Composite sponge and its preparation method, medical materials

Abstract

This application relates to the field of medical materials technology, and in particular to a composite sponge, its preparation method, and medical materials. The composite sponge includes an adjacent gel layer and a liquid-absorbing layer; wherein both the gel layer and the liquid-absorbing layer are porous sponge-like; the gel layer is made of gelatin and hyaluronic acid-based materials, and the liquid-absorbing layer is made of gelatin. The composite sponge provided by this application has high moisture retention and liquid absorption swelling properties.

Description

Technical Field

[0001] This application relates to the field of medical materials technology, and in particular to a composite sponge and its preparation method, as well as medical materials. Background Technology

[0002] Endoscopic functional nasal surgery is a common treatment in nasal surgery used to restore the normal structure of the nasal cavity, facilitating subsequent disease treatment. The surgery causes damage to the nasal mucosa, usually requiring packing to help stop bleeding. The packing needs to be removed again within 48 hours for subsequent debridement and medication. However, traditional packing is usually Vaseline gauze, which relies primarily on pressure for hemostasis, easily leading to headaches and other discomfort during the packing period. Furthermore, Vaseline gauze is not only non-biodegradable but also has limited absorbency, requiring timely removal or replacement. However, the friction between the Vaseline gauze and the nasal mucosal wound during removal is significant, causing secondary damage and potentially triggering further nasal bleeding, resulting in considerable discomfort for the patient.

[0003] Furthermore, during the healing process of the nasal mucosa, commonly used packing materials (such as Vaseline gauze, gelatin sponges alone, etc.) cannot maintain the necessary moist environment, which can irritate peripheral nerves and cause discomfort in the nasal cavity when breathing. Moreover, dry packing materials can easily lead to the formation of hard scabs on the wound, hindering wound cleaning and making it even more difficult to promote wound closure and epithelialization. Although some studies have shown that combining hyaluronic acid and gelatin sponges can prepare nasal hemostatic sponge materials, this mainly utilizes the fact that hyaluronic acid gelling can reduce the rate of liquid penetration and absorption, thereby inhibiting sponge expansion. It is primarily used in hemostasis scenarios where expansion and compression are undesirable, and therefore is not suitable for endoscopic nasal surgery. Summary of the Invention

[0004] Therefore, it is necessary to provide a composite sponge that can improve moisturizing properties, liquid absorption and swelling, and hemostatic effects, as well as its preparation method and medical material.

[0005] In a first aspect, this application provides a composite sponge, comprising: an adjacent gel layer and a liquid absorbent layer; both the gel layer and the liquid absorbent layer are porous sponge-like; the gel layer is made of gelatin and hyaluronic acid-based materials, and the liquid absorbent layer is made of gelatin.

[0006] In some embodiments, the hyaluronic acid-based material includes one or more of hyaluronic acid and its derivatives; the hyaluronic acid derivatives include one or more of sodium hyaluronate, calcium hyaluronate, and hyaluronic acid esters.

[0007] And / or, the gelatin in the liquid absorbent layer is cross-linked gelatin.

[0008] In some embodiments, the mass ratio of the gelatin to the hyaluronic acid material is 1:(0.01 to 15).

[0009] In some embodiments, the thicknesses of the gel layer and the liquid absorbent layer are each independently 0.5 mm to 25 mm;

[0010] And / or, the porosity of the composite sponge is 60% to 86%.

[0011] In some embodiments, the composite sponge is columnar or strip-shaped, and there are multiple gel layers and liquid absorption layers, which are alternately stacked.

[0012] In some embodiments, the composite sponge is columnar or strip-shaped, and the liquid-absorbing layer covers the outer peripheral surface of the gel layer; or

[0013] The gel layer covers the outer peripheral surface of the liquid absorption layer.

[0014] In some embodiments, the gel layer covers the entire outer peripheral surface of the liquid absorbent layer, and the outer peripheral surface of the gel layer has a plurality of through-holes penetrating the thickness of the gel layer, or the outer peripheral surface of the gel layer has a plurality of blind holes; and / or

[0015] The gel layer comprises multiple gel layer blocks, all of which are spaced apart on the outer peripheral surface of the liquid absorbent layer; and / or

[0016] The outer peripheral surface of the liquid absorption layer is also provided with multiple pore structures.

[0017] In some embodiments, the material of the gel layer and / or the material of the liquid absorbent layer further independently include adjuvants; the adjuvants include one or more of antimicrobial agents, glucocorticoids, hemostatic agents, surfactants, plasticizers, and odor modifiers;

[0018] The antimicrobial agents include one or more of the following: quaternized chitosan, polylysine, penicillins, cephalosporins, cephalosporins, lactams, carbapenems, penicillin, oxocephalosporins, aminoglycosides, tetracyclines, glycylcyclines, chloramphenicol, macrolides, lincosamides, rifamycins, glycopeptides, polymyxins, cyclic lipopeptides, oxazolidinones, fosfomycin, quinolones, sulfonamides, furans, nitroimidazoles, antimycobacterial drugs, and antifungal drugs.

[0019] The glucocorticoids include one or more of methylprednisolone, prednisone, mometasone furoate, prednisone, prednisolone, budesonide, dexamethasone, hydrocortisone, fluticasone propionate, beclomethasone propionate, triamcinolone acetonide, and fluticasone furoate.

[0020] The hemostatic agents include thrombin, clotting vitamin, aminocaproic acid, tranexamic acid, desmopressin, and recombinant human coagulation factor.

[0021] The surfactants include one or more of poloxamer, Span, polyoxyethylene fatty alcohol ethers, polyoxyethylene fatty acid esters, sorbitan esters, glyceryl stearate, polyethylene glycol, alkyl sulfonates, alkyl sulfates, and laurates;

[0022] The plasticizer includes one or more of glycerol, polyethylene glycol, sorbitol, mannitol, polysorbate, and polyglycerol;

[0023] The aroma modifier includes one or more of menthol, peppermint oil, menthol, camphor oil, and eucalyptus oil.

[0024] Secondly, this application also provides a method for preparing the composite sponge as described in the first aspect, comprising the following steps:

[0025] Solution A is foamed using a physical foaming process to form foaming liquid A, wherein solution A includes gelatin and hyaluronic acid materials;

[0026] Solution B is foamed using a physical foaming process to form foaming liquid B, wherein solution B includes gelatin; and

[0027] Foaming liquid A and foaming liquid B are injected into a mold and then freeze-dried to prepare the composite sponge.

[0028] In some embodiments, in solution A, the mass concentration of the gelatin is 2% to 10%, and the mass concentration of the hyaluronic acid material is 0.1% to 30%.

[0029] And / or, in solution B, the mass concentration of the gelatin is 0.01% to 10%;

[0030] And / or, the solvent in solution A and the solvent in solution B are each independently selected from water or a buffer solution; the buffer solution includes one or more of acetate buffer, citrate buffer, phosphate buffer, hydrogen phosphate buffer, carbonate buffer, and bicarbonate buffer.

[0031] In some embodiments, prior to the formation of solution B, a step of crosslinking the gelatin with a crosslinking agent is included;

[0032] And / or, the crosslinking agent is an aldehyde solvent, and the mass ratio of the gelatin to the crosslinking agent is 100:(0.01~10).

[0033] In some embodiments, the method further includes a step of compressing and shaping the obtained composite sponge; the compression and shaping step includes: wetting and heating the composite sponge, applying pressure to the composite sponge to obtain a compressed composite sponge, and drying the compressed composite sponge;

[0034] And / or, the preparation method further includes the step of perforating the obtained composite sponge to form through holes in the gel layer and / or the liquid absorption layer.

[0035] Thirdly, this application further provides a medical material comprising the composite sponge as described in the first aspect.

[0036] The composite sponge provided in this application is formed by combining components including hyaluronic acid and gelatin to form a gel layer, and by combining components including gelatin to form a liquid absorption layer, and then combining the gel layer and the liquid absorption layer to form a composite sponge with a layered structure.

[0037] In practice, it has been found that porous sponges made of gelatin have excellent water absorption and swelling properties. However, hyaluronic acid-based materials rapidly form a gel layer upon contact with water. This gel layer has high viscosity, which prevents liquid permeation. When hyaluronic acid-based substances are dispersed in a porous sponge, the high viscosity and low permeability of the gel layer inhibit the sponge's water absorption and swelling. This application proposes a layered (partitioned) structure design that spatially separates the liquid absorption and swelling effect of the gelatin sponge (liquid absorption layer) from the gelation of the hyaluronic acid-based materials (gel layer). Furthermore, the time for the liquid absorption layer of the gelatin sponge to absorb water and swell from a compressed state is typically less than 60 seconds, while the formation of a stable gel layer by hyaluronic acid usually takes several minutes, and under dynamic conditions, it may not even form a stable gel layer. The rate of liquid absorption and swelling of the liquid absorption layer is higher than the rate of gelation of the gel layer, creating a time difference between the liquid absorption and swelling effect of the gelatin sponge and the gelation process of the hyaluronic acid-based materials. This solves the problem that the gel layer formed by hyaluronic acid inhibits the liquid absorption and swelling of the liquid absorption layer. After the liquid-absorbing layer rapidly absorbs liquid and expands in volume, the interfacial forces can disrupt the integrity of the gel layer, further enhancing the liquid absorption capacity of the composite sponge. This also solves the problem of hyaluronic acid inhibiting the expansion of gelatin sponges after liquid absorption. Once the expansion of the liquid-absorbing layer reaches equilibrium, the hyaluronic acid molecules continue to swell, reforming the gel layer. The gel layer and the hyaluronic acid molecules diffusing from it can play a role in moisturizing and preventing adhesion.

[0038] The mechanical force generated by the rapid liquid absorption and expansion of the composite sponge can compress and promote the coagulation reaction, achieving rapid hemostasis. The basic material of the composite sponge is mainly gelatin. The abundant capillary micropores within the gelatin sponge can quickly absorb water from the blood, forcing the blood to concentrate locally; at the same time, gelatin can adsorb and activate platelets and cascade coagulation reactions, thus promoting coagulation.

[0039] Furthermore, the composite sponge provided in this application is mainly composed of biodegradable materials such as hyaluronic acid and gelatin. Therefore, the composite sponge can be completely or partially degraded by substances in the nasal mucosa and wound exudate / blood, disintegrating into fragments or completely liquefying. It can be easily removed or carried away by irrigation fluid, reducing the risk of re-damage to the nasal mucosa during postoperative packing removal and effectively reducing patient discomfort. Moreover, the degradation time of the biodegradable composite sponge is controllable, and the degradation products are safe. It can be placed in the nasal cavity for a relatively long time, playing a physical support and barrier role during the nasal mucosa healing process. This effectively inhibits postoperative edema, prevents adhesion of the nasal mucosa during healing, and significantly improves the success rate of endoscopic nasal surgery. In addition, the gel layer in the composite sponge has high moisturizing properties, which helps reduce stimulation of peripheral nerves, reduces nasal discomfort during breathing, and reduces the formation of hard crusts, facilitating wound cleaning and promoting wound closure and epithelialization.

[0040] In summary, the composite sponge provided in this application has excellent biodegradability, moisture retention, water absorption and swelling properties, anti-adhesion properties, and hemostatic effects.

[0041] Furthermore, the method for preparing the composite sponge provided in this application is simple and solves the problems of low liquid absorption saturation, poor expansion and moisture retention of traditional hemostatic sponges at a low cost. Attached Figure Description

[0042] In order to more clearly illustrate the specific implementation methods of the present application or the technical solutions in the prior art, the following is a brief introduction to the drawings required for use in the specific implementation methods or the description of the prior art. Obviously, the drawings described below are some implementation methods of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without any creative work.

[0043] Figure 1 This is a schematic diagram of the structure of the composite sponge prepared in Example 1;

[0044] Figure 2 and 3 The images shown are a side view and a top view of the composite sponge obtained in Example 1.

[0045] Figure 4 This is a photograph of the composite sponge with an inner dyed layer prepared in Example 1.

[0046] Figures 5-9 These are schematic diagrams of the composite sponges prepared in Examples 2, 3, and 6-8, respectively.

[0047] Figure 10 This is a photograph of the gelatin sponge prepared in Comparative Example 1.

[0048] Figure 11 This is a photograph of the hyaluronic acid-gelatin sponge prepared in Comparative Example 2.

[0049] Figure 12 The images show the actual products of the sponges prepared in Example 1, Comparative Examples 1 and 2 after absorbing liquid for 10 seconds.

[0050] Figure 13 and 14 These are actual images of Example 1 and Comparative Example 2 after being immersed in the buffer solution for approximately 30 seconds;

[0051] Figure 15 The images show a comparison of the moisturizing properties of Example 1, Comparative Example 1, and commercially available sponges.

[0052] Figure labeling: 100: gel layer; 110: gel layer block; 200: liquid absorption layer; 300: through-hole. Detailed Implementation

[0053] To facilitate understanding of this application, a more complete description will be provided below with reference to the accompanying drawings. Preferred embodiments of this application are shown in the drawings. However, this application can be implemented in many different forms and is not limited to the embodiments described herein. Rather, these embodiments are provided to provide a thorough and complete understanding of the disclosure of this application.

[0054] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. The term "and / or" as used herein includes any and all combinations of one or more of the associated listed items.

[0055] Traditional gelatin hemostatic sponges are brittle when dry and typically have a hydrophobic surface, requiring them to be thoroughly soaked in water and squeezed dry before use, which is inconvenient. While gelatin sponges can absorb large amounts of liquid due to their numerous pores, their moisture retention is weak. After clotting, the gelatin sponge adheres to the wound, and fragmented pieces become embedded in the scab, easily causing secondary damage during cleaning. Hyaluronic acid and its derivatives-based hemostatic products are expensive, brittle, have poor liquid absorption, and exhibit poor mechanical and coagulation properties. Currently, a method of uniformly mixing hyaluronic acid and gelatin produces a sponge material with low liquid penetration and absorption rates, inhibiting sponge expansion. Sponges prepared using this method are only suitable for certain surgical procedures requiring low expansion and anti-adhesion hemostatic materials. However, functional ear and nose surgeries require hemostatic materials with sufficient support to compress the wound, prevent mucosal adhesion, and fully degrade over time. Traditionally prepared hyaluronic acid-containing gelatin sponges cannot meet these requirements. Therefore, this application provides a composite sponge made of hyaluronic acid and gelatin for nasal hemostasis and its preparation method, so as to improve the sponge's moisture retention, anti-adhesion and expansion support properties.

[0056] In a first aspect, this application provides a composite sponge, comprising: an adjacent gel layer and a liquid absorbent layer; wherein both the gel layer and the liquid absorbent layer are porous sponge-like; the gel layer is made of gelatin and hyaluronic acid-based materials, and the liquid absorbent layer is made of gelatin.

[0057] The composite sponge provided in this application is formed by combining components including hyaluronic acid and gelatin to form a gel layer, and by combining components including gelatin to form a liquid absorption layer, and then combining the gel layer and the liquid absorption layer to form a composite sponge with a layered structure.

[0058] In practice, it has been found that porous sponges made of gelatin have excellent water absorption and swelling properties. However, hyaluronic acid-based materials rapidly form a gel layer upon contact with water. This gel layer has high viscosity, which prevents liquid permeation. When hyaluronic acid-based substances are dispersed in a porous sponge, the high viscosity and low permeability of the gel layer inhibit the sponge's water absorption and swelling. This application proposes a layered (partitioned) structure design that spatially separates the liquid absorption and swelling effect of the gelatin sponge (liquid absorption layer) from the gelation of the hyaluronic acid-based materials (gel layer). Furthermore, the time for the liquid absorption layer of the gelatin sponge to absorb water and swell from a compressed state is typically less than 60 seconds, while the formation of a stable gel layer by hyaluronic acid usually takes several minutes, and under dynamic conditions, it may not even form a stable gel layer. The rate of liquid absorption and swelling of the liquid absorption layer is higher than the rate of gelation of the gel layer, creating a time difference between the liquid absorption and swelling effect of the gelatin sponge and the gelation process of the hyaluronic acid-based materials. This solves the problem that the gel layer formed by hyaluronic acid inhibits the liquid absorption and swelling of the liquid absorption layer. After the liquid-absorbing layer rapidly absorbs liquid and expands in volume, the interfacial forces can disrupt the integrity of the gel layer, further enhancing the liquid absorption capacity of the composite sponge. This also solves the problem of hyaluronic acid inhibiting the expansion of gelatin sponges after liquid absorption. Once the expansion of the liquid-absorbing layer reaches equilibrium, the hyaluronic acid molecules continue to swell, reforming the gel layer. The gel layer and the hyaluronic acid molecules diffusing from it can play a role in moisturizing and preventing adhesion.

[0059] The mechanical force generated by the rapid liquid absorption and expansion of the composite sponge can compress and promote the coagulation reaction, achieving rapid hemostasis. The basic material of the composite sponge is mainly gelatin. The abundant capillary micropores within the gelatin sponge can quickly absorb water from the blood, forcing the blood to concentrate locally; at the same time, gelatin can adsorb and activate platelets and cascade coagulation reactions, thus promoting coagulation.

[0060] Furthermore, the composite sponge provided in this application is mainly composed of biodegradable materials such as hyaluronic acid and gelatin. Therefore, the composite sponge can be completely or partially degraded by substances in the nasal mucosa and wound exudate / blood, disintegrating into fragments or completely liquefying. It can be easily removed or carried away by irrigation fluid, reducing the risk of re-damage to the nasal mucosa during postoperative packing removal and effectively reducing patient discomfort. Moreover, the degradation time of the biodegradable composite sponge is controllable, and the degradation products are safe. It can be placed in the nasal cavity for a relatively long time, playing a physical support and barrier role during the nasal mucosa healing process. This effectively inhibits postoperative edema, prevents adhesion of the nasal mucosa during healing, and significantly improves the success rate of endoscopic nasal surgery. In addition, the gel layer in the composite sponge has high moisturizing properties, which helps reduce stimulation of peripheral nerves, reduces nasal discomfort during breathing, and reduces the formation of hard crusts, facilitating wound cleaning and promoting wound closure and epithelialization.

[0061] In summary, the composite sponge provided in this application has excellent biodegradability, moisture retention, water absorption and swelling properties, anti-adhesion properties, and hemostatic effects.

[0062] It is understood that the matrix material of the composite sponge provided in this application is mainly gelatin. Since both the gel layer and the liquid absorption layer are based on gelatin, the interfacial bonding is good. Therefore, the composite sponge does not have a "macroscopic interface" in appearance, but appears as a single material.

[0063] In this application, the shape of the composite sponge is not limited and can be selected according to the actual application scenario. As an example, to meet the needs of nasal cavity use, the composite sponge in this application can be cylindrical, prismatic (strip), sheet, cube, or spherical. Considering the need for hemostasis after ENT surgeries such as nasal cavity and ear canal surgery, the composite sponge is preferably long strip (i.e., cylindrical or prismatic) for easy packing.

[0064] In some embodiments, hyaluronic acid-based materials include one or more of hyaluronic acid and its derivatives. In this application, the hyaluronic acid derivatives are not limited; any substance with good moisturizing properties and suitable for medical materials can be selected. In some embodiments, the hyaluronic acid derivatives include hyaluronic acid salts and hyaluronic acid esters. Specifically, the hyaluronic acid salt can be sodium hyaluronate and / or calcium hyaluronic acid.

[0065] Hyaluronic acid materials exhibit variations in weight-average molecular weight distribution due to differences in production methods and purification techniques. In this application, the hyaluronic acid material is selected based on its ability to swell in water, form a mixed solution with gelatin, and generate stable foam. Preferably, the hyaluronic acid derivative is sodium hyaluronate; wherein the weight-average molecular weight of sodium hyaluronate is 30 kDa to 3000 kDa.

[0066] In some embodiments, the gelatin in the gel layer can be cross-linked gelatin and / or uncross-linked gelatin; the gelatin in the liquid absorbent layer is cross-linked gelatin. The use of cross-linked gelatin in the liquid absorbent layer is primarily to improve the stability and support properties of the sponge after wetting, thereby enhancing the compressive hemostasis and space-occupying capacity of the composite sponge after absorbing blood. It also allows the liquid absorbent layer to swell but not dissolve in aqueous solutions. Cross-linked gelatin refers to the introduction of a new three-dimensional network structure into the gelatin system, increasing its structural stability. The use of cross-linked gelatin in the gel layer can improve the stability of the gel layer and prolong the degradation time. It can be understood that the degradation rate of the gelatin sponge can be altered by adjusting the degree of cross-linking of the gelatin.

[0067] In this application, the source of gelatin is not limited, and those skilled in the art can choose according to actual needs; it can be derived from animal skin or animal bones. In some embodiments, the gelatin is pigskin gelatin with a gel strength of 150g to 350g.

[0068] In some embodiments, the mass ratio of hyaluronic acid-based material to gelatin is 1:(0.01-15), for example, 1:0.05, 1:0.1, 1:0.12, 1:0.125, 1:0.15, 1:0.2, 1:0.5, 1:1, 1:2, 1:5, 1:8, 1:10, 1:12, 1:13, 1:14; preferably, the mass ratio of hyaluronic acid-based material to gelatin is 1:(0.07-0.28). Controlling the mass ratio of gelatin to hyaluronic acid-based material within the above range can further improve the foaming performance of the solution and the water absorption, swelling, and moisturizing properties of the composite sponge.

[0069] In some embodiments, the thicknesses of the gel layer and the liquid absorbent layer are independently 0.5 mm to 25 mm, for example, 1 mm, 2 mm, 5 mm, 8 mm, 10 mm, 12 mm, 13 mm, 15 mm, 18 mm, 20 mm, and 22 mm. Adjusting the thicknesses of the gel layer and the liquid absorbent layer within this range allows for further adjustment of the composite sponge's water absorption, swelling, and moisture retention properties. With the same total thickness of the composite sponge, increasing the thickness of the gel layer enhances moisture retention; increasing the thickness of the liquid absorbent layer improves the sponge's swelling and support.

[0070] The porosity of the composite sponge in this application is not limited; any porosity obtainable using processes commonly employed in the field of medical materials is acceptable. In some embodiments, the porosity of the composite sponge is 60%–86%. By controlling the porosity of the composite sponge within this range, its liquid absorption capacity can be further improved while ensuring the sponge's formability, toughness, and stability.

[0071] In some embodiments, the adjacent gel layer and liquid absorbent layer refer to the gel layer and liquid absorbent layer being stacked sequentially. It can be understood that in this structural relationship, the liquid absorbent layer rapidly absorbs liquid and expands in volume. The principle that this expansion, under interfacial forces, can disrupt the integrity of the gel layer is that the increased volume of the liquid absorbent layer exerts a "pull-out" effect on the gel layer, thereby destroying its integrity.

[0072] In the composite sponge provided in this application, the gel layer and liquid absorbent layer with a partitioned structure can be arranged in different combinations in the radial and axial directions. In some embodiments, the composite sponge is columnar or strip-shaped, with multiple gel layers and liquid absorbent layers, which are alternately stacked. The stacking direction is along the height direction of the columnar liquid absorbent layer or the length direction of the strip-shaped liquid absorbent layer. When the composite sponge is used in the nasal cavity, preferably, the alternating stacking direction of the gel layer and liquid absorbent layer is consistent with the nasal cavity direction. Setting the stacking direction along the height direction of the columnar liquid absorbent layer or the length direction of the strip-shaped liquid absorbent layer can better exert the liquid absorption and swelling effect and moisturizing effect of the composite sponge.

[0073] In some embodiments, the adjacent gel layer and liquid absorbent layer refer to a coating relationship between the gel layer and the liquid absorbent layer, that is, one layer is used as the core layer structure and the other as the surface layer structure. In this application, the gel layer (liquid absorbent layer) coating the surface of the liquid absorbent layer (gel layer) can specifically mean that the gel layer (liquid absorbent layer) completely encapsulates the liquid absorbent layer (gel layer); or

[0074] The gel layer (liquid absorbent layer) partially encapsulates the liquid absorbent layer (gel layer).

[0075] Partial wrapping specifically refers to the gel layer (liquid absorbent layer) being flush with the end of the liquid absorbent layer (gel layer) while wrapping the sidewall portion; or, the gel layer (liquid absorbent layer) wrapping a portion of the liquid absorbent layer (gel layer) body while leaving the rest intact.

[0076] In some embodiments, the composite sponge is columnar or strip-shaped, with the liquid-absorbing layer covering the outer peripheral surface of the gel layer. It can be understood that, under this structural relationship, the liquid-absorbing layer rapidly absorbs liquid and expands in volume. The principle that this expansion, under interfacial forces, can disrupt the integrity of the gel layer is that the increased volume of the liquid-absorbing layer exerts a "pull-out" effect on the gel layer, thereby destroying its integrity.

[0077] In some embodiments, the composite sponge is columnar or strip-shaped, with the gel layer covering the outer peripheral surface of the liquid absorbent layer. It can be understood that, under this structural relationship, the liquid absorbent layer rapidly absorbs liquid and expands in volume. The principle that the expansion of the liquid absorbent layer's volume can disrupt the integrity of the gel layer under interfacial forces is that the increased volume of the liquid absorbent layer exerts a pushing force on the gel layer, thereby "expanding" the gel layer and disrupting its integrity.

[0078] To shorten the time it takes for liquid to pass through the gel layer, that is, to allow the liquid absorption layer to come into contact with the external liquid more quickly and fully, the gel layer can also be made into a discontinuous structure.

[0079] In some embodiments, the gel layer covers the entire outer peripheral surface of the liquid-absorbing layer, and the outer peripheral surface of the gel layer has multiple through-holes penetrating the thickness of the gel layer, or multiple blind holes are formed on the outer peripheral surface of the gel layer. It can be understood that the through-holes penetrate the gel layer directly to the liquid-absorbing layer. By providing through-holes or blind holes, the liquid permeation rate can be increased, thereby further improving the liquid absorption rate and expansion rate of the composite sponge.

[0080] In some embodiments, the outer peripheral surface of the liquid-absorbing layer is further provided with multiple pore structures. Specifically, these pore structures can be through-holes and / or blind pores. Providing pore structures on both the gel layer and the liquid-absorbing layer can further improve the liquid absorption rate and expansion rate of the composite sponge. It is understood that the pore structures on the gel layer and the liquid-absorbing layer can be arranged in a one-to-one correspondence or staggered arrangement.

[0081] In this application, the shape, size, and number of through holes or blind holes are not limited, as long as they can simultaneously balance the structural stability and liquid absorption capacity of the composite sponge. For example, the cross-section of the through holes or blind holes can be circular, regular polygonal, or irregular polygonal.

[0082] In some embodiments, the gel layer comprises multiple gel layer blocks, all spaced apart across the entire outer periphery of the liquid-absorbing layer. The spacing between these blocks is not limited, as long as they do not completely cover the liquid-absorbing layer. Similar to creating through-holes in the gel layer, the spaced arrangement of the gel layer blocks can further enhance the liquid absorption and swelling rates of the composite sponge. As the hyaluronic acid-like substances in the gel layer swell / dissolve, a gel layer is eventually formed on the entire exterior of the composite sponge.

[0083] The gel layer blocks can be cylinders, regular polyhedra, or irregular polyhedra; regular polyhedra can be cuboids (strips), cubes, etc. More preferably, the composite sponge is columnar or strip-shaped, the gel layer blocks are strip-shaped, and multiple gel layer blocks are arranged at intervals parallel to the height of the columnar liquid absorption layer or the length of the strip-shaped liquid absorption layer.

[0084] In some embodiments, the materials of the gel layer and / or the liquid absorbent layer also independently include additives. The type and amount of additives are not limited; commonly used additives and amounts in the field of medical sponge preparation can be selected. In this application, the amount of additives is based on the gelatin content in each layer. In this application, the amount of additives is not limited; those skilled in the art can select them according to their efficacy and actual needs. For example, the mass fraction of antimicrobial agents may be <1%, the mass fraction of glucocorticoids <1%, the mass fraction of hemostatic agents <5%, the mass fraction of surfactants <1%, the mass fraction of plasticizers <10%, and the mass fraction of odor modifiers <0.1%.

[0085] In some embodiments, the additives include one or more of antimicrobial agents, glucocorticoids, hemostatic agents, surfactants, plasticizers, and odor modifiers. Surfactants can stabilize the foaming of the composite sponge during the molding process, which is beneficial to the sponge molding; odor modifiers can provide a pleasant odor. Among them, antimicrobial agents may include one or more of the following: quaternized chitosan, polylysine, penicillins, cephalosporins, cephalosporins, lactams, carbapenems, penicillin derivatives, oxocephalosporins, aminoglycosides, tetracyclines, glycylcyclines, chloramphenicol, macrolides, lincosamides, rifamycins, glycopeptides, polymyxins, cyclic lipopeptides, oxazolidinones, fosfomycin, quinolones, sulfonamides, furans, nitroimidazoles, antimycobacterial drugs, and antifungal drugs; glucocorticoids may include one or more of the following: methylprednisolone, prednisone, mometasone furoate, prednisone, prednisolone, budesonide, dexamethasone, hydrocortisone, fluticasone propionate, beclomethasone propionate, triamcinolone, and fluticasone furoate; hemostatic agents may include thrombin and clotting vitamins. Vitamin K, aminocaproic acid, tranexamic acid, desmopressin, and recombinant human coagulation factor; surfactants mainly include anionic surfactants and / or nonionic surfactants; nonionic surfactants include one or more of poloxamer, Span, polyoxyethylene fatty alcohol ethers, polyoxyethylene fatty acid esters (Tween), sorbitan esters, glyceryl stearate, and polyethylene glycol; anionic surfactants include one or more of alkyl sulfonates, alkyl sulfates (sodium lauryl sulfate), and laurates (sodium lauryl and / or potassium lauryl); plasticizers include one or more of glycerin, polyethylene glycol, sorbitol, mannitol, polysorbate, and polyglycerol; odor modifiers include one or more of menthol, peppermint oil, menthol, camphor oil, and eucalyptus oil.

[0086] Secondly, this application also provides a method for preparing the composite sponge as described in the first aspect, comprising the following steps:

[0087] Solution A is foamed using a physical foaming process to form foaming liquid A, wherein solution A includes gelatin and hyaluronic acid materials;

[0088] Solution B is foamed using a physical foaming process to form foaming liquid B, wherein solution B includes gelatin; and

[0089] Foaming liquid A and foaming liquid B are injected into a mold and then freeze-dried to prepare a composite sponge.

[0090] The method for preparing the composite sponge provided in this application is simple and solves the problems of low liquid absorption saturation, poor expansion and moisture retention of traditional hemostatic sponges at a low cost.

[0091] In this application, physical foaming specifically refers to the method of creating pores by dispersing gas in a material. Common methods include: agitation foaming, agitation foaming with gas filling, high-speed convection mixing of gas, and supercritical gas foaming. In this application, injecting foaming liquid A and foaming liquid B into the mold specifically refers to injecting the fluid foaming liquid A and foaming liquid B into the mold to obtain a distributed foam structure. The fluidity of the foam is restricted by cooling to obtain a stable foam. In some embodiments, the method used to inject foaming liquid A and foaming liquid B into the mold includes injecting the foam into the mold using multi-layer coaxial channels (coaxial extrusion process), or injecting the foam into different areas of the mold using partitions (partition injection). The coaxial extrusion process can produce a composite sponge with a covered structure, while the partition injection process can produce a composite sponge with a layered structure. When both foaming liquid A and foaming liquid B have fluidity, a specific combined structure can be obtained through specific equipment. Foaming liquids A and B can fully fuse at the interface, and the composite sponge obtained after freeze-drying has no macroscopic interfacial gaps.

[0092] In some embodiments, the mass concentration of gelatin in solution A is 2% to 10%, for example, 2%, 4%, 5%, 6%, 7%, 8%, or 9%; and the mass concentration of hyaluronic acid-based materials is 0.1% to 30%, for example, 0.5%, 1%, 2%, 5%, 8%, 10%, 12%, 15%, 18%, 20%, 22%, 25%, or 28%.

[0093] In this application, the mass concentration of gelatin in solution B is not limited, as long as it can be formed into a sponge. In some embodiments, the mass concentration of gelatin is 0.01% to 10%.

[0094] In some embodiments, the solvent in solution A and the solvent in solution B are each independently selected from water or a buffer solution; the buffer solution includes one or more of acetate buffer, citrate buffer, phosphate buffer, hydrogen phosphate buffer, carbonate buffer, and bicarbonate buffer.

[0095] In some embodiments, the pH of the buffer solution is 6.5 to 7.5, and the osmotic pressure is preferably isotonic.

[0096] In this application, the freeze-drying conditions are not limited, as long as they enable the sponge to be molded. In some embodiments, the freeze-drying temperature is -20°C to -40°C, and the time is 4 hours to 48 hours.

[0097] In some embodiments, before forming solution B, a step of crosslinking the gelatin with a crosslinking agent is included. The method for crosslinking the gelatin is chemical crosslinking.

[0098] The crosslinking agent is an aldehyde solvent; the aldehyde solvent is mainly selected from lower aldehydes that are soluble in water. In some embodiments, the aldehyde solvent includes one or more of formaldehyde, acetaldehyde, and glyoxal. Formaldehyde is preferred, for example, a formaldehyde solution with a mass concentration of 37%.

[0099] In this application, the mass ratio of gelatin to crosslinking agent is not limited, but is determined by the residual limit that enables the gelatin to crosslink and meets the relevant standard requirements. In some embodiments, the mass ratio of gelatin to crosslinking agent is 100:(0.1 to 1).

[0100] In some embodiments, the process further includes a compression and shaping step of the prepared composite sponge. For ease of application, the compression and shaping process can also be used to compress the composite sponge into a sheet-like sponge material. In some embodiments, the compression and shaping step includes: wetting and heating the composite sponge, pressurizing the composite sponge to obtain a compressed composite sponge, and drying the compressed composite sponge. The wetting medium can be water vapor; the pressurization standard is to reduce the thickness of the composite sponge to 20% of its original thickness; the drying method can specifically be: drying with hot air at 50℃~120℃ for 0.5h~4h. Compression and shaping can obtain a sheet-like composite sponge with stable dimensions and structure, thus providing sufficient field of vision for doctors when applied to hemostasis after nasal or other cavity surgeries, facilitating observation of wound bleeding and the placement of hemostatic materials. Furthermore, compression and shaping can yield composite sponges with a higher expansion ratio.

[0101] In some embodiments, the preparation method further includes the step of perforating the obtained composite sponge to form through-pores in the gel layer and / or liquid absorption layer.

[0102] Thirdly, this application further provides a medical material comprising the composite sponge as described in the first aspect.

[0103] In some implementations, the medical material is a hemostatic sponge for the nasal cavity or a sponge dressing for wound care.

[0104] The present application will be further described in detail below with reference to specific embodiments.

[0105] Example 1

[0106] 1) By weight, 100 parts of gelatin with a freezing power of 250g, 12.5 parts of sodium hyaluronate with a weight average molecular weight of 1700kDa, 2 parts of polyethylene glycol 600, 2 parts of glycerin, 0.01 parts of menthol, and 0.01 parts of sodium lauryl sulfate were dissolved in deionized water and stirred continuously at 55°C until homogeneous. The mixture was then cooled to 35°C, and 0.3 parts of a 37% formaldehyde solution were added for an 8-hour crosslinking reaction to obtain solution A. The mass concentration of gelatin in solution A was 4%. Solution A was then subjected to physical foaming to obtain foaming liquid A. The physical foaming conditions were as follows: a mechanical stirrer with a rotation speed of 1100 rpm was used, the water bath temperature was maintained at 30°C–40°C, and stirring was continued until the foam was uniform and the foam volume no longer increased.

[0107] 2) By weight, dissolve 100 parts of gelatin with a freezing power of 250g, 2 parts of polyethylene glycol 600, 2 parts of glycerin, 0.01 parts of menthol, and 0.01 parts of sodium lauryl sulfate in deionized water and continuously stir and mix evenly at 55℃. Then cool to 35℃ and add 1 part of formaldehyde solution with a mass concentration of 37% for 8 hours of crosslinking reaction to obtain solution B; the mass concentration of gelatin in solution B is 8%. Then, physical foaming is performed on solution B to obtain foaming liquid B, wherein the physical foaming conditions are as follows: use a mechanical stirrer with a speed of 1100rpm, maintain the water bath temperature at 30℃~40℃, and stir until the foam is uniform and the foam volume no longer increases.

[0108] 3) Foaming liquids A and B are extruded into a mold using a multi-layer coaxial extrusion process. Foaming liquid A is located in the outer flow channel, and foaming liquid B is located in the inner flow channel. After the foam fuses, it is stored at 4℃ for 0.5 hours under saturated humidity to obtain relatively stable foam. Then, it is frozen at -40℃ for 24 hours and vacuum dried for 48 hours. The resulting foam is as shown in the image. Figure 1 The composite sponge shown is composed of an outer gel layer (layer A) 100 and an inner liquid absorbent layer (layer B) 200.

[0109] A physical image of the composite sponge prepared in this embodiment is shown below. Figure 2 and 3 As shown. Among them, Figure 2 (a) and Figure 3 (a) are the side view and top view of the composite sponge prepared in this embodiment, respectively. Figure 2 and 3 It can be seen that the dimensions of the composite sponge prepared in this embodiment are: length: 40mm, width: 20mm, thickness: 15mm; that is, the gel layer 100 is 40mm long, 20mm wide, and 3.5mm thick, and the liquid absorption layer 200 is 40mm long, 13mm wide, and 8mm thick.

[0110] Considering the need for a certain field of vision in the actual operation of hemostasis in cavities such as the nasal cavity, a portion of the dried composite sponge was further moistened with steam for 10 seconds, pressurized for 1 minute using a tableting device, the pressing mold was locked, and the sponge was transferred to a 50°C oven to dry for 24 hours, thus producing a product as shown in the image. Figure 2 (b) and Figure 3 (b) shows the sheet-like composite sponge. Figure 2 (b) and Figure 3 (b) are the side and top views of the sheet-like composite sponge, respectively. Figure 2 (b) and Figure 3 (b) It can be seen that the dimensions of the sheet-like composite sponge are: length: 40mm, width: 20mm, thickness: 1.5mm.

[0111] To facilitate observation of the structure of the composite sponge prepared in this embodiment. For example... Figure 4 As shown, during the preparation process, a water-soluble red dye was used to mark the inner liquid absorption layer 200, resulting in a composite sponge with a red inner layer and a white outer layer.

[0112] Example 2

[0113] The preparation method in this embodiment is basically the same as that in Embodiment 1, except that the foaming liquid A channel is set as the inner layer and the foaming liquid B channel is set as the outer layer. In the prepared composite sponge, the gel layer (layer A) 100 is the inner layer and the liquid absorption layer (layer B) 200 is the outer layer. The dimensions of the composite sponge prepared in this embodiment are: length: 40mm, width: 20mm, thickness: 15mm; that is, the gel layer 100 is 40mm long, 13mm wide, and 8mm thick, and the liquid absorption layer 200 is 40mm long, 20mm wide, and 3.5mm thick. A schematic diagram of the structure of the composite sponge prepared in this embodiment is shown below. Figure 5 As shown.

[0114] Example 3

[0115] The preparation method in this embodiment is basically the same as that in Example 1. The difference is that, in order to set the through holes 300, a perforation step needs to be added before freeze-drying. The freeze-fixed foam is removed, and the freezing conditions are maintained. Through holes 300 are set on the gel layer 100, penetrating the thickness direction of the gel layer 100. The diameter of the through holes 300 is 2 mm, thus obtaining the product as shown in Example 1. Figure 6 The image shows a composite sponge with an outer gel layer (layer A) 100 and an inner liquid absorbent layer (layer B) 200. The gel layer 100 is 40 mm long, 20 mm wide, and 3.5 mm thick, while the liquid absorbent layer 200 is 40 mm long, 13 mm wide, and 8 mm thick.

[0116] By providing through holes 300 on the liquid absorption layer 200, liquid (blood) can easily pass through the gel layer 100 to reach the liquid absorption layer 200 and be absorbed as quickly as possible, thereby achieving a faster hemostatic effect.

[0117] Example 4

[0118] The preparation method of this embodiment is basically the same as that of embodiment 3, except that: both the gel layer 100 and the liquid absorption layer 200 are provided with through holes 300, the diameter of the through holes 300 is 2mm, and the depth of the through holes 300 on the liquid absorption layer 200 is 20% of the thickness of the liquid absorption layer 200.

[0119] Example 5

[0120] The preparation method of this embodiment is basically the same as that of embodiment 3, except that: both the gel layer 100 and the liquid absorption layer 200 are provided with through holes 300, and the through holes 300 on the liquid absorption layer 200 penetrate through the thickness direction of the liquid absorption layer 200.

[0121] Example 6

[0122] The preparation method in this embodiment is basically the same as that in Example 1, except for the shape of the runner and mold used. By selecting the runner and mold, a product is obtained as shown... Figure 7 The composite sponge shown is made of... Figure 7 It is known that the gel layer (layer A) 100 of the composite sponge includes multiple strip-shaped gel layer blocks 110, which are spaced apart on the outer circumferential surface along the length of the liquid absorption layer (layer B) 200; wherein each gel layer block 110 is 40mm long, 4mm wide, and 3.5mm thick, and the spacing between two adjacent gel layer blocks 110 is 3mm, and the liquid absorption layer 200 is 40mm long, 13mm wide, and 8mm thick.

[0123] Example 7

[0124] The preparation method in this embodiment is basically the same as that in Example 6, except that the strip-shaped gel layer 100 on each side of the frozen foam is cut, that is, the long strip-shaped gel layer 100 is transformed into a block shape. Multiple gel layer blocks 110 are cuboid in shape. Figure 8 As shown, multiple gel layer blocks 110 are arranged at intervals on the outer peripheral surface of the liquid absorption layer (B layer) 200; wherein, each gel layer block 110 is 4mm long, 4mm wide, and 3.5mm thick, and the distance between two adjacent gel layer blocks 110 along the axial direction of the composite sponge is 4mm, and the distance perpendicular to the axial direction is 3mm. The liquid absorption layer 200 is 40mm long, 13mm wide, and 8mm thick.

[0125] Example 8

[0126] The preparation method in this embodiment is basically the same as that in Example 1, except that a mold with partitions is used for foaming to obtain the product shown in the example. Figure 9 The composite sponge shown is made of... Figure 9 As can be seen, the composite sponge prepared in this embodiment is formed by alternating layers of two gel layers 100 and two liquid absorbent layers 200. The dimensions of the composite sponge are: length: 40mm, width: 20mm, thickness: 15mm; that is, each gel layer 100 has a length of 10mm, a width of 20mm, and a thickness of 3.75mm; each liquid absorbent layer 200 has a length of 10mm, a width of 20mm, and a thickness of 3.75mm.

[0127] Comparative Example 1

[0128] The sponge prepared in this comparative example is a single-layer pure gelatin sponge. That is, the sponge has the same appearance as that in Example 1, only the composition is different.

[0129] The specific steps are as follows:

[0130] 1) By weight, dissolve 100 parts of gelatin with a freezing power of 250g, 2 parts of polyethylene glycol 600, 2 parts of glycerin, 0.01 parts of menthol, and 0.01 parts of sodium lauryl sulfate in deionized water and continuously stir and mix evenly at 55°C. Then cool to 35°C and add 1 part of formaldehyde solution with a mass concentration of 37% for 8 hours of crosslinking reaction to obtain solution B; the mass concentration of gelatin in solution B is 8%. Then, solution B is physically foamed to obtain foaming liquid B, wherein the physical foaming conditions are as follows: use a mechanical stirrer with a speed of 1100rpm, maintain the water bath temperature at 30°C~40°C, and stir until the foam is uniform and the foam volume no longer increases.

[0131] 2) Inject foaming liquid B into the mold and freeze-dry at -40℃ for 24 hours to obtain pure gelatin sponge. A picture of the actual product is shown below. Figure 10 As shown in (a). Using the same compression and shaping process as in Example 1, it was compressed to obtain the product shown in [a]. Figure 10 (b) shows a sheet-like gelatin sponge.

[0132] Comparative Example 2

[0133] The sponge prepared in this comparative example is a single-layer hyaluronic acid-gelatin sponge. The aim is to prepare a sponge with the same appearance as Example 1, but different in composition.

[0134] The specific steps are as follows:

[0135] 1) By weight, 100 parts of gelatin with a freezing power of 250g, 12.5 parts of sodium hyaluronate with a weight-average molecular weight of 1700kDa, 2 parts of polyethylene glycol 600, 2 parts of glycerin, 0.01 parts of menthol, and 0.01 parts of sodium lauryl sulfate were dissolved in deionized water and stirred continuously at 55°C until homogeneous. The mixture was then cooled to 35°C, and 0.3 parts of a 37% formaldehyde solution were added for an 8-hour crosslinking reaction to obtain solution A. The mass concentration of gelatin in solution A was 4%. Solution A was then subjected to physical foaming to obtain foaming liquid A. The physical foaming conditions were as follows: a mechanical stirrer with a rotation speed of 1100 rpm was used, the water bath temperature was maintained at 30°C–40°C, and stirring was continued until the foam was uniform and the foam volume no longer increased.

[0136] 2) Inject foaming liquid A into a mold and freeze-dry at -40℃ for 24 hours to obtain hyaluronic acid-gelatin composite sponge. A picture of the actual product is shown below. Figure 11 As shown in (a). After compression, it is obtained as shown. Figure 11 (b) shows a sheet-like hyaluronic acid-gelatin composite sponge.

[0137] Comparative Example 3

[0138] The sponge prepared in this comparative example is a single-layer hyaluronic acid-gelatin composite sponge. The preparation method of this comparative example is basically the same as that of comparative example 2, except that: the outer peripheral surface of the prepared hyaluronic acid-gelatin composite sponge is provided with through holes 300, and the through holes 300 penetrate through the thickness direction of the hyaluronic acid-gelatin composite sponge.

[0139] Comparative Example 4

[0140] The sponge prepared in this comparative example is a hyaluronic acid-gelatin composite sponge. The preparation method of this comparative example is basically the same as that of comparative example 2, except that: multiple long strips of hyaluronic acid-gelatin composite sponge are arranged at intervals along the length of the hyaluronic acid-gelatin composite sponge on the outer peripheral surface of the hyaluronic acid-gelatin composite sponge.

[0141] The raw materials used in the preparation methods of Examples 1-8 and Comparative Examples 1-4 are listed in Table 1 below:

[0142] Table 1

[0143]

[0144]

[0145] Note: " / " indicates that the component was not added or the content of the component is 0.

[0146] The liquid absorption rate and swelling properties of the sponge materials prepared in Examples 1-7 and Comparative Examples 1-4 were tested. The test conditions for each performance item are as follows:

[0147] Each group of thin-sheet sponges of the same size was immersed in a phosphate buffer solution with a pH of 5.9–7.4, and the sponge absorption and swelling were observed. The sponge thickness measured at different time periods is shown in Table 2.

[0148] Table 2

[0149]

[0150] Images of the sponges prepared in Example 1, Comparative Examples 1 and 2 after absorbing liquid for 10 seconds are shown below. Figure 12 (a) Figure 12 (b) and Figure 12As shown in (c). From the above test results and data, it can be seen that the pure gelatin sponge in Comparative Example 1 has good wetting and liquid absorption swelling properties. After contacting the buffer solution, it can quickly absorb liquid and expand rapidly in volume, changing from white to translucent, and containing many air bubbles, but its moisture retention is very poor. In Comparative Example 2, after the surface of the hyaluronic acid-gelatin sponge is wetted, the sponge thickness does not change significantly. Moreover, due to the rapid liquid absorption and gelation of the external hyaluronic acid, the outer edges become transparent, exhibiting surface gelation. The gelled hyaluronic acid inhibits liquid penetration, and the high viscosity of the gel also significantly inhibits the liquid absorption and expansion of the pores in the sponge, making it difficult for the sponge to absorb liquid overall, and its height does not change significantly over a long period. The composite sponge prepared in Example 1 has an inner layer of gelatin sponge that can rapidly absorb liquid and expand, and an outer layer of gel containing sodium hyaluronate. After being soaked in the surface, although the outer layer also gels and becomes transparent at the edges, the absorption rate and expansion rate of the inner layer are significantly higher than those of the outer layer. Therefore, the expansion of the inner layer after absorbing liquid can stretch the outer gel layer, disrupting the continuity of the gel layer and causing the composite sponge to swell overall (the expansion rate is lower than Comparative Example 1 but higher than Comparative Example 2). This increases the contact area between the sponge and the liquid, weakening the inhibitory effect of the outer layer's gelation on liquid penetration. Thus, the composite sponge with a layered structure provided in this application has high moisturizing properties while solving the problem of hyaluronic acid-containing gelatin sponges being difficult to absorb liquid and expand. In other words, the composite sponge provided in this application has the ability to absorb liquid and expand spontaneously, thereby playing a role in compression hemostasis and wound support (space occupation), making it suitable for use after nasal endoscopy. In the composite sponge prepared in Example 2, because the liquid absorption layer is on the outside, it immediately absorbs liquid and expands upon contact with the buffer solution. The inner gel layer absorbs liquid and gradually forms a gel. Due to the "pulling" effect of the expansion of the outer liquid absorption layer, the inner gel layer is stretched before forming a stable gel, also achieving the effect of rapid water absorption and expansion. The composite sponges in Examples 3-8 have a larger surface area in contact with the external buffer solution in their liquid absorption layer, resulting in a significantly faster expansion rate than in Example 1. Although Comparative Examples 3 and 4 employed the same pore-opening and increased contact surface treatment as the examples, their characteristics are the same as Comparative Example 2: a stable gel layer rapidly forms upon contact with the buffer solution, making it difficult for the sponge to absorb further water and expand.

[0151] To further clarify the liquid absorption and swelling effect of the composite sponge provided in this application, the inner layer of Example 1 was marked with red dye to form a sheet-like sponge. Subsequently, the dyed sheet-like sponge and the sheet-like sponge of Comparative Example 2 were placed simultaneously in a phosphate buffer solution with a pH of 5.9–7.4, and the liquid absorption and swelling of the sponge were observed. Figure 13 and Figure 14 This is Example 1 ( Figure 13 (a) and Figure 14 (a) and Comparative Example 2 ( Figure 13(b) and Figure 14 (b) The expansion state after immersion in the buffer solution for approximately 30 seconds. Figure 13 It can be seen that the sponge in Comparative Example 2 has difficulty absorbing liquid, has a thickness of only about 4 mm, and poor swelling properties. The sponge in Example 1 has the same appearance as the undyed sample in the dry state. After the inner and outer layers absorb liquid and swell, the red dye in the inner layer is clearly visible, and the dye gradually dissolves and diffuses outward as the inner layer fully absorbs liquid and swells. It is worth noting that, due to the molding process, the end areas of some sponges in Example 1 only contain the outer gel layer. Figure 13 (a) The side closer to Figure (b). From Figure 13 and 14 It can be seen that the overall liquid absorption and swelling rate of the sponge in Example 1 is significantly faster than that in Comparative Example 2. The end of the sponge in Example 1, due to containing only a gel layer (due to sample preparation process), has a significantly smaller thickness than other parts, similar to the thickness of Comparative Example 2. This also indicates that the inner liquid absorption and swelling zone in the composite sponge provided in this application plays a crucial role in improving the sponge's liquid absorption and swelling properties; that is, the composite sponge provided in this application has excellent liquid absorption and swelling properties.

[0152] Another key characteristic of the composite sponge provided in this application, which exhibits excellent moisturizing properties, is that hyaluronic acid absorbs liquid and forms a gel layer. This gel layer can lock in externally absorbed moisture, prevent wound adhesion, and provide a moist environment. The water-locking and moisturizing properties of Example 1, Comparative Example 1, commercially available polyurethane hemostatic sponge, commercially available hydroxyethyl cellulose hemostatic sponge, and commercially available absorbable gelatin sponge were tested. The specific test method is as follows: Sponges of equal mass were placed in a 0.1 mol / L phosphate buffer solution with a pH of 7.2 and allowed to stand for approximately 15 minutes. After the hemostatic sponge reached water equilibrium, it was lifted and drained of free water. The drained hemostatic sponge was transferred to three layers of filter paper and filtered under reduced pressure for 1 minute. The mass of the hemostatic sponge was weighed, and the water loss rate was calculated. The test results are as follows: Figure 15 As shown, if the hemostatic sponge has strong moisturizing ability, the water loss rate is low. Figure 15 It is known that simple gelatin sponge has weak moisture retention capacity and loses most of its moisture; commercially available hydroxyethyl cellulose sponge can form cellulose gel, which improves its moisture retention capacity; and since hyaluronic acid has a stronger moisturizing capacity than cellulose, the composite sponge prepared in Example 1 has the lowest moisture loss rate and good moisturizing properties.

[0153] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0154] The embodiments described above are merely illustrative of several implementation methods of this application, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the invention patent. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of this application, and these all fall within the protection scope of this application. Therefore, the protection scope of this patent application should be determined by the appended claims, and the specification and drawings can be used to interpret the scope of the claims.

Claims

1. A composite sponge, characterized in that, include: The gel layer and the liquid absorption layer are arranged adjacently; both the gel layer and the liquid absorption layer are porous sponge-like; the gel layer is made of gelatin and hyaluronic acid, and the liquid absorption layer is made of gelatin; in the gel layer, the mass ratio of the hyaluronic acid to the gelatin is 1:(0.01~15). The composite sponge is cylindrical or strip-shaped; The liquid absorption layer covers the outer peripheral surface of the gel layer; or The gel layer covers the outer peripheral surface of the liquid absorption layer; or There are multiple gel layers and multiple liquid absorption layers, and the gel layers and liquid absorption layers are stacked alternately.

2. The composite sponge as described in claim 1, characterized in that, The hyaluronic acid-based materials include one or more of hyaluronic acid and its derivatives; the hyaluronic acid derivatives include one or more of sodium hyaluronate, calcium hyaluronate, and hyaluronic acid esters.

3. The composite sponge as described in claim 1, characterized in that, The gelatin in the liquid absorbent layer is cross-linked gelatin.

4. The composite sponge as described in claim 1, characterized in that, The thicknesses of the gel layer and the liquid absorbent layer are independently 0.5 mm to 25 mm; And / or, the porosity of the composite sponge is 60%~86%.

5. The composite sponge as described in claim 1, characterized in that, The gel layer covers the entire outer peripheral surface of the liquid absorption layer, and the outer peripheral surface of the gel layer has multiple through holes that penetrate the thickness of the gel layer, or the outer peripheral surface of the gel layer has multiple blind holes.

6. The composite sponge as described in claim 1, characterized in that, The gel layer comprises multiple gel layer blocks, all of which are spaced apart on the outer peripheral surface of the liquid absorption layer.

7. The composite sponge as described in claim 1, characterized in that, The outer peripheral surface of the liquid absorption layer is also provided with multiple pore structures.

8. The composite sponge according to any one of claims 1 to 7, characterized in that, The materials of the gel layer and / or the liquid absorbent layer also independently include adjuvants; the adjuvants include one or more of antimicrobial agents, glucocorticoids, hemostatic agents, surfactants, plasticizers, and odor modifiers; The antimicrobial agents include one or more of the following: quaternized chitosan, polylysine, penicillins, cephalosporins, carbapenems, penicillin derivatives, oxocephalosporins, aminoglycosides, tetracyclines, glycylcyclines, chloramphenicol, macrolides, lincosamides, rifamycins, glycopeptides, polymyxins, cyclic lipopeptides, oxazolidinones, fosfomycin, quinolones, sulfonamides, furans, nitroimidazoles, antimycobacterial drugs, and antifungal drugs. The glucocorticoids include one or more of methylprednisolone, mometasone furoate, prednisone, prednisolone, budesonide, dexamethasone, hydrocortisone, fluticasone propionate, beclomethasone propionate, triamcinolone acetonide, and fluticasone furoate. The hemostatic agents include thrombin, clotting vitamin, aminocaproic acid, tranexamic acid, desmopressin, and recombinant human coagulation factor. The surfactants include one or more of poloxamer, Span, polyoxyethylene fatty alcohol ethers, polyoxyethylene fatty acid esters, glyceryl stearate, polyethylene glycol, alkyl sulfonates, and alkyl sulfates; The plasticizer includes one or more of glycerol, polyethylene glycol, sorbitol, mannitol, polysorbate, and polyglycerol; The odor modifier includes one or more of peppermint oil, menthol, camphor oil, and eucalyptus oil.

9. A method for preparing a composite sponge as described in any one of claims 1 to 8, characterized in that, Includes the following steps: Solution A is foamed using a physical foaming process to form foaming liquid A, wherein solution A includes gelatin and hyaluronic acid materials; Solution B is foamed using a physical foaming process to form foaming liquid B, wherein solution B includes gelatin; and Foaming liquid A and foaming liquid B are injected into a mold and then freeze-dried to prepare the composite sponge.

10. The preparation method according to claim 9, characterized in that, In solution A, the mass concentration of the gelatin is 2% to 10%, and the mass concentration of the hyaluronic acid material is 0.1% to 30%. And / or, in solution B, the mass concentration of the gelatin is 0.01% to 10%; And / or, the solvent in solution A and the solvent in solution B are each independently selected from water or a buffer solution; the buffer solution includes one or more of acetate buffer, citrate buffer, phosphate buffer, hydrogen phosphate buffer, carbonate buffer, and bicarbonate buffer.

11. The preparation method according to claim 9, characterized in that, Before forming the solution B, the method further includes a step of cross-linking the gelatin with a cross-linking agent; And / or, the crosslinking agent is an aldehyde solvent, and the mass ratio of the gelatin to the crosslinking agent is 100:(0.01~10).

12. The preparation method according to any one of claims 9 to 11, characterized in that, It also includes a step of compressing and shaping the obtained composite sponge; the compression and shaping step includes: wetting and heating the composite sponge, pressing the composite sponge to obtain a compressed composite sponge, and drying the compressed composite sponge; And / or, the preparation method further includes the step of perforating the obtained composite sponge to form through holes in the gel layer and / or the liquid absorption layer.

13. A medical material, characterized in that, Includes the composite sponge as described in any one of claims 1 to 8.

Images