A collagen dressing and a method for preparing the same

Abstract

The present application relates to the medical biomaterial and the wound repair technical field, especially collagen dressing and its preparation method, the preparation method includes the following steps: with suspending agent to scolopendra powder is wrapped, obtains A component;Collagen solution and wetting agent are mixed, and B component is obtained;A component and B component are defoamed, mixed, and C component is obtained;The C component is freeze-dried, and collagen sponge is obtained;The collagen sponge is crosslinked at 90~120 DEG C temperature, and collagen dressing is obtained.The present application is through introducing scolopendra powder to give the function of antibacterial, anti-inflammatory, analgesic, anticorrosive, strong healing of dressing;At the same time, through preparation process to improve the physical properties of dressing, strengthen its dressing structure stability and the hydrophilicity and uniformity of scolopendra component, reduce the clinical use safety risk, make it suitable for all kinds of wound, especially infected wound, deep wound and difficult healing wound, meet the clinical treatment demand.

Description

Technical Field

[0001] This invention relates to the field of medical biomaterials and wound repair technology, and in particular to a collagen dressing and its preparation method. Background Technology

[0002] Skin wounds are common clinical injuries, frequently seen in trauma, surgical incisions, burns, chronic ulcers, and difficult-to-heal wounds. Wound healing is a complex physiological process that involves four stages: hemostasis, inflammation, proliferation, and remodeling. Dressings, as key auxiliary materials for wound healing, must possess good biocompatibility, hydrophilicity, structural stability, and certain healing-promoting functions to protect the wound, reduce the risk of infection, and accelerate granulation tissue growth and epithelialization.

[0003] Collagen, as a biological macromolecule, has excellent biocompatibility, biodegradability and cell adhesion. Sponge-like dressings made from collagen have a three-dimensional porous structure that can absorb wound exudate and provide a scaffold for cell growth, and are widely used in the field of wound healing.

[0004] However, existing collagen dressings mainly focus on physical protection and exudate absorption, with limited healing effects. They are insufficient to meet the needs of rapid repair of complex wounds, thus limiting their clinical application. In particular, their application in infected ulcers and difficult-to-heal wounds (such as diabetic foot ulcers and residual burn wounds) is limited, failing to meet diverse clinical treatment needs. Summary of the Invention

[0005] To address the problem of poor healing effects of existing collagen dressings, this invention provides a method for preparing a collagen dressing. This method, by loading natural centipede active ingredients, endows the dressing with antibacterial, anti-inflammatory, analgesic, tissue-regenerating, and highly effective healing-promoting functions, thus solving the problem of poor healing effects of existing collagen dressings.

[0006] The technical solution adopted by this invention to solve its technical problem is: A method for preparing a collagen dressing includes the following steps: S1: Centipede powder is encapsulated with a suspending agent to obtain component A; S2: Mix the collagen solution with a wetting agent to obtain component B; S3: Defoam and mix component A and component B to obtain component C; S4: Freeze-dry the C component to obtain a collagen sponge; S5: Crosslink the collagen sponge at a temperature of 90~120℃ to obtain a collagen dressing.

[0007] Optionally, the centipede powder is selected from at least one of *Scolopendra subspinipes* powder and *Scolopendra multispinipes* powder.

[0008] Optionally, the suspending agent is selected from at least one of xanthan gum, sodium alginate, chitosan, pectin, sodium carboxymethyl cellulose, and hydroxypropyl methyl cellulose.

[0009] Optionally, the mass ratio of the suspending agent to the centipede powder in step S1 is (0.1-6.5):20.

[0010] Optionally, the mass concentration of the collagen solution is 0.53% to 2.50%.

[0011] Optionally, the wetting agent is selected from at least one of surfactants and hydrophilic polymers.

[0012] Optionally, the wetting agent is selected from at least one of poloxamer, Tween, Span, lecithin, and sucrose ester.

[0013] Optionally, the mass ratio of collagen to wetting agent in step S2 is (0.50-2.50):(0.2-2.0).

[0014] Optionally, freeze-drying the C component includes: pre-freezing the C component at -2℃ to -5℃ for 5 to 8 hours to form a frozen product, and then maintaining it at -40 to 45℃ for 5 to 6 hours, at 2℃ for 5 to 6 hours, and at 25 to 30℃ for 6 to 8 hours to obtain a collagen sponge.

[0015] Another object of the present invention is to provide a collagen dressing prepared by the collagen dressing preparation method described above.

[0016] The beneficial effects of this invention are: The preparation method of collagen dressing provided by this invention introduces centipede powder to endow the dressing with antibacterial, anti-inflammatory, analgesic, tissue-regenerating, and highly effective healing functions. At the same time, the preparation process improves the physical properties of the dressing, enhances its structural stability and the hydrophilicity and uniformity of the centipede components, reduces the safety risks of clinical use, and makes it suitable for various wounds, especially infected wounds, deep wounds, and difficult-to-heal wounds, thus meeting the needs of clinical treatment. Detailed Implementation

[0017] The present invention will now be described in further detail. The embodiments described below are exemplary and intended to explain the present invention, and should not be construed as limiting the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

[0018] To address the problem of poor healing effects of existing collagen dressings, this invention provides a method for preparing a collagen dressing, which includes the following steps: S1: Centipede powder is encapsulated with a suspending agent to obtain component A; Centipede powder, as an active ingredient, can endow dressings with antibacterial, anti-inflammatory, analgesic, tissue-regenerating, and highly effective healing-promoting functions. However, centipede powder is a non-water-soluble substance. If it is directly introduced into collagen dressings, it is prone to sedimentation, resulting in uneven distribution of dressing components and affecting the performance of the dressing. Based on this, the present invention uses a suspending agent to encapsulate and suspend the centipede powder, which can prevent the sedimentation of non-water-soluble centipede powder, ensure the uniformity of dressing performance, and at the same time maintain the three-dimensional structure of the final collagen sponge, thereby avoiding the introduction of centipede powder from affecting the mechanical properties of the dressing. S2: Mix the collagen solution with a wetting agent to obtain component B; Introducing wetting agents helps to enhance the hydrophilicity of dressings and improve the absorption rate. S3: Degas and mix components A and B at 2-15℃ and a vacuum of -0.2 to -1.5 bar to obtain component C; Preferably, the mass ratio of component A to component B in this step is (7-14):(100~800); specifically, this step can be carried out as follows: component A and component B are mixed in a mass ratio of (7-14):(100~800) and degassed at a temperature of 2-15℃ and a vacuum degree of -0.2~-1.5 bar, and stirred at a speed of 100-180 rpm for 60-120 minutes until homogeneous to obtain component C; S4: Freeze-dry component C to obtain collagen sponge; Preferably, component C is introduced into the mold and leveled to maintain a horizontal surface without obvious air bubbles; after molding, component C is freeze-dried to form a dried collagen sponge loaded with centipede powder, i.e., collagen sponge. S5: Crosslink the collagen sponge at a temperature of 90~120℃, preferably for 12-15h, to obtain a collagen dressing; Furthermore, it is preferable to form a cross-linked product after cross-linking; the cross-linked product is cut to form dressings of different sizes; specifically, it can be mechanically cut into sheet dressings with a length and width range of 0.5cm to 30cm by a slitting machine; it can be mechanically cut into powder dressings with a powder diameter D95 < 0.3cm by a pulverizer; the cut centipede powder collagen-loaded dressings are sterilized by one of gamma rays or ethylene oxide before use.

[0019] The preparation method of collagen dressing provided by this invention introduces centipede powder to endow the dressing with antibacterial, anti-inflammatory, analgesic, tissue-regenerating, and highly effective healing functions. At the same time, the preparation process improves the physical properties of the dressing, enhances its structural stability and the hydrophilicity and uniformity of the centipede components, reduces the safety risks of clinical use, and makes it suitable for various wounds, especially infected wounds, deep wounds, and difficult-to-heal wounds, thus meeting the needs of clinical treatment.

[0020] Existing collagen dressings have limited biological functions and limited healing-promoting effects. They only act as a physical barrier and simple scaffold, lacking active antibacterial capabilities and unable to inhibit the growth and reproduction of common wound pathogens (such as Staphylococcus aureus and Escherichia coli), resulting in a high risk of infection, especially unsuitable for infected wounds. Their healing-promoting effect is merely passively providing a scaffold for cell growth, lacking anti-inflammatory functions, and is ineffective in treating difficult-to-heal wounds. Furthermore, they lack the functions of removing necrotic tissue, promoting tissue regeneration, and strengthening epithelialization, making it difficult to relieve wound pain and reduce inflammatory responses. Moreover, existing collagen sponges often experience degradation or slow absorption due to several reasons, such as excessively high collagen concentration, which, after drying, easily forms a dense internal structure with low surface porosity, creating a sponge without "capillary channels" and preventing water penetration; collagen itself is weakly hydrophilic and not a highly absorbent material, and if the collagen sponge has excessively high cross-linking, the hydrophilic groups are easily shielded, preventing water molecules from entering, resulting in slower or even no water absorption. This results in dressings that absorb wound exudate slowly during clinical use, failing to rapidly absorb it. Furthermore, collagen sponges soften, collapse, and disintegrate after absorbing fluid, failing to maintain their intact three-dimensional porous structure and lacking sufficient filling and support for cavitary and deep wounds. To improve the structural stability of collagen sponges, current technologies often use cross-linking agents such as glutaraldehyde. However, these cross-linking agents are cytotoxic and easily remain in the dressing after cross-linking, affecting its biocompatibility and increasing the risk of wound sensitization and inflammatory reactions—a key concern during medical device review. Additionally, the porous structure of collagen sponges is difficult to precisely control, and problems such as closed pores, dense surface layers, and uneven pore sizes can easily occur during production, further reducing the dressing's absorbency and lowering its expected clinical efficacy.

[0021] The collagen dressing preparation method provided by this invention produces a collagen dressing loaded with centipede powder, whose physicochemical properties, especially water absorption time, are improved, and the liquid absorption capacity and strength are enhanced, meeting actual clinical needs. When used for diabetic ulcers, the prepared dressing shows significantly improved effectiveness compared to existing technologies in wound area reduction, pain relief, necrotic tissue removal, granulation tissue growth rate, and infection control of wounds (IDSA), demonstrating significant clinical application value. The preparation method is convenient, eliminating the need for chemical cross-linking with cross-linking agents and directly using a thermal cross-linking process, ensuring high safety for the prepared centipede powder-loaded collagen dressing, thus improving its safety profile.

[0022] The centipede powder of the present invention is preferably selected from at least one of the following: Giant Centipede Powder (Salvia splendens) and Giant Centipede Powder (Salvia splendens).

[0023] The bioactive components of *Scolopendra subspinipes* and *Scolopendra multispinipes* are stable and their efficacy is well-defined. Using these two types of centipede powder as raw materials ensures the stability and reliability of the dressing's efficacy. Furthermore, these two types of centipede powder are widely available, easy to obtain and process, facilitating large-scale production and reducing production costs.

[0024] Specifically, the centipede powder of the present invention is preferably prepared by one or two of the medicinal grade giant centipede with few spines and giant centipede with many spines using the legal method, and then pulverized by air jet mill with an air flow rate of 0.5~1.5m / min to obtain an ultrafine powder with a particle size D97≤100μm.

[0025] The preferred suspending agent of this invention is a natural bio-based or semi-synthetic cellulose substance. Specifically, the preferred suspending agent is selected from at least one of xanthan gum, sodium alginate, chitosan, pectin, sodium carboxymethyl cellulose, and hydroxypropyl methyl cellulose. All of the above suspending agents have good biocompatibility and biodegradability and will not cause irritation or residual toxicity to the wound.

[0026] In the preferred step S1 of this invention, the mass ratio of suspending agent to centipede powder is (0.1-6.5):20.

[0027] Furthermore, in this invention, component A preferably comprises the following components by weight: 20.0 parts centipede powder, 0.1 to 6.5 parts suspending agent, and 70.5 to 79.9 parts water; wherein the water is medical-grade purified water or water for injection.

[0028] Specifically, the preferred step S1 of the present invention is performed according to the following process: According to the formula, the suspending agent is slowly added to the water while stirring at 20-200 rpm. It is then allowed to stand for 60-300 minutes to allow for full hydration and swelling. Next, it is stirred at 60-180 rpm until completely dissolved, resulting in a homogeneous suspension with no particles or clumps. During this process, the suspending agent entangles in the water, forming a weak three-dimensional network that increases apparent viscosity and reduces particle settling velocity. Some of the suspending agent carries a charge and electrostatically adsorbs with the centipede powder, preventing agglomeration. Its core functions include thickening, steric hindrance, and electrostatic stabilization. The centipede powder is then slowly added to the water while stirring at 100 rpm until no clumps form. This mixture is then combined with the above suspension and emulsified using a high-speed disperser at 1500-2500 rpm until the suspending agent fully coats the centipede powder, forming a homogeneous, non-settling component A.

[0029] The preferred concentration of the collagen solution in this invention is 0.53% to 2.50%.

[0030] Specifically, the collagen solution of this invention is preferably prepared by the following method: Weigh the dried collagen product according to the formula amount, dissolve it in an acidic solvent with pH 2.0-4.5 at 2-15℃, or mix the extracted or prepared collagen solution with an acidic solvent to prepare a collagen solution with a final protein concentration of 0.53%~2.50%, maintaining the temperature at 2-15℃; preferably, the collagen is derived from one or a mixture of two types of type I and type III collagen extracted from animal tissues or expressed by gene recombination, with a molecular weight of 10-220 kDa and a collagen purity of 90.0-99.9%; the preferred acidic solvent of this invention is an acidic solution with pH 2.0-4.5, and the temperature is 2-15℃. The acidity can be adjusted using one or more acids and their salts selected from acetic acid, phosphoric acid, hydrochloric acid, and citric acid.

[0031] The wetting agent of the present invention is preferably selected from at least one of surfactants and hydrophilic polymers.

[0032] Specifically, the wetting agent of the present invention is preferably selected from at least one of poloxamer (such as P188, P407), Tween (Tween 20, Tween 80), Span (Span20, Span80), lecithin, and sucrose ester.

[0033] The introduction of wetting agents addresses the issues of collagen's weak hydrophilicity and the hydrophobicity of a small amount of centipede components.

[0034] In the preferred embodiment of the present invention, the mass ratio of collagen to wetting agent in step S2 is (0.50-2.50):(0.2-2.0).

[0035] Preferably, according to the weight percentages, component B of this invention comprises the following components: 0.50-2.50 parts collagen, 0.2-2.0 parts humectant, and 96.5-98.4 parts acidic solvent.

[0036] Specifically, step S2 of the present invention is preferably carried out as follows: according to the formula amount, the dried collagen product is weighed and dissolved in an acidic solvent with pH 2.0-4.5 at 2-15℃, or the extracted or prepared collagen solution is mixed with an acidic solvent to prepare a collagen solution with a final protein concentration of 0.53%~2.50%, and the temperature is maintained at 2-15℃; in order to enhance the hydrophilicity of the dressing and increase the absorption speed, a wetting agent with a concentration of 0.02%~5.3% is weighed and completely dissolved in at least a certain amount of acidic solvent and stirred until uniform, and mixed evenly with the above collagen solution, and component B is obtained under the conditions of temperature 2-15℃ and pH 2.0-4.5.

[0037] The present invention preferably freeze-dryes component C by: pre-freezing component C at -2℃ to -5℃ for 5 to 8 hours to form a frozen product, and then maintaining it at -40 to 45℃ for 5 to 6 hours, at 2℃ for 5 to 6 hours, and at 25 to 30℃ for 6 to 8 hours to obtain collagen sponge.

[0038] Another object of the present invention is to provide a collagen dressing prepared by the collagen dressing preparation method described above.

[0039] The collagen dressing provided by this invention, by introducing centipede powder, endows the dressing with antibacterial, anti-inflammatory, analgesic, tissue-regenerating, and highly effective healing-promoting functions. At the same time, the preparation process improves the physical properties of the dressing, enhances its structural stability and the hydrophilicity and uniformity of the centipede components, reduces the safety risks of clinical use, and makes it suitable for various wounds, especially infected wounds, deep wounds and difficult-to-heal wounds, to meet clinical treatment needs.

[0040] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, specific embodiments of the present invention will be described in detail below.

[0041] Unless otherwise specified, the centipede powder in the embodiments and comparative examples of this invention was prepared according to the following method: The medicinal grade centipede was processed according to the centipede processing method in the Chinese Pharmacopoeia (current 2025 edition, Part I) (removing bamboo pieces, washing, roasting over low heat until yellow, and cutting into sections). Then, it was pulverized using an air jet mill at an air flow rate of 1.0 m / min to obtain an ultrafine powder with a particle size D97≤100μm.

[0042] Unless otherwise specified, the collagen in the embodiments and comparative examples of the present invention is type I collagen extracted and expressed from animal tissues, with a molecular weight of 190 kDa and a collagen purity of 95%. Example 1

[0043] (1) Preparation of component A: By mass percentage, 2% of the suspending agent (containing 0.3% xanthan gum, 0.4% sodium alginate, and 1.3% pectin) was sprinkled into 50.00% of the purified water in the formula, and allowed to stand for 120 minutes. The mixture was then stirred at 100 rpm for 120 minutes until completely dissolved to obtain a suspension. 20.00% of the centipede powder in the formula was slowly added to 28% of the purified water while stirring. The mixture was stirred at 100 rpm until moist and free of lumps. The mixture was then mixed with the above suspension at 2000 rpm using a high-speed disperser and dispersed for 20 minutes to obtain component A.

[0044] (2) Preparation of component B: Collagen was dissolved in a 57.60% acetic acid solution at pH 3.5 at 10°C to prepare a collagen solution with a final mass concentration of 1.40%. 1.0% wetting agent (containing 0.2% poloxamer P188, 0.1% Tween 80, and 0.7% lecithin) was added to the remaining 40% acetic acid solution at pH 3.5 and stirred at 100 rpm until homogeneous. This mixture was then added to the collagen solution and stirred continuously at 100 rpm until homogeneous to obtain component B.

[0045] (3) Preparation of component C According to the mass ratio of A:B=7:200, 7 parts of component A are slowly added to 200 parts of component B (the mass ratio of centipede powder to collagen solid content is 1:2). The mixture is stirred at 100 rpm for 60 minutes until homogeneous. The mixture is then stirred continuously at 10℃, vacuum degree of -0.5 bar, and speed of 100 rpm for 60 minutes to remove bubbles until the solution is homogeneous and free of obvious large bubbles, thus obtaining component C.

[0046] (4) Dressing preparation Immediately pour component C slowly into the mold and allow it to level naturally until no obvious air bubbles appear on the surface. Pre-freeze at -2℃ for 8 hours to form a solid frozen product. Then, maintain the product at -40℃ for 6 hours, -2℃ for 5 hours, and 25℃ for 6 hours to form a dried collagen sponge loaded with centipede powder. Place the dried centipede powder-loaded collagen sponge at 110℃ for 12 hours for thermal cross-linking to form a cross-linked centipede powder-loaded collagen sponge. Cut the cross-linked product into 5cm × 5cm sheets. Pack the cut centipede powder-loaded collagen sponge dressings into paper-plastic bags, seal them, and sterilize them with 15-25kGy irradiation to obtain sterile centipede powder-loaded collagen dressings, which can be used for the clinical care of various ulcer wounds. Example 2

[0047] (1) Preparation of component A: By mass percentage, 0.1% of the suspending agent (containing 0.1% xanthan gum) was sprinkled into 50.00% of the purified water in the formula, and allowed to stand for 60 minutes. The mixture was then stirred at 20 rpm for 60 minutes until completely dissolved to obtain a suspension. 20.00% of the centipede powder in the formula was slowly added to 29.9% of the purified water while stirring. The mixture was stirred at 100 rpm until moist and free of lumps. The mixture was then mixed with the above suspension at 1500 rpm using a high-speed disperser and dispersed for 20 minutes to obtain component A.

[0048] (2) Preparation of component B: Collagen was dissolved in a 57.60% acetic acid-phosphoric acid complex solution at 2°C with a final mass concentration of 1.40% to prepare a collagen solution. 1.0% wetting agent (containing 0.5% poloxamer P188 and 0.5% lecithin) was added to the remaining 40% of the above acid complex solution at pH 3.0. After stirring at 100 rpm until homogeneous, the mixture was added to the collagen solution and stirred continuously at 100 rpm until homogeneous to obtain component B.

[0049] (3) Preparation of component C According to the mass ratio of A:B=7:100, 7 parts of component A are slowly added to 100 parts of component B (the mass ratio of centipede powder to collagen solid content is 1:1). The mixture is stirred at 100 rpm for 60 minutes until homogeneous. The mixture is then stirred continuously at 10℃, vacuum degree of -0.2 bar, and speed of 100 rpm for 60 minutes to remove bubbles until the solution is homogeneous and free of obvious large bubbles, thus obtaining component C.

[0050] (4) Dressing preparation Immediately pour component C slowly into the mold and allow it to level naturally until no obvious air bubbles appear on the surface. Pre-freeze at -2℃ for 5 hours to form a solid frozen product. Then, maintain the product at -42℃ for 5 hours, -2℃ for 5 hours, and 25℃ for 6 hours to form a dried collagen sponge loaded with centipede powder. Place the dried centipede powder-loaded collagen sponge at 90℃ for 15 hours for thermal cross-linking to form a cross-linked centipede powder-loaded collagen sponge. Cut the cross-linked product into 5cm × 5cm sheets. Pack the cut centipede powder-loaded collagen sponge dressings into paper-plastic bags, seal them, and sterilize them with 15-25kGy irradiation to obtain sterile centipede powder-loaded collagen dressings, which can be used for the clinical care of various ulcer wounds. Example 3

[0051] (1) Preparation of component A: By mass percentage, 6.5% of the suspending agent (containing 0.4% xanthan gum, 0.6% sodium alginate, 2% sodium alginate, 1% chitosan, 1.0% CMC-Na, and 1.5% HPMC-K4M) was sprinkled into 50.00% of the purified water in the formula. The mixture was allowed to stand for 300 minutes and then stirred at 200 rpm for 180 minutes until completely dissolved to obtain a suspension. 20.00% of the centipede powder in the formula was slowly added to 23.5% of the purified water while stirring. The mixture was stirred at 100 rpm until moist and free of lumps. The mixture was then mixed with the above suspension at 2500 rpm using a high-speed disperser and dispersed for 30 minutes to obtain component A.

[0052] (2) Preparation of component B: Collagen was dissolved in a 57.60% acetic acid and hydrochloric acid solution at 15°C to prepare a collagen solution with a final mass concentration of 1.40%. 1.00% wetting agent (containing 0.4% poloxamer P188, 0.1% Tween 80, and 0.5% Span 20) was added to the remaining 40% of the above acidic compound solution at pH 3.0. After stirring at 100 rpm until homogeneous, the mixture was added to the collagen solution and stirred continuously at 100 rpm until homogeneous, yielding component B.

[0053] (3) Preparation of component C According to the mass ratio of A:B=7:200, 7 parts of component A are slowly added to 200 parts of component B (the mass ratio of centipede powder to collagen solid content is 1:2). The mixture is stirred at 100 rpm for 120 minutes until homogeneous. The mixture is then continuously stirred and degassed at 15℃, vacuum degree of -1.5 bar, and speed of 100 rpm for 120 minutes until the solution is homogeneous and free of obvious large air bubbles, thus obtaining component C.

[0054] (4) Dressing preparation Immediately pour component C slowly into the mold and allow it to level naturally until no obvious air bubbles appear on the surface. Pre-freeze at -5℃ for 8 hours to form a solid frozen product. Then, maintain the product at -45℃ for 6 hours, -2℃ for 6 hours, and 30℃ for 8 hours to form a dried collagen sponge loaded with centipede powder. Place the dried centipede powder-loaded collagen sponge at 95℃ for 15 hours for thermal cross-linking to form a cross-linked centipede powder-loaded collagen sponge. Cut the cross-linked product into 5cm × 5cm sheets for use as a dressing. Pack the cut centipede powder-loaded collagen sponge dressings into paper-plastic bags, seal them, and sterilize them with ethylene oxide to obtain sterile centipede powder-loaded collagen dressings, which can be used for the care of various ulcer wounds in clinical practice. Example 4

[0055] (1) Preparation of component A: By mass percentage, 2.00% of the suspending agent (containing 0.3% xanthan gum, 0.3% sodium alginate, and 1.4% pectin) was sprinkled into 50.00% of the purified water in the formula, and allowed to stand for 120 minutes. The mixture was then stirred at 100 rpm for 120 minutes until completely dissolved to obtain a suspension. 20.00% of the centipede powder in the formula was slowly added to 28% of the purified water while stirring. The mixture was stirred at 100 rpm until moist and free of lumps. The mixture was then mixed with the above suspension at 2000 rpm using a high-speed disperser and dispersed for 20 minutes to obtain component A.

[0056] (2) Preparation of component B: Collagen was dissolved in a 57.60% acetic acid and citric acid solution at pH 2.0 at 10°C to prepare a collagen solution with a final mass concentration of 1.40%. 1.0% wetting agent (containing 0.3% poloxamer P407, 0.2% Tween 20, and 0.5% lecithin) was added to the remaining 40% of the above acidic compound solution at pH 2.0. After stirring at 100 rpm until homogeneous, the mixture was added to the collagen solution and stirred continuously at 100 rpm until homogeneous, yielding component B.

[0057] (3) Preparation of component C According to the mass ratio of A:B=14:100, 14 parts of component A are slowly added to 100 parts of component B (the mass ratio of centipede powder to collagen solid content is 1:0.5). The mixture is stirred at 100 rpm for 60 minutes until homogeneous. The mixture is then stirred continuously at 10℃, vacuum degree of -0.5 bar, and speed of 100 rpm for 60 minutes to remove bubbles until the solution is homogeneous and free of obvious large bubbles, thus obtaining component C.

[0058] (4) Dressing preparation Immediately pour component C slowly into the mold and allow it to level naturally until no obvious air bubbles appear on the surface. Pre-freeze at -5℃ for 8 hours to form a solid frozen product. Then, maintain the product at -45℃ for 6 hours, -2℃ for 5 hours, and 25℃ for 6 hours to form a dried collagen sponge loaded with centipede powder. Place the dried centipede powder-loaded collagen sponge at 100℃ for 12 hours for thermal cross-linking to form a cross-linked centipede powder-loaded collagen sponge. Cut the cross-linked product into 5cm × 5cm sheets. Pack the cut centipede powder-loaded collagen sponge dressings into paper-plastic bags, seal them, and sterilize them with 15-25kGy irradiation to obtain sterile centipede powder-loaded collagen dressings, which can be used for the clinical care of various ulcer wounds. Example 5

[0059] (1) Preparation of component A: By mass percentage, 2.00% of the suspending agent (containing 0.2% xanthan gum, 1.0% pectin, and 0.8% CMC-Na) was sprinkled into 50.00% of the purified water in the formula, and allowed to stand for 120 minutes. The mixture was then stirred at 100 rpm for 120 minutes until completely dissolved to obtain a suspension. 20.00% of the centipede powder in the formula was slowly added to 28% of the purified water while stirring. The mixture was stirred at 100 rpm until moist and free of lumps. The mixture was then mixed with the above suspension at 2000 rpm using a high-speed disperser and dispersed for 20 minutes to obtain component A.

[0060] (2) Preparation of component B: Collagen was dissolved in a 57.60% (pH 4.5) phosphate solution at 10°C to prepare a collagen solution with a final mass concentration of 1.40%. 1.0% wetting agent (containing 0.3% poloxamer P407, 0.3% Tween 80, and 0.4% sucrose ester) was added to the remaining 40% (pH 4.5) of the above acidic solution. After stirring at 100 rpm until homogeneous, the mixture was added to the collagen solution and stirred continuously at 100 rpm until homogeneous, yielding component B.

[0061] (3) Preparation of component C According to the mass ratio of A:B=7:800, 7 parts of component A are slowly added to 800 parts of component B (the mass ratio of centipede powder to collagen solid content is 1:8). The mixture is stirred at 100 rpm for 60 minutes until homogeneous. The mixture is then stirred continuously at 10℃, vacuum degree of -0.5 bar, and speed of 100 rpm for 60 minutes to remove bubbles until the solution is homogeneous and free of obvious large bubbles, thus obtaining component C.

[0062] (4) Dressing preparation Immediately pour component C slowly into the mold and allow it to level naturally until no obvious air bubbles appear on the surface. Pre-freeze at -2℃ for 8 hours to form a solid frozen product. Then, maintain the product at -35℃ for 6 hours, -2℃ for 5 hours, and 25℃ for 6 hours to form a dried collagen sponge loaded with centipede powder. Place the dried centipede powder-loaded collagen sponge at 115℃ for 12 hours for thermal cross-linking to form a cross-linked centipede powder-loaded collagen sponge. Cut the cross-linked product into 5cm × 5cm sheets. Pack the cut centipede powder-loaded collagen sponge dressings into paper-plastic bags, seal them, and sterilize them with 15-25kGy irradiation to obtain sterile centipede powder-loaded collagen dressings, which can be used for the clinical care of various ulcer wounds. Example 6

[0063] (1) Preparation of component A: By mass percentage, 2.00% of the suspending agent (containing 0.3% xanthan gum, 0.3% sodium alginate, and 1.4% HPMC-K4M) was sprinkled into 50.00% of the purified water in the formula, and allowed to stand for 120 minutes. The mixture was then stirred at 100 rpm for 120 minutes until completely dissolved to obtain a suspension. 20.00% of the centipede powder in the formula was slowly added to 28% of the purified water while stirring. The mixture was stirred at 100 rpm until moist and free of lumps. The mixture was then mixed with the above suspension at 2000 rpm using a high-speed disperser and dispersed for 20 minutes to obtain component A.

[0064] (2) Preparation of component B: Collagen was dissolved in a 56% (pH 3.5) phosphoric acid and hydrochloric acid solution at 10°C to prepare a collagen solution with a final mass concentration of 2.0%. 2.0% wetting agent (containing 0.5% poloxamer P188, 0.3% Tween 80, 0.5% Span 80, 0.5% lecithin, and 0.2% sucrose ester) was added to the remaining 40% (pH 3.5) of the above acidic compound solution. After stirring at 120 rpm until homogeneous, the mixture was added to the collagen solution and stirred continuously at 120 rpm until homogeneous, yielding component B.

[0065] (3) Preparation of component C According to the mass ratio of A:B=7:700, 7 parts of component A are slowly added to 700 parts of component B (the mass ratio of centipede powder to collagen solid content is 1:10). The mixture is stirred at 100 rpm for 60 minutes until homogeneous. The mixture is then stirred continuously at 10℃, vacuum degree of -1.0 bar, and speed of 100 rpm for 60 minutes to remove bubbles until the solution is homogeneous and free of obvious large bubbles, thus obtaining component C.

[0066] (4) Dressing preparation Immediately pour component C slowly into the mold and allow it to level naturally until no obvious air bubbles appear on the surface. Pre-freeze at -5℃ for 8 hours to form a solid frozen product. Then, maintain the product at -45℃ for 6 hours, -2℃ for 6 hours, and 30℃ for 8 hours to form a dried collagen sponge loaded with centipede powder. Place the dried centipede powder-loaded collagen sponge at 120℃ for 12 hours for thermal cross-linking to form a cross-linked centipede powder-loaded collagen sponge. Cut the cross-linked product into 5cm × 5cm sheets. Pack the cut centipede powder-loaded collagen sponge dressings into paper-plastic bags, seal them, and sterilize them with 15-25kGy irradiation to obtain sterile centipede powder-loaded collagen dressings, which can be used for the clinical care of various ulcer wounds. Example 7

[0067] (1) Preparation of component A: By mass percentage, 2.00% of the suspending agent (containing 0.1% xanthan gum, 0.4% sodium alginate, 0.5% chitosan, and 1.0% HPMC-K15M) was sprinkled into 50.00% of the purified water in the formula, and allowed to stand for 120 minutes. The mixture was then stirred at 100 rpm for 120 minutes until completely dissolved to obtain a suspension. 20.00% of the centipede powder in the formula was slowly added to 28% of the purified water while stirring. The mixture was stirred at 100 rpm until moist and free of lumps. The mixture was then mixed with the above suspension at 2000 rpm using a high-speed disperser and dispersed for 20 minutes to obtain component A.

[0068] (2) Preparation of component B: Collagen was dissolved at 10°C in a 56.50% (pH 3.5) phosphoric acid and citric acid compound solution to prepare a collagen solution with a final mass concentration of 2.50%. 1.00% wetting agent (containing 0.3% poloxamer P407, 0.3% Tween 20, and 0.4% sucrose ester) was added to the remaining 40% (pH 3.5) of the above acid compound solution. After stirring at 150 rpm until homogeneous, the mixture was added to the collagen solution and stirred continuously at 100 rpm until homogeneous, yielding component B.

[0069] (3) Preparation of component C According to the mass ratio of A:B=7:225, 7 parts of component A were slowly added to 225 parts of component B (the mass ratio of centipede powder to collagen solid content is 1:4). The mixture was stirred at 100 rpm for 60 minutes until homogeneous. The mixture was then stirred continuously at 10℃, vacuum degree of -1.5 bar, and speed of 100 rpm for 120 minutes to remove bubbles until the solution was homogeneous and free of obvious large bubbles, thus obtaining component C.

[0070] (4) Dressing preparation Immediately pour component C slowly into the mold and allow it to level naturally until no obvious air bubbles appear on the surface. Pre-freeze at -5℃ for 8 hours to form a solid frozen product. Then, maintain the product at -45℃ for 6 hours, -2℃ for 6 hours, and 30℃ for 8 hours to form a dried collagen sponge loaded with centipede powder. Place the dried centipede powder-loaded collagen sponge at 110℃ for 12 hours for thermal cross-linking to form a cross-linked centipede powder-loaded collagen sponge. Cut the cross-linked product into 5cm × 5cm sheets. Pack the cut centipede powder-loaded collagen sponge dressings into paper-plastic bags, seal them, and sterilize them with 15-25kGy irradiation to obtain sterile centipede powder-loaded collagen dressings, which can be used for the clinical care of various ulcer wounds. Example 8

[0071] (1) Preparation of component A: By mass percentage, 2.00% of the suspending agent (containing 0.4% xanthan gum, 0.6% sodium alginate, and 1.0% CMC-Na) was sprinkled into 50.00% of the purified water in the formula, and allowed to stand for 120 minutes. The mixture was then stirred at 100 rpm for 120 minutes until completely dissolved to obtain a suspension. 20.00% of the centipede powder in the formula was slowly added to 28% of the purified water while stirring. The mixture was stirred at 100 rpm until moist and free of lumps. The mixture was then mixed with the above suspension at 2000 rpm using a high-speed disperser and dispersed for 20 minutes to obtain component A.

[0072] (2) Preparation of component B: Collagen was dissolved in a 58.47% hydrochloric acid solution with a pH of 3.5 at 10°C to prepare a collagen solution with a final mass concentration of 0.53%. 1.0% wetting agent (containing 0.4% poloxamer P188 and 0.6% Span 20) was added to the remaining 40% of the above acid solution with a pH of 3.5. The solution was stirred at 100 rpm until homogeneous and then added to the collagen solution. The mixture was stirred continuously at 100 rpm until homogeneous to obtain component B.

[0073] (3) Preparation of component C According to the mass ratio of A:B=7:800, 7 parts of component A are slowly added to 200 parts of component B (the mass ratio of centipede powder to collagen solid content is 1:3). The mixture is stirred at 100 rpm for 60 minutes until homogeneous. The mixture is then stirred continuously at 10℃, vacuum degree of -0.5 bar, and speed of 100 rpm for 60 minutes to remove bubbles until the solution is homogeneous and free of obvious large bubbles, thus obtaining component C.

[0074] (4) Dressing preparation Immediately pour component C slowly into the mold and allow it to level naturally until no obvious air bubbles appear on the surface. Pre-freeze at -5℃ for 8 hours to form a solid frozen product. Then, maintain the product at -40℃ for 6 hours, -2℃ for 5 hours, and 25℃ for 6 hours to form a dried collagen sponge loaded with centipede powder. Place the dried centipede powder-loaded collagen sponge at 90℃ for 12 hours for thermal cross-linking to form a cross-linked centipede powder-loaded collagen sponge. Cut the cross-linked product into 5cm × 5cm sheets for use as a dressing. Pack the cut centipede powder-loaded collagen sponge dressings into paper-plastic bags, seal them, and sterilize them with ethylene oxide to obtain sterile centipede powder-loaded collagen dressings, which can be used for the care of various ulcer wounds in clinical practice. Example 9

[0075] (1) Preparation of component A: By mass percentage, 2.00% of the suspending agent (containing 0.3% xanthan gum, 0.5% sodium alginate, and 1.2% CMC-Na) was sprinkled into 50.00% of the purified water in the formula, and allowed to stand for 120 minutes. The mixture was then stirred at 100 rpm for 120 minutes until completely dissolved to obtain a suspension. 20.00% of the centipede powder in the formula was slowly added to 28% of the purified water while stirring. The mixture was stirred at 100 rpm until moist and free of lumps. The mixture was then mixed with the above suspension at 2000 rpm using a high-speed disperser and dispersed for 20 minutes to obtain component A.

[0076] (2) Preparation of component B: Collagen was dissolved at 10°C in a 58.40% hydrochloric acid and citric acid compound solution with a final mass concentration of 1.40% to prepare a collagen solution. 0.2% wetting agent (containing 0.2% poloxamer P188) was added to the remaining 40% of the above acid compound solution with a pH of 3.5. After stirring at 100 rpm until homogeneous, the mixture was added to the collagen solution and stirred continuously at 100 rpm until homogeneous to obtain component B.

[0077] (3) Preparation of component C According to the mass ratio of A:B=7:200, 7 parts of component A are slowly added to 200 parts of component B (the mass ratio of centipede powder to collagen solid content is 1:2). The mixture is stirred at 100 rpm for 60 minutes until homogeneous. The mixture is then stirred continuously at 10℃, vacuum degree of -1.0 bar, and speed of 100 rpm for 60 minutes to remove bubbles until the solution is homogeneous and free of obvious large bubbles, thus obtaining component C.

[0078] (4) Dressing preparation Immediately pour component C slowly into the mold and allow it to level naturally until no obvious air bubbles appear on the surface. Pre-freeze at -2℃ for 8 hours to form a solid frozen product. Then, maintain the product at -45℃ for 6 hours, -2℃ for 5 hours, and 25℃ for 6 hours to form a dried collagen sponge loaded with centipede powder. Place the dried centipede powder-loaded collagen sponge at 95℃ for 12 hours for thermal cross-linking to form a cross-linked centipede powder-loaded collagen sponge. Cut the cross-linked product into 5cm × 5cm sheets. Pack the cut centipede powder-loaded collagen sponge dressings into paper-plastic bags, seal them, and sterilize them with 15-25kGy irradiation to obtain sterile centipede powder-loaded collagen dressings, which can be used for the clinical care of various ulcer wounds. Example 10

[0079] (1) Preparation of component A: By mass percentage, 2.00% of the suspending agent (containing 0.3% xanthan gum, 0.4% sodium alginate, and 1.3% HPMC-K4M) was sprinkled into 50.00% of the purified water in the formula, and allowed to stand for 120 minutes. The mixture was then stirred at 100 rpm for 120 minutes until completely dissolved to obtain a suspension. 20.00% of the centipede powder in the formula was slowly added to 28% of the purified water while stirring. The mixture was stirred at 100 rpm until moist and free of lumps. The mixture was then mixed with the above suspension at 2000 rpm using a high-speed disperser and dispersed for 20 minutes to obtain component A.

[0080] (2) Preparation of component B: Collagen was dissolved at 10°C in a 56.60% (pH 3.5) compound solution of acetic acid, phosphoric acid, and hydrochloric acid at a final mass concentration of 1.40% to prepare a collagen solution. 2.0% wetting agent (containing 0.3% poloxamer P188, 0.4% Tween 80, and 1.3% lecithin) was added to the remaining 40% (pH 3.5) of the above acid compound solution. After stirring at 100 rpm until homogeneous, the mixture was added to the collagen solution and stirred continuously at 100 rpm until homogeneous, yielding component B.

[0081] (3) Preparation of component C According to the mass ratio of A:B=7:200, 7 parts of component A are slowly added to 200 parts of component B (the mass ratio of centipede powder to collagen solid content is 1:2). The mixture is stirred at 100 rpm for 120 minutes until homogeneous. The mixture is then stirred continuously at 10℃, vacuum degree of -1.5 bar, and speed of 100 rpm for 120 minutes to remove bubbles until the solution is homogeneous and free of obvious large bubbles, thus obtaining component C.

[0082] (4) Dressing preparation Immediately pour component C slowly into the mold and allow it to level naturally until no obvious air bubbles appear on the surface. Pre-freeze at -5℃ for 8 hours to form a solid frozen product. Then, maintain the product at -45℃ for 6 hours, -2℃ for 6 hours, and 30℃ for 8 hours to form a dried collagen sponge loaded with centipede powder. Place the dried centipede powder-loaded collagen sponge at 100℃ for 12 hours for thermal cross-linking to form a cross-linked centipede powder-loaded collagen sponge. Cut the cross-linked product into 5cm × 5cm sheets. Pack the cut centipede powder-loaded collagen sponge dressings into paper-plastic bags, seal them, and sterilize them with 15-25kGy irradiation to obtain sterile centipede powder-loaded collagen dressings, which can be used for the clinical care of various ulcer wounds. Example 11

[0083] (1) Preparation of component A: By mass percentage, 4.00% of the suspending agent (containing 0.4% xanthan gum, 0.5% sodium alginate, 1.0% pectin, 1.0% CMC-Na, and 1.1% HPMC-K4M) was sprinkled into 50.00% of the purified water in the formula, and allowed to stand for 150 minutes. The mixture was then stirred at 150 rpm for 150 minutes until completely dissolved to obtain a suspension. 20.00% of the centipede powder in the formula was slowly added to 26% of the purified water while stirring. The mixture was stirred at 100 rpm until moist and free of lumps. The mixture was then mixed with the above suspension at 2200 rpm using a high-speed disperser and dispersed for 20 minutes to obtain component A.

[0084] (2) Preparation of component B: Collagen was dissolved at 10°C in a 57.60% (pH 3.5) solution of acetic acid, phosphoric acid, and citric acid to prepare a collagen solution with a final mass concentration of 1.40%. 1.0% wetting agent (containing 0.4% poloxamer P407, 0.2% Tween 20, and 0.4% sucrose ester) was added to the remaining 40% (pH 3.5) of the above acidic compound solution. After stirring at 100 rpm until homogeneous, the mixture was added to the collagen solution and stirred continuously at 100 rpm until homogeneous, yielding component B.

[0085] (3) Preparation of component C According to the mass ratio of A:B=7:200, 7 parts of component A are slowly added to 200 parts of component B (the mass ratio of centipede powder to collagen solid content is 1:2). The mixture is stirred at 100 rpm for 90 minutes until homogeneous. The mixture is then stirred and degassed at 150 rpm for 90 minutes at a temperature of 10℃, a vacuum degree of -1.0 bar, and a rotation speed of 150 rpm until the solution is homogeneous and free of obvious large bubbles, thus obtaining component C.

[0086] (4) Dressing preparation Immediately pour component C slowly into the mold and allow it to level naturally until no obvious air bubbles appear on the surface. Pre-freeze at -5℃ for 8 hours to form a solid frozen product. Then, maintain the product at -45℃ for 6 hours, -2℃ for 6 hours, and 30℃ for 8 hours to form a dried collagen sponge loaded with centipede powder. Place the dried centipede powder-loaded collagen sponge at 115℃ for 12 hours for thermal cross-linking to form a cross-linked centipede powder-loaded collagen sponge. Cut the cross-linked product into 5cm × 5cm sheets. Pack the cut centipede powder-loaded collagen sponge dressings into paper-plastic bags, seal them, and sterilize them with 15-25kGy irradiation to obtain sterile centipede powder-loaded collagen dressings, which can be used for the clinical care of various ulcer wounds. Example 12

[0087] (1) Preparation of component A: By mass percentage, 6.00% of the suspending agent (containing 0.4% xanthan gum, 0.5% sodium alginate, 1.1% pectin, 1.5% chitosan, 1.0% CMC-Na, and 1.5% HPMC-K15M) was sprinkled into 50.00% of the purified water in the formula. The mixture was allowed to stand for 200 minutes and then stirred at 180 rpm for 160 minutes until completely dissolved to obtain a suspension. 20.00% of the centipede powder in the formula was slowly added to 24% of the purified water while stirring. The mixture was stirred at 100 rpm until moist and free of lumps. The mixture was then mixed with the above suspension at 2300 rpm using a high-speed disperser and dispersed for 25 minutes to obtain component A.

[0088] (2) Preparation of component B: Collagen was dissolved at 10°C in a 57.60% (pH 3.5) compound solution of acetic acid, phosphoric acid, hydrochloric acid, and citric acid to prepare a collagen solution with a final mass concentration of 1.40%. 1.0% wetting agent (containing 0.2% poloxamer P407, 0.6% Span 80, and 0.2% sucrose ester) was added to the remaining 40% (pH 3.5) of the above-mentioned acid compound solution. After stirring at 100 rpm until homogeneous, the mixture was added to the collagen solution and stirred continuously at 100 rpm until homogeneous, yielding component B.

[0089] (3) Preparation of component C According to the mass ratio of A:B=7:200, 7 parts of component A are slowly added to 200 parts of component B (the mass ratio of centipede powder to collagen solid content is 1:2). The mixture is stirred at 100 rpm for 90 minutes until homogeneous. The mixture is then stirred continuously at 10℃, vacuum degree of -1.0 bar, and speed of 180 rpm for 90 minutes to remove bubbles until the solution is homogeneous and free of obvious large bubbles, thus obtaining component C.

[0090] (4) Dressing preparation Immediately pour component C slowly into the mold and allow it to level naturally until no obvious air bubbles appear on the surface. Pre-freeze at -5℃ for 8 hours to form a solid frozen product. Then, maintain the product at -45℃ for 6 hours, -2℃ for 6 hours, and 30℃ for 8 hours to form a dried collagen sponge loaded with centipede powder. Place the dried centipede powder-loaded collagen sponge at 120℃ for 12 hours for thermal cross-linking to form a cross-linked centipede powder-loaded collagen sponge. Cut the cross-linked product into 5cm × 5cm sheets for use as a dressing. Pack the cut centipede powder-loaded collagen sponge dressings into paper-plastic bags, seal them, and sterilize them with ethylene oxide to obtain sterile centipede powder-loaded collagen dressings, which can be used for the care of various ulcer wounds in clinical practice.

[0091] Comparative Example 1 This comparative example does not contain centipede powder, suspending agent, or wetting agent.

[0092] Collagen was dissolved in a 98.60% acetic acid solution (pH 3.5) at 10°C to prepare component B, achieving a final mass concentration of 1.40%. Component B was continuously stirred at 10°C, under a vacuum of -0.5 bar and a rotation speed of 100 rpm for 60 minutes to degas until the solution was homogeneous and free of large air bubbles. The degassed component B was immediately and slowly poured into a mold to allow it to level naturally. After the surface was free of obvious air bubbles, it was pre-frozen at -2°C for 8 hours to form a solid frozen product. This product was then maintained at -40°C for 6 hours, -2°C for 5 hours, and 25°C for 6 hours to form a dried collagen sponge. This dried collagen sponge was then placed at 110°C for 12 hours for thermal cross-linking to form a cross-linked collagen sponge. Finally, it was cut into 5cm × 5cm collagen sheet dressings using a cutter. The cut collagen sponge dressings are placed into paper-plastic bags, sealed, and then sterilized by irradiation with a dose of 15-25 kGy to obtain sterile collagen dressings for clinical care of various ulcer wounds.

[0093] Comparative Example 2 This comparative example does not contain suspending agents or wetting agents.

[0094] (1) Preparation of component A: By mass percentage, 20.00% of the centipede powder in the formula was slowly added to 80% purified water while stirring. The mixture was stirred at 100 rpm until moist and free of lumps. The mixture was then mixed with the suspension at 2000 rpm using a high-speed disperser and dispersed for 5 minutes to obtain component A.

[0095] (2) Preparation of component B: Collagen was dissolved in 98.60% acetic acid solution at 10°C with a final mass concentration of 1.40% to prepare a collagen solution. The solution was stirred continuously at 100 rpm until homogeneous to obtain component B.

[0096] (3) Preparation of component C According to the mass ratio of A:B=7:200, 7 parts of component A are slowly added to 200 parts of component B (the mass ratio of centipede powder to collagen solid content is 1:2). The mixture is stirred at 100 rpm for 60 minutes until homogeneous. The mixture is then stirred continuously at 10℃, vacuum degree of -0.5 bar, and speed of 100 rpm for 60 minutes to remove bubbles until the solution is homogeneous and free of obvious large bubbles, thus obtaining component C.

[0097] (4) Dressing preparation Immediately pour component C slowly into the mold and allow it to level naturally until no obvious bubbles appear on the surface. Pre-freeze at -2℃ for 8 hours to form a solid frozen product. Then, maintain the product at -40℃ for 6 hours, -2℃ for 5 hours, and 25℃ for 6 hours to form a dried collagen sponge loaded with centipede powder. Place the dried centipede powder-loaded collagen sponge at 110℃ for 12 hours for thermal cross-linking to form a cross-linked centipede powder-loaded collagen sponge. Cut the cross-linked product into 5cm × 5cm sheets. Pack the cut centipede powder-loaded collagen sponge sheets into paper-plastic bags, seal them, and sterilize them with 15-25kGy irradiation to obtain sterile centipede powder-loaded collagen dressings.

[0098] Comparative Example 3 This comparative sample does not contain centipede powder or humectant ingredients.

[0099] (1) Preparation of component A: By mass percentage, 2.00% of the suspending agent (containing 0.3% xanthan gum, 0.4% sodium alginate, and 1.3% pectin) was sprinkled into 98.00% of the purified water in the formula, and the mixture was allowed to stand for 120 minutes. Then, it was stirred at 100 rpm for 120 minutes until it was completely dissolved to obtain a suspension solution, which is component A.

[0100] (2) Preparation of component B: Collagen was dissolved in 98.60% acetic acid solution at 10°C with a final mass concentration of 1.40% to prepare a collagen solution. The solution was stirred continuously at 100 rpm until homogeneous to obtain component B.

[0101] (3) Preparation of component C According to the mass ratio of A:B=7:200, 7 parts of component A are slowly added to 200 parts of component B, and the mixture is stirred at 100 rpm for 60 minutes until homogeneous. The mixture is then stirred and degassed at 100 rpm for 60 minutes until the solution is homogeneous and free of large bubbles, thus obtaining component C.

[0102] (4) Dressing preparation Immediately pour component C slowly into the mold and allow it to level naturally until no obvious air bubbles appear on the surface. Pre-freeze at -2℃ for 8 hours to form a solid frozen product. Then, maintain the product at -40℃ for 6 hours, -2℃ for 5 hours, and 25℃ for 6 hours to form a dried collagen sponge. Place the dried collagen sponge at 110℃ for 12 hours for thermal cross-linking to form a cross-linked collagen sponge. Cut the cross-linked collagen sponge into 5cm × 5cm collagen sheets. Pack the cut collagen sponge sheets into paper-plastic bags, seal them, and sterilize them with 15-25kGy irradiation to obtain sterile collagen dressings.

[0103] Comparative Example 4 This comparative example does not contain centipede powder or suspending agent, and does not include the preparation of component A.

[0104] (1) Preparation of component B: Collagen was dissolved in a 57.60% acetic acid solution (pH 3.5) at 10°C to prepare a collagen solution with a final mass concentration of 1.40%. 1.0% wetting agent (containing 0.2% poloxamer P188, 0.1% Tween 80, and 0.7% lecithin) was added to the remaining 40% acetic acid solution (pH 3.5) and stirred at 100 rpm until homogeneous. This mixture was then added to the collagen solution, and the mixture was stirred continuously at 100 rpm until homogeneous, yielding component B. Component B was then subjected to degassing at 10°C and a vacuum of -0.5 bar, with continuous stirring at 100 rpm for 60 minutes until the solution was homogeneous and free of large air bubbles.

[0105] (4) Dressing preparation Immediately pour component B slowly into the mold and allow it to level naturally until no obvious air bubbles appear on the surface. Pre-freeze at -2℃ for 8 hours to form a solid frozen product. Then, maintain the product at -40℃ for 6 hours, -2℃ for 5 hours, and 25℃ for 6 hours to form a dried collagen sponge. Place the dried collagen sponge at 110℃ for 12 hours for thermal cross-linking to form a cross-linked collagen sponge. Cut the cross-linked collagen sponge into 5cm × 5cm collagen sheets for dressing. Pack the cut collagen sponge dressings into paper-plastic bags, seal them, and sterilize them with 15-25kGy irradiation to obtain sterile collagen dressings for clinical ulcer wound care.

[0106] Comparative Example 5 This comparative example uses EDC reagent for cross-linking.

[0107] A collagen solution was prepared by dissolving 0.8% EDC (carbodiimide hydrochloride), 1.40% collagen, and 1.0% humectant (containing 0.2% poloxamer P188, 0.1% Tween 80, and 0.7% lecithin) in a 96.80% acetic acid solution at pH 3.5 at 10°C, yielding component B. Component B was continuously stirred at 10°C, under a vacuum of -0.5 bar and a rotation speed of 100 rpm for 60 minutes to degas until the solution was homogeneous and free of large bubbles. The degassed component B was immediately and slowly poured into a mold to allow it to level naturally. After the surface was free of obvious bubbles, it was pre-frozen at -2°C for 8 hours to form a solid frozen product. This product was then maintained at -40°C for 6 hours, -2°C for 5 hours, and 25°C for 6 hours to form a dried collagen sponge. The dried collagen sponge was then subjected to thermal cross-linking at 110°C for 12 hours to form a cross-linked collagen sponge. Cut the collagen sponge dressing into 5cm x 5cm sheets using a cutter. Pack the cut collagen sponge dressing into a paper-plastic bag, seal it, and then sterilize it by irradiation with a dose of 15-25kGy to obtain a sterile collagen dressing.

[0108] The performance of the collagen dressings prepared in the above embodiments and comparative examples was tested.

[0109] The test items and methods are as follows: (1) Uniformity of appearance Using visual observation, the collagen dressing loaded with centipede powder was observed. Because centipede powder is a non-water-soluble substance, it easily separates into layers when mixed with collagen solution and left to stand, and its distribution is uneven after freeze-drying. However, after being encapsulated and dispersed by a suspending agent, it does not easily separate into layers and forms a sponge with a uniform texture.

[0110] (2) Tensile properties Referring to YY / T 1511-2017 Collagen Sponge 6.7 method, take a collagen sponge and cut it into strips 1cm wide. Fix one end and apply tension to the other end until it breaks. Record the tension value at the time of breakage.

[0111] (3) Liquid absorption time Referring to YY / T0472.1 Medical Nonwoven Dressing Test Methods Part 1: Nonwoven Fabrics for Dressing Production, a 5cm×5cm test sample that has been balanced is dropped into the liquid from a height of 25 mm above the liquid surface, and the time required for the test sample to be completely wetted is measured.

[0112] (4) Liquid absorbency Refer to YY / T0471.1 Test Methods for Contact Wound Dressings, Part 1: Liquid Absorbency, "3. Water Absorbency Test Method". Condition the test sample at 21 ± 2°C. The test should be conducted under relative humidity (RH) of (60 ± 15)%. Place a known mass of 5 cm × 5 cm dressing or 0.2 g (for the sample) in a petri dish, add approximately 100 g of test solution preheated to (37 ± 1)°C, and transfer to a drying oven. Maintain at (37 ± 1)°C for 30 min. Use a clamp to hold one corner or end of the sample, suspend it for 30 s, and weigh it. Calculate the mass of absorbed solution per gram of sample (g / g) to express the liquid absorbency.

[0113] (5) Cell viability Cell viability was tested according to Appendix C of ISO 10993-5 (GB / T 16886.5 Biological evaluation of medical devices - Part 5: In vitro cytotoxicity tests).

[0114] The test results are shown in Table 1.

[0115] Table 1 Performance Test Results In the table above, "+++" indicates that the color and texture are very uniform; "++" indicates that the color and texture are relatively uniform; and "-" indicates that there is a slight color difference or a slight unevenness in texture.

[0116] The wound healing properties of the collagen dressing prepared in Example 1 were tested. The entire wound model was based on clinical treatment and observation of diabetic foot wound healing. The test methods and results are as follows: (1) Wound area reduction rate and method: Place a scale bar next to the wound and take a photo of the wound using your mobile phone, ensuring the camera is perpendicular to the wound and the wound is centered on the screen. Use ImageJ software to analyze the wound area and calculate the wound reduction rate. Wound reduction rate = [(wound area before treatment - wound area after treatment) / wound area before treatment] × 100%.

[0117] The test results are shown in Table 2.

[0118] Table 2 Comparison of wound reduction rate (%) among subjects (2) Pain VAS score: Pain scoring was performed using the Visual Analogue Scale (VAS). A 100 mm long straight line was drawn, with each 10 mm mark. No numbers or words were written on the line to avoid affecting the assessment results. Patients marked the points on the line that best reflected their pain level. Each 10 mm mark was assigned 1 point. Pain scores before and after treatment were analyzed. The comparison results of the two groups of patients' Visual Analogue Scale (VAS) pain scores are shown in Table 3.

[0119] Before treatment, the VAS pain score in the experimental group was 5.15 ± 1.870, and in the control group it was 4.81 ± 1.833. The data from both groups were normally distributed and had homogeneous variances. An independent samples t-test was used for comparison, and the results showed no statistically significant difference (t = 0.674, P = 0.503), indicating that the baseline pain levels of the two groups were comparable before treatment.

[0120] After treatment, the data from both groups did not conform to a normal distribution, so the median and interquartile range M (P25, P75) were used to describe the data. The Mann-Whitney U rank-sum test was used for comparison between the groups. The pain VAS score of the experimental group was 3 (2, 4) points, and that of the control group was 4 (3, 5) points. The difference between the two groups was statistically significant (Z=-2.016, P=0.044), indicating that the experimental group was more effective than the control group in relieving pain.

[0121] Table 3 Comparison of VAS pain scores between groups (3) Percentage of necrotic tissue in the wound and rate of necrotic tissue sloughing off After photographing the wound, ImageJ software was used to analyze the area of ​​necrotic tissue and its proportion in the total wound area, and the necrotic tissue slough-off rate was calculated. Necrotic tissue slough-off rate = [(Percentage of necrotic tissue before treatment - Percentage of necrotic tissue after treatment) / Percentage of necrotic tissue before treatment] × 100%.

[0122] Before treatment (Visit 1), the percentage of necrotic tissue in the wounds of both groups conformed to a normal distribution and had homogeneous variances. An independent samples t-test was used for comparison. The results showed that there was no statistically significant difference between the experimental group (56.91 ± 16.59)% and the control group (47.49 ± 19.26)% (t = -1.892, P = 0.064), and the baselines were comparable.

[0123] After treatment (visit 3), although the data from the two groups conformed to a normal distribution, their variances were unequal. Therefore, a corrected t-test was used for comparison. The results showed that the proportion of necrotic tissue in the wound of the experimental group decreased to (23.97 ± 11.88)%, which was significantly lower than that of the control group (38.30 ± 19.70)%, and the difference was statistically significant (t = -3.177, P = 0.003). The results are shown in Table 4.

[0124] Table 4 Comparison of the percentage of necrotic tissue area in wounds among groups Comparison of wound slough-off rates: The slough-off rates of the two groups did not conform to a normal distribution, so the Mann-Whitney U rank-sum test was used. The results showed that the slough-off rate in the experimental group was 60.42% (43.37%, 68.25%), significantly higher than that in the control group (15.64%, 4.75%, 34.99%), with a statistically significant difference (Z=-5.015, P<0.001). This indicates that the experimental group was significantly more effective than the control group in promoting slough-off. The results are shown in Table 5.

[0125] Table 5 Comparison of slough-off rate (%) between the two groups of subjects (4) Wound granulation tissue coverage ratio and wound granulation tissue growth rate: Comparison of wound granulation tissue coverage ratio between groups: Before treatment (Visit 1), the granulation tissue coverage ratios of the two groups conformed to a normal distribution and had homogeneous variances. An independent samples t-test was used for comparison. The results showed that there was no statistically significant difference between the experimental group and the control group (t = -1.892, P = 0.064), and the baselines were comparable.

[0126] After treatment (visit 3), the data from both groups still conformed to a normal distribution but had unequal variances; therefore, a corrected t-test was used for comparison. The results showed that the granulation tissue coverage ratio in the experimental group increased to (76.03 ± 11.88)%, significantly higher than that in the control group (61.70 ± 19.70)%, with a statistically significant difference (t = 3.177, P = 0.003). This suggests that the experimental group had a greater advantage in promoting granulation tissue growth. The results are shown in Table 6.

[0127] Table 6 Comparison of granulation tissue coverage ratio among groups Comparison of granulation tissue growth rates in wounds: The granulation tissue growth rate data of the two groups of subjects were analyzed using the Mann-Whitney U rank-sum test. The results showed that the granulation tissue growth rate in the experimental group was 66.30% (48.58%, 104.88%), significantly higher than that in the control group (14.24%, 4.35%, 29.64%), with a statistically significant difference (Z=-5.252, P<0.001). This indicates that the experimental group was significantly more effective than the control group in promoting granulation tissue regeneration. The results are shown in Table 7.

[0128] Table 7 Comparison of granulation tissue growth rate in the wounds of the two groups of subjects (4) Wagner and IDSA classification downgrade rates: The Wagner classification system and the IDSA infection classification system were used respectively to calculate the incidence of grade downgrade (i.e., condition improvement) after treatment in the two groups of patients, and to evaluate the improvement of the severity of diabetic foot ulcers by the two treatment regimens.

[0129] To assess the improvement of diabetic foot ulcer severity by the two treatment regimens, the Wagner classification system and the IDSA infection classification system were used, respectively. The incidence of grade downgrade (i.e., improvement) after treatment was calculated in both groups, and inter-group comparisons were performed. Based on the combined assessment results of the two classification systems, although there was no significant difference between the two groups in wound depth (Wagner classification) improvement (P>0.05), the experimental group showed a significant advantage in infection control (IDSA classification) (P=0.032). The results are shown in Tables 8 and 9.

[0130] Table 8. Comparison of Wagner downgrade rates between groups Table 9. Comparison of IDSA downgrade rates between groups In this study, the experimental group used the collagen dressing prepared in Example 1, and the control group used the collagen dressing prepared in Comparative Example 1. V1 refers to visit 1, which is the baseline data on day 0 of enrollment. V2 refers to visit 2, which is the data on day 7 of treatment. V3 refers to visit 3, which is the data on day 14 of treatment.

[0131] Based on the above-described preferred embodiments of the present invention, and through the foregoing description, those skilled in the art can make various changes and modifications without departing from the inventive concept. The technical scope of this invention is not limited to the contents of the specification, but must be determined according to the scope of the claims.

Claims

1. A method for preparing a collagen dressing, characterized in that, Includes the following steps: S1: Centipede powder is encapsulated with a suspending agent to obtain component A; S2: Mix the collagen solution with a wetting agent to obtain component B; S3: Defoam and mix component A and component B to obtain component C; S4: Freeze-dry the C component to obtain a collagen sponge; S5: Crosslink the collagen sponge at a temperature of 90~120℃ to obtain a collagen dressing.

2. The method for preparing the collagen dressing as described in claim 1, characterized in that, The centipede powder is selected from at least one of the following: *Scolopendra subspinipes* powder and *Scolopendra multispinipes* powder.

3. The method for preparing the collagen dressing as described in claim 1, characterized in that, The suspending agent is selected from at least one of xanthan gum, sodium alginate, chitosan, pectin, sodium carboxymethyl cellulose, and hydroxypropyl methyl cellulose.

4. The method for preparing the collagen dressing as described in claim 1, characterized in that, The mass ratio of the suspending agent to the centipede powder in step S1 is (0.1-6.5):

20.

5. The method for preparing the collagen dressing as described in claim 1, characterized in that, The collagen solution has a mass concentration of 0.53% to 2.50%.

6. The method for preparing the collagen dressing as described in claim 1, characterized in that, The wetting agent is selected from at least one of surfactants and hydrophilic polymers.

7. The method for preparing the collagen dressing as described in claim 1, characterized in that, The wetting agent is selected from at least one of poloxamer, Tween, Span, lecithin, and sucrose ester.

8. The method for preparing the collagen dressing as described in claim 1, characterized in that, In step S2, the mass ratio of the collagen solution to the wetting agent is (0.50-2.50):(0.2-2.0).

9. The method for preparing the collagen dressing according to any one of claims 1-8, characterized in that, Freeze-drying of component C includes: pre-freezing component C at -2℃ to -5℃ for 5 to 8 hours to form a frozen product, and then maintaining it at -40 to 45℃ for 5 to 6 hours, at 2℃ for 5 to 6 hours, and at 25 to 30℃ for 6 to 8 hours to obtain collagen sponge.

10. A collagen dressing, characterized in that, The collagen dressing is prepared by the method described in any one of claims 1-9.

Images