Hemostatic foam capable of quickly stopping bleeding as well as preparation method and application of hemostatic foam

Abstract

The invention provides hemostatic foam capable of quickly stopping bleeding as well as a preparation method and application of the hemostatic foam. The hemostatic foam is prepared from the following components in percentage by mass: 5 to 10 percent of polyacrylic acid with the molecular weight of 1000 to 3000Da, 1 to 3 percent of polyacrylamide, 4 to 8 percent of propylene glycol alginate, 12 to 20 percent of chitosan, 0.1 to 0.2 percent of cannabidiol, 0.5 to 1 percent of foaming agent and the balance of normal saline. The hemostatic foam has the functions of rapidly absorbing blood and expanding, physically blocking damaged blood vessels and activating blood coagulation.

Description

Technical Field

[0001] This invention belongs to the field of hemostatic materials technology, specifically relating to a hemostatic foam capable of rapid hemostasis, its preparation method, and its application. Background Technology

[0002] In the medical field, hemostasis is a crucial procedure related to patient safety and recovery. Traditional hemostasis methods and materials have many problems in practical application. For example, traditional gauze compression hemostasis is slow, often requiring prolonged pressure to achieve initial hemostasis, and is largely ineffective for large wounds or arterial bleeding, failing to effectively stop significant blood loss. While electrocoagulation hemostasis is commonly used in surgery, it is complex, requires specialized equipment and technicians, carries a risk of thermal damage to surrounding tissues, potentially affecting normal tissue function, and is unsuitable for heat-sensitive tissue sites.

[0003] Common hemostatic materials, such as gelatin sponges, while possessing some hemostatic properties, have limited blood absorption rates and cannot rapidly form an effective clotting barrier. In cases of severe bleeding, they cannot control the bleeding in a timely manner. Furthermore, the degradation rate of some absorbable hemostatic materials in the body is difficult to control, potentially leading to premature loss of hemostatic effect or residue in the body, causing adverse consequences such as inflammatory reactions. In addition, many hemostatic materials have poor biocompatibility, easily triggering immune responses in the body and posing a potential threat to the patient's health. Summary of the Invention

[0004] The purpose of this invention is to provide a hemostatic foam that can quickly stop bleeding, its preparation method, and its application.

[0005] A hemostatic foam capable of rapid hemostasis comprises the following components in the indicated mass percentages: 5-10% polyacrylic acid with a molecular weight of 1000-3000 Da, 1-3% polyacrylamide, 4-8% propylene glycol alginate, 12-20% chitosan, 0.1-0.2% cannabidiol, 0.5-1% foaming agent, and the balance being physiological saline.

[0006] Optionally, the polyacrylic acid has a molecular weight of 1500-2500 Da.

[0007] Optionally, the polyacrylamide is a cationic polyacrylamide.

[0008] Optionally, the degree of esterification of the propylene glycol alginate is 50-70%.

[0009] Optionally, the degree of deacetylation of the chitosan is 85-95%.

[0010] Optionally, the foaming agent is a mixture of sodium bicarbonate and citric acid in a mass ratio of (1-2):1.

[0011] Optionally, the porosity of the hemostatic foam is 70-90%.

[0012] The application of the hemostatic foam capable of rapid hemostasis in the preparation of drugs for treating traumatic bleeding.

[0013] The method for preparing the hemostatic foam that can quickly stop bleeding includes the following steps: adding polyacrylic acid, polyacrylamide, propylene glycol alginate, chitosan, cannabidiol and foaming agent to physiological saline in sequence, stirring evenly, and then carrying out a foaming reaction.

[0014] Optionally, the temperature of the foaming reaction is 30-40℃ and the pressure is 0.5-1MPa.

[0015] Beneficial effects In the hemostatic foam of this invention, the components work synergistically to achieve rapid blood absorption and expansion, physical sealing of damaged blood vessels, and activation of coagulation. When the hemostatic foam comes into contact with the bleeding site, the polyacrylic acid rapidly absorbs water from the blood and expands, increasing the foam volume and thus physically sealing the damaged blood vessel, preventing further blood flow. Simultaneously, propylene glycol alginate promotes platelet aggregation, and chitosan activates coagulation factors, triggering a coagulation reaction and forming a blood clot in a short time, further enhancing the hemostatic effect. The anti-inflammatory and repairing effects of cannabidiol help reduce wound inflammation, promote wound healing, and improve the overall therapeutic effect. Detailed Implementation

[0016] One embodiment of the present invention provides a hemostatic foam capable of rapid hemostasis, comprising the following components by mass percentage: 5-10% polyacrylic acid with a molecular weight of 1000-3000 Da, 1-3% polyacrylamide, 4-8% propylene glycol alginate, 12-20% chitosan, 0.1-0.2% cannabidiol, 0.5-1% foaming agent, and the balance being physiological saline.

[0017] Polyacrylic acid has strong water absorption, enabling it to quickly absorb water from the blood and expand rapidly, creating favorable conditions for subsequent hemostasis. Polyacrylamide helps enhance the stability and mechanical strength of the foam, allowing it to maintain structural integrity while exerting its hemostatic effect and better physically seal damaged blood vessels. Propylene glycol alginate can promote platelet aggregation and adhesion, accelerate the coagulation process, and improve the hydrophilicity of the foam, allowing it to better contact and act with blood. Chitosan is a natural polysaccharide with good biocompatibility and hemostatic properties; it can effectively promote blood coagulation by activating coagulation factors and initiating intrinsic coagulation pathways. Cannabidiol has anti-inflammatory and cell-repair-promoting effects; during hemostasis, it can reduce inflammation around the wound, promote tissue repair and healing, and also help enhance the hemostatic effect. The role of foaming agents is to create a rich porous structure in the hemostatic foam, increasing the surface area of ​​the foam so that it can contact blood more quickly and act, while also improving the softness and compliance of the foam, making it better adaptable to wounds of different shapes and sizes. Physiological saline, as a solvent, not only provides a good dissolution environment for other components, ensuring that each component can be evenly dispersed and work synergistically, but also maintains the osmotic pressure of the foam, making it compatible with the human physiological environment and reducing irritation to the wound.

[0018] The components listed above work synergistically to achieve the functions of rapid blood absorption and expansion of the hemostatic foam, physical sealing of damaged blood vessels, and activation of coagulation. When the hemostatic foam comes into contact with the bleeding site, the polyacrylic acid rapidly absorbs water from the blood and expands, increasing the foam volume and thus physically sealing the damaged blood vessel, preventing further blood flow. Simultaneously, propylene glycol alginate promotes platelet aggregation, and chitosan activates coagulation factors, triggering a coagulation reaction and forming a blood clot in a short time, further enhancing the hemostatic effect. The anti-inflammatory and repairing effects of cannabidiol help reduce wound inflammation, promote wound healing, and improve the overall treatment outcome.

[0019] In some embodiments, the molecular weight of the polyacrylic acid is 1500-2500 Da. Within this molecular weight range, the water absorption and influence on the foam structure of polyacrylic acid are optimally balanced, enabling more effective rapid blood absorption and expansion, enhancing the hemostatic effect of the hemostatic foam, and also improving the stability and consistency of the product.

[0020] In some embodiments, the polyacrylamide is cationic polyacrylamide. Cationic polyacrylamide can interact electrostatically with negatively charged blood cells and tissue surfaces, enhancing its affinity for blood and wound tissue, thereby better promoting platelet aggregation and adhesion, further strengthening the effect of physically sealing damaged blood vessels, and improving hemostasis efficiency.

[0021] In some embodiments, the degree of esterification of propylene glycol alginate is 50-70%. Different degrees of esterification affect the hydrophilicity, bioactivity, and other properties of propylene glycol alginate. Within the esterification range of 50-70%, propylene glycol alginate exhibits the most significant promoting effect on platelet aggregation and adhesion, and can more effectively activate the coagulation process, thereby improving the coagulation effect of hemostatic foam.

[0022] In some embodiments, the degree of deacetylation of the chitosan is 85-95%. The degree of deacetylation affects the solubility, bioactivity, and hemostatic properties of chitosan. At a degree of deacetylation of 85-95%, the amino content of chitosan is moderate, which can better activate coagulation factors, initiate the intrinsic coagulation pathway, enhance the hemostatic effect, and at the same time ensure the stability and biocompatibility of chitosan in the physiological environment.

[0023] In some embodiments, the foaming agent is a mixture of sodium bicarbonate and citric acid in a mass ratio of (1-2):1. Sodium bicarbonate and citric acid react chemically upon contact to produce carbon dioxide gas, thereby creating a rich and uniform porous structure in the hemostatic foam. This specific combination of foaming agents allows for precise control of the foam generation rate and pore size, resulting in foam with good softness and conformability, better adapting to wound shapes, while also increasing the contact area between the foam and blood, thus improving hemostasis.

[0024] In some embodiments, the porosity of the hemostatic foam is 70-90%. A porosity of 70-90% ensures that the foam has enough space to absorb blood and achieve rapid blood absorption and expansion, while maintaining a certain mechanical strength to effectively physically seal damaged blood vessels. At the same time, it is also conducive to the diffusion and aggregation of coagulation factors and blood cells in the foam pores, promoting the coagulation process.

[0025] Another embodiment of the present invention provides the application of the above-mentioned hemostatic foam capable of rapid hemostasis in the preparation of a drug for treating traumatic bleeding.

[0026] Another embodiment of the present invention provides a method for preparing the above-mentioned hemostatic foam that can quickly stop bleeding, comprising the following steps: adding polyacrylic acid, polyacrylamide, propylene glycol alginate, chitosan, cannabidiol and foaming agent sequentially to physiological saline, stirring evenly, and then carrying out a foaming reaction.

[0027] Optionally, the foaming reaction is carried out at a temperature of 30-40℃ and a pressure of 0.5-1MPa. Under these conditions, the foaming agent can react fully to generate an ideal foam structure, ensuring the quality and performance stability of the hemostatic foam, improving production efficiency and product qualification rate, and further expanding the protection scope of the preparation method.

[0028] This invention addresses the problems of existing hemostasis technologies by screening and proportioning the components of a hemostatic foam and employing a unique preparation process, achieving rapid hemostasis. In component selection, the characteristics of each component and its role in the hemostasis process were fully considered. Polyacrylic acid, with its strong water absorption, was chosen with a molecular weight of 1000-3000 Da because this molecular weight range achieves a good balance between its water absorption and compatibility with the foam system, enabling it to rapidly absorb water from the blood, causing the foam to expand quickly and creating conditions for physically sealing damaged blood vessels. Polyacrylamide, as a component to enhance foam stability and mechanical strength, was chosen as a cationic polyacrylamide. Its cationic properties and electrostatic interaction with blood cells and tissue surfaces enhance its affinity for blood and wound tissue, thereby better promoting platelet aggregation and adhesion, and strengthening the physical sealing effect.

[0029] Propylene glycol alginate promotes platelet aggregation and adhesion, accelerating the coagulation process. Its degree of esterification is controlled at 50-70%, within which its coagulation-promoting effect is most significant. Chitosan activates coagulation factors and initiates the intrinsic coagulation pathway. When the degree of deacetylation is 85-95%, the amino content of chitosan is moderate, allowing it to better exert its function in activating coagulation factors while ensuring its stability and biocompatibility in the physiological environment. Cannabidiol's anti-inflammatory and cell-repair-promoting effects help reduce wound inflammation, promote tissue repair and healing, and further improve hemostasis. A mixture of sodium bicarbonate and citric acid is chosen as the foaming agent. Their reaction produces carbon dioxide gas, allowing precise control over the foam generation rate and pore size, resulting in foam with good softness and conformability, adapting to wound shape and increasing the contact area with blood.

[0030] In terms of ingredient ratios, the mass percentage range of each component is strictly controlled to ensure synergistic effects. For example, polyacrylic acid, propylene glycol alginate, and chitosan work together to rapidly absorb blood and expand, and promote coagulation; polyacrylamide and foaming agents work together to ensure the stability and structural properties of the foam; and cannabidiol assists in the hemostasis process from an anti-inflammatory and repair perspective. Through this carefully designed ingredient selection and formulation, the hemostatic foam possesses the functions of rapid blood absorption and expansion, physical sealing of damaged blood vessels, and activation of coagulation.

[0031] In the preparation process, each component is added sequentially to physiological saline and stirred until homogeneous. Then, a foaming reaction is carried out under specific temperature and pressure conditions. This preparation method ensures the uniform dispersion of each component, resulting in more stable and consistent foam performance. Specific temperature and pressure conditions (30-40℃, 0.5-1MPa) allow the foaming agent to react fully, generating an ideal foam structure and further improving the performance of the hemostatic foam.

[0032] The following are examples and comparative examples.

[0033] Example 1 The preparation method of the hemostatic foam is as follows: Weigh 7% polyacrylic acid with a molecular weight of 1500 Da, 2% cationic polyacrylamide, 6% propylene glycol alginate with a degree of esterification of 60%, 15% chitosan with a degree of deacetylation of 90%, 0.15% cannabidiol, 0.8% foaming agent (sodium bicarbonate and citric acid in a mass ratio of 1.5:1), and the balance being physiological saline. At 28°C, add the polyacrylic acid to the physiological saline and stir at 150 rpm for 45 min to dissolve it. Then, add the polyacrylamide, propylene glycol alginate, and chitosan sequentially, stirring at 200 rpm for 75 min. Dissolve the cannabidiol in anhydrous ethanol to form a 1.5 mg / mL solution, and slowly add it dropwise to the above mixture, stirring at 250 rpm for 20 min during the dropwise addition, and continuing to stir for 45 min after the dropwise addition is complete. Then, add the foaming agent, quickly transfer to a sealed container, and allow the foaming reaction to proceed at 35°C and 0.8 MPa for 20 min. Finally, after stabilizing at room temperature for 1.5 hours, it is cut into appropriate shapes and sizes and sterilized by gamma ray irradiation.

[0034] Example 2 The preparation method of the hemostatic foam is as follows: Weigh 5% polyacrylic acid with a molecular weight of 1000 Da, 1% cationic polyacrylamide, 4% propylene glycol alginate with a degree of esterification of 50%, 12% chitosan with a degree of deacetylation of 85%, 0.1% cannabidiol, 0.5% foaming agent (sodium bicarbonate and citric acid in a mass ratio of 1:1), and the balance being physiological saline. At 28°C, add the polyacrylic acid to the physiological saline and stir at 150 rpm for 45 min to dissolve it. Then, add the polyacrylamide, propylene glycol alginate, and chitosan sequentially, stirring at 200 rpm for 75 min. Dissolve the cannabidiol in anhydrous ethanol to form a 1.5 mg / mL solution, and slowly add it dropwise to the above mixture, stirring at 250 rpm for 20 min during the dropwise addition, and continuing to stir for 45 min after the addition is complete. Then, add the foaming agent, quickly transfer to a sealed container, and allow the foaming reaction to proceed at 35°C and 0.8 MPa for 20 min. Finally, after stabilizing at room temperature for 1.5 hours, it is cut into appropriate shapes and sizes and sterilized by gamma ray irradiation.

[0035] Example 3 The preparation method of the hemostatic foam is as follows: Weigh 10% polyacrylic acid with a molecular weight of 3000 Da, 3% cationic polyacrylamide, 8% propylene glycol alginate with a degree of esterification of 70%, 20% chitosan with a degree of deacetylation of 95%, 0.2% cannabidiol, 1% foaming agent (sodium bicarbonate and citric acid in a mass ratio of 2:1), and the balance being physiological saline. At 28°C, add the polyacrylic acid to the physiological saline and stir at 150 rpm for 45 min to dissolve it. Then, add the polyacrylamide, propylene glycol alginate, and chitosan sequentially, stirring at 200 rpm for 75 min. Dissolve the cannabidiol in anhydrous ethanol to form a 1.5 mg / mL solution, and slowly add it dropwise to the above mixture, stirring at 250 rpm for 20 min during the dropwise addition, and continuing to stir for 45 min after the dropwise addition is complete. Then, add the foaming agent, quickly transfer to a sealed container, and allow the foaming reaction to proceed at 35°C and 0.8 MPa for 20 min. Finally, after stabilizing at room temperature for 1.5 hours, it is cut into appropriate shapes and sizes and sterilized by gamma ray irradiation.

[0036] Comparative Example 1 In Comparative Example 1, the hemostatic material was gelatin foam.

[0037] Comparative Example 2 Compared to Example 1, Comparative Example 2's hemostatic foam consisted of the following components in the indicated weight percentages: 3% polyacrylic acid with a molecular weight of 1500 Da, 5% polyacrylamide, 10% propylene glycol alginate, 10% chitosan, 0.5% cannabidiol, 3% foaming agent, and the balance being physiological saline.

[0038] Test case (1) Hemostasis time test: A rat liver hemorrhage model was used. After anesthetizing the rats, a bleeding wound with a diameter of about 5 mm was created on the surface of their livers. The rats were randomly divided into 5 groups, and hemostasis was performed using the hemostatic foam of Examples 1-3, and the hemostatic materials of Comparative Examples 1 and 2, respectively. The hemostatic material was quickly covered on the bleeding wound, and the time was started. The material was gently peeled off every 5 seconds to observe until the bleeding stopped completely, and the hemostasis time was recorded. Ten parallel samples were set up for each group.

[0039] (2) Blood Absorption Swelling Rate Test: Take a mass (m1) of hemostatic foam and immerse it in simulated blood (prepared according to human blood composition) at a constant temperature of 37℃ for 30 minutes. After removal, gently blot off excess liquid with filter paper and weigh again (m2). Calculate the blood absorption swelling rate according to the formula: Blood Absorption Swelling Rate = (m2-m1) / m1×100%. Repeat each test 5 times.

[0040] (3) Biocompatibility Cytotoxicity test: Prepare hemostatic material extract (1g sample + 10mL culture medium, extract at 37℃ for 24h).

[0041] Co-cultured with L929 cells for 48 hours, then MTT solution (5 mg / mL) was added, and cultured for another 4 hours.

[0042] The absorbance at 570 nm was measured, and the cell viability was calculated as: (absorbance of sample group / absorbance of blank group) × 100%. The average value of each group was taken as the test result for that group. The test results are shown in the table below.

[0043]

[0044] The results above show that: (1) The hemostatic foam of the present invention has a significantly shorter hemostatic time than that of the comparative examples. The hemostatic time of Examples 1-3 is between 35-40 seconds, while the hemostatic time of Comparative Example 1 is over 80 seconds, and the hemostatic time of Comparative Example 2 is about 60 seconds. This indicates that the hemostatic foam of the present invention can achieve hemostasis more quickly, mainly due to the synergistic effect of its multiple components, such as the rapid blood absorption and expansion of polyacrylic acid and the coagulation activation of chitosan.

[0045] (2) The hemostatic foam of the present invention has a significantly higher blood absorption and expansion rate than the comparative examples. The blood absorption and expansion rates of Examples 1-3 are between 240-280%. The blood absorption and expansion rate of Comparative Example 1 is only about 105%, and the blood absorption and expansion rate of the material in Comparative Example 2 is about 180%. This indicates that the polyacrylic acid and other components in the hemostatic foam of the present invention can effectively absorb blood, expand rapidly, and better achieve the function of physically sealing damaged blood vessels.

[0046] (3) The cell survival rate in the examples was over 95%, which indicates that the hemostatic foam of the present invention has extremely low cytotoxicity and no significant inhibitory effect on cell growth. The foam hemostatic foam in the examples has good safety.

[0047] 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.

[0048] 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 foam capable of rapidly stopping bleeding, characterized in that, It consists of the following components in the indicated mass percentages: 5-10% polyacrylic acid with a molecular weight of 1000-3000 Da, 1-3% polyacrylamide, 4-8% propylene glycol alginate, 12-20% chitosan, 0.1-0.2% cannabidiol, 0.5-1% foaming agent, and the balance being physiological saline.

2. The hemostatic foam capable of rapid hemostasis as described in claim 1, characterized in that, The molecular weight of the polyacrylic acid is 1500-2500 Da.

3. The hemostatic foam capable of rapid hemostasis as described in claim 1, characterized in that, The polyacrylamide is a cationic polyacrylamide.

4. The hemostatic foam capable of rapid hemostasis as described in claim 1, characterized in that, The degree of esterification of the propylene glycol alginate is 50-70%.

5. The hemostatic foam capable of rapid hemostasis as described in claim 1, characterized in that, The degree of deacetylation of the chitosan is 85-95%.

6. The hemostatic foam capable of rapid hemostasis as described in claim 1, characterized in that, The foaming agent is a mixture of sodium bicarbonate and citric acid in a mass ratio of (1-2):

1.

7. The hemostatic foam capable of rapid hemostasis as described in any one of claims 1-6, characterized in that, The porosity of the hemostatic foam is 70-90%.

8. The use of the hemostatic foam capable of rapid hemostasis as described in any one of claims 1-6 in the preparation of a medicament for treating traumatic bleeding.

9. The method for preparing a hemostatic foam capable of rapid hemostasis as described in any one of claims 1-6, characterized in that, The process includes the following steps: adding polyacrylic acid, polyacrylamide, propylene glycol alginate, chitosan, cannabidiol, and a foaming agent sequentially to physiological saline, stirring until homogeneous, and then carrying out a foaming reaction.

10. The method for preparing the hemostatic foam capable of rapid hemostasis as described in claim 9, characterized in that, The foaming reaction is carried out at a temperature of 30-40℃ and a pressure of 0.5-1MPa.

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