Hemostatic hydrogel for wound hemorrhage and preparation method thereof

Abstract

The invention provides a hemostatic hydrogel for wound hemorrhage. The hemostatic hydrogel is prepared from the following components in parts by mass: 15 to 18 parts of cationic cassava starch, 9 to 15 parts of polyvinyl alcohol, 5 to 8 parts of oxidized konjac glucomannan, 0.1 to 0.2 part of cannabidiol, 1.5 to 2.5 parts of polydopamine nanoparticles, 0.5 to 0.8 part of panax notoginseng saponins and 2 to 4 parts of polyethylene glycol diacrylate. The hydrogel has the advantages of being rapid in gelling and high in blood coagulation efficiency, is suitable for scenes with massive hemorrhage of wounds, such as acute wound surfaces of accidental incisions, scratches and the like, and environments with limited medical resources, such as fields, battlefields, severe accident and disaster sites, can be used as a first-line first-aid material, rapidly realizes hemostasis and infection resistance, relieves pain of the wounded, and has a good application prospect. The injury condition is stabilized.

Description

Technical Field

[0001] This invention belongs to the field of wound care technology, specifically relating to a hemostatic hydrogel for severe wound bleeding. Background Technology

[0002] In the medical field, hemostatic materials have always been a key element in trauma treatment. Traditional hemostatic methods and materials, such as gauze, bandages, and gelatin sponges, can play a certain role in stopping bleeding in general wounds. However, when faced with severe bleeding from a wound, these traditional materials often reveal many problems.

[0003] First, the slow speed of hemostasis is a major drawback. In cases of massive bleeding, traditional materials cannot effectively stop the loss of blood in a short period of time, which greatly increases the risk of shock or even death due to excessive blood loss.

[0004] Secondly, low clotting efficiency is also a significant issue. These traditional materials cannot fully activate the body's own clotting mechanism, making it difficult to quickly form a stable blood clot to block the bleeding point, thus hindering effective control of bleeding. Furthermore, their poor resistance to infection means that in exposed wounds, they cannot effectively prevent the invasion of external bacteria, easily leading to wound infection, further aggravating the patient's condition, and prolonging the recovery period. Some traditional hemostatic materials are also complex to use, requiring a high level of professional skill from the user, making them ineffective in stopping bleeding in emergency situations where professional medical personnel are unavailable.

[0005] Therefore, it is necessary to further improve traditional hemostatic materials. Summary of the Invention

[0006] This invention aims to solve the problems of slow hemostasis, low coagulation efficiency, and poor anti-infection ability of existing hemostatic materials when facing massive bleeding from wounds, and to provide a hemostatic hydrogel that can quickly form gel, has high coagulation efficiency, and has anti-infection function.

[0007] A hemostatic hydrogel for treating severe wound bleeding comprises the following components in parts by weight: 15-18 parts cationic cassava starch, 9-15 parts polyvinyl alcohol, 5-8 parts oxidized konjac gum, 0.1-0.2 parts cannabidiol, 1.5-2.5 parts polydopamine nanoparticles, 0.5-0.8 parts total saponins of Panax notoginseng, and 2-4 parts polyethylene glycol diacrylate; wherein the cationic cassava starch is synthesized by microwave dry method using cassava starch and 3-chloro-2-hydroxypropyltrimethylammonium chloride as raw materials under sodium hydroxide catalysis, and its degree of substitution is 0.04-0.052.

[0008] Optionally, the degree of polymerization of the polyvinyl alcohol is 1700-1800 and the degree of alcoholysis is 92%-98%.

[0009] Optionally, the preparation method of the oxidized konjac gum is as follows: konjac gum is added to deionized water at a speed of 200-300 r / min to prepare a konjac gum solution with a mass fraction of 3%-5%. The pH value is adjusted to 8-9. At 50-60℃, a hydrogen peroxide solution with a mass fraction of 30% is added dropwise. The mass ratio of hydrogen peroxide solution to konjac gum is (0.5-1):1. After the addition is complete, the reaction is stirred for 2-3 hours. Then, the precipitate is precipitated with anhydrous ethanol, centrifuged, and the precipitate is washed and dried to obtain oxidized konjac gum.

[0010] Optionally, the particle size of the polydopamine nanoparticles ranges from 50 to 100 nm.

[0011] Optionally, the total saponins of Panax notoginseng are extracted from Panax notoginseng by supercritical carbon dioxide extraction.

[0012] Optionally, the molecular weight of the polyethylene glycol diacrylate is in the range of 500-1000.

[0013] A method for preparing the above-mentioned hemostatic hydrogel for massive wound bleeding includes the following steps: Cationic cassava starch was added to deionized water and stirred at 200-300 r / min for 1-2 hours at 50-60℃ to obtain a homogeneous cationic cassava starch solution. Polyvinyl alcohol is added to a cationic cassava starch solution and stirred at 200-300 r / min at 50-60℃ for 1-2 hours to completely dissolve the polyvinyl alcohol and obtain a mixed solution. Add oxidized konjac gum to the mixed solution and stir at 200-300 r / min at 30-40℃ for 30-60 min to uniformly disperse the oxidized konjac gum in the mixed solution to obtain the first dispersion. Cannabidiol, polydopamine nanoparticles and total saponins of Panax notoginseng were added sequentially to the first dispersion, and the mixture was stirred at 100-150 r / min for 30-60 min at 20-25℃ to obtain the second dispersion. Polyethylene glycol diacrylate was added to the second dispersion and stirred at 600-700 r / min for 5-10 min at 20-25℃. The resulting product was then poured into a specific mold and irradiated under 365 nm ultraviolet light for 1-2 min to initiate a cross-linking reaction, thus obtaining a hemostatic hydrogel.

[0014] Beneficial effects In terms of rapid gelation, the hemostatic hydrogel of this invention can form a stable three-dimensional network structure in a short time through the cross-linking reaction initiated by polyethylene glycol diacrylate under ultraviolet light irradiation, achieving rapid gelation. The gelation process can usually be completed within 1-2 minutes, which greatly shortens the time interval from application to hemostasis compared with traditional hemostatic materials.

[0015] Cationic cassava starch interacts with anions in the blood, and polydopamine nanoparticles have excellent adhesion properties, enabling them to quickly adhere to the wound surface and seal bleeding points. At the same time, their unique chemical structure helps to activate clotting factors and accelerate the blood clotting process. Panax notoginseng saponins promote platelet aggregation. These effects work synergistically to significantly shorten clotting time.

[0016] In terms of anti-infection, oxidized konjac gum and cannabidiol play an important role. Oxidized konjac gum itself has antibacterial properties, while cannabidiol has anti-inflammatory and antibacterial activities. The two work synergistically to effectively inhibit the growth and reproduction of bacteria on the wound surface, reduce the chance of wound infection, and create a favorable environment for wound healing.

[0017] This hemostatic hydrogel can alleviate the pain of injured individuals. The anti-inflammatory properties of cannabidiol can relieve pain caused by wound inflammation, while the soft and conforming nature of the hydrogel reduces irritation to the wound. Compared to traditional, rough hemostatic materials, it can significantly reduce the discomfort experienced by injured individuals during the hemostasis process.

[0018] Due to its advantages such as rapid gelation, strong hemostatic efficiency, and anti-infection properties, the hemostatic hydrogel of this invention is suitable for various scenarios involving massive bleeding from wounds. In acute wounds such as accidental cuts and abrasions, it can quickly stop bleeding and prevent infection. In environments with limited medical resources, such as in the field, battlefields, and serious accidents and disaster sites, it can serve as a first-line emergency material, rapidly stabilizing the injury and buying valuable time for subsequent treatment, thus possessing extremely high application value. Detailed Implementation

[0019] One embodiment of the present invention provides a hemostatic hydrogel for massive wound bleeding, comprising the following components in parts by weight: 15-18 parts cationic tapioca starch, 9-15 parts polyvinyl alcohol, 5-8 parts oxidized konjac gum, 0.1-0.2 parts cannabidiol, 1.5-2.5 parts polydopamine nanoparticles, 0.5-0.8 parts total saponins of Panax notoginseng, and 2-4 parts polyethylene glycol diacrylate; the cationic tapioca starch is synthesized by microwave dry method using tapioca starch and 3-chloro-2-hydroxypropyltrimethylammonium chloride as raw materials under sodium hydroxide catalysis, and its degree of substitution is 0.04-0.052.

[0020] The aforementioned hemostatic hydrogel exhibits rapid gelation through a cross-linking reaction induced by polyethylene glycol diacrylate under ultraviolet light. This allows for the formation of a stable three-dimensional network structure within a short time, typically completing the gelation process within 1-2 minutes. Compared to traditional hemostatic materials, this significantly shortens the time interval from application to hemostasis. Cationic cassava starch interacts with anions in the blood, and polydopamine nanoparticles possess excellent adhesion properties, enabling rapid adhesion to the wound surface and sealing bleeding points. Simultaneously, their unique chemical structure helps activate clotting factors, accelerating the blood coagulation process. Panax notoginseng saponins promote platelet aggregation; these effects synergistically shorten clotting time. In terms of anti-infection, oxidized konjac gum and cannabidiol play crucial roles. Oxidized konjac gum itself possesses antibacterial properties, while cannabidiol exhibits anti-inflammatory and antibacterial activity. Their synergistic effect effectively inhibits the growth and reproduction of bacteria on the wound surface, reducing the likelihood of wound infection and creating a favorable environment for wound healing. This hemostatic hydrogel can alleviate the pain of injured individuals. The anti-inflammatory properties of cannabidiol can relieve pain caused by wound inflammation. At the same time, the soft and conforming properties of hydrogel reduce irritation to the wound. Compared with traditional rough hemostatic materials, it can significantly reduce the discomfort of the injured person during the hemostasis process.

[0021] Due to its advantages such as rapid gelation, strong hemostatic efficiency, and anti-infection properties, the hemostatic hydrogel of this invention is suitable for various scenarios involving massive bleeding from wounds. In acute wounds such as accidental cuts and abrasions, it can quickly stop bleeding and prevent infection. In environments with limited medical resources, such as in the field, battlefields, and serious accidents and disaster sites, it can serve as a first-line emergency material, rapidly stabilizing the injury and buying valuable time for subsequent treatment, thus possessing extremely high application value.

[0022] In some embodiments, the degree of polymerization of polyvinyl alcohol is 1700-1800, and the degree of hydrolysis is 92%-98%. In this case, polyvinyl alcohol can better improve the flexibility and toughness of the hydrogel system, promote the uniform dispersion of other components, and thus improve the overall performance and effectiveness of the hemostatic hydrogel.

[0023] In some embodiments, the preparation method of oxidized konjac gum is as follows: Konjac gum is added to deionized water at a speed of 200-300 r / min to prepare a konjac gum solution with a mass fraction of 3%-5%. The pH value is adjusted to 8-9. At 50-60℃, a hydrogen peroxide solution with a mass fraction of 30% is added dropwise. The mass ratio of hydrogen peroxide solution to konjac gum is (0.5-1):1. After the addition is completed, the reaction is stirred for 2-3 hours. Then, the precipitate is precipitated with anhydrous ethanol, centrifuged, and the precipitate is washed and dried to obtain oxidized konjac gum.

[0024] In some embodiments, the polydopamine nanoparticles have a particle size range of 50-100 nm. Polydopamine nanoparticles in this particle size range have superior adhesion properties and the ability to activate coagulation factors, thereby more effectively sealing bleeding points, accelerating the blood coagulation process, and improving hemostasis efficiency.

[0025] In some embodiments, total saponins of Panax notoginseng are extracted from Panax notoginseng by supercritical carbon dioxide extraction. The extraction method of total saponins of Panax notoginseng ensures its purity and activity, enabling it to more effectively promote platelet aggregation, shorten clotting time, and enhance the hemostatic effect of hemostatic hydrogels.

[0026] In some embodiments, the molecular weight of polyethylene glycol diacrylate ranges from 500 to 1000. This molecular weight range helps to precisely control the crosslinking reaction of the hydrogel, enabling it to form an ideal three-dimensional network structure, achieving rapid gelation, while ensuring the shape stability and mechanical properties of the hydrogel.

[0027] Another embodiment of the present invention provides a method for preparing the above-mentioned hemostatic hydrogel for massive wound bleeding, comprising the following steps: Cationic cassava starch was added to deionized water and stirred at 200-300 r / min for 1-2 hours at 50-60℃ to obtain a homogeneous cationic cassava starch solution. Polyvinyl alcohol is added to a cationic cassava starch solution and stirred at 200-300 r / min at 50-60℃ for 1-2 hours to completely dissolve the polyvinyl alcohol and obtain a mixed solution. Add oxidized konjac gum to the mixed solution and stir at 200-300 r / min at 30-40℃ for 30-60 min to uniformly disperse the oxidized konjac gum in the mixed solution to obtain the first dispersion. Cannabidiol, polydopamine nanoparticles and total saponins of Panax notoginseng were added sequentially to the first dispersion, and the mixture was stirred at 100-150 r / min for 30-60 min at 20-25℃ to obtain the second dispersion. Polyethylene glycol diacrylate was added to the second dispersion and stirred at 600-700 r / min for 5-10 min at 20-25℃. The resulting product was then poured into a specific mold and irradiated under 365 nm ultraviolet light for 1-2 min to initiate a cross-linking reaction, thus obtaining a hemostatic hydrogel.

[0028] The following are examples and comparative examples.

[0029] (1) Cationic cassava starch is synthesized by microwave dry method using cassava starch and 3-chloro-2-hydroxypropyltrimethylammonium chloride in a mass ratio of 3:1 under sodium hydroxide catalysis, and its degree of substitution is 0.05.

[0030] (2) Oxidized konjac gum was prepared by the following method: Konjac gum was added to deionized water at a speed of 200 r / min to prepare a konjac gum solution with a mass fraction of 4%. The pH value was adjusted to 8. At 55℃, a hydrogen peroxide solution with a mass fraction of 30% was added dropwise. The mass ratio of hydrogen peroxide solution to konjac gum was 0.8:1. After the addition was completed, the reaction was stirred for 2 hours. Then, anhydrous ethanol was used to precipitate the konjac gum. The precipitate was separated by centrifugation, washed and dried to obtain oxidized konjac gum.

[0031] (3) Total saponins of Panax notoginseng were extracted from Panax notoginseng by supercritical carbon dioxide extraction.

[0032] (4) The preparation method of the hemostatic hydrogel is as follows: Cationic cassava starch was added to deionized water and stirred at 300 r / min for 1 h at 55°C to obtain a homogeneous cationic cassava starch solution. Polyvinyl alcohol (degree of polymerization 1700, degree of alcoholysis 95%) was added to a cationic cassava starch solution and stirred at 300 r / min for 1 h at 55 °C to completely dissolve the polyvinyl alcohol and obtain a mixed solution. Oxidized konjac gum was added to the mixed solution and stirred at 300 r / min for 40 min at 30℃ to ensure that the oxidized konjac gum was evenly dispersed in the mixed solution, thus obtaining the first dispersion. Cannabidiol, polydopamine nanoparticles (60 nm in diameter) and total saponins of Panax notoginseng were added sequentially to the first dispersion, and the mixture was stirred at 100 r / min for 30 min at 20 °C to obtain the second dispersion. Polyethylene glycol diacrylate (molecular weight 600) was added to the second dispersion. After stirring at 700 r / min for 8 min at 20 °C, the resulting product was poured into a specific mold and irradiated under 365 nm ultraviolet light for 1 min to initiate a cross-linking reaction, thus obtaining a hemostatic hydrogel.

[0033] The differences between Examples 1-3 and Comparative Examples 1-2 are shown in Table 1.

[0034] Table 1

[0035] Comparative Example 3 This study employed a common hydrogel dressing formulation and preparation method found in existing technologies. A hydrogel dressing with chitosan and gelatin as the main components was selected, with a formulation of 10 parts chitosan, 5 parts gelatin, 3 parts glycerin, and 0.5 parts glutaraldehyde as a cross-linking agent. The preparation method was as follows: chitosan was dissolved in a 2% (w / w) acetic acid solution and stirred at 50°C until completely dissolved. Gelatin was added to deionized water and stirred at 60°C until dissolved. The two solutions were mixed, glycerin and glutaraldehyde were added, and the mixture was stirred thoroughly before being poured into a mold and allowed to stand at 37°C to cross-link and solidify. Finally, the dressing was rinsed with deionized water and dried to obtain the control dressing.

[0036] Test case (1) Hemostatic performance: The coagulation time was determined using the slide method in in vitro coagulation experiments. The specific procedure was to drop an appropriate amount of fresh blood onto a clean glass slide, then cover the blood with the prepared hydrogel dressing, and quickly start a stopwatch. The state of the blood was observed, and the time was stopped when the blood stopped flowing and a clear blood clot was formed. The time from the contact between the blood and the dressing to the completion of coagulation was recorded.

[0037] (2) Antibacterial properties: An inhibition zone test was conducted, with *Escherichia coli* selected as the test strain. The strain was inoculated into liquid culture medium and cultured with shaking at 37°C and 180 r / min for 12 hours to allow it to reach the logarithmic growth phase. The bacterial solution was then diluted with sterile physiological saline to a concentration of 1×10⁻⁶. 6 CFU / mL. Cool the melted agar medium to approximately 50°C, add 1 mL of diluted bacterial solution, shake well, and pour into a sterile petri dish to prepare a bacterial plate. Use a punch to cut the hemostatic hydrogel into 6 mm diameter discs and place them on the bacterial plate. Incubate the plates at 37°C for 12-24 hours, observe and measure the diameter of the inhibition zone; the larger the diameter of the inhibition zone, the stronger the antibacterial properties of the hemostatic hydrogel.

[0038] (3) Cytotoxicity: Prepare dressing extract (1g sample + 10mL culture medium, extract at 37℃ for 24h). Co-culture with L929 cells for 48h, add MTT solution (5mg / mL), and continue culturing for 4h. Measure the absorbance at 570nm and calculate the cell viability: (sample group absorbance / blank group absorbance) × 100%. Take the average value of each group as the test result for that group.

[0039] The test results are shown in Table 2.

[0040] Table 2

[0041] The results above show that the hemostatic hydrogel of the present invention has both immediate hemostatic and antibacterial properties, and good biocompatibility.

[0042] 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, and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

[0043] For those skilled in the art, based on the ideas of this invention, there will be changes in the specific implementation methods and application scope. Therefore, the content of this specification should not be construed as a limitation of this invention.

Claims

1. A hemostatic hydrogel for massive bleeding from a wound, characterized in that, The composition is composed of the following components in mass fraction: 15-18 parts of cationic tapioca starch, 9-15 parts of polyvinyl alcohol, 5-8 parts of oxidized konjac gum, 0.1-0.2 parts of cannabidiol, 1.5-2.5 parts of polydopamine nanoparticles, 0.5-0.8 parts of total notoginseng saponins, and 2-4 parts of polyethylene glycol diacrylate; the cationic tapioca starch is synthesized by a microwave dry method using tapioca starch and 3-chloro-2-hydroxypropyltrimethylammonium chloride as raw materials and sodium hydroxide as a catalyst, and has a degree of substitution of 0.04-0.

052.

2. The hemostatic hydrogel for massive hemorrhage of wounds according to claim 1, wherein, The polyvinyl alcohol has a degree of polymerization of 1700-1800 and an alcoholysis degree of 92%-98%.

3. The hemostatic hydrogel for massive hemorrhage of wounds according to claim 1, wherein, The oxidized konjac gum is prepared by the following method: konjac gum is added to deionized water at a speed of 200-300 r / min to prepare a konjac gum solution with a mass fraction of 3%-5%, the pH value is adjusted to 8-9, a 30% hydrogen peroxide solution is added dropwise at 50-60°C, the mass ratio of the hydrogen peroxide solution to the konjac gum is (0.5-1):1, after the dropwise addition is completed, the stirring is continued for 2-3 h, then anhydrous ethanol is used for precipitation, centrifugal separation is performed, the precipitate is washed and dried to obtain the oxidized konjac gum.

4. The hemostatic hydrogel for massive hemorrhage of wounds according to claim 1, wherein, The polydopamine nanoparticles have a particle size range of 50-100 nm.

5. The hemostatic hydrogel for massive hemorrhage of wounds of claim 1, wherein, The total notoginseng saponins are extracted from notoginseng by a supercritical carbon dioxide extraction method.

6. The hemostatic hydrogel for massive hemorrhage of wounds as claimed in claim 1, wherein, The polyethylene glycol diacrylate has a molecular weight range of 500-1000.

7. A method of preparing the hemostatic hydrogel against massive bleeding from wounds according to any one of claims 1-6, characterized by, The method comprises the following steps: The cationic tapioca starch is added to deionized water, stirred at a speed of 200-300 r / min at a temperature of 50-60°C for 1-2 h to obtain a uniform cationic tapioca starch solution; The polyvinyl alcohol is added to the cationic tapioca starch solution, stirred at a speed of 200-300 r / min at a temperature of 50-60°C for 1-2 h to completely dissolve the polyvinyl alcohol, and a mixed solution is obtained; The oxidized konjac gum is added to the mixed solution, stirred at a speed of 200-300 r / min at a temperature of 30-40°C for 30-60 min to uniformly disperse the oxidized konjac gum in the mixed solution, and a first dispersion is obtained; The cannabidiol, the polydopamine nanoparticles, and the total notoginseng saponins are sequentially added to the first dispersion, stirred at a speed of 100-150 r / min at a temperature of 20-25°C for 30-60 min to obtain a second dispersion; The polyethylene glycol diacrylate is added to the second dispersion, stirred at a speed of 600-700 r / min at a temperature of 20-25°C for 5-10 min, and then the obtained product is poured into a specific mold, irradiated under ultraviolet light at 365 nm for 1-2 min to initiate a crosslinking reaction, and a hemostatic hydrogel is obtained.

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