Collagen sheet dressing and method of making the same

Abstract

The application relates to the technical field of medical dressings, and discloses a collagen sheet dressing and a preparation method thereof. The collagen sheet dressing comprises fibrous collagen, an auxiliary component, an excipient and a protective agent; wherein the solid content of the fibrous collagen in the composition is greater than 10 mg / ml. The preparation method of the collagen sheet dressing comprises the following steps: preparing a homogenate; drying the homogenate to obtain a dry product; adjusting the humidity of the dry product and irradiating the dry product to form the collagen sheet dressing. Through the above method, the problems of large porosity, low protein concentration and fast degradation speed of the existing products can be solved. In addition, the preparation method of the collagen component provided by the application has cost advantages, and the process is simple and easy to mass-produce.

Description

Technical Field

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

[0002] Currently, the preparation of wound dressings using collagen materials extracted from animal tissues generally involves using acid to prepare a low-concentration solution of the soluble collagen material before forming a low-density porous sponge. However, this method is not specifically designed for complex wounds such as chronic or full-layer wounds, and inevitably suffers from problems such as high porosity, low protein concentration, and easy degradation in a short period of time. Summary of the Invention

[0003] The main technical problem addressed by this application is to provide a collagen sheet dressing and its preparation method, which can solve the problems of large porosity, low protein concentration, and easy degradation in a short time of existing products.

[0004] To solve the above-mentioned technical problems, one technical solution adopted in this application is to provide a collagen sheet dressing. The collagen sheet dressing includes fibrous collagen, auxiliary ingredients, excipients, and protective agents; wherein the solid content of fibrous collagen in the composition is greater than 10 mg / ml.

[0005] In some embodiments, the collagen sheet dressing has a unit area mass of 100 g / m². 2 -1000 g / m 2 .

[0006] In some embodiments, the porosity of the collagen sheet dressing is less than 80%.

[0007] In some embodiments, the moisture content of the collagen sheet dressing is less than or equal to 17%.

[0008] In some embodiments, the mechanical strength of the collagen sheet dressing is greater than or equal to 0.2 MPa.

[0009] In some embodiments, the pH of the collagen sheet dressing is 4.0-7.0.

[0010] In some embodiments, the auxiliary components include one or more of glycine, lysine, or tyrosine.

[0011] In some embodiments, the excipients include one or more of glycerol, ethanol, mannitol, or isopropanol.

[0012] In some embodiments, the protective agent includes one or more of vitamin C, vitamin D, or vitamin E.

[0013] In some embodiments, fibrous collagen can swell but not dissolve in an acidic solution at room temperature, with a swelling degree of 2-3.

[0014] In some embodiments, the acidic solution includes one or more of hydrochloric acid, acetic acid, citric acid, or lactic acid.

[0015] One technical solution adopted in this application is: a method for preparing a collagen sheet dressing. The preparation method includes: preparing a homogenized slurry; drying the homogenized slurry to obtain a dried product; adjusting the humidity of the dried product and subjecting it to irradiation cross-linking and irradiation sterilization to form the aforementioned collagen sheet dressing.

[0016] In some embodiments, the step of preparing a homogenized slurry includes: weighing 100 parts of fibrous collagen raw material, 0-2 parts of auxiliary components, 0-5 parts of excipients, and 0-1 parts of protectant and adding them into a reaction vessel; adding an acidic solution and stirring to homogenize and form a homogenized slurry.

[0017] In some embodiments, the fiber length of the fibrous collagen raw material is 50μm-500μm.

[0018] In some embodiments, the step of forming a homogenized slurry is to form a homogenized slurry with a concentration of fibrous collagen of 10 mg / ml to 50 mg / ml.

[0019] In some embodiments, the step of drying the homogenized slurry to obtain a dried product includes: freeze-drying the homogenized slurry to form an intermediate product; and heat-treating the intermediate product to form a dried product.

[0020] In some embodiments, the steps of adjusting the humidity of the dried product and irradiating it include: adjusting the humidity of the dried product to 10%-15%, then performing irradiation crosslinking and irradiation sterilization to form the collagen sheet dressing described above.

[0021] The beneficial effects of this application are as follows: Unlike the prior art, the collagen component provided in this application includes fibrous collagen, auxiliary components, excipients, and protective agents; wherein, the solid content of fibrous collagen in the composition is greater than 10 mg / ml, and it has the advantages of small porosity, high protein concentration, and long degradation time. Attached Figure Description

[0022] Figure 1 This is a flowchart illustrating the steps of an embodiment of the preparation method of the collagen sheet dressing of this application;

[0023] Figure 2 This is a flowchart of another embodiment of the preparation method of the collagen sheet dressing of this application;

[0024] Figure 3This is a flowchart illustrating the steps of another embodiment of the preparation method of the collagen sheet dressing of this application;

[0025] Figure 4 This is the thermal stability curve of Example 1 of the collagen sheet dressing of this application;

[0026] Figure 5 This is the thermal stability curve of Example 2 of the collagen sheet dressing of this application;

[0027] Figure 6 It is the thermal stability curve of a commercially available product;

[0028] Figure 7 This is a scanning electron microscope image of Example 1 of the collagen sheet dressing of this application;

[0029] Figure 8 This is a scanning electron microscope image of Example 2 of the collagen sheet dressing of this application;

[0030] Figure 9 This is a scanning electron microscope image of a commercially available product. Detailed Implementation

[0031] The technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of this application, and not all of them. All other embodiments obtained by those skilled in the art based on the embodiments of this application without creative effort are within the scope of protection of this application.

[0032] In this document, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features indicated. The term "and / or" in this document merely describes the relationship between related objects, indicating that three relationships can exist. For example, A and / or B can represent: A alone, A and B simultaneously, or B alone. Furthermore, the character " / " in this document generally indicates that the preceding and following related objects are in an "or" relationship. Additionally, "many" in this document indicates two or more objects.

[0033] The inventors of this application have discovered through long-term research that, compared to acute wounds, chronic wounds often maintain a high level of inflammation for an extended period. The wound bed contains a large number of matrix metalloproteinases (MMPs). MMPs not only degrade wound debris but also substances beneficial to tissue repair, such as growth factors and collagen. Therefore, collagen dressings used for chronic wounds require higher density, mechanical strength, and greater enzyme tolerance. This is particularly relevant for complex wounds such as pressure ulcers, venous ulcers, diabetic ulcers, and stagnant wounds. Compared to superficial / semi-dermal wounds, full-dermal wounds (especially those extending into fascia, muscle, or bone, and even those with necrotic tissue, deep cavities, and exudate) are more challenging to care for. Collagen dressings used for this type of wound need to provide an ideal scaffold for cell proliferation and tissue formation, with degradation times adapted to tissue repair, providing a suitable healing microenvironment for the wound.

[0034] In view of this, the following embodiments of this application provide a collagen sheet dressing. The collagen sheet dressing may be white or slightly yellow and can be directly applied to a wound. The collagen sheet dressing includes fibrous collagen, auxiliary ingredients, excipients, and protective agents; wherein the solid content of fibrous collagen in the composition is greater than 10 mg / ml.

[0035] Fibrous collagen refers to pure, natural, insoluble fibrous collagen, which is a quaternary structure formed by the polymerization and linkage of collagen molecules into stable collagen microfibers, and is insoluble in acids and water. The fibrous collagen provided in this application is a pure, natural fibrous collagen material obtained through extraction and purification from animal tissue materials that comply with medical laws and regulations (ISO 22442 series of regulations for animal-derived medical devices). In some embodiments, the solid content of the fibrous collagen in its composition can be 10 mg / ml, 20 mg / ml, 30 mg / ml, 40 mg / ml, 50 mg / ml, etc., or any range of the above values, for example, 10 mg / ml-20 mg / ml, 20 mg / ml-30 mg / ml, 30 mg / ml-50 mg / ml, etc.

[0036] The collagen sheet dressing provided in this application includes fibrous collagen, auxiliary components, excipients, and protective agents. The fibrous collagen has a solid content greater than 10 mg / ml, giving the collagen sheet dressing advantages such as density, good mechanical strength, long degradation time, good biocompatibility, and non-toxicity. This improves the application of collagen sheet dressings in complex wounds such as pressure ulcers, venous ulcers, diabetic ulcers, and stagnant wounds.

[0037] In some embodiments, the collagen sheet dressing has a unit area mass of 100 g / m². 2 -1000 g / m 2For example, the mass per unit area of ​​collagen sheet dressings can be 100g / m². 2 200g / m 2 400g / m 2 500g / m 2 600g / m 2 700g / m 2 800g / m 2 850g / m 2 900g / m 2 950g / m 2 1000g / m 2 etc., or any range of the above values, for example, 100g / m 2 -200 g / m 2 200g / m 2 -500 g / m 2 500g / m 2 -700g / m 2 700g / m 2 -850 g / m 2 850g / m 2 -950 g / m 2 950g / m 2 -1000 g / m 2 0, etc. Selecting the unit area mass of the collagen sheet dressing within the above range ensures the structural stability of the collagen sheet dressing, improves its density, and enhances its tolerance to collagenase. The unit area mass of the collagen sheet dressing can be tested using the following method: accurately weigh the sample (accurate to 0.0001g), then measure its length and width to calculate its area, thus obtaining the mass per square meter of the sample.

[0038] In some embodiments, the porosity of the dressing is less than 80%. For example, the porosity of the collagen sheet dressing can be 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, or any range of the above values, such as 40%-50%, 50%-60%, 60%-65%, 65%-75%, 75%-80%, etc. Selecting the porosity of the collagen sheet dressing within the above range is beneficial for cell attachment and proliferation on the collagen sheet dressing. The porosity of the collagen sheet dressing can be tested according to the method in the standard ISO 5017:2013 Dense shaped refractory products—Determination of bulk density, apparent porosity and true porosity.

[0039] In some embodiments, the moisture content of the collagen sheet dressing is less than or equal to 17%. For example, the moisture content of the collagen sheet dressing can be 5%, 8%, 10%, 11%, 12%, 13%, 13.5%, 14%, 15%, 15.5%, 16%, 16.5%, 17%, etc., or any range of the above values, such as 5%-8%, 8%-11%, 11%-13%, 13%-14%, 15%-15.5%, 16%-16.5%, 16.5%-17%, etc. Selecting the moisture content of the collagen sheet dressing within the above range can maintain the stability of the collagen components and improve the wound repair effect of the collagen sheet dressing. The moisture content of the collagen sheet dressing can be referenced in USP34. <731> The method of loss on drying was tested using reduced pressure drying.

[0040] In some embodiments, the mechanical strength of the collagen sheet dressing is greater than or equal to 0.2 MPa. For example, the mechanical strength of the collagen sheet dressing can be 0.2 MPa, 0.25 MPa, 0.3 MPa, 0.35 MPa, 0.4 MPa, 0.45 MPa, 0.5 MPa, 0.55 MPa, 0.6 MPa, 0.65 MPa, 0.7 MPa, 0.75 MPa, 0.8 MPa, or any range of the above values, such as 0.2 MPa-0.25 MPa, 0.25 MPa-0.35 MPa, 0.35 MPa-0.45 MPa, 0.45 MPa-0.55 MPa, 0.55 MPa-0.65 MPa, 0.7 MPa-0.8 MPa, etc. Selecting the mechanical strength of collagen sheet dressings within the aforementioned range ensures their stability and facilitates their application on wounds. The mechanical strength of collagen sheet dressings can be determined according to the method described in standard ISO 1798:2008 Flexible cellular polymeric materials—Determination of tensile strength and elongation at break, using a 15mm wide product for mechanical strength testing.

[0041] In some embodiments, the pH of the collagen sheet dressing is 4.0-7.0. For example, the pH of the collagen sheet dressing can be 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, or any range of the above values, such as 4.0-4.5, 4.5-5.5, 6.0-6.5, 6.5-7.0, etc. Selecting the pH of the collagen sheet dressing within the above range ensures that the pH of the collagen sheet dressing is compatible with the wound, which is beneficial to wound healing. The pH of the collagen sheet dressing can be tested using the following method: according to the extraction ratio of 3cm... 2 / ml (add additional absorbent volume), extract with purified water in an oven at 37℃±1℃ for 24h±2h, and measure the pH value of the extract with a pH meter.

[0042] In some embodiments, the auxiliary component includes one or more of glycine, lysine, or tyrosine. For example, the auxiliary component may be glycine, lysine, or tyrosine, or a mixture of glycine and lysine, or a mixture of lysine and tyrosine, etc. Selecting the auxiliary component within the above range can enhance the cross-linking of fibrous collagen, resulting in higher mechanical strength and greater stability of the collagen sheet dressing.

[0043] In some embodiments, the excipient includes one or more of glycerol, ethanol, mannitol, or isopropanol. For example, the excipient may be glycerol, ethanol, mannitol, or isopropanol, or a mixture of glycerol and ethanol, or a mixture of ethanol and isopropanol, etc. Selecting excipients within the above range helps to improve the orderly arrangement of collagen sheet dressings and the retention of their shape after molding.

[0044] In some embodiments, the protective agent includes one or more of vitamin C, vitamin D, or vitamin E. The protective agent may be vitamin C, vitamin D, or vitamin E, or a mixture of vitamin C and vitamin D, or a mixture of vitamin D and vitamin E, etc. Selecting a protective agent within the above range enables the protection of the collagen molecular structure during the sterilization process of preparing collagen sheet dressings.

[0045] In some embodiments, the acidic solution includes one or more of hydrochloric acid, acetic acid, citric acid, or lactic acid. For example, the acidic solution may be a hydrochloric acid solution, an acetic acid solution, a citric acid solution, or a lactic acid solution, or a mixed solution of hydrochloric acid and acetic acid, or a mixed solution of acetic acid and citric acid, etc. In some embodiments, the pH of the acidic solution is 2-6. For example, the pH of the acidic solution may be 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, etc., or a range of any of the above values, such as 2.0-2.5, 2.5-3.5, 3.5-4.5, 4.5-5.5, 5.5-6.0, etc.

[0046] like Figure 1 As shown in the following embodiments, this application provides a method for preparing a collagen sheet dressing. The preparation method includes the following steps:

[0047] S10: Prepare a homogenized slurry.

[0048] This process involves using a low-concentration acid to rapidly homogenize and slurry the fibrous collagen raw material, auxiliary components, excipients, and protective agents to form a uniform fibrous collagen raw material dispersion. This fibrous collagen raw material dispersion is the homogenized slurry.

[0049] S20: Dry the homogenized slurry to obtain the dried product.

[0050] Drying can include freeze-drying and vacuum drying. Freeze-drying involves freezing and crystallizing a solvent and a suspension medium at low temperatures, then directly sublimating the solvent from a solid to a gaseous state for drying. Specifically, the homogenized slurry can be injected into a metal freeze-drying tray made of stainless steel or aluminum, with a thickness of 2-10 mm, and then placed in a freeze dryer to freeze-shape it. Vacuum drying involves removing residual solvents (acids and water) from the frozen homogenized slurry under vacuum conditions by heating. Simultaneously, heavy dehydration can be used to cross-link collagen without adding chemical cross-linking agents, thus improving the product's mechanical strength.

[0051] S30: Adjust the humidity of the dried product and irradiate it to form a collagen sheet dressing as described above.

[0052] Among these methods, adjusting the humidity ensures that the collagen sheet dressing has a certain moisture content, and irradiation can cross-link and sterilize the collagen sheet dressing.

[0053] like Figure 2 As shown, in some embodiments, step S10: preparing a homogenized slurry includes the following steps:

[0054] S101: Weigh 100 parts of fibrous collagen raw material, 0-2 parts of auxiliary ingredients, 0-5 parts of excipients, and 0-1 parts of protectant and add them to the homogenizer.

[0055] The number of each component is measured by weight ratio.

[0056] In some embodiments, the fiber length of the fibrous collagen raw material can be 50μm, 70μm, 90μm, 100μm, 130μm, 160μm, 200μm, 220μm, 270μm, 290μm, 300μm, 330μm, 350μm, 390μm, 400μm, 420μm, 455μm, 470μm, 490μm, or 500μm. The length of the fibers can be denoted as 50μm-90μm, 90μm-130μm, 130μm-200μm, 200μm-270μm, 270μm-290μm, 300μm-350μm, 330μm-390μm, 400μm-455μm, 455μm-470μm, 470μm-500μm, etc. The fiber length of fibrous collagen raw materials can be observed and measured using an optical microscope.

[0057] S102: Add acidic solution and stir to form a homogeneous slurry.

[0058] Acidic solutions may include one or more of hydrochloric acid, acetic acid, citric acid, or lactic acid, with a pH of 2.0-6.0. First, use a mechanical stirrer to disperse the materials, and then turn on a high-speed homogenizer to homogenize for 5-15 minutes (3000-8000 RPM) to form a uniform dispersion.

[0059] like Figure 2 As shown, in some embodiments, the step of forming a homogenized slurry includes: forming a homogenized slurry with a collagen concentration of 10 mg / ml to 50 mg / ml.

[0060] An acidic solution can be added to the fibrous collagen raw material to achieve a solid content ratio of 1%-10% (by mass), resulting in a fibrous collagen raw material concentration of 10mg / ml-50mg / ml.

[0061] like Figure 2 As shown, in some embodiments, step S20: drying the homogenized slurry to obtain a dried product includes:

[0062] S201: Freeze-dry the homogenized slurry to form an intermediate product.

[0063] The freeze-drying process can be referred to in step S20, and will not be repeated here.

[0064] S202: Heat treatment of the intermediate product to form a dried product.

[0065] One approach is to use vacuum drying to heat-treat the intermediate products. That is, under vacuum conditions, the intermediate products are transferred to a vacuum drying oven, and residual solvents (acids and water) are removed by heating. Simultaneously, heavy dehydration can be used to cross-link the fibrous collagen raw materials without adding chemical cross-linking agents, thus improving the product's mechanical strength.

[0066] In some embodiments, step S30: adjusting the humidity of the dried product and irradiating it includes:

[0067] S301: After adjusting the humidity of the dried product to 10%-15%, irradiation cross-linking and irradiation sterilization are carried out to form collagen sheet dressing.

[0068] Specifically, the dried product is placed in a sealed humidification chamber filled with sterilized purified water at a temperature of 30°C-37°C. The humidity of the product is controlled within the range of 10%-15% through humidification. Then, it is packaged in a water- and gas-barrier material, such as Tyvek bags, aluminum foil bags, aluminum-plastic bags, or blister packs, and sealed.

[0069] Furthermore, irradiation crosslinking includes: subjecting the packaged dried product to Co... 60Gamma rays are used for cross-linking, with an irradiation dose of 5-10 kgy.

[0070] Furthermore, irradiation sterilization includes: on the basis of irradiation cross-linking, applying 25-35 kgy of Co again. 60 The product is sterilized by irradiation with gamma rays.

[0071] In some embodiments, such as Figure 3 As shown, step S20: drying the homogenized slurry may also include the following steps:

[0072] Step S203: Die-cut the dried product to form a third intermediate product.

[0073] Step S203 occurs after step S202.

[0074] After vacuum drying, the fibrous collagen sheet is placed in a laser cutting machine and cut into sheet dressings of a certain size.

[0075] For example, dried products can be die-cut using laser cutting. Laser cutting refers to feeding the product to be die-cut into the designated cutting position of the die-cutting machine. The laser at the cutting station is designed according to the required shape of the product (such as round, square, or rectangular), and under the action of laser energy, the fibrous collagen sheet is die-cut into the required shape.

[0076] In some embodiments, the collagen sheet dressing includes the collagen sheet dressing described above or a collagen sheet dressing prepared by the method described above.

[0077] The beneficial effects of this application are further illustrated below with reference to the embodiments.

[0078] To make the technical problems, technical solutions, and beneficial effects solved by the embodiments of this application clearer, the following will provide a more detailed description in conjunction with the embodiments and accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of this application, and not all of them. The following description of at least one exemplary embodiment is merely illustrative and is in no way intended to limit this application or its applications. Based on the embodiments of this application, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this application.

[0079] Example 1:

[0080] Step 1: Add 1.5 kg of fibrous collagen raw material, lysine, glycerol, ethanol, and vitamin C (10 g: 5 g: 70 g: 10 g) to a high-speed homogenizer. Then add 100 L of hydrochloric acid aqueous solution with pH 2.0. Turn on the mechanical agitator (30-60 min, 30 RPM) until the materials are dispersed, and then turn on the high-speed homogenizer (5 min, 3000 RPM) to homogenize the mixture. It should be noted that all reagents used in the above process are analytical grade, and the water is purified water. The entire process is carried out in a Class 100,000 cleanroom.

[0081] Step Two: Inject the uniformly dispersed liquid from Step One into a stainless steel freeze-drying tray using a precision metering pump. The material thickness in the tray should be 10 mm, spread evenly, and allowed to self-level naturally for 0.5 hours. Then, place the freeze-drying tray containing the material into the freeze dryer and set the freeze dryer program according to the parameters in Table 1 for vacuum freeze-drying. It should be noted that the entire process is carried out in a Class 100,000 cleanroom.

[0082] Table 1: Freeze-drying parameters in Example 1

[0083]

[0084] Step 3: Remove the freeze-dried collagen sheets from Step 2 and transfer them to a clean stainless steel tray. Then, transfer them to a vacuum drying oven for further drying. The vacuum drying parameters should be as required in Table 2 below. It should be noted that the entire process is carried out in a Class 100,000 cleanroom.

[0085] Table 2: Vacuum Drying Parameters of Example 1

[0086] Temperature (°C) Time (hours) Pressure (MPa) 140℃ 8 <-0.099Mpa

[0087] Step 4: Remove the dried collagen sheets from Step 3 and place them in a transport device. Transport the sheets to the designated station on the pneumatic die-cutting machine, where they will be die-cut into 5cm x 5cm sheets. It should be noted that the entire process is carried out in a Class 100,000 cleanroom.

[0088] Step 5: Place the die-cut sheets from Step 4 into a sealed humidification chamber, set the chamber temperature to 30℃, and run for 2 hours. Then, pack them into Tyvek bags and seal them. It should be noted that the entire process is performed in a Class 100,000 cleanroom.

[0089] Step Six: Apply the bagged sheet dressing from Step Five to Co twice consecutively. 60 Gamma-ray irradiation treatment, with the first irradiation dose being 5 kgy and the second irradiation dose being 25 kgy-30 kgy.

[0090] Step 7: Perform performance testing on the fibrous collagen sheet dressing from Step 6.

[0091] Example 2

[0092] Step 1: Add 5 kg of fibrous collagen raw material, lysine, glycerol, mannitol, and vitamin C (50 g: 20 g: 5 g: 50 g) to a high-speed homogenizer. Then add 100 L of acetic acid aqueous solution (pH 4.5). Turn on the mechanical agitator (60-90 min, 50 RPM) until the materials are dispersed. Then turn on the high-speed homogenizer (10 min, 5000 RPM) to homogenize the mixture. It should be noted that all reagents used in the above process are analytical grade, and the water is purified water. The entire process is carried out in a Class 100,000 cleanroom.

[0093] Step Two: Inject the uniformly dispersed liquid from Step One into a stainless steel freeze-drying tray using a precision metering pump. The material thickness in the tray should be 4 mm, spread evenly, and allowed to self-level naturally for 45 minutes. Then, place the freeze-drying tray containing the material into the freeze dryer and set the freeze dryer program according to the parameters in Table 3 for vacuum freeze-drying. It should be noted that the entire process is carried out in a Class 100,000 cleanroom.

[0094] Table 3: Freeze-drying parameters for Example 2

[0095]

[0096] Step 3: Remove the freeze-dried collagen sheets from Step 2 and transfer them to a clean stainless steel tray. Then, transfer them to a vacuum drying oven for further drying. The vacuum drying parameters should be as required in Table 4 below. It should be noted that the entire process is carried out in a Class 100,000 cleanroom.

[0097] Table 4: Vacuum Drying Parameters of Example 2

[0098] Temperature (°C) Time (hours) Pressure (MPa) 120℃ 24 <-0.099Mpa

[0099] Step 4: Remove the dried collagen sheets from Step 3 and place them in a transport device. Transport the sheets to the designated station on the pneumatic die-cutting machine, where they will be die-cut into 10cm x 10cm sheets. It should be noted that the entire process is carried out in a Class 100,000 cleanroom.

[0100] Step 5: Place the die-cut sheets from Step 4 into a sealed humidification chamber, set the chamber temperature to 37℃, and run for 3 hours. Then, pack them into a blister pack and seal it. It should be noted that the entire process is carried out in a Class 100,000 cleanroom.

[0101] Step Six: Apply the bagged sheet dressing from Step Five to Co twice consecutively. 60 Gamma-ray irradiation treatment, with the first irradiation dose being 10 kgy and the second irradiation dose being 25 kgy-35 kgy.

[0102] Step 7: Perform performance testing on the fibrous collagen sheet dressing from Step 6.

[0103] III. Performance Testing and Safety Testing

[0104] Table 5: Test Results of Example 1, Example 2 and Commercially Available Products

[0105]

[0106]

[0107] The test methods in Table 5 can be found in Table 6 below:

[0108] Table 6: Performance Testing and Safety Testing Methods

[0109]

[0110]

[0111] As can be seen from Table 5 above, compared with commercially available products, the performance and safety tests of samples prepared with different ratios and process parameters in Examples 1 and 2 of this application show that the collagen sheet dressing provided in this application has a longer in vitro degradation time and better biocompatibility.

[0112] IV. Thermal Stability (DSC) Analysis

[0113] The products in Example 1, Example 2, and the commercially available products were tested and characterized in accordance with Appendix C of GB / T 1453-2016 Characterization Method for Type I Collagen Sheets and Dressings of Tissue Engineering Medical Devices.

[0114] Please refer to the thermal stability curves of Example 1, Example 2, and commercially available products respectively. Figure 4 , Figure 5 and Figure 6 The triple helix structure of collagen sheet dressings is maintained by three polypeptide chains linked by hydrogen bonds. These hydrogen bonds are broken by heat, and the number of hydrogen bonds directly reflects the melting point. Determining the melting point of collagen sheet dressings can be used as a structural characterization to assess their thermal stability; higher temperatures indicate better thermal stability. Figure 4 , Figure 5 and Figure 6 It can be seen that the thermal stability of Examples 1 and 2 is better than that of commercially available products.

[0115] V. Scanning Electron Microscopy (SEM) Analysis

[0116] Scanning electron microscopy (SEM) can be used to observe the microscopic morphology, structure, and distribution of internal pores of a product.

[0117] Please refer to the electron microscope scan images of Examples 1 and 2 and commercially available products respectively. Figure 7 , Figure 8 and Figure 9 .Depend on Figure 7 , Figure 8 and Figure 9 It can be seen that Examples 1 and 2 have a denser structure compared to commercially available products.

[0118] In summary, the collagen sheet dressing provided in this application has the advantages of being dense, having good mechanical strength, being stable in degradation, having good biocompatibility, being non-toxic and safe, and being easy to use. Furthermore, the raw materials for the collagen sheet dressing are widely available, and the preparation method is simple, economical, and has broad prospects for industrialization.

[0119] The above description is merely an embodiment of this application and does not limit the patent scope of this application. Any equivalent structural or procedural transformations made using the content of this application's specification and drawings, or direct or indirect applications in other related technical fields, are similarly included within the patent protection scope of this application.

Claims

1. A method for preparing a collagen sheet dressing, characterized in that, include: Prepare a homogenized slurry; The homogenized slurry was dried to obtain a dried product; The humidity of the dried product is adjusted, and it is subjected to irradiation cross-linking and irradiation sterilization to form a collagen sheet dressing. The dressing comprises fibrous collagen, auxiliary ingredients, excipients, and a protective agent; the fibrous collagen has a solid content greater than 10 mg / ml; and the dressing has a unit area mass of 100 g / m². 2 -1000 g / m 2 The porosity of the dressing is less than 80%; the fiber length of the fibrous collagen raw material is 50 μm-500 μm. The auxiliary components include one or more of glycine, lysine, or tyrosine; The excipients include one or more of glycerol, ethanol, mannitol or isopropanol; The protective agent includes one or more of vitamin C, vitamin D, or vitamin E.

2. The method for preparing collagen sheet dressing as described in claim 1, characterized in that, The step of preparing the homogenized slurry includes: Weigh 100 parts of fibrous collagen raw material, 0-2 parts of auxiliary ingredients, 0-5 parts of excipients, and 0-1 parts of protective agent and add them to the reaction vessel; Add an acidic solution and stir to homogenize, forming a homogeneous slurry.

3. The method for preparing the collagen sheet dressing as described in claim 1, characterized in that, The step of forming a homogenized slurry is to form a homogenized slurry with a concentration of fibrous collagen of 10 mg / ml-50 mg / ml.

4. The method for preparing the collagen sheet dressing as described in claim 1, characterized in that, The step of drying the homogenized slurry to obtain a dried product includes: The homogenized slurry is freeze-dried to form an intermediate product; The intermediate product is subjected to heat treatment to form a dried product.

5. The method for preparing the collagen sheet dressing as described in claim 1, characterized in that, The steps of adjusting the humidity of the dried product and irradiating it include: After adjusting the humidity of the dried product to 10%-15%, it is subjected to irradiation cross-linking and irradiation sterilization to form the collagen sheet dressing.

6. The method for preparing the collagen sheet dressing as described in claim 1, characterized in that, The moisture content of the dressing is less than or equal to 17%.

7. The method for preparing the collagen sheet dressing as described in claim 1, characterized in that, The mechanical strength of the dressing is greater than or equal to 0.2 MPa.

8. The method for preparing the collagen sheet dressing as described in claim 1, characterized in that, The pH of the dressing is 4.0-7.

0.

9. The method for preparing the collagen sheet dressing as described in claim 1, characterized in that, The fibrous collagen can swell but not dissolve in acidic solutions at room temperature, with a swelling degree of 2-3.

10. The method for preparing the collagen sheet dressing as described in claim 1, characterized in that, The acidic solution includes one or more of hydrochloric acid, acetic acid, citric acid, or lactic acid.

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