Self-gelation expandable self-propelling coagulation-promoting portable hemostatic powder as well as preparation method and application of self-gelation expandable self-propelling coagulation-promoting portable hemostatic powder

Abstract

The invention discloses self-gelation expandable self-propelling coagulation-promoting portable hemostatic powder as well as a preparation method and application thereof, and belongs to the technical field of biomedical materials. The hemostatic powder adopts a composite strategy of polyethyleneimine / polyacrylic acid loaded dopamine modified montmorillonite powder with ultrafast self-setting and wet adhesion characteristics to synergistically enhance the adhesion performance and hemostatic ability of the material; meanwhile, a foaming mechanism of organic acid protonated tranexamic acid and sodium carbonate is introduced, and a self-gelation and expandable self-propelling hemostatic powder system is constructed. According to the design, the composite system has the characteristics of rapid wet adhesion, efficient hemostasis and controllable foaming, rapid closing and blood coagulation regulation of complex wounds can be achieved through the synergistic effect of physical crosslinking and chemical foaming, and the composite system has good application potential in the fields of wound first aid, surgical hemostasis and the like.

Description

Technical Field

[0001] This invention belongs to the field of biomedical materials technology, specifically relating to a self-gelling, expandable, self-propelled, coagulating, portable hemostatic powder, its preparation method, and its application. Background Technology

[0002] Hemorrhage is a leading cause of preventable post-traumatic death, causing more than 2 million deaths globally each year. The body's natural clotting system is unable to effectively stop massive bleeding caused by trauma. Rapid and effective on-site hemostasis using hemostatic materials is crucial for saving the lives of trauma patients and preventing bleeding complications. Traditional hemostatic materials require manual / physical pressure for rapid hemostasis, but their effectiveness is often unsatisfactory in situations where bleeding at amputations or limb junctions is impossible to stop due to small-caliber firearms or explosions on the battlefield or in routine emergency care. Therefore, developing novel hemostasis strategies for non-compressible bleeding to reduce bleeding volume and duration is a pressing need in battlefield and routine emergency care, significantly lowering the mortality rate of post-traumatic hemorrhage.

[0003] Given that non-compressible bleeding typically occurs in deep wounds and within internal organs, involving significant bleeding volume and often accompanied by irregular wound depths and ruptured arteries and veins deep within the tissue, manual or physical pressure is difficult to apply, necessitating emergency treatment and pre-hospital hemostasis. Researchers have developed various novel hemostatic materials for non-compressible bleeding based on different hemostatic mechanisms, including sponge / foam materials, sealants / adhesives, and platelet mimics. Among these, expandable hemostatic materials, with their wound-adaptive properties and immediate physical sealing effect, rapidly control bleeding and are widely recognized as the most promising technological approach for translational applications.

[0004] Existing expandable hemostatic materials can be mainly divided into shape memory foam-based expandable hemostatic materials and fluid foam-based expandable hemostatic materials. Shape memory foam-based expandable hemostatic materials can rapidly expand to fill and apply pressure to deep, non-compressible wounds to stop bleeding. However, they lack biochemical coagulation ability, and their low blood absorption rate and compression strength can prolong hemostasis time and lead to increased blood loss. Over-expansion may tear the wound, leading to secondary bleeding. To better adapt to wound characteristics and avoid excessive pressure on the wound, fluid foam-based expandable hemostatic materials mainly work by generating foam upon contact with blood flow after injection into the wound site, which can compress the wound to stop bleeding. However, this method is complex, and the risk of accidental injection can lead to serious complications or even death, limiting its application in emergency care. Therefore, retaining the high hemostatic performance of fluid foam-based expandable hemostatic materials while improving the sterilization challenges and mechanical strength deficiencies of liquid formulations has become a major bottleneck in the development of non-compressible bleeding hemostatic materials. Summary of the Invention

[0005] The purpose of this invention is to overcome the shortcomings of the prior art and provide a self-gelling, expandable, self-propelled, coagulating, portable hemostatic powder, its preparation method, and its application, so as to solve the technical problem that existing hemostatic materials cannot effectively deal with deep, irregular wounds.

[0006] To achieve the above objectives, the present invention employs the following technical solution: A method for preparing a self-gelling, expandable, self-propelled, coagulant-promoting, portable hemostatic powder includes the following steps: S1, dopamine-modified montmorillonite powder was prepared by means of montmorillonite, dopamine, hydrochloric acid solution and tris(hydroxymethyl)aminomethane solution; S2, Organic acid protonated tranexamic acid powder is prepared by reacting tranexamic acid with hydrochloric acid solution; S3, prepare polyacrylic acid solution and polyethyleneimine solution respectively; S4. Add dopamine-modified montmorillonite powder to a mixed solution of polyacrylic acid solution and polyethyleneimine solution, freeze-dry, grind and pulverize to obtain polyacrylic acid / polyethyleneimine / dopamine-modified montmorillonite powder, which is a PP / PT composite powder. S5, the PP / PT composite powder, protonated tranexamic acid powder, and sodium carbonate powder are mixed evenly; after drying, a self-gelling, expandable, self-propelled, coagulating, portable hemostatic powder is obtained.

[0007] A further improvement of the present invention is that: Preferably, the specific process of S1 is as follows: montmorillonite is added to hydrochloric acid, stirred and centrifuged, and the supernatant is dried to obtain reaction system A; the pH of the tris(hydroxymethyl)aminomethane solution is adjusted to 8.5 by hydrochloric acid, and then dopamine is added, stirred and dissolved to obtain reaction system B; reaction system A and reaction system B are mixed, stirred and reacted, and the reaction product is washed and freeze-dried to obtain dopamine-modified montmorillonite powder.

[0008] Preferably, in S1, the mass ratio of montmorillonite to dopamine is 5:1.5.

[0009] Preferably, in S2, the process of preparing protonated tranexamic acid from tranexamic acid and hydrochloric acid solution is as follows: adding hydrochloric acid solution to tranexamic acid to adjust the pH to 4.3, and freeze-drying the entire system to obtain protonated tranexamic acid from the organic acid.

[0010] Preferably, in S3, the volume ratio of the polyacrylic acid solution to the polyethyleneimine solution is 1:1.

[0011] Preferably, in S3, the concentrations of both the polyacrylic acid solution and the polyethyleneimine solution are 10 wt%.

[0012] Preferably, in S4, the mass fraction of the dopamine-modified montmorillonite powder in the mixed solution of polyacrylic acid solution and polyethyleneimine solution is 1%-20%.

[0013] Preferably, in S5, the mixing mass ratio of the PP / PT composite powder, the protonated aminomethyl tranexamic acid powder, and the sodium carbonate powder is (8-40):4:1.

[0014] A self-gelling, expandable, self-propelled, coagulating, portable hemostatic powder prepared by any of the above preparation methods, comprising PP / PT composite powder, protonated tranexamic acid powder, and sodium carbonate powder.

[0015] An application of the above-mentioned self-gelling, expandable, self-propelled, coagulating, portable hemostatic powder, wherein the self-gelling, expandable, self-propelled, coagulating, portable hemostatic powder is used to prepare hemostatic materials.

[0016] Compared with the prior art, the present invention has the following beneficial effects: This invention discloses a method for preparing a rapidly self-gelling, expandable, self-propelled, coagulating, portable hemostatic powder. The method first improves the dispersibility of montmorillonite in water using hydrochloric acid, allowing dopamine to self-assemble on the montmorillonite to obtain dopamine-modified montmorillonite (PT). Then, PT is introduced into a polyacrylic acid and polyethyleneimine system with ultra-fast self-gelling and wet adhesion properties to enhance its adhesion and hemostatic ability. After freeze-drying and grinding, the powder (PP / PT) is prepared, which can rapidly self-gelleave upon contact with water and has good wet tissue adhesion. The organic acid protonated tranexamic acid (TXA-NH3) is introduced into the system. 3 + The sodium carbonate foaming agent, through its rapid reaction upon contact with blood, continuously releases CO2 bubbles, giving the system rapid expansion and self-propelled properties. The organic acid protonated tranexamic acid, sodium carbonate, polyacrylic acid, and polyethyleneimine of this invention are all in powder form. When mixed and used, they achieve rapid foaming upon contact with blood. Tranexamic acid, as a procoagulant, remains in the system to maintain coagulation stability, further improving the hemostatic performance of the material. This invention is the first to pulverize all core materials, combining PP / PT with TXA-NH... 3+Na2CO3 was mixed in a certain proportion and dried to obtain an expandable, self-propelled, coagulant-promoting, portable hemostatic powder. The expandable, self-propelled, coagulant-promoting, portable hemostatic powder prepared by this invention exhibits good wet adhesion, rapid self-gelation, expandable self-propelling, and immediate physical sealing effect, as well as the ability to quickly control non-pressable bleeding in cavities, demonstrating excellent hemostatic performance. It also possesses the characteristics of easy storage, portability, and no need for manual intervention, and can be applied to wounds in daily life and even on the battlefield to achieve hemostasis for non-pressable bleeding, providing an efficient solution for the treatment of massive bleeding from non-pressable cavity wounds. The preparation method of this invention is simple in steps, mild in reaction conditions, requires minimal equipment, and is easy to operate, enabling industrial production.

[0017] This invention discloses a rapid self-gelling, expandable, self-propelled, coagulating, and portable hemostatic powder. It uses polyacrylic acid and polyethyleneimine, which have ultra-fast self-coagulation and wet adhesion properties, as the base materials. The coagulation ability of the system is improved by introducing dopamine-modified montmorillonite. The foaming reaction of the organic acid protonated tranexamic acid and sodium carbonate gives the material expandable properties, which can effectively solve the technical problem of the inefficiency of existing hemostatic materials in dealing with deep, irregular wounds that cannot be pressed for bleeding. Simultaneously, the self-gelling effect generated by physical interactions such as hydrogen bonding in the polymer network effectively traps and fixes blood components. The dopamine-modified montmorillonite nanofiller, through its high specific surface area of ​​layered structure, generates a significant synergistic effect of capillary adsorption, resulting in excellent blood adsorption properties, crucial for achieving efficient hemostasis. Furthermore, the polyacrylic acid and polyethyleneimine-based materials exhibit excellent swelling stability, and the addition of dopamine-modified montmorillonite further ensures structural stability through the steric hindrance effect of its nanosheets and the hydrophilic regulation of dopamine, which is of significant clinical importance in preventing secondary bleeding. This innovative technological fusion approach, proposed for the first time, not only resolves the contradiction between the wound conformability of solid materials and the stability of liquid materials but also provides an innovative solution for battlefield first aid that enables individual soldier self-rescue. The self-propelled portable hemostatic material developed in this invention, with its rapid expansion and high procoagulant properties, is portable, easy to store, simple to operate, and highly effective in hemostasis, possessing significant military medical value and clinical translational potential.

[0018] This invention also discloses the application of a rapid self-gelling, expandable, self-propelled, portable hemostatic powder. This material combines the advantages of hemostatic powder and expandable hemostatic materials, exhibiting excellent hemostatic ability for massive bleeding from cavity wounds where pressure is not possible, as demonstrated in rat models of liver columnar defects, femoral artery transection, cardiac puncture, and tail transection bleeding. Simultaneously, the rapid self-gelling, expandable, self-propelled, portable hemostatic powder demonstrates the ability to promote the healing of full-skin incisions. In emergency hemostasis scenarios, the self-gelling, self-expanding, highly adhesive, portable hemostatic powder requires no cumbersome pre-treatment procedures and can be directly and evenly sprinkled onto the bleeding wound or precisely pushed with a syringe. This diverse application method flexibly adapts to various scenarios such as field first aid, domestic accidents, and battlefield trauma. Through its rapid self-gelling and self-expanding mechanisms upon contact with blood, the material ensures rapid onset and stability of action in complex bleeding environments, providing a more convenient and reliable solution for emergency hemostasis. Attached Figure Description

[0019] Figure 1 In the image, (a) is a schematic diagram of the preparation and application of a rapidly self-gelling, expandable, self-propelled, coagulant-promoting portable hemostatic powder; (b) is a schematic diagram of the expansion mechanism of the rapidly self-gelling, expandable, self-propelled, coagulant-promoting portable hemostatic powder. Figure 2 For the adhesion properties of PP and PP / PTn powder, *p<0.05, **p<0.01, ***p<0.001; Figure 3 Infrared spectra of dopamine-modified montmorillonite (PT), polyethyleneimine (PEI), polyacrylic acid (PAA), and polyacrylic acid / polyethyleneimine / dopamine-modified montmorillonite (PP / PT); Figure 4 In the image, (a) is a representative SEM image of montmorillonite; (b) is a representative SEM image of dopamine-modified montmorillonite; (c) is a representative SEM image of polyacrylic acid / polyethyleneimine; and (d) is a representative SEM image of polyacrylic acid / polyethyleneimine / dopamine-modified montmorillonite. Figure 5 In the image, (a) shows the EDS spectrum, elemental content, and elemental distribution of montmorillonite; (b) shows the EDS spectrum, elemental content, and elemental distribution of dopamine-modified montmorillonite; and (c) shows the EDS spectrum, elemental content, and elemental distribution of polyacrylic acid / polyethyleneimine / dopamine-modified montmorillonite. Figure 6 A flowchart and schematic diagram of the coagulation and adhesion mechanism of a rapidly self-gelling, expandable, self-propelled, coagulant, portable hemostatic powder (hereinafter referred to as "hemostatic powder") for controlling non-pressable bleeding. Figure 7 Blood uptake rate of hemostatic powder, *p<0.05; Figure 8 The swelling ratio of the hemostatic powder; Figure 9 In the image, (a) shows the rapid self-gelling process of PP / PT5 under an optical microscope; (b) shows the formation of a self-gelling hydrogel with an "XJTU" shape by pre-formed PP / PT5 hemostatic powder and water. Figure 10 Self-healing properties and tensile strength of hemostatic powder after self-gelling; Figure 11 Rheological properties of hemostatic powder after gelation; Figure 12 In the figure, (a) is the uniaxial compressive stress-strain curve after the hemostatic powder has gelled; (b) is the stress-strain curve after the hemostatic powder has gelled. Figure 13 Demonstration of the self-gelling, self-expansion, and self-propelling properties of hemostatic powder upon contact with anticoagulated blood; Figure 14 Volume expansion rate of hemostatic powder (PP / PT5-TXA30); Figure 15 In the image, (a) demonstrates strong bioadhesion of hemostatic powder on pig skin; (b) demonstrates the twisting and water-wash resistance of hemostatic powder adhering to pig skin; and (c) demonstrates strong bioadhesion of hemostatic powder on rat organs. Figure 16 The adhesion strength of hemostatic powder after in-situ hygroscopic self-gelling on soaked pigskin, *p<0.05, **p<0.01, ***p<0.001; Figure 17 In the figure, (a) is the pressure-time curve of the hemostatic powder under uniform pressure; (b) is the burst pressure of the hemostatic powder, *p<0.05, **p<0.01, ***p<0.001; Figure 18 In the image, (a) is a representative SEM image of blood cells adhering to the control group and the hemostatic powder; (b) is a representative SEM image of blood cells adhering to the surface and cross-section of PP / PT5-TXA30 powder; and (c) is a representative SEM image of fibrin deposited on the hemostatic powder and gauze. Figure 19 The in vitro coagulation capacity test of hemostatic powder was performed, where (a) was plasma recalcification time, *p<0.05, **p<0.01, ***p<0.001; and (b) was dynamic whole blood coagulation index. Figure 20 Demonstration of blood clotting states after different materials have been in contact with blood for 120 seconds; Figure 21 In the data, (a) is the blood compatibility of the hemostatic powder, *p<0.05, **p<0.01, ***p<0.001; (b) is the cell compatibility of the hemostatic powder; Figure 22 Representative Live / Dead staining merge images of different materials after 24 hours of co-culturing; Figure 23 The biocompatibility of hemostatic powder in vivo. Detailed Implementation

[0020] The present invention will now be described in further detail with reference to the accompanying drawings: 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.

[0021] In this article, unless otherwise specified, “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.”

[0022] 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.

[0023] 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.

[0024] As mentioned in the background section, existing fluid-foaming expandable hemostatic materials mainly generate foam upon contact with blood flow after injection into the wound site. However, they are prone to bacterial growth due to easy contact with air and lack sufficient mechanical strength. While general powdered materials have good wound contact performance, they cannot achieve rapid self-gelling for quick hemostasis and have poor wound conformation.

[0025] To address the aforementioned problems, this invention discloses a method for preparing a rapid self-gelling, expandable, self-propelled, coagulating, portable hemostatic powder, comprising the following steps: Step 1: Dopamine-modified montmorillonite (PT) is prepared using montmorillonite, dopamine, hydrochloric acid solution, and tris(hydroxymethyl)aminomethane solution; the specific steps are as follows: The process for preparing dopamine-modified montmorillonite is as follows: montmorillonite is added to a hydrochloric acid solution and stirred at 45°C for 8 hours. The mixed solution is centrifuged several times, and the supernatant is dried to obtain reaction system A. Hydrochloric acid is added to a tris(hydroxymethyl)aminomethane solution to adjust the pH to 8.5, and dopamine is added to the solution. The mixture is stirred at room temperature until completely dissolved to obtain reaction system B. Reaction system A is added to reaction system B and stirred at room temperature for 24 hours. The supernatant is discarded, and the solution is washed until clear. The obtained product is freeze-dried to obtain dopamine-modified montmorillonite.

[0026] Step 2: Prepare protonated tranexamic acid (TXA-NH3) using tranexamic acid and hydrochloric acid solution. 3+ The process for preparing protonated tranexamic acid is as follows: an appropriate amount of hydrochloric acid solution is added to tranexamic acid to adjust the pH to 4.3, and then the mixture is freeze-dried to obtain protonated tranexamic acid.

[0027] Step 3: Prepare polyacrylic acid and polyethyleneimine solutions using deionized water; the mass fraction of both polyacrylic acid and polyethyleneimine solutions is 10 wt%.

[0028] Step 4: Dopamine-modified montmorillonite powder is added to equal volumes of polyacrylic acid solution and polyethyleneimine solution, respectively, and then freeze-dried and ground to obtain polyacrylic acid / polyethyleneimine / dopamine-modified montmorillonite (PP / PT); the mass percentage of dopamine-modified montmorillonite in the composite material is 1%~20%.

[0029] Step 5: Mix the powder (PP / PT) prepared in Step 4 with the organic acid protonated tranexamic acid (TXA-NH4+). 3+ Sodium carbonate was mixed evenly in a certain proportion and dried to obtain a rapidly self-gelling, expandable, self-propelled, coagulating, portable hemostatic powder. In the preparation of this self-gelling, expandable, self-propelled, coagulating, portable hemostatic powder, the mass ratio of polyacrylic acid / polyethyleneimine / dopamine-modified montmorillonite (PP / PT), protonated tranexamic acid, and sodium carbonate was (8-40):4:1.

[0030] This invention discloses a method for preparing a rapid self-gelling, expandable, self-propelled, portable hemostatic powder. First, hydrochloric acid modification improves the dispersibility of montmorillonite in water, resulting in dopamine-modified montmorillonite (PDA-MMT), which imparts excellent wet adhesion properties to the material. The modified montmorillonite combines the physical coagulant properties of natural clay, the wet adhesion and bioactivity regulation functions of dopamine, and the mechanical blocking effect of a foaming system, providing a stable matrix for hemostasis and coagulation. Second, the pressure of the gas generated by the foaming reaction of protonated tranexamic acid and sodium carbonate imparts expandability to the material. Simultaneously, the polyethyleneimine / polyacrylic acid system exhibits ultra-fast self-gelling and wet adhesion properties.

[0031] A second aspect of the present invention discloses a rapidly self-gelling, expandable, self-propelled, coagulating, portable hemostatic powder, the powder comprising PP / PT composite powder, protonated tranexamic acid powder, and sodium carbonate.

[0032] This rapidly self-gelling, expandable, self-propelled, portable hemostatic powder combines the powder's large specific surface area, hygroscopic self-gelling properties, and expandable material's wound adaptability and immediate physical sealing effect to quickly control bleeding in cavities where pressure is not possible. During the self-gelling process, polyacrylic acid and polyethyleneimine exhibit excellent swelling stability through electrostatic interactions and hydrogen bonding. After the foaming reaction ends, the procoagulant tranexamic acid remains in the system, achieving coagulation homeostasis by inhibiting in-situ activation of plasmin, demonstrating excellent hemostatic performance. Furthermore, its ease of storage, portability, immediate use, and lack of human intervention shorten hemostasis time, providing a window of opportunity for battlefield treatment.

[0033] The present invention will be further described in detail below with reference to specific embodiments.

[0034] Example 1 (1) Dopamine-modified montmorillonite was prepared by reacting montmorillonite, dopamine, hydrochloric acid solution, and tris(hydroxymethyl)aminomethane solution (Tris solution). 5 g of montmorillonite was added to 100 mL of 3 M HCl and stirred at 45 °C for 8 h. The solution was then centrifuged 5-6 times. After confirming the absence of chloride in the supernatant by silver nitrate testing, the precipitate was dried overnight in a 50 °C oven. Hydrochloric acid was added to 150 mL of Tris solution to adjust the pH to 8.5. 1.5 g of dopamine was then added to the solution and stirred at room temperature until completely dissolved. The acid-modified montmorillonite was added to the above solution and stirred at room temperature for 24 h. Finally, the supernatant was discarded, and the residue was washed with water 3-4 times until the solution was clear. The product (hereinafter referred to as PT) was obtained by freeze-drying.

[0035] (2) Preparation of protonated tranexamic acid from tranexamic acid and hydrochloric acid solution. Add an appropriate amount of HCl (1 M) to 0.5 M tranexamic acid to pH 4.3, freeze-dry, and collect the solid TXA-NH. 3+ .

[0036] (3) Prepare polyacrylic acid and polyethyleneimine solutions using deionized water. Prepare 1000 mL of 10 wt% polyethyleneimine aqueous solution (70,000 Mn) and 1000 mL of 10 wt% polyacrylic acid aqueous solution (240,000 Mn) using deionized water.

[0037] (4) Polyacrylic acid / polyethyleneimine / dopamine-modified montmorillonite was obtained by adding dopamine-modified montmorillonite powder to equal volumes of polyacrylic acid solution and polyethyleneimine solution, freeze-drying, and then grinding. 2g of PT was added to equal volumes of 1000mL of 10 wt% polyethyleneimine aqueous solution and 1000mL of 10 wt% polyacrylic acid aqueous solution, and the mixture was shaken to ensure uniform mixing. The mixture was then immediately immersed in liquid nitrogen for rapid cooling and held for 15 min, followed by freeze-drying to remove moisture. Finally, the freeze-dried solid was ground to obtain PP / PT1 powder.

[0038] Example 2 Unlike Example 1, the PT content added in step (4) was changed to 6 g to obtain PP / PT3; Example 3 Unlike Example 1, the PT content added in step (4) was changed to 10 g to obtain PP / PT5; Example 4 Unlike Example 1, the PT content added in step (4) was changed to 20 g to obtain PP / PT10; Example 5 Unlike Example 1, the PT content added in step (4) was changed to 40 g to obtain PP / PT20; Example 6 Unlike Example 1, the PT content in step (4) was changed to 10 g to obtain PP / PT5; 1000 mg of PP / PT5 and 100 mg of TXA-NH were added. 3+ 25 mg of sodium carbonate (mass ratio 40:4:1) were uniformly mixed and dried and stored to obtain a hemostatic powder, which was named PP / PT5-TXA10.

[0039] Example 7 Unlike Example 1, the PT content in step (4) was changed to 10 g to obtain PP / PT5; 1000 mg of PP / PT5 and 200 mg of TXA-NH were added. 3+ 50 mg of sodium carbonate (mass ratio 20:4:1) were uniformly mixed and dried and stored to obtain a hemostatic powder, which was named PP / PT5-TXA20. Example 8 Unlike Example 1, the PT content in step (4) was changed to 10 g to obtain PP / PT5; 1000 mg of PP / PT5 and 300 mg of TXA-NH were added. 3+ 75 mg of sodium carbonate (mass ratio 12:4:1) were uniformly mixed and dried and stored to obtain a hemostatic powder, which was named PP / PT5-TXA30. Example 9 Unlike Example 1, the PT content in step (4) was changed to 10 g to obtain PP / PT5; 1000 mg of PP / PT5 and 400 mg of TXA-NH were added. 3+ 100 mg of sodium carbonate (mass ratio 10:4:1) was uniformly mixed and dried and stored to obtain a hemostatic powder, which was named PP / PT5-TXA40. Example 10 Unlike Example 1, the PT content in step (4) was changed to 10 g to obtain PP / PT5; 1000 mg of PP / PT5 and 500 mg of TXA-NH were added. 3+ 125 mg of sodium carbonate (mass ratio 8:4:1) was uniformly mixed and dried and stored to obtain a hemostatic powder, which was named PP / PT5-TXA50.

[0040] This invention provides a rapid self-gelling, expandable, self-propelled, and portable hemostatic powder with coagulation-promoting properties. This injectable, highly adhesive, self-expanding, and self-propelled hemostatic powder is used for rapid hemostasis in cases of massive, non-compressible bleeding from internal trauma. The hemostatic powder also exhibits excellent tissue adhesion, antibacterial properties, biocompatibility, and in vitro coagulation performance. The introduction of dopamine catechol groups into PT enhances the adhesion of the hemostatic powder to tissues and activates coagulation factors, accelerating coagulation. Specifically, in rat models of hepatic columnar defects, femoral artery transection, cardiac puncture, and tail truncation bleeding, the blood loss and / or hemostasis time of PP / PT5-TXA30 hemostatic powder were lower than those of commercial chitosan-based hemostatic powder. In a lethal rabbit model of complete transection of the subclavian artery / vein and non-compressible bleeding, due to the self-expanding and self-propelling properties of the self-gelling hemostatic powder, the blood loss and hemostasis time were also significantly lower than those of commercial chitosan-based hemostatic powder, prolonging the survival time of rabbits and reducing mortality. This rapidly self-gelling, expandable, self-propelled, coagulant-promoting portable hemostatic powder has great potential for controlling non-compressible bleeding from intracavitary trauma.

[0041] The following is a detailed analysis with reference to the attached figures and experimental data: Such as the adhesion strength of PP and PP / PTn powder ( Figure 2 As shown in the figure, the introduction of catechol groups enhances the adhesion properties of the powder, but as the PT content increases, the adhesion strength of the powder may show a trend of first increasing and then decreasing. When the PT content is 5 wt%, PP / PT exhibits the best adhesion strength. In subsequent experiments, a self-gelling hemostatic powder with a PT content of 5 wt%, namely PP / PT5, was used.

[0042] like Figure 3 The Fourier transform infrared spectrum, as shown, verifies the successful preparation of the material. In the PT spectrum, at 1603 cm⁻¹... -1 A significant in-plane bending vibration characteristic absorption peak of NH was observed at [insert value here], confirming that dopamine was successfully coated and modified into the montmorillonite matrix. Further comparison of spectral characteristics revealed that the characteristic absorption peak of the carboxylic acid group (-COOH) in pure PAA is located at 1696 cm⁻¹. -1 The vibrational peak of primary / secondary amines (-NH2 / -NH) in PEI appears at 1587 cm⁻¹. -1 Region. When constructing the PP / PT5 composite system, the aforementioned characteristic peaks shifted to 1632 cm⁻¹. -1 and 1541 cm -1 Furthermore, no new characteristic peaks were observed. This demonstrates that the crosslinking between PEI, PAA, and PT in the system primarily originates from physical bonding mechanisms such as hydrogen bonding and electrostatic interactions, rather than the formation of covalent bonds.

[0043] By scanning electron microscopy (SEM) Figure 4 ) and Energy Dispersive Spectrometer (EDS) Figure 5 The microstructure and elemental composition of the product were characterized and determined. For example... Figure 4 As shown in the SEM images of the four samples, dopamine modification makes the layered structure of montmorillonite more pronounced. Dopamine-modified montmorillonite enhances its dispersibility in water and also enables its self-assembly on the template. The composite system prepared from polyacrylic acid / polyethyleneimine tends to form disordered, cross-linked, micron-sized flocculent aggregates under unmodified conditions, while the introduction of dopamine-modified montmorillonite causes these flocculents to bind to the powder surface. Figure 5 As shown, the EDS results display the proportions of C, O, Na, Si, Al, Mg, and N elements and their corresponding elemental mapping images. The increase in C content confirms that dopamine molecules form a continuous coating layer on the montmorillonite surface through oxidative self-polymerization, indicating successful dopamine modification. In the PP / PT5 composite system, the first appearance of N and the dramatic increase in C content (…) Figure 5 The composition of PP / PT5 is directly attributed to the introduction of PT, as shown in Figure (c).

[0044] The liquid absorption capacity of hemostatic powder was quantitatively evaluated through systematic blood adsorption performance testing. For example... Figure 7 As shown, commercial chitosan-based hemostatic powders HP, PP powder, PP / PT5, and the composite system PP / PT5-TXA30 all exhibited excellent blood adsorption properties. Among them, the PP / PT5 group showed the best adsorption performance under the same mass conditions, with a blood uptake rate of 290%.

[0045] Systematic swelling assessment was performed on gels formed from equal masses of hemostatic powder in PBS at 37 °C, such as... Figure 8 As shown, chitosan-based HP powder exhibits a rapid swelling trend in the initial stage, but then undergoes structural disintegration. Its swelling rate reaches a critical value after 180 min, accompanied by complete dispersion of the gel network. This phenomenon can be attributed to the lack of a stable physical / chemical cross-linking network, leading to instability in the dynamic equilibrium of the three-dimensional structure. In contrast, PP-based composite systems (including PP, PP / PT5, and PP / PT5-TXA30) demonstrate excellent swelling stability; their swelling curves remain stable after reaching equilibrium, confirming that the materials can maintain stable mechanical properties during hemostasis. In particular, the PP / PT5-TXA30 system shows a swelling equilibrium time approximately 25% shorter than the PP group, thanks to the synergistic stabilizing effect of the steric hindrance of the PT nanosheets and the hydrophilic regulation of dopamine. This controllable swelling behavior and stable network structure have significant clinical implications for achieving precise hemostasis and preventing secondary bleeding.

[0046] When exposed to anticoagulated blood or aqueous media, PP / PT5 particles exhibit unique swelling kinetics: each discrete component rapidly absorbs the liquid phase to form microgel units. Figure 9 (Figure (a)). Notably, these swollen microgels can spontaneously undergo topological entanglement and recombination at the contact interface. Without the intervention of exogenous crosslinking agents, a complete three-dimensional hydrogel network can be constructed through interfacial fusion effect in just 2 seconds. This is due to the synergistic dynamic balance of multiple hydrogen bonds and charge interactions between polymer chains during this self-healing process. This supramolecular mechanism ensures both rapid bonding response and maintains appropriate binding energy for structural remodeling. Dry PP / PT5 powder was pre-arranged into an "XJTU" letter configuration. After liquid-phase activation, the material was successfully transformed into a structured hydrogel with high morphological fidelity. Figure 9 Figure (b) in the text strongly demonstrates the unique advantages of this material in the construction of biomimetic structures. This instant self-assembly characteristic and morphological controllability provide an important materials science basis for the development of non-pressable hemostatic materials.

[0047] Based on the dynamically reversible physical cross-linking structure of the PP / PT5 system, this material exhibits significant intrinsic self-healing capabilities. To systematically evaluate the self-healing properties of the gelation products, a staining comparison experiment was conducted for verification: when PP / PT5 hydrogel samples labeled with different staining agents came into contact, effective adhesion and structural reconstruction were rapidly achieved at the interface, such as... Figure 10 As shown, by constructing a double-ring structure with four strip-shaped gels and using the contact interface as the self-healing core area, the composite gel not only maintains structural integrity during lateral stretching but also exhibits extremely high elongation, fully verifying the material's excellent self-healing performance and mechanical ductility.

[0048] Strong mechanical strength is crucial for hydrogels to maintain structural integrity and resist external forces to prevent breakage. Rheological testing, compressive strain testing, and tensile strain testing were used to evaluate the mechanical properties of the powder after gelation. Frequency sweep spectroscopy showed that all samples exhibited typical solid viscoelastic behavior, such as… Figure 11 As shown, within the test frequency range, the energy storage modulus G' is always higher than the loss modulus G", and with TXA-NH 3+ With increasing Na2CO3 content, G' and G" continuously decreased at an accelerating rate, exhibiting a transition between PP / PT5-TXA30 and PP / PT5-TXA50, with G' decreasing from 87 kPa to 21 kPa. These results indicate that the hydrogel exhibits higher stiffness at lower foaming agent content, while its stiffness decreases in the presence of excessive foaming agent.

[0049] In addition, a uniaxial compression test was performed on the gelled powder. Figure 12As shown in Figure (a), with the gradual increase of foaming agent content, the compressive strength of PP / PT5, PP / PT5-TXA10, PP / PT5-TXA20, PP / PT5-TXA30, PP / PT5-TXA40, and PP / PT5-TXA50 hydrogels gradually decreased, with ultimate compressive strengths at 80% strain of 127, 124, 109, 97, 62, and 32 kPa, respectively. This is consistent with the trend of the rheological results discussed above, where the compressive strength decreases with increasing acid content. To better investigate the effect of the foaming agent addition ratio on the mechanical properties of the materials, the tensile properties of the hemostatic powder after gelation were investigated, such as... Figure 12 As shown in Figure (b), the experimental results show that as the foaming agent content increases, the peak stress and tensile modulus of the hydrogel gradually decrease, but the flexibility improves and the peak strain increases accordingly.

[0050] PP / PT5-TXA30 was injected into a quantitative amount of heparinized whole blood, and its swelling properties after blood absorption and self-gelation were studied. Figure 13 Upon contact with blood, the powder begins to self-gel and expand, with an expansion rate reaching 400% within 5 seconds. Figure 14 This study validated its excellent self-expanding and self-propelling properties, demonstrating that the expandable hemostatic powder may perform well in rapidly stopping bleeding.

[0051] The adhesion properties of hemostatic powder on different biological tissue surfaces were evaluated. Using pigskin as a model substrate, in-situ gelation of the powder was achieved by varying the order of dye addition, such as... Figure 15 As shown in (a). Adhesion tests show that the gelled material maintains stable interfacial adhesion even after undergoing harsh conditions such as 180° inversion, fluid rinsing, mechanical stretching, multi-directional bending, and torsion, without peeling or detachment. Furthermore, the hemostatic powder gels and forms in-situ adhesion after absorbing tissue fluid from the organ surface. PP / PT5-TXA30 also exhibits good adhesion properties on various tissues and organs such as the lungs, intestines, stomach, liver, kidneys, spleen, and heart. Figure 15 As shown in (b) and (c). Furthermore, the adhesion strength of the powder to fresh pigskin was quantitatively determined by an overlap shear test. The results showed that the adhesion strength of the PP / PT5 powder was 42.84 kPa, significantly higher than that of the PP powder (22.21 kPa). This was mainly attributed to the wet adhesion of the catechol groups on the PDA to the tissue interface and the diffusion bonding between the polymer and the tissue interface. Figure 16 ).

[0052] The material's tissue sealing properties were further evaluated through burst pressure testing. Figure 17As shown, thanks to their excellent tissue adhesion, the burst pressures of PP, PP / PT5, and PP / PT5-TXA30 hemostatic powders all significantly exceed the normal systolic blood pressure (90-140 mmHg). Furthermore, due to the enhanced mechanical properties of the materials, the burst pressures of PP / PT5 (439.3 kPa) and PP / PT5-TXA30 (421.3 kPa) powders are significantly higher than those of PP powder (349.5 kPa), demonstrating their ability to withstand the impact of blood pressure. These results indicate that PP / PT5-TXA30 powder can effectively absorb interfacial water, forming a physically cross-linked hydrogel in situ, possessing the potential to achieve hemostasis through rapid tissue adhesion and wound sealing.

[0053] The in vitro coagulation effect of hemostatic powder was qualitatively evaluated using erythrocyte and platelet adhesion and fibrin deposition tests. For example... Figure 18 As shown in (a), the number of erythrocytes aggregated in the three powder groups (PP, PP / PT5, and PP / PT5-TXA30) was significantly higher than that in the three control groups: gauze, sponge, and chitosan-based HP powder. Most of the aggregates exhibited a pseudopodia-like activated state, primarily attributed to the powder groups' efficient liquid absorption and self-expansion properties. This indicates that upon contact with blood, the powder can rapidly encapsulate the blood and form a hydrogel / blood clot complex, possessing the potential to stop bleeding by sealing the bleeding site. Furthermore, the swellable montmorillonite, in conjunction with the catechol groups of PDA, interacted with erythrocytes, resulting in greater erythrocyte aggregation in the PP / PT5 powder group compared to the PP group. Further, the introduction of positively charged TXA-NH... 3+ This causes electrostatic interaction between PP / PT5-TXA30 powder and erythrocytes, more effectively promoting the adhesion and aggregation of erythrocytes. Figure 18 (b) ), thereby achieving rapid coagulation. In the coagulation pathway, erythrocytes have been shown to induce or enhance platelet activation, forming platelet thrombi and completing primary hemostasis. The adhesion and aggregation of activated platelets can further induce thrombin to participate in fibrin formation and stabilization, completing secondary hemostasis. Therefore, the adhesion and aggregation abilities of gauze with PP / PT5 and PP / PT5-TXA30 groups on platelets were further compared ( Figure 18 (c)). The results were consistent with the erythrocyte adhesion assay, with platelet aggregation in the powder group being significantly higher than that in the gauze group, and the in vitro coagulation effect of the PP / PT5-TXA30 group being significantly better than that of PP / PT5.

[0054] The coagulation properties of the powder were qualitatively evaluated using plasma recalcification time and dynamic whole blood coagulation tests. In the plasma recalcification time test, a shorter time indicates a faster blood coagulation rate. Figure 19As shown in (a), the clotting time of all powder groups was within 21 s, significantly lower than that of the sponge group (36 s). With the introduction of PT, the clotting time was further shortened to 13.5 s, while with the addition of TXA-NH 3+ The increasing content of the foaming component led to a continuous decrease in clotting time, demonstrating that its introduction not only provides expansion properties but also further promotes coagulation and thus hemostasis. In the dynamic whole blood coagulation test, the lower the absorbance value of the hemoglobin solution, the faster the powder's coagulation speed. The blood coagulation performance of PP / PT5-TXA30 hemostatic powder was evaluated using sponge, gauze, chitosan-based HP powder, PP powder, and PP / PT5 powder as controls, with the untreated group serving as a blank control. Equal volumes of ACD whole blood were dropped onto different materials at 37°C, and after 120 seconds, water was added to rinse away the uncoagulated blood. Figure 20 Visually, the blank control group appears dark red, indicating that the blood did not clot effectively within 120 seconds, while the color gradually lightens from left to right. Figure 19 The experimental data in (b) are consistent with the above phenomena, further verifying the excellent procoagulant properties of PP / PT5-TXA30 hemostatic powder.

[0055] Comparison of blood clotting status after 120 seconds of contact with different materials Figure 20 As shown, the hemostatic process mediated by PP / PT5-TXA30 powder is as follows: When PP / PT5-TXA30 powder comes into contact with the wound interface, it can rapidly absorb blood and self-gel in situ, forming a strong adhesion with the tissue as a sealing barrier. Simultaneously, it concentrates coagulation factors within the gel structure, further promoting coagulation. Furthermore, the hydrogel derived from PP / PT5-TXA30 powder can aggregate blood cells, activate platelets, and inhibit plasminogen, thereby reducing fibrinolysis and enhancing hemostasis. In summary, PP / PT5-TXA30 powder exhibits excellent hemostatic effects and superior in vitro coagulation capabilities.

[0056] Hemostatic materials should have good blood compatibility; therefore, the hemolysis rate of the material is tested by directly contacting the hemostatic powder with blood cells. For example... Figure 21As shown in (a), the colorimetric characteristics of the solutions in the experimental groups (seven types of hemostatic powder) and the positive control group (Triton X-100) showed significant differences. The supernatant of each test sample group remained pale pink, while the control group solution exhibited characteristic hemolytic color, preliminarily confirming that this series of hemostatic powders did not induce a significant hemolytic reaction. Hemolysis rate tests showed that the hemolysis rates of all seven hemostatic powders were below 5%, consistent with the visual colorimetric results. Therefore, these experimental results confirm that the hemostatic powders did not cause significant hemolysis upon contact with blood cells, indicating good blood compatibility. Hemostatic materials should also have no significant cytotoxicity. The cell compatibility of the hemostatic powders was tested using a model method of co-culturing L929 fibroblasts with an equal amount of pre-gelled disc hemostatic powder (20 mg) for 24 h. Figure 21 As shown in (b), compared with the TCP group, the cell survival rate of all hemostatic powder groups reached over 94%, with the cell survival rate of the PP / PT5 group reaching 104%. This may be due to the introduction of dopamine increasing the cell compatibility of the material, which can enhance cell viability and promote cell proliferation. Figure 22 The results of live / dead staining were consistent with the cell viability results. Microscopic observation showed that L929 cells in all experimental groups maintained typical fibroblast morphology, similar to the TCP control group. Due to normal cell metabolism, only a few sporadic cells were detected as red. The results indicate that the rapidly self-gelling hemostatic powder has good cell compatibility.

[0057] To further verify the biocompatibility of the material, pre-gelled PP / PT5-TXA30 hemostatic powder was implanted subcutaneously into SD rats, with PP, PP / PT5, and commercially available chitosan-based hemostatic powder serving as controls. Figure 23 The H&E staining results showed that all four samples exhibited relatively mild acute and chronic inflammatory responses 7 and 28 days after subcutaneous implantation. However, the fibrous capsule thickness of the PP / PT5 sample was lower than that of the PP group. This suggests that the introduction of dopamine can alleviate the inflammatory response. These results indicate that PP / PT5-TXA30 hemostatic powder has good biocompatibility and can be used as a hemostatic material for in vivo application.

[0058] This study further used a lethal porcine subclavian artery / vein complete transection hemorrhage model to verify the in vivo hemostatic effect of the developed rapid self-gelling, self-expanding, self-propelling, highly adhesive, and coagulant-promoting portable hemostatic powder (PP / PT5-TXA30) on large animals. This wound model accurately simulates the pathological characteristics of lethal massive hemorrhage in combat wounds, and this type of penetrating suture wound also has a high morbidity and mortality rate in civilian environments. At the end of the 1-hour observation period after hemostasis, the mean arterial pressure and blood oxygen saturation of the hemostatic powder group were higher than those of the control group, while the fluid resuscitation volume was less than that of the control group (Table 1). At the same time, the survival rate of the hemostatic powder group reached 100%, while two pigs in the control group died successively within 3 hours after the end of the observation period.

[0059] Table 1. Relevant indicators of the complete transection hemostasis test of the subclavian artery / vein in pigs.

[0060] In summary, this novel, ultra-rapidly self-gelling, self-expanding, self-propelling, and highly adhesive coagulant-promoting portable hemostatic powder exhibited superior hemostatic performance in a lethal, non-compressible bleeding model. Its significantly reduced bleeding volume and shortened hemostasis time demonstrate that this hemostatic powder can rapidly and effectively control massive hemorrhage and improve survival rates. This significant performance improvement stems from the self-gelling and expandable properties of the hemostatic powder, enabling it to rapidly fill wound cavities and apply appropriate pressure, preventing secondary damage. Simultaneously, its high adhesiveness ensures stable hemostatic effects. Furthermore, its ease of storage, portability, immediate use, and lack of human intervention provide significant advantages in battlefield and emergency situations. It can shorten hemostasis time, gaining a window of opportunity for battlefield treatment, achieving tactical time gains, improving emergency response efficiency, and reducing the risk of complications. Its individual soldier operability enhances battlefield applicability. Its rapid and efficient hemostatic capabilities also offer a potential solution for patients with coagulopathy, acidosis, and hypothermia.

[0061] 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 self-gelling, expandable, self-propelled, coagulating, portable hemostatic powder, characterized in that, Includes the following steps: S1, dopamine-modified montmorillonite powder was prepared by means of montmorillonite, dopamine, hydrochloric acid solution and tris(hydroxymethyl)aminomethane solution; S2, Organic acid protonated tranexamic acid powder is prepared by reacting tranexamic acid with hydrochloric acid solution; S3, prepare polyacrylic acid solution and polyethyleneimine solution respectively; S4. Add dopamine-modified montmorillonite powder to a mixed solution of polyacrylic acid solution and polyethyleneimine solution, freeze-dry, grind and pulverize to obtain polyacrylic acid / polyethyleneimine / dopamine-modified montmorillonite powder, which is a PP / PT composite powder. S5, the PP / PT composite powder, protonated tranexamic acid powder, and sodium carbonate powder are mixed evenly; after drying, a self-gelling, expandable, self-propelled, coagulating, portable hemostatic powder is obtained.

2. The method for preparing a self-gelling, expandable, self-propelled, coagulating, portable hemostatic powder according to claim 1, characterized in that, The specific process of S1 is as follows: Montmorillonite is added to hydrochloric acid, stirred and centrifuged, and the supernatant is dried to obtain reaction system A; the pH of the tris(hydroxymethyl)aminomethane solution is adjusted to 8.5 by hydrochloric acid, and then dopamine is added, stirred and dissolved to obtain reaction system B; reaction system A and reaction system B are mixed, stirred and reacted, and the reaction product is washed and freeze-dried to obtain dopamine-modified montmorillonite powder.

3. The method for preparing a self-gelling, expandable, self-propelled, coagulating, portable hemostatic powder according to claim 2, characterized in that, In S1, the mass ratio of montmorillonite to dopamine is 5:1.

5.

4. The preparation method of a self-gelling, expandable, self-propelled, coagulating, portable hemostatic powder according to claim 1, characterized in that, In S2, the process of preparing protonated tranexamic acid from tranexamic acid and hydrochloric acid solution is as follows: add hydrochloric acid solution to tranexamic acid to adjust the pH to 4.3, and freeze-dry the entire system to obtain protonated tranexamic acid from the organic acid.

5. The method for preparing a self-gelling, expandable, self-propelled, coagulating, portable hemostatic powder according to claim 1, characterized in that, In S3, the volume ratio of the polyacrylic acid solution to the polyethyleneimine solution is 1:

1.

6. The method for preparing a self-gelling, expandable, self-propelled, coagulating, portable hemostatic powder according to claim 1, characterized in that, In S3, the concentrations of both the polyacrylic acid solution and the polyethyleneimine solution are 10 wt%.

7. The preparation method of a self-gelling, expandable, self-propelled, coagulating, portable hemostatic powder according to claim 1, characterized in that, In S4, the mass fraction of the dopamine-modified montmorillonite powder in the mixed solution of polyacrylic acid solution and polyethyleneimine solution is 1%-20%.

8. The method for preparing a self-gelling, expandable, self-propelled, coagulating, portable hemostatic powder according to claim 1, characterized in that, In S5, the mixing mass ratio of the PP / PT composite powder, the protonated aminomethyl tranexamic acid powder, and the sodium carbonate powder is (8-40):4:

1.

9. A self-gelling, expandable, self-propelled, coagulating, portable hemostatic powder prepared by the preparation method according to any one of claims 1-8, characterized in that, It includes PP / PT composite powder, protonated tranexamic acid powder, and sodium carbonate powder.

10. The application of the self-gelling, expandable, self-propelled, coagulant-promoting, portable hemostatic powder according to claim 9, characterized in that, The self-gelling, expandable, self-propelled, coagulating, portable hemostatic powder is used to prepare hemostatic materials.

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