Anti-inflammatory and healing-promoting hemostatic powder and preparation method thereof

Abstract

The invention provides anti-inflammatory and healing-promoting hemostatic powder and a preparation method thereof. The rapid hemostatic powder is prepared from the following components in percentage by mass: 10 to 15 percent of cannabidiol, 4 to 8 percent of polyvinyl alcohol, 18 to 24 percent of polyacrylamide and the balance of quaternary ammonium salt-based chitosan. All the components are synergistically matched in proper mass percent, so that the effects of good blood compatibility and cell compatibility, fast gelling, high tissue adhesion and rapid hemostasis can be achieved. Meanwhile, the hemostatic powder has the advantages of good inflammation resistance and healing promotion. The hemostatic powder is suitable for accidents, operations and other scenes. In addition, the preparation method of the hemostatic material is simple and easy to implement, does not need to depend on complex processes and equipment, and is convenient for large-scale popularization.

Description

Technical Field

[0001] This invention belongs to the field of hemostatic materials technology, specifically relating to an anti-inflammatory and healing-promoting hemostatic powder and its preparation method. Background Technology

[0002] In the medical field, hemostatic materials are crucial, widely used in bleeding scenarios such as accidents and surgeries. However, currently common hemostatic materials have many shortcomings.

[0003] Traditional gauze-based hemostatic materials primarily rely on physical pressure to stop bleeding. This method is slow and often fails to quickly control bleeding, especially in cases of heavy or arterial bleeding. Furthermore, gauze tends to adhere to the wound, potentially causing secondary bleeding and increasing patient discomfort during gauze changes. For instance, in some surgical procedures, removing gauze after it has been used for hemostasis often tears newly formed tissue, creating new bleeding points.

[0004] While gelatin sponges can promote blood clotting to some extent, their biocompatibility is limited, and some patients may experience an immune response. Furthermore, gelatin sponges are unstable in moist environments, easily deforming and dissolving, affecting hemostasis and making them unsuitable for wounds with prolonged bleeding or significant exudation. In the treatment of large wounds with substantial exudate, gelatin sponges may lose their proper shape and function within a short period.

[0005] Therefore, further improvements are needed to existing hemostatic materials. Summary of the Invention

[0006] The purpose of this invention is to overcome the shortcomings of existing hemostatic materials and provide a hemostatic powder with rapid hemostasis, good cell compatibility, and anti-inflammatory and healing-promoting functions, as well as its preparation method. This hemostatic powder is suitable for various bleeding scenarios such as accidents and surgeries, and its preparation method is simple and easy to implement, facilitating large-scale application.

[0007] An anti-inflammatory and hemostatic powder, comprising the following components in weight percentages: 10-15% cannabidiol, 4-8% polyvinyl alcohol, 18-24% polyacrylamide, and the balance quaternary ammonium chitosan.

[0008] Optionally, the hemostatic powder has an average particle size of 50-100 μm.

[0009] Optionally, the particle size of the cannabidiol is 5-10 μm.

[0010] Optionally, the hemostatic powder is composed of the following components in the indicated mass percentages: 10-15% cannabidiol, 4-8% polyvinyl alcohol, 18-24% polyacrylamide, 0.1-0.5% silver nanoparticles, and the balance being quaternary ammonium-based chitosan.

[0011] Optionally, the hemostatic powder is composed of the following components in mass percentage: 12% cannabidiol, 5% polyvinyl alcohol, 20% polyacrylamide, 0.2% nano-silver particles, and the rest of quaternary ammonium salt-based chitosan.

[0012] A preparation method of the above-mentioned anti-inflammatory and healing-promoting hemostatic powder, comprising the following steps: Mixing: cannabidiol, polyvinyl alcohol, polyacrylamide, and quaternary ammonium salt-based chitosan are stirred at 20-30℃ first at a stirring speed of 500-700rpm for 30-35min, and then at a stirring speed of 1000-1200rpm for 15-20min, and deionized water is added during the stirring process to adjust the humidity of the mixture to 30-32%, obtaining a mixture; Molding: the mixture is molded by spray drying, with an inlet temperature of 130-150℃, an outlet temperature of 70-80℃, and a feeding speed of 5-10mL / min.

[0013] Optionally, after molding, it further comprises: sterilizing the molded product by γ-ray sterilization method, with a γ-ray dose of 20-30kGy and a sterilization time of 25-35min.

[0014] Optionally, after sterilization, it further comprises: vacuum packaging the sterilized product in an aluminum foil bag.

[0015] Optionally, the polyvinyl alcohol is treated by the following method: polyvinyl alcohol particles are soaked in deionized water for 2-3h to fully swell, then insoluble impurities are removed by filtration, the obtained polyvinyl alcohol solution is concentrated on a rotary evaporator to remove excess water, and finally the concentrated polyvinyl alcohol is placed in a freeze dryer and freeze-dried at -50℃ for 10-15h to obtain dry polyvinyl alcohol powder.

[0016] Optionally, the quaternary ammonium salt-based chitosan is treated by the following method: the quaternary ammonium salt-based chitosan is soaked in a 75% volume fraction ethanol solution for 1-2h for disinfection treatment, then washed with deionized water to remove residual ethanol, and the washed quaternary ammonium salt-based chitosan is placed in a vacuum drying oven and dried at 45-55℃ for 15-20h to obtain dry quaternary ammonium salt-based chitosan powder.

[0017] Beneficial effects The anti-inflammatory and healing hemostatic powder is prepared by synergistic cooperation of the components in the specific mass percentage range, the anti-inflammatory effect of cannabidiol, the film-forming protective effect of polyvinyl alcohol, the rapid water absorption and gelation effect of polyacrylamide, and the hemostatic and antibacterial effect of the quaternary ammonium salt-based chitosan are fully exerted, the technical problems of slow hemostatic speed, poor cell compatibility, poor anti-inflammatory and healing effect of the existing hemostatic materials are solved, and the effects of rapid hemostasis, good cell compatibility, and anti-inflammatory and healing are achieved. DETAILED DESCRIPTION

[0018] The anti-inflammatory and healing hemostatic powder is prepared by synergistic cooperation of the components in the specific mass percentage range, the anti-inflammatory effect of cannabidiol, the film-forming protective effect of polyvinyl alcohol, the rapid water absorption and gelation effect of polyacrylamide, and the hemostatic and antibacterial effect of the quaternary ammonium salt-based chitosan are fully exerted, the technical problems of slow hemostatic speed, poor cell compatibility, poor anti-inflammatory and healing effect of the existing hemostatic materials are solved, and the effects of rapid hemostasis, good cell compatibility, and anti-inflammatory and healing are achieved.

[0019] Cannabidiol has good anti-inflammatory and analgesic effects, and can interact with cannabinoid receptors in the human body to regulate the signal pathway related to inflammatory response and inhibit the release of inflammatory factors, thereby reducing the inflammatory response at the wound site. In the wound healing process, timely control of inflammation is crucial for promoting cell proliferation and migration, and the anti-inflammatory effect of cannabidiol creates a good environment for wound healing.

[0020] Polyvinyl alcohol is a water-soluble polymer with good hydrophilicity and biocompatibility. It can form a protective film on the wound surface, which can prevent the invasion of external pathogens such as bacteria and reduce the risk of infection. On the other hand, this protective film can maintain a moist environment for the wound, which is conducive to cell growth and migration and promotes wound healing. Polyvinyl alcohol can also synergize with other ingredients to enhance the overall performance of the hemostatic powder.

[0021] Polyacrylamide is a commonly used polymer material with strong water absorption and water retention. During hemostasis, it can quickly absorb blood and tissue fluid exuded from the wound to form a gel-like substance, thereby plugging the wound and preventing blood from flowing out, achieving the purpose of rapid hemostasis. The gel formed by polyacrylamide also has certain viscosity, which can enhance the adhesion of the hemostatic powder to the wound tissue, making it better play its role.

[0022] Quaternary ammonium salt-based chitosan is a derivative of chitosan, which itself has certain hemostatic, antibacterial and wound healing-promoting abilities. After quaternization modification, quaternary ammonium salt-based chitosan not only retains the excellent properties of chitosan, but also has better water solubility and antibacterial performance. It can interact with proteins and cells in blood, activate blood clotting factors, promote platelet aggregation and thrombus formation, thereby accelerating the hemostatic process. Quaternary ammonium salt-based chitosan can also regulate the microenvironment at the wound site, promote cell proliferation and differentiation, and is conducive to wound healing.

[0023] These ingredients can achieve good cell compatibility, fast gelation, high tissue adhesion, and realize the effect of rapid hemostasis, while also exerting the advantages of anti-inflammatory and wound healing promotion through synergistic cooperation of appropriate mass percentages.

[0024] In some embodiments, the average particle size of the hemostatic powder is 50-100 μm. Hemostatic powder with an average particle size in this range has better flowability and dispersibility, and can more evenly cover the wound during use, improving the hemostatic effect.

[0025] In some embodiments, the particle size of cannabidiol is 5-10 μm. Cannabidiol has a smaller particle size and a larger specific surface area, which can be more evenly dispersed in the hemostatic powder and better exert the anti-inflammatory effect, improving the overall performance of the hemostatic powder. In some embodiments, the hemostatic powder is composed of the following mass percentages of each component: 10-15% cannabidiol, 4-8% polyvinyl alcohol, 18-24% polyacrylamide, 0.1-0.5% nano-silver particles, and the balance of quaternary ammonium salt-based chitosan. Nano-silver particles can improve the antibacterial effect of the hemostatic powder, reduce the risk of wound infection, and further improve the hemostatic effect of the hemostatic powder.

[0026] In some embodiments, the hemostatic powder is composed of the following mass percentages of each component: 12% cannabidiol, 5% polyvinyl alcohol, 20% polyacrylamide, 0.2% nano-silver particles, and the balance of quaternary ammonium salt-based chitosan.

[0027] Another embodiment of the present application provides a preparation method of the above-mentioned anti-inflammatory and wound healing-promoting hemostatic powder, comprising the following steps: Mixing: Mix cannabidiol, polyvinyl alcohol, polyacrylamide and quaternary ammonium salt-based chitosan at 20-30℃, first stirring at a stirring speed of 500-700 rpm for 30-35 min, then increasing the stirring speed to 1000-1200 rpm and continuing to stir for 15-20 min, adding deionized water during stirring to adjust the moisture content of the mixture to 30-32%, obtaining a mixture; Molding: the mixture is molded by spray drying, the inlet temperature is 130-150℃, the outlet temperature is 70-80℃, and the feeding speed is 5-10 mL / min.

[0028] The preparation method is simple and easy to operate, does not need to rely on complex process and equipment, and is convenient for large-scale production. The hemostatic powder is suitable for various scenes such as accidents and operations, and has a wide application prospect.

[0029] In some embodiments, after molding, further comprising: sterilizing the molded product by using a gamma ray sterilization method, the dose of the gamma ray is 20-30 kGy, and the sterilization time is 25-35 min.

[0030] In some embodiments, after sterilization, further comprising: vacuum packaging the sterilized product by using an aluminum foil bag.

[0031] In some embodiments, the polyvinyl alcohol is treated by the following method: polyvinyl alcohol particles are soaked in deionized water for 2-3 h to make them fully swell, then insoluble impurities are removed by filtration, the obtained polyvinyl alcohol solution is concentrated on a rotary evaporator to remove excess water, and finally the concentrated polyvinyl alcohol is placed in a freeze dryer and freeze-dried at -50℃ for 10-15 h to obtain dry polyvinyl alcohol powder. The polyvinyl alcohol treated in this way has reduced impurity content, optimized hydrophilicity and biocompatibility, and can better synergize with other ingredients to form a stable protective film on the wound surface, enhancing the performance of the hemostatic powder in maintaining a moist wound environment and preventing infection.

[0032] In some embodiments, the quaternary ammonium salt-based chitosan is treated by the following method: the quaternary ammonium salt-based chitosan is soaked in an ethanol solution with a volume fraction of 75% for 1-2 h for disinfection treatment, then washed with deionized water to remove residual ethanol, and the washed quaternary ammonium salt-based chitosan is placed in a vacuum drying oven and dried at 45-55℃ for 15-20 h to obtain dry quaternary ammonium salt-based chitosan powder. Such treatment makes the quaternary ammonium salt-based chitosan completely sterilized, with enhanced stability, more effective activation of blood clotting factors, promotion of platelet aggregation, adjustment of the wound microenvironment, and promotion of wound healing, thereby improving the performance of the hemostatic powder in promoting blood clotting and healing.

[0033] The following are examples and comparative examples.

[0034] Example 1 In this embodiment, the hemostatic powder is composed of the following components in mass percentage: 12% cannabidiol, 5% polyvinyl alcohol, 20% polyacrylamide, 0.2% nano-silver particles, and the balance of quaternary ammonium salt-based chitosan. The particle size of cannabidiol is 10 μm. The polyvinyl alcohol is treated by the following method: polyvinyl alcohol particles are soaked in deionized water for 2 h to fully swell, then insoluble impurities are removed by filtration, the obtained polyvinyl alcohol solution is concentrated on a rotary evaporator to remove excess water, and finally the concentrated polyvinyl alcohol is placed in a freeze dryer and freeze-dried at -50°C for 12 h to obtain dry polyvinyl alcohol powder. The quaternary ammonium salt-based chitosan is treated by the following method: the quaternary ammonium salt-based chitosan is soaked in a 75% volume fraction of ethanol solution for 1.5 h for sterilization treatment, then washed with deionized water to remove residual ethanol, and the washed quaternary ammonium salt-based chitosan is placed in a vacuum drying oven and dried at 50°C for 15 h to obtain dry quaternary ammonium salt-based chitosan powder. The average particle size of the hemostatic powder is 60 μm.

[0035] The preparation method of the hemostatic powder is as follows: Mixing: cannabidiol, polyvinyl alcohol, polyacrylamide, nano-silver particles, and quaternary ammonium salt-based chitosan are stirred at 25°C first at a stirring speed of 600 rpm for 30 min, then the stirring speed is increased to 1100 rpm and stirring is continued for 15 min, and deionized water is added during stirring to adjust the humidity of the mixture to 30% to obtain a mixture.

[0036] Molding: the mixture is molded by spray drying, the inlet air temperature is 140°C, the outlet air temperature is 75°C, and the feeding speed is 8 mL / min.

[0037] The molded product is sterilized by γ-ray sterilization method, the dose of γ-ray is 25 kGy, and the sterilization time is 30 min.

[0038] The differences between Example 2-3, Comparative Example 1-3 and Example 1 are shown in Table 1.

[0039] Table 1

[0040] Comparative Example 4 In Comparative Example 4, the hemostatic powder is composed of the following components in mass percentage: 12% cannabidiol, 5% polyvinyl alcohol, 20% polyacrylamide, 0.2% nano-silver particles, and the balance of quaternary ammonium salt-based chitosan. The preparation method is as follows: The components are stirred at 25°C first at a stirring speed of 600 rpm for 45 min to obtain a mixture. The mixture is sterilized by γ-ray sterilization method, the dose of γ-ray is 25 kGy, and the sterilization time is 30 min.

[0041] Test Example (1) Coagulation time In the animal experiment, the femoral artery of the rat was pricked with a blood collection needle, and the hemostatic powder was applied to the wound. After the blood flowed out naturally, a clean glass slide was placed beside the blood, and the time from the blood flow to the appearance of fibrin filaments by picking the blood with a needle tip was recorded, which was the coagulation time.

[0042] (2) Cytotoxicity test Using the MTT method, L929 cells were inoculated in a 96-well plate, and after 24 hours of culture, hemostatic powder extract was added respectively, and continued to culture for 24 hours. Then 20 μL of MTT solution (5 mg / mL) was added to each well, incubated for 4 hours, then the supernatant was discarded, 150 μL of DMSO was added, and shaken for 10 minutes to dissolve the crystals. The absorbance value of each well was measured at 490 nm wavelength by enzyme-labeled instrument, the cell survival rate was calculated, and the cytotoxicity of the hemostatic powder was evaluated.

[0043] (3) Anti-inflammatory performance test Inflammation factor content test: a mouse skin wound inflammation model was established, a circular wound was made on the back of the mouse, and the hemostatic powder was applied to the wound. On the 3rd day after the operation, the tissue around the wound was taken, and the content of inflammatory factor interleukin-6 (IL-6) in the tissue was determined by enzyme-linked immunosorbent assay (ELISA), and the anti-inflammatory performance of the hemostatic powder was evaluated.

[0044] (4) Wound healing time A mouse skin wound inflammation model was established, a circular wound was made on the back of the mouse, and the hemostatic powder was applied to the wound. From the completion of the wound, the wound healing was observed every day, and the time of complete wound healing (epidermis completely covering the wound) was recorded.

[0045] The test results are shown in Table 2.

[0046] Table 2

[0047] As can be seen from the above table, the hemostatic powder of the present application can obtain good hemostasis, anti-inflammatory and wound healing promotion effect through the matching of components and specific preparation method.

[0048] The above only describes the preferred embodiments of the present application, and is not intended to limit the present application. Any modification, equivalent replacement and improvement made within the spirit and principle of the present application shall be included in the protection scope of the present application.

[0049] For those skilled in the art, according to the idea of the present application, there will be changes in specific embodiments and application scope. In summary, the content of the specification should not be understood as a limitation of the present application.

Claims

1. An anti-inflammatory, pro-healing hemostatic powder, characterized in that, The hemostatic powder is composed of the following components in mass percentage: 10-15% cannabidiol, 4-8% polyvinyl alcohol, 18-24% polyacrylamide, and the rest of quaternary ammonium salt-based chitosan.

2. The anti-inflammatory, healing-promoting hemostatic powder according to claim 1, characterized in that The average particle size of the hemostatic powder is 50-100 μm.

3. The anti-inflammatory, healing-promoting hemostatic powder according to claim 1, characterized in that The particle size of the cannabidiol is 5-10 μm.

4. An anti-inflammatory, healing-promoting hemostatic powder according to any one of claims 1 to 3, characterized in that, The hemostatic powder is composed of the following components in mass percentage: 10-15% cannabidiol, 4-8% polyvinyl alcohol, 18-24% polyacrylamide, 0.1-0.5% nano-silver particles, and the rest of quaternary ammonium salt-based chitosan.

5. An anti-inflammatory, healing-promoting hemostatic powder according to claim 4, characterized in that, The hemostatic powder is composed of the following components in mass percentage: 12% cannabidiol, 5% polyvinyl alcohol, 20% polyacrylamide, 0.2% nano-silver particles, and the rest of quaternary ammonium salt-based chitosan.

6. A process for the preparation of an anti-inflammatory, healing, haemostatic powder according to any one of claims 1 to 5, characterized in that, The method comprises the following steps: Mixing: the cannabidiol, polyvinyl alcohol, polyacrylamide, and quaternary ammonium salt-based chitosan are stirred at 20-30 ℃ first at a stirring speed of 500-700 rpm for 30-35 min, and then at a stirring speed of 1000-1200 rpm for 15-20 min, and deionized water is added during the stirring process to adjust the humidity of the mixture to 30-32%, to obtain a mixture; Molding: the mixture is molded by spray drying, the inlet air temperature is 130-150 ℃, the outlet air temperature is 70-80 ℃, and the feeding speed is 5-10 mL / min.

7. The method of preparing an anti-inflammatory, healing, haemostatic powder according to claim 6, characterised in that, After molding, the molded product is sterilized by a γ-ray sterilization method, the dose of the γ-ray is 20-30 kGy, and the sterilization time is 25-35 min.

8. The method of preparing an anti-inflammatory, healing, hemostatic powder according to claim 6, characterized in that, After sterilization, the sterilized product is vacuum-packed in an aluminum foil bag.

9. Process for the preparation of an anti-inflammatory, healing-promoting haemostatic powder according to any one of claims 6-8, characterised in that, The polyvinyl alcohol is treated by the following method: polyvinyl alcohol particles are soaked in deionized water for 2-3 h to make them fully swollen, then insoluble impurities are removed by filtration, the obtained polyvinyl alcohol solution is concentrated on a rotary evaporator to remove excess water, and finally the concentrated polyvinyl alcohol is placed in a freeze dryer and freeze-dried at -50 ℃ for 10-15 h to obtain dry polyvinyl alcohol powder.

10. Process for the preparation of an anti-inflammatory, healing-promoting hemostatic powder according to any one of claims 6-8, characterized in that, The quaternary ammonium salt-based chitosan is treated by the following method: the quaternary ammonium salt-based chitosan is soaked in an ethanol solution with a volume fraction of 75% for 1-2 h for disinfection treatment, then washed with deionized water to remove residual ethanol, and the washed quaternary ammonium salt-based chitosan is placed in a vacuum drying oven and dried at 45-55 ℃ for 15-20 h to obtain dry quaternary ammonium salt-based chitosan powder.

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