Preparation method of gradient calcified alginate hemostatic bandage

Abstract

This invention relates to the field of medical dressings and hemostatic bandaging materials, specifically disclosing a method for preparing a gradient calcified alginate hemostatic bandage. The method includes: preparing a composite film-forming slurry containing sodium alginate, carboxymethyl chitosan, cellulose derivatives, a softener, polyvinyl alcohol, and polyethylene glycol 1000; coating or impregnating the composite film-forming slurry onto a medical strip substrate, and pre-freezing and freeze-drying to form a porous strip matrix; setting a liquid-resistant support layer on the side of the porous strip matrix away from the wound contact surface, and applying a calcium chloride aqueous calcification solution from the wound contact surface for unilateral confined rapid calcification; then applying a calcium lactate or calcium gluconate calcium supplementation dispersion from the same side; subsequently applying a softening solution from the back side, and obtaining a gradient calcified alginate hemostatic bandage after drying, cutting, and winding. This invention is suitable for preparing auxiliary hemostatic bandaging products for superficial wounds, postoperative wounds with minor bleeding, or wounds with low to moderate exudation.

Description

Technical Field

[0001] This invention belongs to the technical field of medical dressings and hemostatic bandage materials, specifically relating to a method for preparing gradient calcified alginate hemostatic bandages. Background Technology

[0002] Alginate materials, containing carboxylate groups, can form ion cross-linked structures with calcium ions and are often used in wound dressings, absorbent dressings, and hemostatic bandages. When calcium alginate dressings come into contact with wound exudate or blood, they can undergo ion exchange and form a gel-like structure, thus having a basis for application in absorbing exudate, covering wounds, and assisting in hemostasis.

[0003] In the prior art, there are technical solutions for preparing calcium alginate sponge medical dressings by freeze-drying sodium alginate solution, cross-linking with calcium ions, and treatment with softeners; there are also technical solutions for combining carboxymethyl chitosan, cellulose materials, and calcium alginate to form hemostatic sponges; and there are also technologies that disclose sodium alginate / chitosan quaternary ammonium salt systems, which prepare double cross-linked medical dressings with gradient pore structures by adding calcium carbonate of different particle sizes, freeze-drying, and ethanol-acid treatment.

[0004] The aforementioned technical solutions provide multiple pathways for the development of alginate medical dressings, but further improvements are still possible. For example, integral calcification or integral immersion crosslinking tends to result in a uniform degree of crosslinking along the thickness of the strip material, making it difficult to simultaneously ensure calcium ion supply to the wound contact side and soft bandaging performance on the dorsal side; the scheme utilizing the precipitation of calcium carbonate of different particle sizes followed by acid treatment to form gradient pores is highly dependent on the conditions of carbonate dispersion, precipitation, and acid treatment; and composite systems containing chitosan quaternary ammonium salts may be limited by existing publicly available solutions in terms of formulation design. Therefore, it is necessary to develop a gradient calcification alginate hemostatic bandage preparation method that differs from the calcium carbonate precipitation and acidic pore-forming routes. Summary of the Invention

[0005] The purpose of this invention is to provide a method for preparing a gradient calcified alginate hemostatic bandage, which allows the wound-contact side and the wound-averse side of the alginate composite strip matrix to undergo different calcification and post-treatment conditions, thereby facilitating the formation of differences in the degree of calcification in the thickness direction, while taking into account the calcium supply, fluid absorption and coverage on the wound-contact side, and the conformability of the strip material for bandaging.

[0006] To achieve the above objectives, the present invention adopts the following technical solution: This invention provides a method for preparing a gradient calcified alginate hemostatic bandage, comprising the following steps: S1. Preparation of composite film-forming slurry: Based on 100% total non-volatile solids, 52-58% sodium alginate, 16-22% carboxymethyl chitosan, 8-14% cellulose derivative, 5-9% softener, 1-4% polyvinyl alcohol, and 10000-4% polyethylene glycol are dispersed in water to obtain a composite film-forming slurry with a solids content of 3.0-5.0 wt%; wherein the softener is one or more of glycerol, sorbitol, or polyethylene glycol 400. S2. Molding and Freeze-drying: The composite film-forming slurry is coated or impregnated onto a medical strip substrate, controlling the wet coating thickness to be 0.5-1.8 mm, and the coating amount based on non-volatile solids to be 20-60 g / m². 2 A wet strip-shaped matrix is ​​obtained; the wet strip-shaped matrix is ​​pre-frozen at -30℃ to -60℃ for 1-3 hours, and then freeze-dried at -40℃ to -60℃ and 5-30Pa for 18-36 hours to obtain a porous strip-shaped matrix; S3. Preparation of calcium supplementation dispersion: Disperse calcium lactate or calcium gluconate in water to obtain a calcium supplementation dispersion containing 0.4-1.0 wt% calcium lactate or calcium gluconate and 0.05-0.20 wt% sodium carboxymethyl cellulose. S4. Single-sided confined rapid calcification: A liquid-resistant support layer is provided on the side of the porous strip matrix away from the wound contact side, allowing the wound contact side of the porous strip matrix to contact the single-sided calcification solution; the single-sided calcification solution consists of 1.2-2.5 wt% calcium chloride, 35-45 vol% ethanol, and the balance water, with a pH of 6.0-7.0, a contact temperature of 18-30℃, a contact time of 15-60 s, and an application rate of 0.10-0.22 mL / cm². 2 ; S5. Second-stage calcium supplementation: Apply the calcium dispersion solution from the same side that was in contact with the single-sided calcification solution, at a rate of 0.05-0.15 mL / cm². 2 The duration of action is 90-240 seconds; S6, Dorsal softening and drying: Apply a softening solution from the side away from the wound contact surface. The softening solution contains one or more of glycerin, sorbitol, or polyethylene glycol 400, with a softening agent mass fraction of 2-5 wt%, and an application rate of 0.03-0.12 mL / cm². 2 The action time is 30-180s; then it is dried at 25-40℃ for 1-6h, cut and rolled to obtain gradient calcified alginate hemostatic bandage; The preparation method does not include the step of adding calcium carbonate of different particle sizes to the composite film-forming slurry to form a sedimentation gradient, nor does it include the step of dissolving carbonates in an ethanol-acid mixture with a pH less than 4.0 to form pores.

[0007] Furthermore, in step S1, the sodium alginate has a weight-average molecular weight of 100,000-300,000, the carboxymethyl chitosan has a degree of deacetylation of 75-90%, and a degree of carboxymethyl substitution of 0.4-0.9.

[0008] Furthermore, in step S1, the cellulose derivative is a combination of sodium carboxymethyl cellulose and nanocellulose, with a mass ratio of (2-5):1; the nanocellulose has an average diameter of 30-120 nm and an average length of 0.5-3.0 μm.

[0009] Further, in step S1, sodium alginate is first stirred at 30-45℃ and 400-700rpm for 1.5-3h to form a sodium alginate solution, then carboxymethyl chitosan aqueous solution is added and stirred for 20-40min, then cellulose derivative dispersion is added and sheared and dispersed at 3000-8000rpm for 5-15min, and finally softener and polyvinyl alcohol are added and degassed for 10-25min.

[0010] Furthermore, in step S2, the medical strip substrate is medical degreased cotton gauze, viscose fiber nonwoven fabric, or polyester / viscose composite nonwoven fabric; the medical strip substrate is washed with water, dried at 40-70℃, and treated with ultraviolet light for 5-30 minutes before coating or impregnation.

[0011] Furthermore, in step S4, the liquid-blocking support layer is a peelable liquid-blocking support layer temporarily attached to the porous strip substrate on the side away from the wound contact surface. The liquid-blocking support layer is selected from polyethylene film, polypropylene film, polytetrafluoroethylene film, or silicone release paper. The thickness of the liquid-blocking support layer is 20-150 μm, and the side in contact with the porous strip substrate is a low surface energy peeling surface. During the single-sided confined rapid calcification process, the mass of liquid seeping from the side away from the wound contact surface does not exceed 5% of the mass of the single-sided calcification liquid applied. After the single-sided confined rapid calcification is completed, the liquid-blocking support layer is peeled off from the porous strip substrate on the side away from the wound contact surface.

[0012] The liquid-blocking support layer is a peelable liquid-barrier support layer temporarily attached to the porous strip matrix away from the wound contact side during the single-sided confined rapid calcification step. This liquid-blocking support layer does not serve as the wound contact material in the final hemostatic bandage, nor does it participate in the calcium cross-linking reaction of the alginate composite porous layer. Its function is to block and support the side away from the wound contact side when the single-sided calcification fluid enters the composite porous layer from the wound contact side, ensuring that the calcification fluid mainly remains on the wound contact side and its adjacent area, and forming a structure in the thickness direction where the degree of calcification on the wound contact side is higher than that on the side away from the wound contact side. After the single-sided confined rapid calcification is completed, the liquid-blocking support layer is peeled off from the side away from the wound contact side, followed by sterile water spraying, dorsal softening, and drying treatment.

[0013] Furthermore, after step S5 and before step S6, the strip-shaped substrate is sprayed with sterile water from the contact side of the wound 1-3 times, with each spray volume being 0.02-0.08 mL / cm², and left to stand at 20-30℃ for 3-10 minutes.

[0014] Furthermore, the resulting gradient calcified alginate hemostatic bandage has a thickness of 0.8-3.0 mm, a width of 2-10 cm, and a winding radius of 3-20 mm.

[0015] Furthermore, step S6 includes sterilization and packaging, with sterilization methods including ethylene oxide sterilization or irradiation sterilization.

[0016] Furthermore, the resulting gradient calcified alginate hemostatic bandage is used to prepare auxiliary hemostatic dressings for superficial wounds, postoperative wounds with minor bleeding, or wounds with low to medium exudation.

[0017] In summary, due to the adoption of the above technical solution, the beneficial effects of the present invention are: 1. This invention uses sodium alginate, carboxymethyl chitosan and cellulose derivatives to construct a composite film-forming system. Sodium alginate provides calcium ion crosslinking sites; carboxymethyl chitosan contains amino, carboxyl and hydroxyl groups, which participate in ionic interactions or hydrogen bonding; cellulose derivatives, as hydrophilic skeleton components, are beneficial for the formation of strip-shaped composite layers and the retention of structure after liquid absorption.

[0018] 2. The present invention adopts a single-sided confined rapid calcification method, which introduces calcium chloride alcohol water calcification solution from the wound contact side and restricts the penetration of calcification solution through the back liquid-blocking support layer, which is conducive to forming different calcification conditions on the wound contact side and the side away from the wound.

[0019] 3. After rapid calcification in a confined area, the present invention applies calcium lactate or calcium gluconate calcium supplementation dispersion from the same side, which helps to prolong the calcium source action process on the wound contact side and reduces the risk of local over-hardening caused by one-time high-concentration calcification; by softening the material from the side away from the wound contact side, it helps to improve the wrapping and conformity of the strip material. Attached Figure Description

[0020] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0021] Figure 1 This is a flowchart illustrating the preparation process of the gradient calcified alginate hemostatic bandage of the present invention.

[0022] Figure 2This is a schematic diagram of the layered structure after the composite slurry is coated or impregnated onto a medical strip substrate in this invention.

[0023] Figure 3 This is a schematic diagram of the two-stage calcium supplementation process in this invention.

[0024] Figure 4 This is a schematic diagram illustrating the synergistic effect of sodium alginate, carboxymethyl chitosan, cellulose derivatives, and calcium ions in this invention.

[0025] Figure 5 This is a schematic diagram of the cross-sectional sampling areas of the wound contact side, the intermediate layer, and the side away from the wound in this invention. Detailed Implementation

[0026] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0027] The sodium alginate used in this invention is selected as medical or pharmaceutical grade sodium alginate with a weight-average molecular weight of 100,000-300,000. Its 1wt% aqueous solution has a viscosity of 50-500 mPa·s at 25°C, and a G-unit molar percentage content of 35-70%. The polyvinyl alcohol has a degree of alcoholysis of 87-99% and a viscosity-average degree of polymerization of 500-1800. The carboxymethyl chitosan is selected with a degree of deacetylation of 75-90% and a degree of carboxymethyl substitution of 0.4-0.9. The cellulose derivative is carboxymethyl... The combination of sodium cellulose and nanocellulose, wherein the average diameter of the nanocellulose is 30-120 nm and the average length is 0.5-3.0 μm; the softener is one or more of glycerol, sorbitol or polyethylene glycol 400; the medical strip substrate is medical degreased cotton gauze, viscose fiber nonwoven fabric or polyester / viscose composite nonwoven fabric; the single-sided calcification solution is composed of calcium chloride, ethanol and water; the calcium supplementation dispersion contains calcium lactate or calcium gluconate and sodium carboxymethyl cellulose is added as a dispersion stabilizing component.

[0028] Figure 2This diagram illustrates a layered structure formed after a composite slurry is coated or impregnated onto a medical strip substrate. The composite porous layer has a pre-defined wound contact side, an intermediate transition region, and a side away from the wound contact side in the thickness direction, providing a structural basis for subsequent directional treatments. The composite porous layer on the wound contact side corresponds to the subsequent single-sided confined rapid calcification and two-stage calcium supplementation treatment side. This side forms a calcification-rich region during subsequent treatments, which facilitates the formation of ionic crosslinks between alginate carboxylate groups and calcium ions, and provides an exchangeable calcium source upon contact with blood or wound exudate. The intermediate composite porous layer serves as a transition region; its function is not simply to increase thickness, but rather to connect the calcification-rich region on the wound contact side with… Connecting pores and gradient transitions are formed between the softened areas on the dorsal side. This structure helps reduce the risk of cracking, delamination, or localized hardening and brittleness caused by abrupt changes in the degree of cross-linking between the highly calcified layer and the less calcified soft layer, while retaining the fluid absorption channels. The composite porous layer on the side opposite to the wound contact corresponds to the side that is subsequently softened on the dorsal side. This side is not used as the main calcium supply surface, but is treated with softening liquids such as glycerin, sorbitol, or polyethylene glycol 400 to improve the flexibility of the strip material when it is rolled, bent, and bandaged. This directional design makes the wound side biased towards calcification and calcium supply, and the dorsal side biased towards softness and fit, thus distinguishing it from the uniform cross-linking in the thickness direction caused by overall immersion calcification.

[0029] The medical strip substrate, made of gauze or nonwoven fabric, is essential for providing dimensional stability and mechanical support for the composite porous layer. Sodium alginate, carboxymethyl chitosan, and cellulose derivatives in the composite slurry can form a hydrophilic composite network; both the carboxymethyl chitosan / sodium alginate hydrogel system and the nanocellulose-reinforced alginate composite system can be used to construct composite networks or reinforcing structures related to wound dressings. Therefore, loading the composite slurry onto the medical strip substrate is beneficial for balancing absorbent coverage, wet structure maintenance, and bandage-like application.

[0030] Figure 3 This describes a two-stage calcium supplementation process. The first stage corresponds to rapid, confined calcification on one side, while the second stage corresponds to mild, ipsilateral calcium supplementation. The necessity of this two-stage calcium supplementation lies in the fact that rapid, confined calcification on one side has a shorter time and is mainly used to quickly fix the structures on the wound contact side. If this step is relied upon alone, the exchangeable calcium source on the wound side may be insufficient, or the surface cross-linking may be concentrated while the internal continuity is limited. By applying calcium lactate or calcium gluconate dispersion to the same side, a mild calcium source can continue to be provided on the basis of the already formed calcified layer on the wound side, so that the wound contact side and adjacent areas can receive continuous calcium supplementation.

[0031] Using calcium lactate or calcium gluconate as calcium supplement salts, compared to continuing to use higher concentrations of calcium chloride, helps reduce the risk of excessively high local instantaneous calcium ion concentrations causing surface hardening, pore blockage, or decreased liquid absorption. Adding a small amount of sodium carboxymethyl cellulose to the calcium supplement dispersion helps improve the spreading and retention of the calcium supplement solution on the porous composite layer surface, making the calcium supplementation process more suitable for continuous processing of strip materials.

[0032] Figure 4 Sodium alginate, carboxymethyl chitosan, cellulose derivatives and Ca are shown. 2+ The components work synergistically; the sodium alginate chain mainly provides carboxylate groups, which can react with Ca... 2+ The process involves the formation of ionic crosslinking points. Carboxymethyl chitosan contains amino, carboxyl, and hydroxyl groups, which can form charge interactions, hydrogen bonds, or ionic coordination interactions with alginate, cellulose derivatives, and calcium ions. Cellulose derivatives contain a large number of hydroxyl groups, which can serve as a hydrophilic framework and participate in the hydrogen bond network. The necessity of this multi-component composite network lies in the fact that a single alginate freeze-dried layer may soften, swell, or become structurally loose after liquid absorption; relying solely on calcium crosslinking may result in a material that is too hard. The introduction of carboxymethyl chitosan helps to improve the multi-point interaction of the composite layer, while the introduction of cellulose derivatives helps to provide skeletal support and shape retention after liquid absorption. Polyvinyl alcohol and softeners are used to improve film formation, flexibility, and processing properties.

[0033] Example 1: See Figures 1-2 As shown, the preparation method of the gradient calcified alginate hemostatic bandage in this embodiment includes the following steps: weighing 2.24g of sodium alginate, 0.80g of carboxymethyl chitosan, 0.36g of sodium carboxymethyl cellulose, 0.12g of nanocellulose, 0.32g of glycerol, 0.12g of polyvinyl alcohol, and 0.04g of polyethylene glycol 1000, with a total of 4.00g of non-volatile solids; wherein, based on the total mass of non-volatile solids as 100%, sodium alginate accounts for 56%, carboxymethyl chitosan for 20%, cellulose derivative for 12%, glycerol for 8%, polyvinyl alcohol for 3%, and polyethylene glycol 1000 for 1%, and adding deionized water to a total mass of 100g to obtain a composite film-forming slurry with a solid content of 4.0wt%.

[0034] To prepare the composite film-forming slurry, sodium alginate was first added to a portion of deionized water and stirred at 40°C and 600 rpm for 2 hours to form a sodium alginate solution. Carboxymethyl chitosan was then added to a portion of deionized water and stirred at 30°C for 1 hour to form a carboxymethyl chitosan aqueous solution. Sodium carboxymethyl cellulose and nanocellulose were added to a portion of deionized water and sheared and dispersed at 6000 rpm for 10 minutes to obtain a cellulose derivative dispersion. The carboxymethyl chitosan aqueous solution was added to the sodium alginate solution and stirred for 30 minutes. Then, the cellulose derivative dispersion was added and stirred for 20 minutes. Finally, glycerol, polyvinyl alcohol, and polyethylene glycol 1000 were added, and the mixture was stirred and degassed for 15 minutes to obtain the composite film-forming slurry.

[0035] Medical degreased cotton gauze was washed with deionized water, dried at 60℃ for 30 minutes, and then treated with ultraviolet light for 15 minutes. A composite film-forming slurry was then coated onto the pretreated medical degreased cotton gauze, with a wet coating thickness of 1.2 mm and a coating amount of 40 g / m² based on non-volatile solids. 2 A wet strip matrix was obtained; the wet strip matrix was pre-frozen at -45℃ for 2 hours, and then freeze-dried at -50℃ and 12Pa for 24 hours to obtain a porous strip matrix.

[0036] A single-sided calcification solution was prepared, consisting of 1.8 wt% calcium chloride, 40 vol% ethanol, and water, with a pH of 6.5. A 50 μm thick polyethylene film was placed on the side of the porous strip substrate away from the wound as a liquid-resistant support layer. The area of ​​the polyethylene film extended approximately 2 mm beyond the porous strip substrate on both sides in the width direction, and the side in contact with the porous strip substrate was a flat, hydrophobic surface. During bonding, a flat glass plate was used to apply a pressure of approximately 2.0 kPa to temporarily bond the polyethylene film to the porous strip substrate on the side away from the wound. Subsequently, the single-sided calcification solution was applied from the wound contact side using a roller coating method. After single-sided confined rapid calcification, the polyethylene film was peeled off, and the second-stage calcium supplementation and subsequent treatment steps were performed. The contact temperature was 25°C, the contact time was 30 s, and the application rate of the single-sided calcification solution was 0.16 mL / cm². 2 .

[0037] A calcium-supplementing dispersion was prepared, comprising 0.7 wt% calcium lactate, 0.10 wt% sodium carboxymethyl cellulose, and water. The dispersion was sprayed from the same side that was in contact with the single-sided calcification solution, at a rate of 0.10 mL / cm². 2 The application time is 180 seconds; then, sterile water is sprayed twice from the contact side of the wound, with each spray volume being 0.05 mL / cm². 2 And let it stand at 25℃ for 5 minutes.

[0038] Prepare a dorsal softening solution comprising 3.0 wt% glycerol and water; apply the dorsal softening solution from the side away from the wound contact surface at a rate of 0.08 mL / cm². 2 The action time is 90s; then it is dried at 35℃ for 3h, cut into strips with a width of 6cm, and wound with a winding radius of 8mm to obtain a gradient calcified alginate hemostatic bandage.

[0039] Example 2: See Figures 1-2As shown, the preparation method of the gradient calcified alginate hemostatic bandage in this embodiment includes the following steps: weighing 2.08g of sodium alginate, 0.88g of carboxymethyl chitosan, 0.42g of sodium carboxymethyl cellulose, 0.14g of nanocellulose, 0.32g of sorbitol, and 0.16g of polyvinyl alcohol, with a total of 4.00g of non-volatile solids; wherein, based on the total mass of non-volatile solids as 100%, sodium alginate accounts for 52%, carboxymethyl chitosan for 22%, cellulose derivative for 14%, sorbitol for 8%, and polyvinyl alcohol for 4%, and adding deionized water to a total mass of 100g to obtain a composite film-forming slurry with a solid content of 4.0wt%.

[0040] To prepare the composite film-forming slurry, sodium alginate was first added to a portion of deionized water and stirred at 35°C and 500 rpm for 2.5 h to form a sodium alginate solution. Carboxymethyl chitosan was added to a portion of deionized water and stirred at 30°C for 1 h to form a carboxymethyl chitosan aqueous solution. Sodium carboxymethyl cellulose and nanocellulose were added to a portion of deionized water and sheared and dispersed at 5000 rpm for 12 min to obtain a cellulose derivative dispersion. The carboxymethyl chitosan aqueous solution was added to the sodium alginate solution and stirred for 30 min. Then, the cellulose derivative dispersion was added and stirred for 25 min. Finally, sorbitol and polyvinyl alcohol were added, and stirring and degassing were continued for 20 min to obtain the composite film-forming slurry.

[0041] The viscose fiber nonwoven fabric was washed with deionized water, dried at 55℃ for 40 min, and then treated with ultraviolet light for 20 min. The composite film-forming slurry was then impregnated into the pretreated viscose fiber nonwoven fabric, with the wet coating thickness controlled at 1.0 mm and the coating amount based on non-volatile solids at 32 g / m². 2 A wet strip matrix was obtained; the wet strip matrix was pre-frozen at -40℃ for 2.5h, and then freeze-dried at -50℃ and 15Pa for 26h to obtain a porous strip matrix.

[0042] A single-sided calcification solution was prepared, consisting of 1.5 wt% calcium chloride, 38 vol% ethanol, and water, with a pH of 6.4. A 60 μm thick polypropylene membrane was placed on the side of the porous strip substrate away from the wound as a liquid-resistant support layer. The area of ​​the polypropylene membrane extended approximately 2 mm beyond the porous strip substrate on both sides in the width direction, and the side in contact with the porous strip substrate was a flat, hydrophobic surface. During bonding, a silicone roller was used to apply a pressure of approximately 2.0 kPa to temporarily bond the polypropylene membrane to the porous strip substrate on the side away from the wound. After single-sided confined rapid calcification, the polypropylene membrane was peeled off, and the second-stage calcium supplementation and subsequent treatment steps were performed. The single-sided calcification solution was applied from the wound contact side by spraying at a contact temperature of 24°C for 45 seconds, with an application rate of 0.14 mL / cm². 2 .

[0043] A calcium supplementation dispersion was prepared, comprising 0.8 wt% calcium gluconate, 0.12 wt% sodium carboxymethyl cellulose, and water. The dispersion was sprayed from the same side that was in contact with the single-sided calcification solution, at a rate of 0.09 mL / cm². 2 The application time was 210 seconds; subsequently, sterile water was sprayed twice from the contact side of the wound, with each spray volume being 0.04 mL / cm². 2 And let it stand at 25℃ for 6 minutes.

[0044] Prepare a dorsal softening solution comprising 3.5 wt% sorbitol and water; apply the dorsal softening solution from the side away from the wound contact surface at a rate of 0.07 mL / cm². 2 The action time is 120s; then it is dried at 35℃ for 4h, cut into strips with a width of 5cm, and wound with a winding radius of 10mm to obtain a gradient calcified alginate hemostatic bandage.

[0045] Example 3: See Figures 1-2 As shown, the preparation method of the gradient calcified alginate hemostatic bandage in this embodiment includes the following steps: weighing 2.32g of sodium alginate, 0.64g of carboxymethyl chitosan, 0.42g of sodium carboxymethyl cellulose, 0.14g of nanocellulose, 0.28g of glycerol, 0.12g of polyvinyl alcohol, and 0.08g of polyethylene glycol 1000, with a total of 4.00g of non-volatile solids; wherein, based on the total mass of non-volatile solids as 100%, sodium alginate accounts for 58%, carboxymethyl chitosan for 16%, cellulose derivative for 14%, glycerol for 7%, polyvinyl alcohol for 3%, and polyethylene glycol 1000 for 2%, and adding deionized water to a total mass of 100g, to obtain a composite film-forming slurry with a solid content of 4.0wt%.

[0046] To prepare the composite film-forming slurry, sodium alginate was first added to a portion of deionized water and stirred at 45°C and 650 rpm for 1.8 h to form a sodium alginate solution. Carboxymethyl chitosan was added to a portion of deionized water and stirred at 35°C for 1 h to form a carboxymethyl chitosan aqueous solution. Sodium carboxymethyl cellulose and nanocellulose were added to a portion of deionized water and sheared and dispersed at 7000 rpm for 8 min to obtain a cellulose derivative dispersion. The carboxymethyl chitosan aqueous solution was added to the sodium alginate solution and stirred for 25 min. Then, the cellulose derivative dispersion was added and stirred for 20 min. Finally, glycerol, polyvinyl alcohol, and polyethylene glycol 1000 were added, and the mixture was stirred and degassed for 15 min to obtain the composite film-forming slurry.

[0047] The polyester / viscose composite nonwoven fabric was washed with deionized water, dried at 60°C for 35 min, and then treated with ultraviolet light for 10 min. The composite film-forming slurry was then coated onto the pretreated polyester / viscose composite nonwoven fabric, with a wet coating thickness of 1.5 mm and a coating amount of 52 g / m² based on non-volatile solids. 2 A wet strip matrix was obtained; the wet strip matrix was pre-frozen at -50℃ for 2 hours, and then freeze-dried at -52℃ and 10Pa for 28 hours to obtain a porous strip matrix.

[0048] A single-sided calcification solution was prepared, consisting of 2.2 wt% calcium chloride, 42 vol% ethanol, and water, with a pH of 6.6. A 60 μm thick silicone release paper was placed on the side of the porous strip substrate away from the wound contact surface as a liquid-blocking support layer. The area of ​​the silicone release paper extended approximately 2 mm beyond the porous strip substrate on both sides in the width direction, with the release surface facing the porous strip substrate. During bonding, a flat glass plate was used to apply a pressure of approximately 2.0 kPa to temporarily bond the silicone release paper to the porous strip substrate on the side away from the wound contact surface. After single-sided confined rapid calcification, the polypropylene membrane was peeled off, and then the second-stage calcium supplementation and subsequent treatment steps were performed. The single-sided calcification solution was applied from the wound contact surface using a roller coating method, with a contact temperature of 25°C, a contact time of 25 s, and an application rate of 0.18 mL / cm². 2 .

[0049] A calcium-supplementing dispersion was prepared, comprising 1.0 wt% calcium lactate, 0.15 wt% sodium carboxymethyl cellulose, and water. The dispersion was sprayed from the same side that was in contact with the single-sided calcification solution, at a rate of 0.12 mL / cm². 2 The application time is 150 seconds. Then, sterile water is sprayed three times from the contact side of the wound, with each spray volume being 0.03 mL / cm². 2 And let it stand at 25℃ for 5 minutes.

[0050] Prepare a dorsal softening solution comprising 4.0 wt% polyethylene glycol 400 and water; apply the dorsal softening solution from the side away from the wound contact surface at a rate of 0.10 mL / cm². 2 The action time is 100s; then it is dried at 38℃ for 3h, cut into strips with a width of 8cm, and wound with a winding radius of 12mm to obtain a gradient calcified alginate hemostatic bandage.

[0051] Example 4: See Figures 1-2As shown, the preparation method of the gradient calcified alginate hemostatic bandage in this embodiment includes the following steps: Weigh 2.16g of sodium alginate, 0.84g of carboxymethyl chitosan, 0.39g of sodium carboxymethyl cellulose, 0.13g of nanocellulose, 0.20g of glycerol, 0.16g of sorbitol, 0.08g of polyvinyl alcohol, and 0.04g of polyethylene glycol 1000, with a total of 4.00g of non-volatile solids; wherein, based on the total mass of non-volatile solids as 100%, sodium alginate accounts for 54%, carboxymethyl chitosan for 21%, cellulose derivative for 13%, softener for 9%, polyvinyl alcohol for 2%, and polyethylene glycol 1000 for 1%, and add deionized water to a total mass of 100g to obtain a composite film-forming slurry with a solid content of 4.0wt%.

[0052] To prepare the composite film-forming slurry, sodium alginate was first added to a portion of deionized water and stirred at 38°C and 600 rpm for 2.2 h to form a sodium alginate solution. Carboxymethyl chitosan was then added to a portion of deionized water and stirred at 30°C for 1.2 h to form a carboxymethyl chitosan aqueous solution. Sodium carboxymethyl cellulose and nanocellulose were added to a portion of deionized water and sheared and dispersed at 6000 rpm for 10 min to obtain a cellulose derivative dispersion. The carboxymethyl chitosan aqueous solution was added to the sodium alginate solution and stirred for 35 min, followed by the addition of the cellulose derivative dispersion and stirring for 20 min. Finally, glycerol, sorbitol, polyvinyl alcohol, and polyethylene glycol 1000 were added, and stirring and degassing were continued for 20 min to obtain the composite film-forming slurry.

[0053] Medical degreased cotton gauze was washed with deionized water, dried at 50℃ for 45 minutes, and then treated with ultraviolet light for 20 minutes. The composite film-forming slurry was then impregnated into the pretreated medical degreased cotton gauze, with the wet coating thickness controlled at 0.8 mm and the coating amount based on non-volatile solids at 28 g / m². 2 A wet strip matrix was obtained; the wet strip matrix was pre-frozen at -45℃ for 1.5h, and then freeze-dried at -48℃ and 18Pa for 22h to obtain a porous strip matrix.

[0054] A single-sided calcification solution was prepared, consisting of 1.3 wt% calcium chloride, 35 vol% ethanol, and water, with a pH of 6.2. An 80 μm thick polypropylene membrane was placed on the side of a porous strip substrate away from the wound surface as a liquid-resistant support layer. The area of ​​the polypropylene membrane extended approximately 2 mm beyond the porous strip substrate on both sides in the width direction, with the side in contact with the substrate being a flat, hydrophobic surface. During bonding, a pressure of approximately 2.0 kPa was applied using a flat glass plate or silicone roller to temporarily bond the polypropylene membrane to the side of the porous strip substrate away from the wound surface. Subsequently, the single-sided calcification solution was applied from the wound surface using a roller coating method. After rapid, confined calcification on one side, the polypropylene membrane was peeled off, and the second-stage calcium supplementation and subsequent treatment steps were initiated. Finally, the single-sided calcification solution was applied from the wound surface using a spray coating method at a contact temperature of 22°C, a contact time of 60 seconds, and an application rate of 0.12 mL / cm². 2 .

[0055] A calcium supplementation dispersion was prepared, comprising 0.5 wt% calcium gluconate, 0.08 wt% sodium carboxymethyl cellulose, and water. The dispersion was sprayed from the same side that was in contact with the single-sided calcification solution, at a rate of 0.07 mL / cm². 2 The application time is 240 seconds; subsequently, sterile water is sprayed once from the contact side of the wound at a rate of 0.06 mL / cm². 2 And let it stand at 25℃ for 8 minutes.

[0056] Prepare a dorsal softening solution comprising 2.0 wt% glycerol, 1.0 wt% sorbitol, and water; apply the dorsal softening solution from the side away from the wound contact surface at a rate of 0.06 mL / cm². 2 The action time is 150s; then it is dried at 32℃ for 5h, cut into strips with a width of 4cm, and wound with a winding radius of 6mm to obtain a gradient calcified alginate hemostatic bandage.

[0057] Example 5: See Figures 1-2 As shown, the preparation method of the gradient calcified alginate hemostatic bandage in this embodiment includes the following steps: Weigh 2.28g of sodium alginate, 0.72g of carboxymethyl chitosan, 0.33g of sodium carboxymethyl cellulose, 0.11g of nanocellulose, 0.24g of polyethylene glycol 400, 0.16g of polyvinyl alcohol, and 0.16g of polyethylene glycol 1000, with a total of 4.00g of non-volatile solids; wherein, based on the total mass of non-volatile solids as 100%, sodium alginate accounts for 57%, carboxymethyl chitosan for 18%, cellulose derivative for 11%, softener for 6%, polyvinyl alcohol for 4%, and polyethylene glycol 1000 for 4%, and add deionized water to a total mass of 100g to obtain a composite film-forming slurry with a solid content of 4.0wt%.

[0058] To prepare the composite film-forming slurry, sodium alginate was first added to a portion of deionized water and stirred at 42°C and 700 rpm for 1.5 h to form a sodium alginate solution. Carboxymethyl chitosan was then added to a portion of deionized water and stirred at 35°C for 1 h to form a carboxymethyl chitosan aqueous solution. Sodium carboxymethyl cellulose and nanocellulose were added to a portion of deionized water and sheared and dispersed at 8000 rpm for 6 min to obtain a cellulose derivative dispersion. The carboxymethyl chitosan aqueous solution was added to the sodium alginate solution and stirred for 20 min, followed by the addition of the cellulose derivative dispersion and stirring for another 20 min. Finally, polyethylene glycol 400, polyvinyl alcohol, and polyethylene glycol 1000 were added, and the mixture was stirred and degassed for 12 min to obtain the composite film-forming slurry.

[0059] Viscose fiber nonwoven fabric was washed with deionized water, dried at 65°C for 25 min, and then treated with ultraviolet light for 15 min. A composite film-forming slurry was then coated onto the pretreated viscose fiber nonwoven fabric, with a wet coating thickness of 1.6 mm and a coating weight of 58 g / m² based on non-volatile solids. 2 A wet strip matrix was obtained; the wet strip matrix was pre-frozen at -55℃ for 2.5h, and then freeze-dried at -55℃ and 8Pa for 30h to obtain a porous strip matrix.

[0060] A single-sided calcification solution was prepared, consisting of 2.4 wt% calcium chloride, 45 vol% ethanol, and water, with a pH of 6.8. A 100 μm thick polytetrafluoroethylene (PTFE) membrane was placed on the side of the porous strip substrate away from the wound surface as a liquid-resistant support layer. The PTFE membrane extended approximately 2 mm beyond the porous strip substrate on both sides in the width direction, with the side in contact with the porous strip substrate being a flat, hydrophobic surface. During bonding, a silicone roller was used to apply a pressure of approximately 2.0 kPa to temporarily bond the PTFE membrane to the porous strip substrate on the side away from the wound surface. After single-sided confined rapid calcification, the polypropylene membrane was peeled off, and the second-stage calcium supplementation and subsequent treatment steps were initiated. The single-sided calcification solution was applied from the wound surface using a roller coating method at a contact temperature of 26°C, a contact time of 20 seconds, and an application rate of 0.20 mL / cm². 2 .

[0061] A calcium-supplementing dispersion was prepared, comprising 0.9 wt% calcium lactate, 0.18 wt% sodium carboxymethyl cellulose, and water. The dispersion was sprayed from the same side that was in contact with the single-sided calcification solution at an application rate of 0.14 mL / cm². 2 The application time is 120 seconds. Then, sterile water is sprayed twice from the contact side of the wound, with each spray volume being 0.06 mL / cm². 2 And let it stand at 25℃ for 4 minutes.

[0062] Prepare a dorsal softening solution comprising 5.0 wt% polyethylene glycol 400 and water; apply the dorsal softening solution from the side away from the wound contact surface at a rate of 0.11 mL / cm². 2 The action time is 60s; then it is dried at 40℃ for 2h, cut into strips with a width of 10cm, and wound with a winding radius of 15mm to obtain a gradient calcified alginate hemostatic bandage.

[0063] Comparative Example 1: Comparative Example 1 is the overall immersion calcification group. The composite film-forming slurry, wet strip matrix and porous strip matrix were prepared according to the method of Example 1. The difference is that: no liquid-blocking support layer was set on the back side of the porous strip matrix, and single-sided confined rapid calcification was not performed. Instead, the porous strip matrix was immersed in an aqueous solution containing 1.8 wt% calcium chloride and acted at 25°C for 180 s. Then, the calcium dispersion was treated, sterile water was sprayed, the back side was softened, dried, cut and wound according to the method of Example 1.

[0064] Comparative Example 2: Comparative Example 2 is the group without two-stage calcium supplementation. The composite film-forming slurry, wet strip matrix, and porous strip matrix were prepared according to the method of Example 1, and single-sided confined rapid calcification was performed. The difference is that after single-sided confined rapid calcification, calcium lactate or calcium gluconate calcium supplementation dispersion was not applied, and sterile water spraying, back-side softening, drying, cutting and winding were performed directly.

[0065] Comparative Example 3: Comparative Example 3 was the group without carboxymethyl chitosan. The sample was prepared according to the method of Example 1, except that carboxymethyl chitosan was not added to the composite film-forming slurry, and sodium alginate was used to make up the corresponding non-volatile solids mass. The rest of the preparation steps were the same as those in Example 1.

[0066] Test example: Unless otherwise specified, the sample performance tests shall be conducted under the fixed test conditions specified in this instruction manual; the test approach for liquid absorbability may be referenced to YY / T 0471.1-2004, but it shall not be used as the basis for current mandatory standards; the biological evaluation of medical devices shall be conducted in accordance with GB / T 16886.1 and related current valid standards; the ethylene oxide sterilization process shall be confirmed and routinely controlled in accordance with the current valid version after the implementation of GB 18279.1-2015.

[0067] Before testing, all samples from the examples and comparative examples were placed in an environment with a temperature of 23°C and a relative humidity of 50% for 24 hours to equilibrate; at least 5 parallel samples were taken from each group of samples, and unless otherwise specified, the results were averaged.

[0068] The calcium distribution along the thickness direction was quantitatively measured using inductively coupled plasma atomic emission spectrometry (ICP-OES). Samples were cut into 20mm x 20mm pieces, frozen and fixed in liquid nitrogen, and then divided along the thickness direction into three regions: the one-third region on the wound contact side, the middle third region, and the one-third region away from the wound contact side. Samples from each layer were weighed, and nitric acid and hydrogen peroxide were added for microwave digestion. The digestion solution was brought to a final volume of 25mL, and the calcium content was detected by ICP-OES at 317.933nm. The ratio of calcium content on the wound side to that on the back side was calculated by dividing the calcium content of the one-third region on the wound contact side by the calcium content of the one-third region away from the wound contact side. This project was used to verify whether single-sided confined rapid calcification and ipsilateral two-segment calcium supplementation could create a difference in the degree of calcification along the thickness direction. Figure 5 The cross-sectional sampling areas of the wound contact side, the intermediate layer, and the side away from the wound contact side are shown; sampling area A is used to evaluate the rapid calcification and calcium supplementation effect on the wound contact side; sampling area B is used to evaluate the transitional calcification layer formed after calcium ions diffuse from the wound side inward; sampling area C is used to evaluate whether the dorsal side avoids excessive calcification and maintains the softness characteristics.

[0069] The back-side exudation rate test was conducted during the single-sided confinement rapid calcification step. First, the mass of the liquid-blocking support layer and the back-side absorbent paper was weighed and recorded as m0. After the single-sided calcification was completed, the back-side absorbent paper was immediately removed and weighed, and recorded as m1. The mass of the single-sided calcification solution applied was recorded as m2. The back-side exudation rate was calculated as (m1-m0) / m2×100%. This project was used to verify the confinement effect of the liquid-blocking support layer.

[0070] The liquid absorption performance test follows the liquid absorption evaluation approach of YY / T 0471.1-2004, and the following test conditions are fixed in this embodiment: the sample is cut into 50mm×50mm pieces and weighed dry weight m0; the test solution is simulated wound exudate containing 8.30g / L NaCl and 0.25g / L CaCl2, with a pH of 7.0; the sample is completely immersed in the 37℃ test solution for 30min, and after removal, it is vertically suspended for 30s without squeezing to drain the liquid, and the mass after liquid absorption m1 is weighed; the liquid absorption volume is calculated as (m1-m0) / m0; this project is used to verify the hydrophilic liquid absorption effect of freeze-dried porous structures, alginate, carboxymethyl chitosan and cellulose derivatives.

[0071] The liquid retention rate test was conducted immediately after the liquid absorption test. The sample after liquid absorption was placed between two layers of dust-free absorbent paper and subjected to a pressure of 3.0 kPa for 5 minutes. The mass m2 after the pressure test was measured. The liquid retention rate was calculated as (m2-m0) / (m1-m0)×100%. This test was used to evaluate the liquid retention capacity and gel layer structure retention capacity after liquid absorption.

[0072] Wet tensile strength testing was performed using a universal testing machine. Samples were cut into 10mm × 80mm strips, immersed in simulated wound exudate at 37℃ for 5 minutes, and then removed by gently touching the surface to filter paper to remove free liquid. The clamping distance was 50mm, the tensile speed was 50mm / min, and the maximum tensile load F was recorded. Wet tensile strength was calculated as F / strip width, in N / cm. This project was used to verify the contributions of carboxymethyl chitosan, cellulose derivatives, and calcium crosslinking networks to wet structure retention.

[0073] The winding integrity test adopted the fixed radius round bar method; the sample was cut into 50mm×100mm pieces, and after being equilibrated in an environment of 23℃ and 50% relative humidity, it was wound 3 times along the length direction around a stainless steel round bar with a radius of 8mm. After holding for 1 minute, it was unwound, and the presence of continuous cracks, fractures, interlayer peeling and composite layer detachment was observed; this project was used to verify the back side softening treatment and the conformability of the strip material wrapping.

[0074] The calcium release test was performed using a 37°C phosphate buffer extraction method. The sample was cut into 20mm × 20mm pieces and placed in 10mL of phosphate buffer solution with a pH of 7.4. The sample was then allowed to stand at 37°C. After 10 minutes of extraction, the sample was taken and the calcium content in the extract was tested using ICP-OES. The results were converted into the calcium release per unit area per 10 minutes. This test was used to evaluate the level of available calcium sources on the contact side of the wound.

[0075] The in vitro whole blood coagulation index was tested using the recalcified anticoagulated sheep whole blood method. A 10mm × 10mm sample was placed in a 24-well plate and preheated at 37℃ for 5 min. 200 μL of sodium citrate anticoagulated sheep whole blood and 20 μL of 0.2 mol / L CaCl2 solution were added to the sample surface, and the reaction was carried out at 37℃ for 5 min. Then, 20 mL of deionized water was added, and the mixture was allowed to stand for 5 min to allow uncoagulated red blood cells to hemolyze. The supernatant was collected, and the absorbance (A) was measured at 540 nm. 样品 The blank group consisted of blood without samples, containing only the same volume of recalcified blood, and treated in the same way; the absorbance A was measured. 空白 Whole blood coagulation index (BCI) is calculated according to A... 样品 / A 空白 The value is calculated as ×100%, and the lower the value, the stronger the procoagulant tendency of the sample surface under the test conditions.

[0076] The in vitro coagulation time test used the calcium-reinforced sheep whole blood tilt observation method. A 10 mm × 10 mm sample was placed at the bottom of a glass tube and preheated at 37 °C for 5 min. 500 μL of sodium citrate anticoagulated sheep whole blood and 50 μL of 0.2 mol / L CaCl2 solution were added to the sample surface, and timing was started immediately. The glass tube was tilted 45° every 15 s to observe whether the blood flowed. When no visible flow was observed for 5 consecutive s, the coagulation time was recorded. This test was used to evaluate the procoagulant response trend of the sample under fixed in vitro conditions.

[0077] The specific performance test data are shown in the table below:

[0078] Analysis of experimental results: The wound side / dorsal calcium content ratios in Examples 1 to 5 were 1.72-2.63, all higher than those in Comparative Example 1, which underwent overall immersion calcification. The wound side / dorsal calcium content ratio in Comparative Example 1 was 1.08, indicating that overall immersion calcification is more likely to form a calcium distribution with a near-uniform thickness direction. The dorsal exudation rates in Examples 1 to 5 were 2.0%-3.7%, all lower than 5%, indicating that under the set conditions, the dorsal fluid-blocking support layer can limit the penetration of unilateral calcification fluid to the dorsal side, which is beneficial for establishing unilateral confined calcification conditions.

[0079] The calcium release over 10 minutes in Examples 1 to 5 ranged from 63.5 to 112.6 μg / cm³. 2 In Examples 3 and 5, due to the high concentrations and application rates of calcium chloride in the single-sided calcification solution or the high concentration of the calcium-supplementing dispersion, the calcium release amounts were 101.7 μg / cm³, respectively. 2 and 112.6 μg / cm 2 The calcium release was higher than that in Examples 2 and 4; in Comparative Example 2, no two-stage calcium supplementation was performed, and the calcium release in 10 minutes was 51.4 μg / cm³. 2 The results were lower than those of Examples 1 to 5; this result is used to illustrate that the ipsilateral two-stage calcium supplementation step can continue the calcium source effect on the wound contact side and support the formation of a calcium source available for release on the wound side.

[0080] The liquid absorption capacity of Examples 1 to 5 was 13.2-16.2 g / g, and the liquid retention rate was 69.1%-76.3%. Among them, Example 4 used milder calcification conditions and had a higher proportion of softener, with a liquid absorption capacity and liquid retention rate of 16.2 g / g and 76.3%, respectively, which were higher than those of the five examples. Examples 3 and 5 had higher liquid absorption capacities of 13.6 g / g and 13.2 g / g, respectively, due to their higher degree of calcification, which were lower than those of Examples 2 and 4, but their wet tensile strength was higher. This result shows that the degree of calcification, freeze-dried pore structure, and hydrophilic skeleton jointly affect the liquid absorption and retention performance. Compared with Comparative Example 1, Examples 1 to 5 generally maintained a higher liquid absorption capacity, indicating that the combination of single-sided confined calcification and back-side softening is beneficial to forming calcification differences while retaining the liquid absorption space.

[0081] The wet tensile strength of Examples 1 to 5 was 0.50-0.74 N / cm; Comparative Example 3, which did not contain carboxymethyl chitosan, had a wet tensile strength of 0.38 N / cm, lower than all the examples, and the wet edges were easily dispersed; this result is used to illustrate that the combined effect of carboxymethyl chitosan with sodium alginate, cellulose derivatives and calcium ions is beneficial to improving the structure retention after liquid absorption; Examples 3 and 5, due to their relatively high degree of calcification, had wet tensile strengths of 0.70 N / cm and 0.74 N / cm, respectively, which were higher than the five groups of examples, but slight edge indentations appeared during winding observation, indicating that excessively high calcification may lead to a trend of reduced flexibility.

[0082] The BCI of Examples 1 to 5 ranged from 36.5% to 48.4%, and the in vitro coagulation time ranged from 105 to 145 seconds. Comparative Example 2, without secondary calcium supplementation, had a BCI of 52.2% and an in vitro coagulation time of 160 seconds. Comparative Example 3, without carboxymethyl chitosan, had a BCI of 58.4% and an in vitro coagulation time of 175 seconds. These results indicate that the calcium source on the wound side, the cross-linking structure of calcium alginate, and the carboxymethyl chitosan complex network all influence the in vitro coagulation trend. Example 5 had the lowest BCI and the shortest in vitro coagulation time due to the relatively high calcium content on the wound side / dorsal side and the high calcium release at 10 minutes. However, its fluid absorption volume was lower than that of Examples 2 and 4, indicating that excessively high calcification strength may sacrifice some fluid absorption space.

[0083] Comparative Example 1, with its overall immersion and calcification, exhibited a wet tensile strength of 0.79 N / cm, higher than that of the other examples. However, its wound-side / dorsal calcium content ratio was close to 1, and it showed an overall stiffness and elasticity after wrapping. This result indicates that while overall calcification may improve the overall wet strength, it is not conducive to forming calcification differences in the thickness direction, nor is it conducive to maintaining soft dorsal dressing. Examples 1 to 5, through single-sided calcification on the wound side, two-segment calcium supplementation on the same side, and dorsal softening, achieved a more balanced performance combination among calcium gradient, absorbency, wet structure, and wrapping integrity.

[0084] In summary, single-sided confined rapid calcification is conducive to achieving a higher degree of calcification on the wound side than on the dorsal side; two-stage calcium supplementation is conducive to improving the sustained effect of calcium sources on the wound side; carboxymethyl chitosan and cellulose derivatives are conducive to maintaining the structure after liquid absorption; and dorsal softening is conducive to improving the conformity of wrapping and bandaging.

[0085] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.

[0086] The preferred embodiments of the present invention disclosed above are merely illustrative of the invention. These preferred embodiments do not exhaustively describe all details, nor do they limit the invention to the specific implementations described above. Clearly, many modifications and variations can be made based on the content of this specification. This specification selects and specifically describes these embodiments to better explain the principles and practical applications of the invention, thereby enabling those skilled in the art to better understand and utilize the invention. The invention is limited only by the claims and their full scope and equivalents.

Claims

1. A method for preparing a gradient calcified alginate hemostatic bandage, characterized in that, Includes the following steps: S1. Preparation of composite film-forming slurry: Based on 100% total non-volatile solids, 52-58% sodium alginate, 16-22% carboxymethyl chitosan, 8-14% cellulose derivative, 5-9% softener, 1-4% polyvinyl alcohol, and 0-4% polyethylene glycol 1000 are dispersed in water to obtain a composite film-forming slurry with a solids content of 3.0-5.0 wt%; wherein the softener is one or more of glycerol, sorbitol, or polyethylene glycol 400. S2. Molding and Freeze-drying: The composite film-forming slurry is coated or impregnated onto a medical strip substrate, controlling the wet coating thickness to be 0.5-1.8 mm, and the coating amount based on non-volatile solids to be 20-60 g / m². 2 A wet strip-shaped matrix is ​​obtained; the wet strip-shaped matrix is ​​pre-frozen at -30℃ to -60℃ for 1-3 hours, and then freeze-dried at -40℃ to -60℃ and 5-30Pa for 18-36 hours to obtain a porous strip-shaped matrix; S3. Preparation of calcium supplementation dispersion: Disperse calcium lactate or calcium gluconate in water to obtain a calcium supplementation dispersion containing 0.4-1.0 wt% calcium lactate or calcium gluconate and 0.05-0.20 wt% sodium carboxymethyl cellulose. S4. Single-sided confined rapid calcification: A liquid-resistant support layer is provided on the side of the porous strip matrix away from the wound contact side, allowing the wound contact side of the porous strip matrix to contact the single-sided calcification solution; the single-sided calcification solution consists of 1.2-2.5 wt% calcium chloride, 35-45 vol% ethanol, and the balance water, with a pH of 6.0-7.0, a contact temperature of 18-30℃, a contact time of 15-60 s, and an application rate of 0.10-0.22 mL / cm². 2 ; S5, Two-stage calcium supplementation: Apply the calcium dispersion from the same side that was in contact with the single-sided calcification solution, at a rate of 0.05-0.15 mL / cm². 2 The action time is 90-240 seconds; S6. Dorsal softening and drying: Apply a softening solution from the side away from the wound contact surface. The softening solution contains one or more of glycerin, sorbitol, or polyethylene glycol 400, with a softening agent mass fraction of 2-5 wt%, and an application rate of 0.03-0.12 mL / cm². 2 The action time is 30-180s; then it is dried at 25-40℃ for 1-6h, cut and rolled to obtain gradient calcified alginate hemostatic bandage.

2. The method for preparing the gradient calcified alginate hemostatic bandage according to claim 1, characterized in that, In step S1, the sodium alginate has a weight-average molecular weight of 100,000 to 300,000; the carboxymethyl chitosan has a degree of deacetylation of 75-90% and a degree of carboxymethyl substitution of 0.4-0.

9.

3. The method for preparing the gradient calcified alginate hemostatic bandage according to claim 1, characterized in that, In step S1, the cellulose derivative is a combination of sodium carboxymethyl cellulose and nanocellulose, with a mass ratio of (2-5):1; the nanocellulose has an average diameter of 30-120 nm and an average length of 0.5-3.0 μm.

4. The method for preparing the gradient calcified alginate hemostatic bandage according to claim 1, characterized in that, In step S1, sodium alginate is first stirred at 30-45℃ and 400-700rpm for 1.5-3h to form a sodium alginate solution. Then, carboxymethyl chitosan aqueous solution is added and stirred for 20-40min. Next, cellulose derivative dispersion is added and sheared and dispersed at 3000-8000rpm for 5-15min. Finally, softener and polyvinyl alcohol are added and degassed for 10-25min.

5. The method for preparing the gradient calcified alginate hemostatic bandage according to claim 1, characterized in that, In step S2, the medical strip substrate is medical degreased cotton gauze, viscose fiber nonwoven fabric, or polyester / viscose composite nonwoven fabric; the medical strip substrate is washed with water, dried at 40-70℃, and treated with ultraviolet light for 5-30 minutes before coating or impregnation.

6. The method for preparing the gradient calcified alginate hemostatic bandage according to claim 1, characterized in that, In step S4, the liquid-blocking support layer is a peelable liquid-blocking support layer temporarily attached to the porous strip substrate on the side away from the wound contact surface. The liquid-blocking support layer is selected from polyethylene film, polypropylene film, polytetrafluoroethylene film, or silicone release paper. The thickness of the liquid-blocking support layer is 20-150 μm, and the side in contact with the porous strip substrate is a low surface energy peeling surface. During the single-sided confined rapid calcification process, the mass of liquid seeping from the side away from the wound contact surface does not exceed 5% of the mass of the single-sided calcification liquid applied. After the single-sided confined rapid calcification is completed, the liquid-blocking support layer is peeled off from the porous strip substrate on the side away from the wound contact surface.

7. The method for preparing the gradient calcified alginate hemostatic bandage according to claim 1, characterized in that, After step S5 and before step S6, spray the strip-shaped substrate with sterile water from the contact side of the wound 1-3 times, with each spray volume being 0.02-0.08 mL / cm². 2 Let it stand at 20-30℃ for 3-10 minutes.

8. The method for preparing the gradient calcified alginate hemostatic bandage according to claim 1, characterized in that, The resulting gradient calcified alginate hemostatic bandage has a thickness of 0.8-3.0 mm, a width of 2-10 cm, and a winding radius of 3-20 mm.

9. The method for preparing the gradient calcified alginate hemostatic bandage according to claim 1, characterized in that, Step S6 is followed by sterilization and packaging, with sterilization methods including ethylene oxide sterilization or irradiation sterilization.

10. The method for preparing the gradient calcified alginate hemostatic bandage according to any one of claims 1-9, characterized in that, The resulting gradient calcified alginate hemostatic bandages are used to prepare auxiliary hemostatic dressings for superficial wounds, postoperative wounds with minor bleeding, or wounds with low to medium exudation.

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