Hemostatic compound and application thereof in hemostasis

Abstract

The invention relates to a hemostasis compound and application thereof in hemostasis, poly (propylene glycol fumarate) (PPF) and polyvinyl alcohol (PVA) sponge are blended to prepare an injectable and absorbable composite material with good flowability, mechanical property and hemostasis activity, and fluid is solidified through a cross-linking reaction and then fills a wound cavity to achieve a hemostasis effect. Compared with a traditional hemostatic material, the PPF-PVA compound shows clinical application potentials of injectability, adaptability, drug loading, healing promotion and low heat injury.

Description

Technical Field

[0001] This application relates to a hemostatic compound and its application, and more particularly to a compound for hemostasis by tamponade, the compound containing polypropylene fumarate (PPF). Background Technology

[0002] Uncontrolled bleeding, a core challenge in trauma care, accounts for nearly 50% of casualties in military medicine, and its mortality rate among hospitalized trauma patients is as high as 15%-25%. Notably, even persistent bleeding from non-fatal trauma can significantly increase the risk of disability through secondary pathological reactions: hypothermia, coagulation cascade disorders, and internal environment imbalances caused by massive blood loss can further induce traumatic coagulopathy (TIC), which can progress to multiple organ dysfunction syndrome (MODS) in severe cases. Such fatal complications are particularly prevalent in battlefield casualties. Clinical evidence shows that effective hemostasis intervention within the "golden treatment window" of 10-30 minutes after injury can successfully prevent more than 50% of bleeding-related deaths. This real need has driven innovative research in global trauma medicine, making the development of hemostatic materials and interventional techniques a key breakthrough in improving survival rates from combat trauma.

[0003] Stab wounds are common in daily life, military activities, and terrorist attacks. The wounds caused by stab wounds are called puncture wounds. Puncture wounds are characterized by small incisions, deep wounds, and superficial superficial damage to the body surface while causing severe damage to internal organs. They commonly occur on the trunk, limbs, and the junctions between these areas. Although the wounds appear small on the skin, if deep vascular damage is involved, bleeding can be rapid and profuse. Stab wounds easily cause non-compressible bleeding injuries, i.e., bleeding from injuries to the trunk and the junctions between the trunk and limbs, which cannot be controlled before hospital using conventional compression methods such as tourniquets. Non-compressible bleeding is a major reason for the high pre-hospital morbidity and mortality rates.

[0004] For patients with non-compressible bleeding injuries, whether on the battlefield, in daily life, or in remote areas with limited medical resources, early bleeding control in pre-hospital emergency care is crucial for survival. Currently used treatment methods, such as resuscitation endovascular balloon occlusion, lateral aortic compression, and tourniquet application at the abdominal aortic junction, typically require professional medical personnel. Before these procedures, injured patients often struggle to perform self-rescue and are prone to missing the optimal treatment window. Therefore, developing a hemostatic product that can effectively control non-compressible bleeding before hospitalization is of great significance for injured patients.

[0005] In existing technologies, regarding tamponade-type hemostasis, some foreign institutions have developed a novel local pressure hemostatic device called Xstat for dealing with non-compressible bleeding. It contains a cellulose sponge with an outer layer covered in chitosan, which absorbs blood and expands to achieve pressure hemostasis. Other institutions have developed a synthetic polyvinyl alcohol (PVA) sponge crosslinked with CS (carbonyl ester), creating a polyvinyl alcohol-chitosan hemostatic sponge that can be injected into the bleeding wound. After absorbing blood, it expands to eight times its original size, and its hemostasis time is significantly better than other materials. However, the hemostatic materials formed by the above methods are not slowly absorbed by the body and must be surgically removed after hemostasis, causing secondary harm to the patient.

[0006] Therefore, for quick and convenient hemostasis, there is a need for a hemostatic compound that can be rapidly stopped by packing, does not need to be removed after hemostasis, and can be slowly absorbed by the human body. Summary of the Invention

[0007] The purpose of this application is to provide a hemostatic compound comprising polypropylene fumarate that achieves hemostasis by filling wound cavities; based on this purpose, another purpose of this application is the application of the hemostatic compound.

[0008] This application is implemented as follows: a method for preparing a hemostatic compound, comprising the following steps: Step 1, Raw material ratio: 1-1 Diethyl fumarate and 1,2-propanediol were added to a three-necked round-bottom flask at a mass ratio of 1:3 to obtain mixture A; 1-2 Zinc chloride with a mass ratio of 0.01:1 to mixture A was introduced as a catalyst, and hydroquinone with a mass ratio of 0.002:1 to mixture A was added as a double bond protectant; Step 2, heating reaction: A gradient heating strategy is adopted, with the temperature gradually increased at 30-minute intervals, each increase being 10°C, and finally stabilized at 150°C for 8 hours of isothermal reaction, thereby obtaining a mixture B of the precursor diethyl fumarate DEF and the byproduct ethanol. Step 3, vacuum polycondensation: After the temperature of mixture B is uniformly reduced to 100°C over 4 hours using an intelligent temperature control device, the vacuum system is activated to gradually reduce the pressure to below 10 mmHg; at this time, the temperature is gradually increased to 150°C at 50-minute intervals, and the reaction is continued for 12 hours. Step 4, cooling: First, allow it to cool naturally to below 100℃. Then, slowly balance the pressure inside and outside the system through the air inlet valve of the buffer bottle and close the vacuum device. Step 5, Dissolving: Add the ingredients in batches to dissolve in dichloromethane; Step 6, Purification: The organic phase was washed sequentially with 1M hydrochloric acid and saturated sodium chloride solution, then dried with anhydrous sodium sulfate particles and allowed to stand for 12 hours. Step 7, Solvent removal: The solvent removal is completed using a rotary evaporator at a constant temperature of 40°C in conjunction with a vacuum decompression device. The final product is then processed in a vacuum drying oven to obtain a brownish-yellow transparent viscous liquid, which is polypropylene fumarate (PPF). Step 8, Preparation of the final mixture: Polypropylene fumarate (PPF) and PVA sponge are mixed at a mass ratio of 20:1, and the mixture is stirred and sheared to obtain a paste-like PPF-PVA mixture, which is the hemostatic complex of this application.

[0009] Furthermore, in step 5, an equal volume of dichloromethane as mixture B is added for each batch for dissolution.

[0010] Furthermore, in step 8, the PVA sponge is sheared to a particle size of less than 0.2 cm.

[0011] Furthermore, the hemostatic complex (PPF-PVA mixture) was obtained according to the above-described method for preparing the hemostatic complex.

[0012] Furthermore, the hemostatic compound is used in the preparation of plug-type hemostatic materials.

[0013] By employing the above technical solution, a composite material with good flowability, mechanical properties and hemostatic activity is prepared by blending polypropylene fumarate (PPF) with polyvinyl alcohol (PVA) sponge. The composite material is then filled into the wound cavity to achieve hemostasis after the fluid is solidified by a cross-linking reaction. Compared with traditional hemostatic materials, PPF-PVA complexes exhibit unique clinical application potential: (1) Injectability and adaptability: Compared with the pre-molded limitations of gelatin sponges, the fluidity of PPF-PVA makes it suitable for irregular wound cavities, especially for NCTH (non-compressible trunk bleeding) and NCJH (junctional hemorrhage); (2) Drug loading: PPF is currently well-established in clinical use for drug loading, and can be combined with coagulation factors and anti-inflammatory factors to enter the wound cavity, preventing inflammation while stopping bleeding; (3) Promoting healing: SALARIAN M, SAMIMI R, XU WZ, et al. Microfluidic synthesis and angiogenic activity of ginsenoside Rg1-loadedPPF microspheres[J]. ACS Biomaterials Science & Engineering, 2016, 2(11):1872-1882. Experiments have shown that PPF compound ginsenoside Rg1 can promote angiogenesis, which can promote the healing of local wounds; (4) Low thermal damage: The crosslinking temperature of PPF (50℃) is significantly lower than that of polymethyl methacrylate (PMMA, >80℃), which reduces thermal damage to surrounding tissues. Detailed Implementation

[0014] The technical solutions in the embodiments of this application will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of this application, and not all embodiments. Based on the embodiments in this application, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this application.

[0015] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs; the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the application. The terms “comprising” and “having”, and any variations thereof, in the specification and claims of this application are intended to cover non-exclusive inclusion.

[0016] In this application, "and / or" is merely a way of describing the relationship between related objects, indicating that three relationships can exist; for example, A and / or B can represent three cases: A existing alone, A and B existing simultaneously, and B existing alone. Additionally, the character " / " in this document generally indicates that the preceding and following related objects have an "or" relationship.

[0017] It should be noted that in this application, the words "in some embodiments," "exemplarily," and "for example" are used to indicate examples, illustrations, or descriptions. Any embodiment or design described in this application as "in some embodiments," "exemplarily," or "for example" should not be construed as being more preferred or advantageous than other embodiments or design solutions. Specifically, the use of words such as "in some embodiments," "exemplarily," and "for example" is intended to present related concepts in a specific manner, meaning that a particular feature, structure, or characteristic described in connection with the embodiment may be included in at least one embodiment of this application. The appearance of the above words in various places in the specification does not necessarily refer to the same embodiment, nor is it a separate or alternative embodiment that is mutually exclusive with other embodiments. Those skilled in the art will explicitly and implicitly understand that the embodiments described herein can be combined with other embodiments.

[0018] Polypropylene fumarate (PPF) is a linear biodegradable unsaturated polyester material. In vitro degradation and cytotoxicity experiments have shown that PPF materials have good biodegradability and biocompatibility. Currently, it is used in biomedical engineering, drug delivery, and other fields with good results.

[0019] Polypropylene fumarate (PPF) has the following characteristics: ① It can be degraded in the body to produce fumaric acid and propylene glycol, which are then excreted after metabolism; ② The degradation products have no effect on human blood pH and do not interfere with cell growth; ③ The polymerization temperature of PPF is lower than that of PMMA, and the thermal crosslinking polymerization temperature of PPF is around 50℃, which will not cause excessive thermal damage to body tissues; ④ The unique unsaturated double bonds in the PPF molecular structure can undergo crosslinking reactions with other molecules. A method for preparing a hemostatic compound includes the following steps: Step 1, Raw material ratio: 1-1 Diethyl fumarate and 1,2-propanediol were added to a three-necked round-bottom flask at a mass ratio of 1:3 to obtain mixture A; 1-2 Zinc chloride with a mass ratio of 0.01:1 to mixture A was introduced as a catalyst, and hydroquinone with a mass ratio of 0.002:1 to mixture A was added as a double bond protectant; Step 2, heating reaction: A gradient heating strategy is adopted, with the temperature gradually increased at 30-minute intervals, each increase being 10°C, and finally stabilized at 150°C for 8 hours of isothermal reaction, thereby obtaining a mixture B of the precursor diethyl fumarate DEF and the byproduct ethanol. Step 3, vacuum polycondensation: After the temperature of mixture B is uniformly reduced to 100°C over 4 hours using an intelligent temperature control device, the vacuum system is activated to gradually reduce the pressure to below 10 mmHg; at this time, the temperature is gradually increased to 150°C at 50-minute intervals, and the reaction is continued for 12 hours. Step 4, cooling: First, allow it to cool naturally to below 100℃. Then, slowly balance the pressure inside and outside the system through the air inlet valve of the buffer bottle and close the vacuum device. Step 5, Dissolving: Add the ingredients in batches to dissolve in dichloromethane; Step 6, Purification: The organic phase was washed sequentially with 1M hydrochloric acid and saturated sodium chloride solution, then dried with anhydrous sodium sulfate particles and allowed to stand for 12 hours. Step 7, Solvent removal: The solvent removal is completed using a rotary evaporator at a constant temperature of 40°C in conjunction with a vacuum decompression device. The final product is then processed in a vacuum drying oven to obtain a brownish-yellow transparent viscous liquid, which is polypropylene fumarate (PPF). Step 8, Preparation of the final mixture: Polypropylene fumarate (PPF) and PVA sponge are mixed at a mass ratio of 20:1, and the mixture is stirred and sheared to obtain a paste-like PPF-PVA mixture, which is the hemostatic complex of this application.

[0020] Furthermore, in step 5, an equal volume of dichloromethane as mixture B is added for each batch for dissolution.

[0021] Furthermore, in step 8, the PVA sponge is sheared to a particle size of less than 0.2 cm.

[0022] Furthermore, the hemostatic complex (PPF-PVA mixture) was obtained according to the above-described method for preparing the hemostatic complex.

[0023] Furthermore, the hemostatic compound is used in the preparation of plug-type hemostatic materials.

[0024] The 1H-NMR spectrum of PPF shows that the peak at chemical shift 6.88 corresponds to the double bond hydrogen atom on the fumaric acid fragment; 5.31 and 4.27 correspond to the hydrogen atoms of the methine and methylene groups in the propylene glycol fragment, respectively; and the peaks at 1.22–1.37 represent methyl hydrogen atoms.

[0025] The contact angles of PPF and the PPF-PVA mixture were both less than 90°, indicating good hydrophilicity and wettability of the material surface, allowing liquids to penetrate more easily into the material. The contact angle of PPF was 83.152°, and that of the PPF-PVA mixture was 75.489°, suggesting that blending with PVA enhances the liquid absorption capacity of PPF, aiding in blood adsorption, restricting blood flow, and further effectively and rapidly promoting blood clotting.

[0026] The average hemolysis rates of PPF and PPF-PVA complex were 0.08% and 0.13%, respectively, both exceeding the safe hemolysis index of 5%, demonstrating excellent blood compatibility.

[0027] In vitro hemostatic ability test: The in vitro hemostatic effect of PPF-PVA mixture was evaluated by measuring BCI in vitro. Test subjects were divided into a blank control group, a gauze group, a negative control group, and the PPF-PVA mixture group. Coagulation effects were observed after coagulation experiments. After fresh blood was in contact with the sample for 5 minutes, deionized water was added to collect free red blood cells. The liquid in the blank group was dark red, followed by the gauze group and the control group. The PPF-PVA mixture group had a lighter color than the other groups, and a firm blood clot was visible on the surface. Coagulation ability was analyzed by quantitatively analyzing the BCI value. BCI is a commonly used indicator for evaluating the coagulation ability of materials; a higher BCI value indicates poorer hemostatic ability. The results showed that the PPF-PVA mixture group (40.3±4.6%) had a lower BCI value compared to the gauze group (53.4±6.8%), the control group (51.2±4.2%), and the negative control group (73.1±2.3%), indicating that this material has better coagulation ability.

[0028] In vivo hemostasis test: After hemostasis was achieved in a pig hind limb puncture model, the PPF-PVA mixture group, blank control group and negative control group were applied to the wound and a certain pressure was applied. After a certain period of time, all three groups of materials were able to achieve complete hemostasis.

[0029] Table 1 shows the statistical differences in hemostatic performance indicators among the three experimental groups. The hemostatic effect of each group was analyzed by statistically analyzing hemostasis time and bleeding volume. Compared with the blank group (115.67±7.41 s) and the negative control group (92.67±1.70 s), the PPF-PVA mixture group (77.67±7.41 s) had a relatively shorter hemostasis time; compared with the blank group (5.81±0.16 g) and the negative control group (5.16±0.08 g), the PPF-PVA mixture group (4.78±0.14 g) had a relatively smaller bleeding volume. These results indicate that the PPF-PVA mixture has a superior hemostatic effect compared to the negative control group. Table 1 Comparison of hemostatic performance indicators Grouping Bleeding time (s) Blood loss (g) White blood cell count (×10⁹ / L) Platelets (×10⁹ / L) PPF-PVA mixture 77.67±7.41 4.78±0.14 15.17±1.53 329.33±74.21 gauze group 115.67±4.11 5.81±0.16 25.98±0.95 295.33±9.53 control group 92.67±1.70 5.16±0.08 16.33±0.94 320±21.35 F 29.438 32.139 51.153 0.306 P ＜0.05 ＜0.05 ＜0.05 0.747 Statistical differences in white blood cell and platelet counts after 24 hours of hemostasis using the three materials were observed. The white blood cell count in the blank control group (25.98±0.95 ×10⁹ / L) was significantly lower than that in the PPF-PVA mixture group (15.17±1.53 ×10⁹ / L), indicating less inflammatory cell exudation. There were no statistically significant differences in white blood cell counts between the PPF-PVA mixture group (329.33±74.21 ×10⁹ / L), the blank control group (295.33±9.53 ×10⁹ / L), and the negative control group (320±21.35 ×10⁹ / L).

[0030] Table 2 shows the statistical differences in biochemical indicators 24 hours after hemostasis using the three groups of materials. Statistical differences were observed: ALT levels were significantly different between the PPF-PVA mixture group (52.95±0.99 U / L) and the blank control group (67.59±2.05 U / L); AST levels were significantly different between the PPF-PVA mixture group (49.06±3.58 U / L) and the blank control group (90.15±6.66 U / L), indicating that the PPF-PVA mixture had minimal impact on liver function; and UREA levels were significantly different between the PPF-PVA mixture group (25.87±2.25 mg / dL) and the blank control group (36.18±0.62 mg / dL), indicating that the PPF-PVA mixture had minimal impact on kidney function. No statistical differences were found among the remaining groups. Table 2 Statistical Results of Biochemical Indicators Group ALT (U / L) AST (U / L) UREA (mg / dL) ALB (g / L) CREA (μmol / L) PPF-PVA mixture 52.95±0.99 49.06±3.58 25.87±2.25 34.93±1.36 54.09±3.82 Blank control group 67.59±2.05 90.15±6.66 36.18±0.62 36.24±0.43 59.41±8.18 negative control group 52.97±0.87 51.49±1.32 25.59±2.68 36.98±2.60 57.62±3.07 F 71.975 54.181 17.266 0.734 0.483 P ＜0.05 ＜0.05 ＜0.05 0.519 0.639

[0031] Mouse embryonic fibroblasts were selected for cytotoxicity experiments. Cell viability was measured using the CCK-8 assay to evaluate the effect of the three materials on cell survival. The PPF-PVA mixture group, gauze group, and control group were co-cultured with cells for 3 days. There was no significant difference in cell viability among the three groups over three days, and the survival rate of all groups was higher than 75%, which met the cytotoxicity criteria.

[0032] This application uses Panamanian piglets as experimental subjects. By creating a stab wound model of the piglet's hind limb, hemostasis is achieved using a PPF-PVA mixture. Various physicochemical characteristics of the mixture are tested, providing a theoretical basis for its later optimization and application in daily, wartime, and clinical hemostasis.

[0033] PPF is viscous at room temperature and can flow into the wound cavity. It can flow to the deepest part of the wound cavity according to its shape. After cross-linking, it can harden. Theoretically, it can fill and compress the wound without toxic side effects. It can also be combined with other hemostatic materials and act as a carrier.

[0034] Polypropylene fumarate (PPF) is synthesized as a yellow, viscous liquid. When blended with polyvinyl alcohol (PVA), it exhibits good fluidity, allowing it to flow into deeper wound cavities for hemostasis. After cross-linking, it forms a harder substance that can be removed entirely during secondary debridement. The hardness after cross-linking can be controlled by the proportion of PVA; the higher the amount of PVA, the less complete the cross-linking, resulting in a softer texture. In this experiment, the PPF-PVA mixture hardened after being applied to the wound cavity, effectively filling the cavity and thus achieving hemostasis.

[0035] The above experiments show that by utilizing the property that polypropylene fumarate readily undergoes cross-linking reactions with other molecules, this application prepares an injectable and absorbable composite material with good flowability, mechanical properties, and hemostatic activity by blending polypropylene fumarate (PPF) with polyvinyl alcohol (PVA) sponge. After the fluid solidifies through a cross-linking reaction, it can fill the wound cavity and achieve a good hemostatic effect.

[0036] Biological hemostatic materials (including the PPF-PVA mixture in this application) are widely used in oral and maxillofacial surgery due to their unique water absorption and swelling properties, good biocompatibility and hemostatic effect, including tooth extraction, oral tumor resection, dental implant surgery, fracture repair and osseointegration, etc. Biological hemostatic materials have significant advantages in reducing intraoperative bleeding, maintaining a clear surgical field and promoting postoperative healing.

[0037] Applications in Tooth Extraction: Tooth extraction is one of the most common surgeries in oral and maxillofacial surgery, often accompanied by a series of complications. For example, patients taking anticoagulants may have difficulty forming blood clots, leading to uncontrollable bleeding after extraction. Failure to form a blood clot, clot dislodgement, and bacterial infection frequently result in dry socket. Dry socket can cause severe pain, affecting chewing and swallowing, and significantly impacting a patient's daily life. Suturing or mechanical compression methods are commonly used to treat extraction wounds, but these methods have inherent drawbacks, such as challenging and time-consuming suturing techniques and the potential for local tissue damage. Traditional dressings cannot provide lasting and effective hemostasis and healing protection in the complex oral environment, leading to complications such as secondary bleeding, delayed wound healing, and infection. Studies have shown that chitosan hemostasis can effectively shorten wound stasis time and significantly reduce the incidence of postoperative complications such as infection and pain. Furthermore, collagen sponges can prevent bleeding during and after tooth extraction, prevent inferior alveolar nerve damage, and promote soft tissue healing. Studies have shown that regenerated oxidized cellulose hemostatic materials can effectively reduce the bleeding rate after tooth extraction in patients who have been taking warfarin for a long time, reduce the probability of needing to visit a second clinic due to bleeding, and avoid the risk of thrombosis caused by discontinuation of medication.

[0038] Applications in Tumor Resection: Recurrence and metastasis are common after surgical resection of oral and maxillofacial tumors, and hemostasis is a crucial aspect of tumor resection. The oral and maxillofacial region has a rich blood supply, making bleeding during surgery a frequent occurrence; effective hemostasis is essential for surgical success and patient safety. Research has found that a sandwich-structured fiber / sponge composite with both in-situ chemotherapy and hemostatic functions can be used as an in-situ implantable material after tumor resection for postoperative hemostasis, prevention of recurrence, and treatment of metastasis. Other studies have shown that photothermal fiber chitosan / polydopamine sponge can induce cross-linking between fibers and polydopamine through shear flow, enhancing mechanical properties, hemostatic efficacy, and antitumor activity. These biological hemostatic materials, with their excellent hemostatic and tumor elimination effects and unique immune memory protection function, provide a promising clinical intervention for adjuvant hemostasis during tumor resection and prevention of tumor recurrence.

[0039] Applications in dental implant surgery: In dental implant surgery, the key role of biological hemostatic materials is mainly reflected in maintaining the clarity of the surgical field and promoting osseointegration. Immediate implantation refers to the placement of the implant in a fresh extraction socket, which has advantages such as shortening the total treatment time, reducing the number of surgical procedures, alleviating patient pain, and preserving alveolar bone. However, soft tissue defects in the implant area can make it difficult to close the wound tightly, making wound healing uncertain. Therefore, without affecting osseointegration, using biological hemostatic materials to stop bleeding and protect the wound surface can be an effective method for early healing of gingival soft tissue. Studies have found that when collagen sponges are used to cover the wound, they can not only effectively collect blood but also act as a membrane, providing a certain barrier against bacterial invasion and reducing the risk of infection. Successful hemostasis was achieved by filling the maxillary sinus artery with collagen and using semiconductor laser sintering.

[0040] Applications in maxillofacial fracture repair and promoting osseointegration: Bleeding is a common risk in maxillofacial fracture repair surgery, making effective hemostasis crucial. Failure to achieve timely hemostasis during surgery can lead to patient deterioration and obstructed surgical vision. Studies have found that in tibial fracture surgery, patients using medical gelatin sponges experienced less intraoperative blood loss and better postoperative fracture healing compared to the control group (those who did not use medical sponges). Research shows that fibrin adhesives can reduce bleeding and drainage after total joint replacement surgery with good safety. Studies have also demonstrated that chitosan composite materials not only provide good hemostasis during filling but also act as a diaphragm, preventing invasive soft tissue growth and promoting bone defect repair.

[0041] The above technical features constitute the embodiments of this application, which have strong adaptability and implementation effect. Non-essential technical features can be added or removed according to actual needs to meet the needs of different situations.

Claims

1. A method for preparing a hemostatic complex, comprising the following steps: Step 1, Raw material ratio: Diethyl fumarate and 1,2-propanediol are added to a three-necked round-bottom flask at a mass ratio of 1:3 to obtain mixture A; Zinc chloride with a mass ratio of 0.01:1 to mixture A is introduced as a catalyst, and hydroquinone with a mass ratio of 0.002:1 to mixture A is added as a double bond protectant. Step 2, heating reaction: A gradient heating strategy is adopted, with the temperature gradually increased at 30-minute intervals, each increase being 10°C, and finally stabilized at 150°C for 8 hours of isothermal reaction, thereby obtaining a mixture B of precursor HPF and byproduct ethanol. Step 3, vacuum polycondensation: After the temperature of mixture B is uniformly reduced to 100°C over 4 hours using an intelligent temperature control device, the vacuum system is activated to gradually reduce the pressure to below 10 mmHg; at this time, the temperature is gradually increased to 150°C at 50-minute intervals, and the reaction is continued for 12 hours. Step 4, cooling: First, allow it to cool naturally to below 100℃. Then, slowly balance the pressure inside and outside the system through the air inlet valve of the buffer bottle and close the vacuum device. Step 5, Dissolving: Add dichloromethane in batches, with an equal volume to mixture B, to dissolve the mixture. Step 6, Purification: The organic phase was washed sequentially with 1M hydrochloric acid and saturated sodium chloride solution, and then dried overnight with anhydrous sodium sulfate particles; Step 7, Solvent removal: This is completed using a rotary evaporator at a constant temperature of 40°C in conjunction with a vacuum decompression device. The final product is then treated in a vacuum drying oven to obtain a brownish-yellow transparent viscous liquid. Step 8, Preparation of the final mixture: PPF and PVA sponge are mixed in a mass ratio of 20:1, and after stirring and shearing, a paste-like PPF+PVA mixture is obtained, which is the hemostatic complex of this application.

2. The method for preparing the hemostatic complex according to claim 1, characterized in that: In step 5, dichloromethane of the same volume as mixture B is added to each batch for dissolution.

3. The method for preparing the hemostatic complex according to claim 1, characterized in that: In step 8, the PVA sponge is sheared to a particle size of less than 0.2 cm.

4. The hemostatic complex obtained by the preparation method of the hemostatic complex according to claim 1.

5. The application of the hemostatic compound according to claim 4 in the preparation of plug-type hemostatic materials.