076] The hydrogen NMR spectrum is attached. Figure 2 As shown, this demonstrates the successful synthesis of quaternized chitosan.

[0077] (3) The preparation method of self-gelling hemostatic powder is as follows:

[0078] The prepared urea-modified methacrylic acid monomer was dissolved in dimethyl sulfoxide to prepare a solution with a molar concentration of 6 mol / L. 6% (w / v) of quaternized chitosan was added to the above solution, followed by 2% (w / v) of (2,4,6-trimethylbenzoyl) lithium phosphonate photoinitiator. The solution was cured under blue light for 60 minutes, then demolded to obtain a gel. The gel was soaked in ultrapure water for 3 days until swelling equilibrium was reached. The equilibrated gel was then freeze-dried and ground to obtain a self-gelling hemostatic powder.

[0079] The adhesion strength of the self-gelling hemostatic powder to two pieces of pigskin was further tested using a universal testing machine. The amount of powder added was 40 mg, and the adhesion area was 1 cm². 2 With the addition of 80 μL of water, the shear adhesion strength of the self-gelling hemostatic powder reached 45 kPa. This is attributed to the hydrogen bonding and electrostatic interaction between the self-gelling hemostatic powder and the pigskin tissue, which tightly adheres the two pieces of pigskin together. The compressive strength of the self-gelling hemostatic powder was further tested by adding water to a cylindrical mold at a solid content of 66 wt% to form a gel. The compressive fracture stress at 90% strain after gelation reached 4.2 MPa. The hemostatic effect of the self-gelling hemostatic powder was tested using a rat liver hemorrhage model. Compared with the blank control group, the application of the self-gelling hemostatic powder significantly reduced hemostasis in the rat liver, resulting in a substantial decrease in bleeding. The blood loss in the control group was 846 mg, while the blood loss in the self-gelling hemostatic powder group was only 49 mg.

[0080] Adjusting the process parameters according to the present invention can achieve the preparation of self-gelling hemostatic powder, which, after testing, exhibits performance essentially consistent with that of the present invention. The present invention has been described above as exemplary. Without departing from the core of the present invention, any simple modifications, alterations, or other equivalent substitutions that can be made by those skilled in the art without inventive effort fall within the protection scope of the present invention.

Claims

1. A process for the preparation of a self-gelling hemostatic powder based on multiple non-covalent interactions, characterized in that, Urea-modified (meth)acrylic acid monomers are dissolved in water, dimethyl sulfoxide, or a mixture of both to prepare a solution with a molar concentration of 1-7 mol / L. Then, 0-20% (w / v) of quaternized chitosan or ε-polylysine (not zero) is added, followed by 0.1-2% (w / v) of a photoinitiator or thermal initiator equivalent to the mass fraction of the urea-modified (meth)acrylic acid monomers. After mixing and deoxygenation, the mixture is injected into a sealed mold. Monomer polymerization is initiated by photoinitiation or thermal initiation. When photoinitiation is selected, the reaction time is 10-180 minutes; when thermal initiation is selected, the reaction time is 12 hours. The prepared gel is demolded and soaked in water for at least one day to remove unreacted monomers. The gel is then freeze-dried and ground to obtain a self-gelling hemostatic powder. The structure of the urea-modified (meth)acrylic acid monomer is shown below: Where R is CH3 or H, The quaternized chitosan structure is shown below: wherein R is or H; m is the degree of polymerization of the quaternized chitosan, which has a value of 600-2000, The ε-polylysine structure is shown below: Where n is the degree of polymerization of ε-polylysine, with a value of 10-100.

2. A process for the preparation of a self-gelling hemostatic powder based on multiple non-covalent interactions according to claim 1, characterized in that, The initiator is 2-hydroxy-2-methyl-1-phenyl-1-propanone or 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone or lithium phenyl(2,4,6-trimethylbenzoyl)phosphinic acid or ammonium persulfate as a photoinitiator or thermal initiator.

3. A process for the preparation of a self-gelling hemostatic powder based on multiple non-covalent interactions according to claim 1, characterized in that, When 2-hydroxy-2-methyl-1-phenyl-1-propanone or 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone is selected as the initiator for crosslinking, the monomer polymerization is initiated in a UV crosslinking instrument for a reaction time of 10-180 minutes. When lithium phenyl (2,4,6-trimethylbenzoyl)phosphines is selected as the photoinitiator, the monomer polymerization is initiated in a blue light crosslinking instrument for a reaction time of 10-180 minutes. When ammonium persulfate is selected as the thermal initiator, the monomer polymerization is initiated in an oven at a temperature of 60-80℃ for a polymerization time of 12 hours.

4. A process for the preparation of a self-gelling hemostatic powder based on multiple non-covalent interactions according to claim 1, characterized in that, The method for synthesizing urea-modified (meth)acrylic acid monomers is as follows: (Meth)acrylate isocyanate ethyl ester and amino-containing glycine are reacted to generate urea-modified (meth)acrylate monomers. First, glycine and sodium hydroxide are dissolved in water at a molar ratio of 1:(1~1.5) and reacted at 0~10℃ for 15~45 minutes to obtain an aqueous solution of sodium glycinate. Then, (meth)acrylate isocyanate ethyl ester is dissolved in tetrahydrofuran at 1~1.5 equivalents of glycine, and then added to the sodium glycinate aqueous solution. The reaction is continued at room temperature for 1~6 hours. The resulting solution is extracted with ethyl acetate, and the pH of the extracted aqueous solution is adjusted to 1-3 with hydrochloric acid to obtain an acidic aqueous solution. The acidic aqueous solution was then extracted with ethyl acetate, and the resulting ethyl acetate solution was dried with anhydrous magnesium sulfate and filtered. The filtered solution was then precipitated in n-hexane to obtain a white precipitate, which was dried in a vacuum drying oven to obtain a urea-modified (meth)acrylic acid monomer, the structural formula of which is as follows: Where R is CH3 or H.

5. The method for preparing a self-gelling hemostatic powder based on multiple non-covalent interactions according to claim 1, characterized in that, The synthesis method of quaternized chitosan is as follows: Chitosan with a mass concentration of 1-6% was dissolved in an aqueous solution of acetic acid with a mass concentration of 0.5-1%. The solution was continuously stirred at 45-60°C for 30-60 minutes. 2,3-epoxypropyltrimethylammonium chloride was added by weight according to a molar ratio of amino groups on chitosan to 2,3-epoxypropyltrimethylammonium chloride of 1:(1-5) to react with the chitosan. After reacting for 15-18 hours with stirring at 45-60°C, the product was centrifuged at room temperature. The supernatant was precipitated with acetone to obtain a solid crude product. The crude product was then dried in a vacuum drying oven to obtain quaternized chitosan, the structure of which is shown below: Where R is Or H; m is the degree of polymerization of quaternized chitosan, with a value of 600-2000.

6. The method for preparing a self-gelling hemostatic powder based on multiple non-covalent interactions according to claim 1, characterized in that, The solvent used to prepare the hydrogel is water, dimethyl sulfoxide, or a mixture thereof.

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