A highly efficient hemostatic dressing, a preparation method and uses thereof

Abstract

The application provides a high-efficiency hemostatic dressing, a preparation method and application thereof. The hemostatic dressing is a crosslinked product containing hydroxypropyl chitosan and low molecular weight eucommia ulmoides gum. The hemostatic dressing has a high swelling rate, can better absorb water-soluble exudates, and is beneficial to rapid hemostasis. The hemostatic dressing has better mechanical strength, which indicates that the hemostatic dressing has excellent compression resistance and high-load impact resistance, so that appropriate eucommia ulmoides gum-based dressing can be selected according to specific application scenes and wound characteristics, so as to improve the treatment effect.

Description

Technical Field

[0001] This application relates to the field of medical dressing technology, and in particular to a high-efficiency hemostatic dressing, its preparation method and its use. Background Technology

[0002] In critical situations such as disasters, accidents, and conflicts, uncontrolled bleeding is a major contributing factor to increased mortality. Massive blood loss often leads to pre-hospital death due to hypotension and multiple organ dysfunction, causing severe physical and psychological suffering to affected individuals. Clinical evidence suggests that in cases of acute bleeding, the lack of timely and effective initial intervention can result in death within a critical time window of 6–20 minutes. Shock occurs when blood loss exceeds 20% of total blood volume, and death occurs when blood loss exceeds 40% of total blood volume.

[0003] As the most complex vascular anatomy structure, the liver is characterized by its large blood flow and fragile texture. Therefore, liver hemorrhage is the most dangerous type of internal bleeding in clinical practice, often life-threatening. Incisions during liver surgery, as well as traumatic liver injury, can lead to uncontrollable bleeding. This massive hemorrhage not only impairs the surgeon's field of vision and complicates the surgical procedure, but also causes serious systemic complications, including liver inflammation, infection, hypokalemia, coagulation disorders, hemorrhagic shock, and multiple organ dysfunction. The liver's natural hemostatic capacity is insufficient to prevent life-threatening bleeding, requiring rapid external intervention. Topical medications can promote clotting at liver incision sites, but their effectiveness is usually limited and may lead to further damage. Therefore, effectively controlling liver hemorrhage is crucial to reducing patient mortality and complications.

[0004] Traditional compression hemostasis, such as gauze, cotton pads, absorbent cotton, and tourniquets, is considered standard treatment in many military and civilian wound care cases. However, traditional hemostatic agents lack sufficient mechanical strength, antibacterial properties, and adhesiveness, resulting in poor hemostatic efficacy, wound adhesion leading to secondary damage, poor biocompatibility, and the risk of further infection and subsequent trauma. Therefore, the development of multifunctional wound dressings with high-efficiency hemostasis for application in the biomedical field is urgently needed. Summary of the Invention

[0005] In view of the technical problems existing in the prior art, this application provides a high-efficiency hemostatic dressing, a preparation method thereof and its use. The hemostatic dressing has good blood compatibility, cell biocompatibility, excellent compressive mechanical properties and can achieve rapid hemostasis for external injuries and internal bleeding.

[0006] The specific technical solution of this application is as follows:

[0007] 1. A highly effective hemostatic dressing, wherein the hemostatic dressing is a crosslinked compound comprising hydroxypropyl chitosan and oligomeric eucommia gum.

[0008] 2. The hemostatic dressing according to item 1, wherein the degree of polymerization of the oligomeric eucommia gum is 1000-4000.

[0009] 3. The hemostatic dressing according to item 1 or 2, wherein the hemostatic dressing is obtained by crosslinking hydroxypropyl chitosan and oligomeric eucommia gum in the presence of glutaraldehyde.

[0010] 4. The hemostatic dressing according to claim 3, wherein the hemostatic dressing is prepared by a method comprising the steps of:

[0011] Hydroxypropyl chitosan was dissolved to obtain a hydroxypropyl chitosan solution;

[0012] Oligomeric eucommia gum is dissolved to obtain an oligomeric eucommia gum solution;

[0013] The oligomeric eucommia gum solution was added dropwise to the hydroxypropyl chitosan solution while stirring to obtain a white solution, and glutaraldehyde was added dropwise to the white solution to obtain a pale yellow emulsion;

[0014] The pale yellow emulsion was left to stand and then frozen to obtain a hemostatic dressing.

[0015] 5. The hemostatic dressing according to item 4, wherein the mass ratio of hydroxypropyl chitosan to oligomeric eucommia gum is 1:0.2-5, preferably 1:0.5-3, and more preferably 1:0.5-2.

[0016] 6. The hemostatic dressing according to item 4 or 5, wherein the concentration of the hydroxypropyl chitosan in the hydroxypropyl chitosan solution is 1-5% (w / v), preferably 2-4% (w / v).

[0017] 7. The hemostatic dressing according to any one of items 4-6, wherein the concentration of the oligomeric eucommia gum in the oligomeric eucommia gum solution is 2-24% (w / v), preferably 6-18% (w / v), and more preferably 8-15% (w / v).

[0018] 8. The hemostatic dressing according to any one of items 4-7, wherein the glutaraldehyde is 1-50% of the oligomeric eucommia gum, preferably 2.5-20%, more preferably 5-20%.

[0019] 9. Use of glutaraldehyde as a crosslinking agent in the preparation of hemostatic dressings containing crosslinked compounds of hydroxypropyl chitosan and oligomeric eucommia gum.

[0020] 10. The use according to item 9, wherein the degree of polymerization of the oligomeric eucommia gum is 1000-4000.

[0021] 11. The use according to item 9 or 10, wherein the mass ratio of the hydroxypropyl chitosan to the oligomeric eucommia gum is 1:0.2-5, preferably 1:0.5-3, more preferably 1:0.5-2; and / or

[0022] The glutaraldehyde is 1-50% of the oligomeric eucommia gum, preferably 2.5-20%, and more preferably 5-20%.

[0023] 12. A method for preparing a hemostatic dressing, comprising:

[0024] Hydroxypropyl chitosan was dissolved to obtain a hydroxypropyl chitosan solution;

[0025] Oligomeric eucommia gum is dissolved to obtain an oligomeric eucommia gum solution;

[0026] The oligomeric eucommia gum solution was added dropwise to the hydroxypropyl chitosan solution while stirring to obtain a white solution, and glutaraldehyde was added dropwise to the white solution to obtain a pale yellow emulsion;

[0027] The pale yellow emulsion was left to stand and then freeze-dried to obtain a hemostatic dressing.

[0028] 13. The method according to item 12, wherein the mass ratio of hydroxypropyl chitosan to oligomeric eucommia gum is 1:0.2-5, preferably 1:0.5-3, and more preferably 1:0.5-2.

[0029] 14. The method according to item 12 or 13, wherein the concentration of the hydroxypropyl chitosan in the hydroxypropyl chitosan solution is 1-5% (w / v), preferably 2-4% (w / v).

[0030] 15. The method according to any one of claims 12-14, wherein the concentration of the oligomeric eucommia gum in the oligomeric eucommia gum solution is 2-24% (w / v), preferably 6-18% (w / v), and more preferably 8-15% (w / v).

[0031] 16. The method according to any one of items 12-15, wherein the glutaraldehyde is 1-50% of the oligomeric eucommia gum, preferably 2.5-20%, more preferably 5-20%.

[0032] 17. The method according to any one of items 12-16, wherein the degree of polymerization of the oligomeric eucommia gum is 1000-4000.

[0033] 18. Use of the hemostatic dressing of any one of items 1-11 or the hemostatic dressing prepared by any one of items 12-17 in preventing traumatic bleeding.

[0034] 19. Use of the hemostatic dressing of any one of items 1-11 or the hemostatic dressing prepared by any one of items 12-17 in the preparation of a medicament for treating visceral bleeding.

[0035] The effects of the invention

[0036] The hemostatic dressing described in this application has a high swelling rate, which can better absorb water-soluble exudates and facilitate rapid hemostasis. The hemostatic dressing also has better mechanical strength, which indicates that it has excellent resistance to pressure and high-load impact. Therefore, appropriate Eucommia ulmoides gelatin-based dressings can be selected according to specific application scenarios and wound characteristics to improve treatment effects.

[0037] The hemolysis rate of the hemostatic dressing described in this application is less than 5% within a certain concentration range, which meets the hemolysis rate standard for biomedical materials. This indicates that the hemostatic dressing hardly undergoes hemolysis in vitro, red blood cells can maintain their function and integrity, and it has good blood compatibility and biocompatibility. Attached Figure Description

[0038] Figure 1 These are scanning electron microscope (SEM) schematic diagrams of the hemostatic dressings obtained in Examples 1-3, where a is a SEM schematic diagram of the hemostatic dressing obtained in Example 1, b is a SEM schematic diagram of the hemostatic dressing obtained in Example 2, and c is a SEM schematic diagram of the hemostatic dressing obtained in Example 3.

[0039] Figure 2 The diagrams show cell survival rates under different concentrations of hemostatic dressings. In the diagrams, a is the cell survival rate at 24 hours under different concentrations of hemostatic dressings, b is the cell survival rate at 48 hours under different concentrations of hemostatic dressings, and c is the cell survival rate at 72 hours under different concentrations of hemostatic dressings. Dressing 1 in the diagrams is the hemostatic dressing obtained in Example 1, dressing 2 is the hemostatic dressing obtained in Example 2, and dressing 3 is the hemostatic dressing obtained in Example 3. Detailed Implementation

[0040] The present application will now be described in detail with reference to the described embodiments. Although specific embodiments of the present application are shown, it should be understood that the present application can be implemented in various forms and should not be limited to the embodiments set forth herein. Rather, these embodiments are provided so that this application will be thorough and complete, and will fully convey the scope of the present application to those skilled in the art.

[0041] It should be noted that certain terms are used in the specification and claims to refer to specific components. Those skilled in the art will understand that different terms may be used to refer to the same component. This specification and claims do not distinguish components based on differences in terminology, but rather on differences in function. The terms "comprising" or "including" used throughout the specification and claims are open-ended and should be interpreted as "comprising but not limited to." The following descriptions in the specification are preferred embodiments for carrying out this application; however, these descriptions are for the purpose of understanding the general principles of the specification and are not intended to limit the scope of this application. The scope of protection of this application shall be determined by the appended claims.

[0042] This application provides a hemostatic dressing, wherein the hemostatic dressing is a crosslinked compound comprising hydroxypropyl chitosan and oligomeric eucommia gum.

[0043] In this application, the structure of the obtained crosslinked compound is as follows:

[0044]

[0045] The hemostatic dressing described in this application is a cross-linked product obtained by cross-linking hydroxypropyl chitosan and oligomeric eucommia gum.

[0046] Hydroxypropyl chitosan is a water-soluble derivative of chitosan. Compared to regular chitosan, hydroxypropyl chitosan has an added hydroxypropyl group at the C6 position, allowing it to dissolve in aqueous solutions of any pH value. Hydroxypropyl chitosan exhibits good gelling properties, hygroscopic and moisturizing properties, antibacterial properties, and biodegradability. It has wide applications in drug sustained release, tissue engineering, and wound dressings.

[0047] The hydroxypropyl chitosan described in this application can be prepared by conventional methods in the art or obtained commercially.

[0048] This application uses hydroxypropyl chitosan to prepare a hemostatic dressing, which exhibits excellent hemostatic properties. In this application, the hydroxypropyl chitosan is commercially available.

[0049] Eucommia gum is a strategic natural polymer material unique to my country, widely found in the gum-containing cells of the roots, bark, leaves, and seeds of the Eucommia tree. Structurally, eucommia gum is an isomer of natural rubber. In its trans-1,4-polyisoprene structure, the two methylene groups are located on either side of the double bond axis, making its molecular chains more easily arranged in an orderly manner. Eucommia gum possesses the dual properties of rubber and plastic, thus exhibiting a crystalline hard plastic at room temperature with a leather-like appearance.

[0050] Eucommia ulmoides gum, as a special functional polymer material, possesses excellent fatigue resistance, wear resistance, impact resistance, and tear resistance. It also exhibits superior properties such as easy crystallization, low melting point, strong insulation, water resistance, acid and alkali resistance, and chloride ion resistance. As a natural polymer material, Eucommia ulmoides gum does not contain the residual small-molecule additives commonly found in synthetic polymers, and it has excellent processing performance, leading to its widespread application in medical materials, such as root canal filling materials in dentistry or fracture fixation splints. This application utilizes oligomeric Eucommia ulmoides gum and hydroxypropyl chitosan for cross-linking, resulting in a hemostatic dressing with good blood compatibility, cell biocompatibility, excellent compressive mechanical properties, and high-efficiency hemostasis for external trauma and internal bleeding. In this application, the oligomeric eucommia gum refers to eucommia gum with a lower degree of polymerization compared to natural, untreated eucommia gum, preferably eucommia gum with a degree of polymerization of less than 5000; more preferably, the degree of polymerization of the oligomeric eucommia gum is 1000-4000, and more preferably 1500-2500.

[0051] For example, the degree of polymerization of the oligomeric Eucommia ulmoides gum is 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, 2000, 2100, 2200, 2300, 2400, 2500, 2600, 2700, 2800, 2900, 3000, 3100, 3200, 3300, 3400, 3500, 3600, 3700, 3800, 3900, 4000, etc.

[0052] In this application, the oligomeric eucommia gum is prepared by conventional methods in the art, such as by degrading natural eucommia gum, for example by UV degradation, thermal degradation, oxygen degradation or a combination of the above conditions.

[0053] The formula for calculating the degree of polymerization is as follows:

[0054] Average degree of polymerization = average molecular weight of polymer / molecular weight of polymer unit

[0055] This application enables crosslinking of Eucommia ulmoides gum with hydroxypropyl chitosan by setting the degree of polymerization within the above-mentioned range. However, if the degree of polymerization is exceeded, Eucommia ulmoides gum may not crosslink with hydroxypropyl chitosan.

[0056] In some embodiments, the hemostatic dressing is obtained by crosslinking hydroxypropyl chitosan and oligomeric eucommia gum in the presence of glutaraldehyde to obtain a crosslinked product. In some embodiments, the hemostatic dressing is prepared by a method comprising the following steps:

[0057] Hydroxypropyl chitosan was dissolved to obtain a hydroxypropyl chitosan solution;

[0058] Oligomeric eucommia gum is dissolved to obtain an oligomeric eucommia gum solution;

[0059] The oligomeric eucommia gum solution was added dropwise to a hydroxypropyl chitosan solution while stirring to obtain a white emulsion. Glutaraldehyde was then added dropwise to the white emulsion to obtain a pale yellow emulsion. The pale yellow emulsion was allowed to stand and then freeze-dried to obtain a hemostatic dressing.

[0060] In some embodiments, the oligomeric eucommia gum solution is added dropwise to a hydroxypropyl chitosan solution while stirring to obtain a white emulsion, and the glutaraldehyde solution is added dropwise to the white emulsion to obtain a pale yellow emulsion; the hemostatic dressing obtained by allowing the pale yellow emulsion to stand and freeze-drying refers to the process of adding the oligomeric eucommia gum solution dropwise to a hydroxypropyl chitosan solution while stirring to obtain a white homogeneous emulsion, adding glutaraldehyde dropwise to the white homogeneous emulsion, stirring and crosslinking until the solution becomes a pale yellow emulsion, and then allowing the pale yellow emulsion to stand and freeze-drying to obtain the hemostatic dressing.

[0061] In this application, hydroxypropyl chitosan is dissolved to obtain a hydroxypropyl chitosan solution. For example, hydroxypropyl chitosan can be dissolved in water and a surfactant can be added to solubilize it to obtain a hydroxypropyl chitosan solution.

[0062] In this application, no restrictions are placed on the surfactant used for solubilization; conventional surfactants in the art can be used, including but not limited to Tween-60, Tween-40, Span-40, Span-60, PEG-2000, sodium dodecylbenzenesulfonate, sodium dodecyl sulfate, and combinations thereof. In this application, no restrictions are placed on the amount of surfactant used; it can be selected as needed. For example, in the hydroxypropyl chitosan solution, the surfactant is 0.3-8% (w / v), preferably 1-5% (w / v), and more preferably 2-4% (w / v).

[0063] For example, in the hydroxypropyl chitosan solution, the surfactant can be 0.3% (w / v), 0.4% (w / v), 0.5% (w / v), 0.6% (w / v), 0.7% (w / v), 0.8% (w / v), 0.9% (w / v), 1.0% (w / v), 2.0% (w / v), 2.1% (w / v), 2.2% (w / v), 2.3% (w / v), 2.4% (w / v), 2.5% (w / v), 2.6% (w / v), 2. 7% (w / v), 2.8% (w / v), 2.9% (w / v), 3.0% (w / v), 3.1% (w / v), 3.2% (w / v), 3.3% (w / v), 3.4% (w / v), 3.5% (w / v), 3 .6% (w / v), 3.7% (w / v), 3.8% (w / v), 3.9% (w / v), 4.0% (w / v), 5.0% (w / v), 6.0% (w / v), 7.0% (w / v), 8.0% (w / v), etc.

[0064] In some embodiments, the concentration of the hydroxypropyl chitosan in the hydroxypropyl chitosan solution is 1-5% (w / v), preferably 2-4% (w / v).

[0065] For example, the concentration of the hydroxypropyl chitosan in the hydroxypropyl chitosan solution can be 2% (w / v), 2.5% (w / v), 3% (w / v), 3.5% (w / v), 4% (w / v), 4.5% (w / v), 5% (w / v), etc.

[0066] In some embodiments, dissolving oligomeric eucommia gum to obtain an oligomeric eucommia gum solution refers to dissolving oligomeric eucommia gum in a solvent to obtain an oligomeric eucommia gum solution. In some embodiments, the concentration of the oligomeric eucommia gum in the oligomeric eucommia gum solution is 2-24% (w / v), preferably 6-18% (w / v), and more preferably 8-15% (w / v).

[0067] For example, the concentration of the oligomeric eucommia gum in the oligomeric eucommia gum solution can be 2% (w / v), 3% (w / v), 4% (w / v), 5% (w / v), 6% (w / v), 7% (w / v), 8% (w / v), 8.5% (w / v), 9% (w / v), 9.5% (w / v), 10% (w / v), 11% (w / v), 12% (w / v), 13% (w / v), 14% (w / v), 15% (w / v), 16% (w / v), 17% (w / v), 18% (w / v), 19% (w / v), 20% (w / v), 21% (w / v), 22% (w / v), 23% (w / v), 24% (w / v), etc.

[0068] In this application, no restrictions are placed on the solvent. Those in the art can make conventional selections as needed. For example, the solvent can be chloroform, petroleum ether, dichloromethane, cyclohexane, etc.

[0069] In some embodiments, the mass ratio of hydroxypropyl chitosan to oligomeric eucommia gum is 1:0.2-5, preferably 1:0.5-3, and more preferably 1:0.5-2.

[0070] For example, the mass ratio of hydroxypropyl chitosan to oligomeric eucommia gum (m 羟丙基壳聚糖 :m 低聚杜仲胶 The ratios can be 1:0.2, 1:0.3, 1:0.4, 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1:0.9, 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, etc.

[0071] In some embodiments, the hydroxypropyl chitosan solution is continuously stirred at 45-55°C before being added dropwise to the oligomeric eucommia gum solution; for example, it can be continuously stirred at 45°C, 46°C, 47°C, 48°C, 49°C, 50°C, 51°C, 52°C, 53°C, 54°C, 55°C, etc.

[0072] In some embodiments, the glutaraldehyde is 1-50% of the oligomeric eucommia gum, preferably 2.5-20%, and more preferably 5-20%.

[0073] In this application, the glutaraldehyde being the oligomeric eucommia gum means that the glutaraldehyde accounts for 1-50% of the oligomeric eucommia gum. For example, when the oligomeric eucommia gum is 1g, the glutaraldehyde is 10-500mg.

[0074] For example, the glutaraldehyde is 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 20%, 25%, 30%, 35%, 40%, 45%, 50% of the oligomeric Eucommia ulmoides gum.

[0075] In some embodiments, adding the glutaraldehyde solution dropwise to a white solution to obtain a pale yellow emulsion refers to adding glutaraldehyde dropwise to a uniform white emulsion solution obtained by mixing hydroxypropyl chitosan solution and oligomeric eucommia gum solution, stirring until the emulsion turns pale yellow, indicating that a cross-linking reaction has occurred and a pale yellow emulsion has been obtained. The mixing of the hydroxypropyl chitosan solution and the oligomeric eucommia gum solution and the cross-linking reaction are both carried out at a temperature of 45-55°C.

[0076] In some embodiments, the process of obtaining a hemostatic dressing by allowing the obtained pale yellow emulsion to stand and freeze-drying involves placing the pale yellow emulsion in a mold and allowing it to stand, preferably until it becomes gel-like; then freeze-drying to obtain the hemostatic dressing.

[0077] In this application, freeze drying involves pre-freezing at -80 to -20°C, for example, at -80°C, -75°C, -70°C, -65°C, -60°C, -55°C, -50°C, -45°C, -40°C, -35°C, -30°C, -25°C, -20°C, etc., and then heating is performed to sublimate the solvent, thereby obtaining a dried dressing.

[0078] The hemostatic dressing described in this application has a high swelling rate, which can better absorb water-soluble exudates and facilitate rapid hemostasis.

[0079] This application provides the use of glutaraldehyde as a crosslinking agent in the preparation of hemostatic dressings comprising crosslinked compounds of hydroxypropyl chitosan and oligomeric eucommia gum.

[0080] This application uses glutaraldehyde as a crosslinking agent to crosslink hydroxypropyl chitosan and oligomeric eucommia gum to obtain a hemostatic dressing.

[0081] In some embodiments, the degree of polymerization of the oligomeric eucommia gum is 1000-4000. In some embodiments, the mass ratio of the hydroxypropyl chitosan to the oligomeric eucommia gum is 1:0.2-5, preferably 1:0.5-3, and more preferably 1:0.5-2.

[0082] The glutaraldehyde is 1-50% of the oligomeric eucommia gum, preferably 2.5-20%, and more preferably 5-20%.

[0083] For example, the degree of polymerization of the oligomeric Eucommia gum is 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, 2000, 2100, 2200, 2300, 2400, 2500, 3000, 4000, etc.

[0084] For example, the mass ratio of hydroxypropyl chitosan to oligomeric eucommia gum (m 羟丙基壳聚糖 :m 低聚杜仲胶 The ratios can be 1:0.2, 1:0.3, 1:0.4, 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1:0.9, 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, etc.

[0085] The glutaraldehyde is 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 20%, 25%, 30%, 40%, 50% of the oligomeric Eucommia ulmoides gum.

[0086] This application provides a method for preparing a hemostatic dressing, which includes: dissolving hydroxypropyl chitosan to obtain a hydroxypropyl chitosan solution;

[0087] Oligomeric eucommia gum is dissolved to obtain an oligomeric eucommia gum solution;

[0088] While stirring, the oligomeric eucommia gum solution is added dropwise to a hydroxypropyl chitosan solution to obtain a white emulsion. Glutaraldehyde is then added dropwise to the white emulsion to obtain a pale yellow emulsion. The pale yellow emulsion is then allowed to stand and freeze-dried to obtain a hemostatic dressing. In some embodiments, the white emulsion is a homogeneous white emulsion solution. In some embodiments, glutaraldehyde is added dropwise to the white emulsion to obtain a pale yellow emulsion; the pale yellow emulsion is then allowed to stand and freeze-dried to obtain the hemostatic dressing. Specifically, glutaraldehyde is added dropwise to the homogeneous white emulsion solution, and stirring continues until the emulsion turns pale yellow. The pale yellow emulsion is then allowed to stand and freeze-dried to obtain the hemostatic dressing.

[0089] In some embodiments, the mass ratio of hydroxypropyl chitosan to oligomeric eucommia gum is 1:0.2-5, preferably 1:0.5-3, and more preferably 1:0.5-2. In some embodiments, the concentration of hydroxypropyl chitosan in the hydroxypropyl chitosan solution is 1-5% (w / v), preferably 2-4% (w / v). In some embodiments, the concentration of oligomeric eucommia gum in the oligomeric eucommia gum solution is 2-24% (w / v), preferably 6-18% (w / v), and more preferably 8-15% (w / v). In some embodiments, the glutaraldehyde is 1-50% of the oligomeric eucommia gum, preferably 2.5-20%, and more preferably 5-20%. In some embodiments, the degree of polymerization of the oligomeric eucommia gum is 1000-4000.

[0090] The hemostatic dressing prepared by the method described above has better hemostatic properties than the gelatin sponge in the prior art, thus exhibiting superior hemostatic performance.

[0091] Example

[0092] This application provides a general and / or specific description of the materials and test methods used in the experiments. In the following examples, unless otherwise specified, % represents wt%, i.e., weight percentage. Reagents or instruments used, unless otherwise specified, are all commercially available conventional reagent / instrument products.

[0093] Example 1

[0094] Experimental materials: Hydroxypropyl chitosan: Nantong Lvshen Bioengineering Co., Ltd.; Glutaraldehyde: Shanghai Maclean Biochemical Technology Co., Ltd. (high-purity medical grade); Chloroform: Sinopharm Chemical Reagent Co., Ltd.; Tween-80: Shanghai Aladdin Biochemical Technology Co., Ltd.; PBS solution (pH=7.4): Beijing Solarbio Science & Technology Co., Ltd.; Oligomeric Eucommia gum (degree of polymerization 2364, molecular weight 16.07×10⁻⁶). 4 (g / mol): Self-made, preparation process: Block-shaped Eucommia ulmoides gum extracted in the laboratory was ground into granules using liquid nitrogen. The ground granules were then passed through a stainless steel sieve with a pore size of 0.85 mm to obtain Eucommia ulmoides gum with uniform particle size. According to the requirements of GB / T 14522-2008, a certain amount of the sieved Eucommia ulmoides gum was placed 25 cm directly below a 310 nm ultraviolet lamp (illuminance: 12000 lux) and degraded under ultraviolet light for 48 hours to obtain oligomeric Eucommia ulmoides gum.

[0095] Experimental equipment: DF-101S thermostatic magnetic stirrer (Shanghai Lichen Bangxi Instrument Technology Co., Ltd.); 0.01% electronic balance (Mettler Toledo Corporation, USA).

[0096] Experimental procedure:

[0097] (1) Weigh 0.45g of hydroxypropyl chitosan, add 15mL of 0.2% Tween-80 aqueous solution, and stir at 45℃ for 1h to obtain hydroxypropyl chitosan solution.

[0098] (2) Weigh 0.45g of oligomeric eucommia gum, dissolve it in 5mL of chloroform at 45℃, and stir for 0.5h to obtain oligomeric eucommia gum solution.

[0099] (3) At 45°C, the oligomeric eucommia gum solution was added dropwise to the hydroxypropyl chitosan solution, and stirring was continued until a uniform white emulsion was formed. Then, 0.045 g of glutaraldehyde was added dropwise to the white emulsion under continuous stirring at 45°C, and stirring was continued until the emulsion turned pale yellow. The pale yellow solution was poured into a mold and allowed to stand for 6 hours to form a pale yellow gel. Then, it was pre-frozen at -20°C for 12 hours and freeze-dried in a vacuum freeze dryer for 48 hours. The freeze-dried gel was removed from the mold to obtain the hemostatic dressing, which has a loose and porous honeycomb three-dimensional network structure.

[0100] (5) Weigh a portion of the above-mentioned dressing with dimensions of 0.5cm (length) × 0.5cm (width) × 0.5cm (height), record the weight as M0g, and immerse it in a centrifuge tube containing 5mL of PBS solution. Remove the dressing from the PBS solution every 10 minutes, blot off the excess PBS solution on the surface of the dressing with filter paper, and measure the wet weight of the dressing until the wet weight no longer increases, recording this as M. t g. Calculate the swelling ratio (SR) of the dressing using the following formula, and test each sample in triplicate.

[0101] SR(%) = (M) t -M0) / M0×100%

[0102] Results: The dressing prepared in Example 1 reached swelling equilibrium within 60 minutes, and the swelling rate of the dressing, measured by gravimetric method, was 2668±49%.

[0103] Example 2

[0104] The difference between Example 2 and Example 1 is that the amount of oligomeric eucommia gum used is different. The amount of oligomeric eucommia gum used is 0.675g, which is dissolved in 5mL of chloroform to obtain a hemostatic dressing.

[0105] The swelling rate of the hemostatic dressing obtained in Example 2 was determined using the same method as in Example 1. The swelling rate was 2362±93%, and it reached swelling equilibrium within 60 minutes.

[0106] Example 3

[0107] The difference between Example 3 and Example 1 is that the amount of oligomeric eucommia gum used is different. The amount of oligomeric eucommia gum used is 0.9g, which is dissolved in 5mL of chloroform to obtain a hemostatic dressing.

[0108] The swelling rate of the hemostatic dressing obtained in Example 3 was determined using the same method as in Example 1. The swelling rate was 2160 ± 44%, and it reached swelling equilibrium within 60 minutes.

[0109] Example 4

[0110] The difference between Example 4 and Example 1 is that the amount of oligomeric eucommia gum used is different. The amount of oligomeric eucommia gum used is 0.09g, which is dissolved in 1mL of chloroform to obtain a hemostatic dressing.

[0111] The swelling rate of the hemostatic dressing obtained in Example 4 was determined using the same method as in Example 1. The swelling rate was 2803 ± 70%, and it reached swelling equilibrium within 60 minutes.

[0112] Example 5

[0113] The difference between Example 5 and Example 1 is that the amount of oligomeric eucommia gum used is different. The amount of oligomeric eucommia gum used is 0.225g, which is dissolved in 2.5mL of chloroform to obtain a hemostatic dressing.

[0114] The swelling rate of the hemostatic dressing obtained in Example 5 was determined using the same method as in Example 1. The swelling rate was 2711 ± 37%, and it reached swelling equilibrium within 60 minutes.

[0115] Example 6

[0116] The difference between Example 6 and Example 1 is that the amount of oligomeric eucommia gum used is different. The amount of oligomeric eucommia gum used is 1.8g, which is dissolved in 10mL of chloroform to obtain a hemostatic dressing.

[0117] The swelling rate of the hemostatic dressing obtained in Example 6 was determined using the same method as in Example 1. The swelling rate was 2064 ± 24%, and it reached swelling equilibrium within 60 minutes.

[0118] Example 7

[0119] The difference between Example 7 and Example 1 is that the amount of oligomeric eucommia gum used is different. The amount of oligomeric eucommia gum used is 2.25g, which is dissolved in 12mL of chloroform to obtain a hemostatic dressing.

[0120] The swelling rate of the hemostatic dressing obtained in Example 7 was determined using the same method as in Example 1. The swelling rate was 1949 ± 37%, and it reached swelling equilibrium within 60 minutes.

[0121] Example 8

[0122] The difference between Example 8 and Example 3 is that the degree of polymerization of the oligomeric eucommia gum used is 1105, resulting in a hemostatic dressing. The preparation method of the oligomeric eucommia gum is as follows: blocky eucommia gum extracted in the laboratory is ground into granules using liquid nitrogen. The ground granules are then passed through a stainless steel sieve with a pore size of 0.85 mm to obtain eucommia gum with uniform particle size. According to the requirements of GB / T 14522-2008, a certain amount of the sieved eucommia gum is placed 25 cm directly below a 310 nm ultraviolet lamp (illuminance: 12000 lux) and degraded under ultraviolet light for 120 hours, yielding a chloroform volume of 5 mL to dissolve the oligomeric eucommia gum.

[0123] The swelling rate of the hemostatic dressing obtained in Example 8 was determined using the same method as in Example 1. The swelling rate was 1874.32 ± 41.25%, and it reached swelling equilibrium within 50 minutes.

[0124] Example 9

[0125] The difference between Example 9 and Example 3 is that the degree of polymerization of the oligomeric eucommia gum used is 3871, resulting in a hemostatic dressing. The preparation method of the oligomeric eucommia gum is as follows: blocky eucommia gum extracted in the laboratory is ground into granules using liquid nitrogen. The ground granules are then passed through a stainless steel sieve with a pore size of 0.85 mm to obtain eucommia gum with uniform particle size. According to the requirements of GB / T 14522-2008, a certain amount of the sieved eucommia gum is placed 25 cm directly below a 310 nm ultraviolet lamp (illuminance: 12000 lux) and degraded under ultraviolet light for 24 hours, yielding 5 mL of chloroform to dissolve the oligomeric eucommia gum.

[0126] The swelling rate of the hemostatic dressing obtained in Example 9 was determined using the same method as in Example 1. The swelling rate was 2126 ± 19%, and it reached swelling equilibrium within 60 minutes.

[0127] Example 10

[0128] The difference between Example 10 and Example 1 is that the concentration of hydroxypropyl chitosan used is 0.018 g / mL. 0.45 g of hydroxypropyl chitosan was weighed and added to 25 mL of 0.2% Tween-80 aqueous solution. The mixture was stirred at 45°C for 1 h to obtain a hydroxypropyl chitosan solution with a concentration of 0.018 g / mL, which was used to prepare a hemostatic dressing.

[0129] The swelling rate of the hemostatic dressing obtained in Example 10 was determined using the same method as in Example 1. The swelling rate was 2160.84 ± 14.21%, and it reached swelling equilibrium within 60 minutes.

[0130] Example 11

[0131] The difference between Example 11 and Example 1 is that the concentration of hydroxypropyl chitosan used is 0.045 g / mL. 0.45 g of hydroxypropyl chitosan was weighed and added to 10 mL of 0.2% Tween-80 aqueous solution. The mixture was stirred at 45°C for 1 h to obtain a hydroxypropyl chitosan solution with a concentration of 0.045 g / mL, which was used to prepare a hemostatic dressing.

[0132] The swelling rate of the hemostatic dressing obtained in Example 11 was determined using the same method as in Example 1. The swelling rate was 2392.77 ± 12.60%, and it reached swelling equilibrium within 60 minutes.

[0133] Example 12

[0134] The difference between Example 12 and Example 1 is that 22.5 mg of glutaraldehyde was used to prepare the hemostatic dressing.

[0135] The swelling rate of the hemostatic dressing obtained in Example 12 was determined using the same method as in Example 1. The swelling rate was 2046.46 ± 34.91%, and it reached swelling equilibrium within 60 minutes.

[0136] Example 13

[0137] The difference between Example 13 and Example 1 is that 90 mg of glutaraldehyde was used to prepare the hemostatic dressing.

[0138] The swelling rate of the hemostatic dressing obtained in Example 13 was determined using the same method as in Example 1. The swelling rate was 2314.43 ± 69.16%, and it reached swelling equilibrium within 60 minutes.

[0139] Table 1

[0140]

[0141] Example 1: Scanning Electron Microscopy Characterization of Dressing

[0142] The hemostatic dressings prepared in Examples 1-3 were rapidly frozen by immersing them in liquid nitrogen for 1 minute, and smooth cross-sections were cut out with a blade. Before testing, the samples were fixed to a metal base using conductive adhesive (Nippon Nisshin Co., Ltd., Japan). Scanning electron microscopy (SEM) images of the dressing samples were obtained using a scanning electron microscope (S-3400N, Hitach i, Japan) at an accelerating voltage of 10 kV. The results are as follows. Figure 1 As shown, a is a scanning electron microscope (SEM) schematic diagram of the hemostatic dressing obtained in Example 1, b is a scanning electron microscope (SEM) schematic diagram of the hemostatic dressing obtained in Example 2, and c is a scanning electron microscope (SEM) schematic diagram of the hemostatic dressing obtained in Example 3.

[0143] from Figure 1 It can be seen that the surface of the hemostatic dressing has a highly porous three-dimensional structure, and the three-dimensional network structure of the dressing becomes denser as the content of oligomeric eucommia gum increases.

[0144] Experiment Example 2: Comparison of Contact Angles of Different Dressings

[0145] Contact angle reflects the hydrophilicity of a material. Since oligomeric eucommia gum is a strongly hydrophobic material, its hydrophilicity is enhanced after modification with hydroxypropyl chitosan and glutaraldehyde. This enhanced hydrophilicity also facilitates the absorption of plasma and exudate from the wound by the hemostatic dressing. Therefore, the contact angle of the prepared hemostatic dressing was measured and compared with that of unmodified oligomeric eucommia gum.

[0146] Experimental equipment: Surface contact angle measuring instrument (Kunshan Shengding SDC 350KS)

[0147] Experimental Procedure: The hemostatic dressings from Examples 1-3 were all cut into cubes measuring 1.0 cm (length) × 1.0 cm (width) × 0.5 cm (height) and fixed on the stage of a surface contact angle measuring instrument. A 10 μL drop of deionized water was placed on the surface of each hemostatic dressing sample. After 30 seconds, the deionized water droplet was photographed using the camera of the contact angle measuring instrument, and the contact angle was measured using the protractor method. Three independent measurements were performed at three different locations on each dressing, and the results are shown in Table 2.

[0148] Table 2

[0149] Sample Name Surface contact angle (°) Oligomeric Eucommia Gum 107.03±3.04 Example 1 44.14±1.65 Example 2 61.84±1.67 Example 3 73.20±0.88

[0150] As shown in Table 2, the surface contact angle of the oligomeric eucommia gum is 107.03°. After modification, the surface contact angles of the resulting hemostatic dressings are all less than 90°, indicating that the modified hemostatic dressings have significant hydrophilicity and suggest their ability to absorb wound exudate. The surface contact angle of the hemostatic dressing decreases with decreasing oligomeric eucommia gum content, indicating that the hydrophilicity of the hemostatic dressing increases with decreasing oligomeric eucommia gum dosage. Therefore, the appropriate amount of oligomeric eucommia gum base can be selected according to the nature of the wound to adapt to different wound hemostasis scenarios.

[0151] Experiment Example 3: Comparison Test of Swelling Rate of Different Dressings

[0152] Using a 0.01 g electronic balance (Mettler Toledo, USA), weigh cubic hemostatic dressings (Examples 1-13) and gelatin sponge dressings (Nanchang Hushida Medical Technology Co., Ltd.) with dimensions of 0.5 cm (length) × 0.5 cm (width) × 0.5 cm (height), and record the weight as M0g. Immerse them in centrifuge tubes containing 5 mL of PBS solution (Beijing Solarbio Technology Co., Ltd.). Every 10 minutes, remove the dressings from the PBS solution, blot off the PBS solution on the surface of the dressings with filter paper, and measure the wet weight of the dressings until the wet weight of the dressings no longer increases, and record this as M. t g. The swelling ratio (SR) of the hemostatic dressing was calculated using the following formula. Each sample was tested in parallel three times, and the results are shown in Table 3.

[0153] SR(%) = (M) t -M0) / M0×100%

[0154] Table 3

[0155]

[0156]

[0157] As shown in Table 3, the swelling rates of Examples 1-13 were significantly higher than those of the control group gelatin sponge dressing (1383%), indicating that the hemostatic dressing can better absorb water-soluble exudate and is beneficial for rapid hemostasis.

[0158] Experiment Example 4: Compression Performance Test of Different Dressings

[0159] The hemostatic dressing samples from Examples 1-9 were prepared into uniform cylinders with a height of 10 mm and a diameter of 10 mm. Compression tests were performed at room temperature using a universal testing machine (Instron 3343, USA) at a compressive strain of 85% and a compression rate of 1 mm·min⁻¹. -1 A commercially available gelatin sponge dressing of the same size was used as a control. Each sample was tested three times, and the average value was taken. The results are shown in Table 4.

[0160] Table 4

[0161]

[0162]

[0163] As shown in Table 4, the prepared hemostatic dressing exhibits better compressive stress and mechanical strength compared to conventional gelatin sponge dressings, indicating that this novel dressing possesses excellent resistance to compression and high-load impact. Furthermore, Examples 1-7 demonstrate that increasing the amount of oligomeric eucommia gum significantly improves the mechanical strength of the hemostatic dressing. Therefore, appropriate dressings can be selected based on specific application scenarios and wound characteristics to enhance therapeutic efficacy.

[0164] Experimental Example 5: Comparison of Hemolysis Rate of Hemostatic Dressings

[0165] Since this dressing is primarily used for hemostasis, it should possess good safety characteristics. Therefore, its hemolytic activity was tested; lower hemolytic activity indicates higher safety. Thus, the hemolysis rate of the prepared hemostatic dressing was determined and compared with commonly used gelatin sponge dressings.

[0166] Fresh anticoagulated rabbit blood was mixed with 0.9% sodium chloride solution at a ratio of 1:10, centrifuged at 1000 rpm for 15 minutes, and the supernatant was discarded. The precipitated red blood cells were washed 2-3 times with 0.9% sodium chloride solution (Sichuan Kelun Pharmaceutical Co., Ltd.) as described above until the supernatant no longer appeared red, thus obtaining rabbit blood red blood cells. 5 mL of rabbit blood red blood cells were diluted with 95 mL of 0.9% sodium chloride solution to obtain a red blood cell suspension. The hemostatic dressings from Examples 1-3 were prepared into hemostatic dressing solutions of different concentrations using 0.9% sodium chloride solution at concentrations of 0.5 mg / mL, 1.0 mg / mL, and 2.0 mg / mL, respectively. The red blood cell suspension was mixed with the hemostatic dressing solution at a volume ratio of 1:1 to obtain the experimental group sample solution. The negative control group was 0.9% sodium chloride solution, and the positive control group was distilled water. The sample group and control group were incubated in a 37℃ water bath for 3 hours and centrifuged at 3000 rpm for 5 minutes. The supernatant from each centrifuge tube was transferred to a 96-well plate, and the absorbance of each group was measured at 540 nm using a microplate reader (Thermof i sher). The hemolysis rate (H%) of the hemostatic dressing was calculated according to the following formula, and the results are shown in Table 5.

[0167] H(%)=(A S -A n ) / (A p -A n )×100%

[0168] In the formula, A S A n and A p The absorbance values ​​are for the sample group, negative control group, and positive control group, respectively.

[0169] Table 5

[0170]

[0171]

[0172] Table 5 shows that the hemolysis rates of the three prepared hemostatic dressings, within the concentration range of 0.5–2 mg / mL, were all below 5%, meeting the hemolysis rate standards for biomedical materials. This indicates that the hemostatic dressings hardly undergo hemolysis in vitro, and red blood cells maintain their function and integrity, demonstrating good blood compatibility. Compared to currently commonly used gelatin sponge dressings, the hemostatic dressings have a lower hemolysis rate, indicating higher biocompatibility.

[0173] Experimental Example 6: Cell Biocompatibility Test of Hemostatic Dressing

[0174] According to the requirements of ISO / EN 10993-5, evaluating the toxicity of biomaterial extracts to specific cells through in vitro cell culture is an important testing indicator before the clinical application of biomaterials. The hemostatic dressings from Examples 1-3 were sterilized by UV irradiation for 2 hours. After sterilization, the dressings were added to the extraction medium (i.e., DMEM complete medium containing 10% fetal bovine serum and 1% penicillin-dextrose antibodies). Three concentration groups were set up for each dressing, with the low, medium, and high concentration groups each containing 3 cm³ of the medium. 2 / mL, 6cm 2 / mL, 9cm 2 / mL, and incubated in an incubator (37℃, 5% CO2) for 24h. The extract was then filtered through a 0.22μm filter membrane to obtain the dressing extract, which was stored in a refrigerator at 4℃ for later use.

[0175] Experimental group: Mouse fibroblast L929 cells (Xiamen Yimo Biotechnology Co., Ltd.) were seeded in DMEM complete medium (Gibco, USA) containing 10% fetal bovine serum and 1% penicillin and streptomycin, and cultured in an incubator (37℃, 5% CO2). When the L929 cell density reached 80% at the third passage, the cells were digested with trypsin (Gibco, USA) for 30 seconds, and then 2 mL of DMEM complete medium was added to terminate the digestion. The cells were then incubated at 1000 rpm·min. -1 Centrifuge for 5 minutes and discard the supernatant. Use a pipette to thoroughly mix L929 cells with 2 mL of DMEM complete culture medium, and adjust the cell suspension density to 1 × 10⁻⁶ cells / mL using a cell counting chamber. 4 Cells / mL. 200 μL of cell suspension was seeded per well in a 96-well plate and incubated for 24 h. 200 μL of high, medium, and low concentrations of each dressing extract were added, with three replicates per group, and incubated for 24 h, 48 h, and 72 h, respectively. After each incubation period, the supernatant was aspirated, and 180 μL of DMEM complete medium and 20 μL of CCK-8 reagent (Beijing Beiren Chemical Technology Co., Ltd.) were added to each well. After another 1 h of incubation, the absorbance of the experimental group wells was measured at 450 nm using a microplate reader and recorded as A. s .

[0176] Control group: L929 cells were seeded in DMEM complete medium containing 10% fetal bovine serum and 1% penicillin antibiotics and cultured in an incubator (37℃, 5% CO2). When the L929 cell density reached 80% at the third generation, the cells were digested with trypsin for 30 seconds, and then 2 mL of complete medium was added to stop the digestion. The cells were then incubated at 1000 rpm·min. -1Centrifuge for 5 minutes and discard the supernatant. Use a pipette to thoroughly mix L929 cells with 2 mL of complete culture medium, and adjust the cell suspension density to 1 × 10⁻⁶ cells / mL using a cell counting chamber. 4 Cells / mL. 200 μL of cell suspension was seeded per well, and 96-well plates were incubated for 24 h, 48 h, and 72 h. After each incubation period, the original complete culture medium was aspirated, and 180 μL of complete culture medium and 20 μL of CCK-8 reagent were added to each well. After another 1 h of incubation, the absorbance of the control wells was measured at 450 nm using a microplate reader and recorded as A. c .

[0177] Control group: DMEM complete medium containing 10% fetal bovine serum and 1% penicillin antibiotics was added to each well, and the plates were incubated in an incubator (37℃, 5% CO2) for 24h, 48h, and 72h. After each incubation period, the original complete medium was removed, and 180μL of complete medium and 20μL of CCK-8 reagent were added to each well. After another 1h of incubation, the absorbance of the control group wells was measured at 450nm using a microplate reader and recorded as A. b .

[0178] Cell viability (CV) is calculated using the following formula, and the result is as follows: Figure 2 As shown:

[0179] CV(%) = (A) s -A b ) / (A c -A b )×100%

[0180] In the above formula, A s A represents the absorbance value of the experimental group's wells. b A represents the absorbance value of the blank group wells. c The absorbance value is for the control group well.

[0181] Depend on Figure 2 It can be seen that the hemostatic dressings in Examples 1-3 are within 3cm. 2 / mL, 6cm 2 / mL and 9cm 2 The cell viability at concentrations of 100 g / mL was higher than 70%, indicating that the three dressings prepared had good cell compatibility and high safety.

[0182] Experimental Example 7: In vitro evaluation of the hemostatic performance of wound dressings – relative coagulation index test

[0183] Experimental materials: hemostatic dressings (dressing 1, dressing 2, dressing 3) from Examples 1-3, gelatin sponge dressings (Nanchang Husida Medical Technology Co., Ltd.), and anticoagulated rabbit blood.

[0184] The hemostatic dressings and gelatin sponge dressings from Examples 1-3 were cut into uniform cubes measuring 5mm × 5mm × 5mm (length × width × height) and placed at the bottom of centrifuge tubes. Three sets of each dressing were prepared in parallel, with no dressing added to the control group. 100 μL of anticoagulated rabbit blood and 40 μL of 0.2 mol / L sodium chloride solution were added to each centrifuge tube. -1 The CaCl2 solution was incubated in a 37°C water bath for 5 minutes. Then, 5 mL of double-distilled water was added, and the solution was incubated for another 5 minutes. The supernatant from each centrifuge tube was pipetted into a 96-well plate, and the absorbance at 540 nm was measured using a microplate reader. The relative coagulation index (Relative BCI) was calculated using the following formula, and the results are shown in Table 6.

[0185] Relative coagulation index = (A s ) / (A b )×100%

[0186] Among them, A s and A b The absorbance values ​​at 545 nm are for the experimental group and the blank group, respectively.

[0187] Table 6

[0188] Group Relative coagulation index (%) Example 1 45.77±2.80 Example 2 38.94±3.19 Example 3 29.88±1.75 Gelatin sponge 64.46±1.03

[0189] As shown in Table 6, the relative coagulation index values ​​of the hemostatic dressings in Examples 1-3 were significantly lower than those of the gelatin sponge dressing group, indicating that the hemostatic dressings have superior coagulation ability. Among the three hemostatic dressings prepared, the hemostatic dressing in Example 3 had the lowest relative coagulation index value, at 29.88%, which is about half that of the gelatin sponge dressing. This indicates that the hemostatic dressing in Example 3 has the strongest hemostatic ability, suggesting that increasing the amount of oligomeric eucommia gum in the dressing within a certain range is beneficial to improving the hemostatic performance of the hemostatic dressing.

[0190] Example 8: Evaluation of Hemostasis in Traumatic Bleeding Model

[0191] The hemostatic effect of the prepared dressing was evaluated using a mouse tail-loss hemorrhage model and compared with a commercially available gelatin sponge dressing.

[0192] Experimental Procedure: Forty-two male Kunming mice (male, 8 weeks old, weight: 45±3g, purchased from Beijing Spef Biotechnology Co., Ltd.) weighing 45±3g were randomly divided into seven groups: blank group, dressing group 1 (hemostatic dressing of Example 1), dressing group 2 (hemostatic dressing of Example 2), dressing group 3 (hemostatic dressing of Example 3), dressing group 4 (hemostatic dressing of Example 4), dressing group 5 (hemostatic dressing of Example 5), and gelatin control group, with six mice in each group. The mice were fasted for 12 hours before surgery. After anesthetizing the mice by intraperitoneal injection of 0.6% sodium pentobarbital, the tails were disinfected with 75% alcohol. After the tails became congested, the tails were severed at the midpoint. After 15 seconds of bleeding, the hemostatic dressings of each group were quickly applied to the tail incision site. Place pre-weighed, dried filter paper (denoted as M0g) under the rat's tail. After 4 minutes, weigh the filter paper after it has absorbed blood (denoted as M). t g). Calculate the blood loss M from the mouse tail within 4 minutes. t -M0g. The results are shown in Table 7.

[0193] Table 7

[0194]

[0195]

[0196] #, P < 0.05 compared to the control group; ##, P < 0.01 compared to the control group.

[0197] * Compared with the gelatin sponge dressing group, P<0.05; ** Compared with the gelatin sponge dressing group, P<0.01. Table 7 shows that in the mouse tail-cutting hemorrhage model, the bleeding volume of each dressing group (3 dressings + gelatin sponge dressing) was significantly lower than that of the blank group (P<0.01), indicating that all dressings have good hemostatic effects in traumatic bleeding models. Comparing the hemostatic dressings of Examples 1-5 with the commercially available gelatin sponge dressing (control group), the bleeding volume of the hemostatic dressings of Examples 1-5 was significantly lower than that of the control group gelatin sponge dressing (P<0.05 or P<0.01), indicating that the hemostatic performance of the hemostatic dressings of Examples 1-5 is significantly better than that of commonly used commercially available gelatin sponge dressings, especially Examples 1-3 and 5.

[0198] Example 9: Evaluation of Hemostasis in the Visceral Hemorrhage Model

[0199] The hemostatic effect of the prepared hemostatic dressing was evaluated using a mouse liver hemorrhage model and compared with that of a commercially available gelatin sponge dressing.

[0200] Thirty Kunming mice were randomly divided into five groups of six each: a control group (using commercially available gelatin sponge dressing), dressing group 1 (the hemostatic dressing from Example 1), dressing group 2 (the hemostatic dressing from Example 2), dressing group 3 (the hemostatic dressing from Example 3), and a blank control group. The mice were fasted for 12 hours prior to surgery and anesthetized with an intraperitoneal injection of 0.6% sodium pentobarbital. The liver was exposed by opening the abdomen of the mice, and a weighed filter paper was placed underneath the liver; the mass of the filter paper was denoted as M. a g, induce liver bleeding by puncturing with an 18G needle. Immediately cover the liver with the dressing after needle puncture, and weigh the filter paper after absorbing blood 4 minutes later (denoted as M). b g), calculate the blood loss M from the liver over 4 minutes. b -M a g, the results are shown in Table 8.

[0201] Table 8

[0202] Group Blood loss (g) Dressing Set 1 <![CDATA[0.229±0.012 ##** ]]> Dressing Set 2 <![CDATA[0.171±0.051 ##** ]]> Dressing Set 3 <![CDATA[0.145±0.009 ##** ]]> Gelatin sponge dressing <![CDATA[0.304±0.063 # ]]> blank 0.428±0.099

[0203] #, P < 0.05 compared to the control group; ##, P < 0.01 compared to the control group.

[0204] * Compared with the gelatin sponge dressing group, P<0.05; ** Compared with the gelatin sponge dressing group, P<0.01. Table 8 shows that in the mouse liver puncture hemorrhage model, all dressing groups (3 types of hemostatic dressings + gelatin sponge dressing) showed better hemostatic effects on liver bleeding compared to the control group, and the 3 types of hemostatic dressings were superior to the commercially available gelatin dressing group. Comparing the hemostatic effects of each dressing, it can be found that the hemostatic ability of the dressings significantly increased with the increase of oligomeric eucommia gum content.

[0205] The above description is merely a preferred embodiment of this application and is not intended to limit the application in any other way. Any person skilled in the art may make changes or modifications to the disclosed technical content to create equivalent embodiments. However, any simple modifications, equivalent changes, and modifications made to the above embodiments based on the technical essence of this application without departing from the scope of the technical solution of this application shall still fall within the protection scope of this application.

Claims

1. A highly effective hemostatic dressing, wherein, The hemostatic dressing is a cross-linked compound containing hydroxypropyl chitosan and oligomeric eucommia gum.

2. The hemostatic dressing according to claim 1, wherein, The degree of polymerization of the oligomeric Eucommia ulmoides gum is 1000-4000.

3. The hemostatic dressing according to claim 1 or 2, wherein the hemostatic dressing is obtained by crosslinking hydroxypropyl chitosan and oligomeric eucommia gum in the presence of glutaraldehyde; Preferably, the hemostatic dressing is prepared by a method comprising the following steps: Hydroxypropyl chitosan was dissolved to obtain a hydroxypropyl chitosan solution; Oligomeric eucommia gum is dissolved to obtain an oligomeric eucommia gum solution; The oligomeric eucommia gum solution was added dropwise to the hydroxypropyl chitosan solution while stirring to obtain a white solution, and glutaraldehyde was added dropwise to the white solution to obtain a pale yellow emulsion; The pale yellow emulsion was left to stand and then frozen to obtain a hemostatic dressing.

4. The hemostatic dressing according to claim 3, wherein, The mass ratio of hydroxypropyl chitosan to oligomeric eucommia gum is 1:0.2-5, preferably 1:0.5-3, and more preferably 1:0.5-2; Preferably, the concentration of hydroxypropyl chitosan in the hydroxypropyl chitosan solution is 1-5% (w / v), more preferably 2-4% (w / v); Preferably, the concentration of the oligomeric eucommia gum in the oligomeric eucommia gum solution is 2-24% (w / v), more preferably 6-18% (w / v), and even more preferably 8-15% (w / v); Preferably, the glutaraldehyde is 1-50% of the oligomeric eucommia gum, more preferably 2.5-20%, and even more preferably 5-20%.

5. Use of glutaraldehyde as a crosslinking agent in the preparation of hemostatic dressings containing crosslinked compounds of hydroxypropyl chitosan and oligomeric eucommia gum.

6. The use according to claim 5, wherein, The degree of polymerization of the oligomeric Eucommia ulmoides gum is 1000-4000; and / or The mass ratio of hydroxypropyl chitosan to oligomeric eucommia gum is 1:0.2-5, preferably 1:0.5-3, and more preferably 1:0.5-2; and / or The glutaraldehyde is 1-50% of the oligomeric eucommia gum, preferably 2.5-20%, and more preferably 5-20%.

7. A method for preparing a hemostatic dressing, comprising: Hydroxypropyl chitosan was dissolved to obtain a hydroxypropyl chitosan solution; Oligomeric eucommia gum is dissolved to obtain an oligomeric eucommia gum solution; The oligomeric eucommia gum solution was added dropwise to the hydroxypropyl chitosan solution while stirring to obtain a white solution, and glutaraldehyde was added dropwise to the white solution to obtain a pale yellow emulsion; The pale yellow emulsion was left to stand and then freeze-dried to obtain a hemostatic dressing.

8. The method according to claim 7, wherein, The mass ratio of hydroxypropyl chitosan to oligomeric eucommia gum is 1:0.2-5, preferably 1:0.5-3, and more preferably 1:0.5-2; Preferably, the concentration of hydroxypropyl chitosan in the hydroxypropyl chitosan solution is 1-5% (w / v), more preferably 2-4% (w / v); Preferably, the concentration of the oligomeric eucommia gum in the oligomeric eucommia gum solution is 2-24% (w / v), more preferably 6-18% (w / v), and even more preferably 8-15% (w / v); and / or Preferably, the glutaraldehyde is 1-50% of the oligomeric eucommia gum, more preferably 2.5-20%, and even more preferably 5-20%. Preferably, the degree of polymerization of the oligomeric eucommia gum is 1000-4000.

9. Use of the hemostatic dressing according to any one of claims 1-6 or the hemostatic dressing prepared by the method according to any one of claims 7-8 in preventing traumatic bleeding.

10. Use of the hemostatic dressing according to any one of claims 1-6 or the hemostatic dressing prepared by the method according to any one of claims 7-8 in the preparation of a medicament for treating visceral bleeding.

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