Medical silver-containing porous polyurethane foam

Abstract

The invention relates to a polyurethane foam technology in the technical field of medical dressings, in particular to medical silver-containing porous polyurethane foam. The composite material comprises a foam matrix, the foam matrix adopts gradient layering design and comprises a matrix inner layer, a matrix middle layer and a matrix outer layer, the aperture of each layer is sequentially increased, the porosity is gradually increased layer by layer, the matrix inner layer is provided with randomly dispersed inner-layer hollow silver-loaded fibers capable of slowly releasing silver ions for bacteriostasis, the matrix middle layer is fixedly provided with pH response microcapsules, and the pH response microcapsules are fixed on the matrix outer layer. In an alkaline environment, antibacterial peptides are released for synergic antibiosis, and silver-loaded fibers in the outer layer of the matrix outer layer are arranged in the radial direction to form a flow guide channel and release silver ions. Through gradient layered design, different sterilization structures are added, the temperature-sensitive hydrogel layer covering the surface of the outer layer of the base body is matched, sterilization and seepage are managed through environmental changes, and the advantages of being excellent in antibacterial performance, high in seepage management capacity, intelligent in adjustment and the like are achieved.

Description

Technical Field

[0001] The present invention relates to polyurethane foam technology in the field of medical dressings, and specifically, to a medical silver-containing porous polyurethane foam. Background Art

[0002] Due to its high liquid absorption, air permeability, and softness, porous polyurethane foam has been widely used in the field of medical dressings. In recent years, to improve its antibacterial performance, researchers have developed silver-containing porous polyurethane foam by introducing silver nanoparticles or silver ion compounds into the polyurethane matrix. For example, phenolic hydroxyl groups in lignin are used to in-situ reduce silver ions to form silver nanoparticles, significantly improving the antibacterial rate of the foam against Escherichia coli within 1 hour. Such materials inhibit bacterial proliferation through the slow release of silver ions while maintaining the original liquid absorption and mechanical support properties of polyurethane.

[0003] With the development of clinical needs towards the dynamic management of complex infected wounds, the existing technology still faces further challenges: the silver ion release mechanism depends on preset slow release parameters and lacks the ability to actively respond to environmental changes, which may lead to a mismatch between the local concentration and the degree of infection; although the pore structure optimizes the liquid absorption efficiency through gradient design, it cannot adjust the liquid absorption rate and moisture retention balance in real time according to the exudate volume, easily resulting in liquid retention or excessive drying. Summary of the Invention

[0004] The purpose of the present invention is to provide a medical silver-containing porous polyurethane foam to solve the problems in the existing technology that the release of silver ions does not match the degree of infection, and the liquid absorption rate and moisture retention balance cannot be adjusted in real time according to the wound exudate volume.

[0005] To achieve the above purpose, a medical silver-containing porous polyurethane foam is provided, including a foam matrix. The foam matrix adopts a gradient layered design and includes an inner matrix layer, an intermediate matrix layer, and an outer matrix layer, where:

[0006] The pore size of the inner matrix layer is smaller than that of the intermediate matrix layer, and the pore size of the intermediate matrix layer is smaller than that of the outer matrix layer;

[0007] Inner hollow silver-loaded fibers are arranged in the inner matrix layer, and the inner hollow silver-loaded fibers are randomly dispersed in the pores of the inner matrix layer;

[0008] pH-responsive microcapsules are arranged in the intermediate matrix layer, and the pH-responsive microcapsules are fixed on the inner wall of the pores of the intermediate matrix layer;

[0009] Outer hollow silver-loaded fibers are arranged in the outer matrix layer, and the outer hollow silver-loaded fibers are arranged radially along the outer matrix layer.

[0010] Furthermore, the pore structures of the inner matrix layer, the middle matrix layer, and the outer matrix layer are naturally connected through pore size gradients, and the porosity increases layer by layer from the inner matrix layer to the outer matrix layer.

[0011] Still further, the pore network of the inner matrix layer directly adheres to the wound surface, the pore network of the middle layer balances the diversion and temporary storage requirements through a transition pore size, and the pore network of the outer matrix layer forms a leakage storage area.

[0012] In the above technical solution, the single structure of traditional foam dressings is difficult to cope with complex wound changes. Therefore, the foam matrix adopts a gradient layered design, and different structures are designed according to different functional areas. The pore size and porosity of the inner matrix layer are smaller than those of the middle matrix layer, and the pore size and porosity of the middle matrix layer are smaller than those of the outer matrix layer, so that its functions are rapid liquid absorption in the inner layer, transition and temporary storage in the middle layer, and storage in the outer layer. Different antibacterial agents are added at appropriate positions according to the different structures and functions of the three layers, namely hollow silver-loaded fibers and pH-responsive microcapsules in the inner layer, and hollow silver-loaded fibers in the outer layer.

[0013] On this basis, the hollow silver-loaded fibers in the outer layer penetrate through the pore network of the middle matrix layer to the outer matrix layer, forming a continuous diversion channel from the middle matrix layer to the outer matrix layer.

[0014] Furthermore, the inner cavity size of the hollow silver-loaded fibers in the outer layer is larger than that of the hollow silver-loaded fibers in the inner layer, and the wall thickness is smaller than that of the hollow silver-loaded fibers in the inner layer.

[0015] Still further, the distribution density and pore size of the micropores on the outer surface of the hollow silver-loaded fibers in the inner layer are smaller than those of the micropores of the hollow silver-loaded fibers in the outer layer.

[0016] In another technical solution, the hollow silver-loaded fibers in the inner layer and the hollow silver-loaded fibers in the outer layer are different in size due to their different positions and functions. The hollow silver-loaded fibers in the outer layer are used for rapid diversion and antibacterial, and the hollow silver-loaded fibers in the inner layer are used for slow release and mechanical support. The fibers in the outer layer require a larger inner diameter or a thinner wall thickness to promote rapid liquid flow, while the fibers in the inner layer require a smaller or thicker one to achieve the effects of mechanical support and slow release.

[0017] In addition, the pH-responsive microcapsules are linearly distributed along the direction of leakage flow on the inner wall of the pores of the middle matrix layer. The shell layer of the pH-responsive microcapsules is exposed to the leakage contact surface and dissolves in an alkaline environment to release antibacterial components.

[0018] In this technical solution, the pH-responsive microcapsules encapsulate antibacterial peptides with a pH-sensitive shell material and are linearly distributed along the direction of leakage flow, maximizing the exposure of the surface area of the microcapsules, ensuring that the leakage is in contact with the microcapsules throughout the process, and ensuring the release timing of the microcapsules. When the pH of the leakage caused by bacterial proliferation > 7.0, the shell material dissolves and releases antibacterial peptides to target and kill drug-resistant bacteria.

[0019] In addition, the surface of the matrix outer layer is covered with a temperature-sensitive hydrogel layer, which fits to the pore openings of the matrix outer layer and adjusts the pore size through temperature changes.

[0020] In this technical solution, the temperature-sensitive hydrogel layer is composed of poly(N-isopropylacrylamide) and sodium alginate, with a phase transition temperature of 32-37°C. When the local inflammatory response caused by infection leads to an increase in the wound surface temperature, the temperature will be conducted to the temperature-sensitive hydrogel layer at this time, and the conformation of the hydrogel molecular chain changes, swelling and expanding the pores, accelerating the evaporation and cooling of exudate. After the temperature returns to normal, the pores shrink and close, reducing water loss.

[0021] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0022] 1. In this medical silver-containing porous polyurethane foam, a multi-level antibacterial barrier is constructed by arranging inner-layer hollow silver-loaded fibers in the inner layer of the matrix, pH-responsive microcapsules in the middle layer of the matrix, and outer-layer hollow silver-loaded fibers in the outer layer of the matrix. The inner-layer hollow silver-loaded fibers slowly release silver ions to maintain the antibacterial concentration at the wound contact surface. The pH-responsive microcapsules release antibacterial peptides in the alkaline region (pH>7.0) where bacteria proliferate actively, synergistically targeting and killing drug-resistant bacteria with silver ions, expanding the antibacterial spectrum and inhibiting the expression of drug-resistant genes, reducing the dosage of silver ions, and reducing the risk of toxicity accumulation. The outer-layer hollow silver-loaded fibers continuously release silver ions to inhibit the growth of bacteria in the exudate storage area.

[0023] 2. In this medical silver-containing porous polyurethane foam, the foam matrix adopts a gradient layered design. The small pore diameter in the inner layer of the matrix provides high capillary force, quickly absorbs wound exudate and reduces the frictional pressure on the wound, ensuring sufficient storage space to avoid backflow; the intermediate pore diameter in the middle layer of the matrix balances the requirements of diversion and temporary storage, promoting the diffusion of exudate; the large pore diameter in the outer layer of the matrix reduces the flow resistance of exudate, and the high porosity maximizes the storage capacity. At the same time, the outer-layer hollow silver-loaded fibers form a directional diversion channel to accelerate the liquid flow. In addition, the temperature-sensitive hydrogel layer covered on the surface of the matrix outer layer can adjust the pore size according to the temperature change of the wound. When the wound temperature rises above 32°C due to infection, the hydrogel swells and expands the pores to accelerate the evaporation of exudate; after the temperature returns to normal, the hydrogel shrinks and closes the pores to reduce water loss and maintain the wet balance of the wound surface. Brief Description of the Drawings

[0024] Figure 1 It is a schematic diagram of the overall structure of the present invention;

[0025] Figure 2 It is a schematic diagram of the exudate flow in the inner layer of the matrix of the present invention;

[0026] Figure 3 It is a schematic diagram of the exudate flow from the inner layer to the middle layer of the matrix of the present invention;

[0027] Figure 4 Schematic diagram of the seepage flow from the intermediate layer to the outer layer of the matrix of the present invention;

[0028] Figure 5 Schematic diagram of the high-temperature deformation of the thermosensitive hydrogel layer of the present invention;

[0029] Figure 6 Schematic diagram of the normal-temperature deformation of the thermosensitive hydrogel layer of the present invention;

[0030] Figure 7 Schematic diagram of the structures of the outer-layer hollow silver-loaded fibers and the inner-layer hollow silver-loaded fibers of the present invention.

[0031] The meanings of the various reference numerals in the figure are as follows:

[0032] 1. Foam matrix; 11. Inner layer of the matrix; 12. Intermediate layer of the matrix; 13. Outer layer of the matrix; 2. Thermosensitive hydrogel layer; 3. Outer-layer hollow silver-loaded fiber; 4. pH-responsive microcapsule; 5. Inner-layer hollow silver-loaded fiber. Specific embodiments

[0033] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

[0034] Please refer to Figure 1 As shown, the purpose of this embodiment is to provide a medical silver-containing porous polyurethane foam, including a foam matrix 1. The foam matrix 1 adopts a gradient layer design and is specifically divided into an inner layer 11 of the matrix, an intermediate layer 12 of the matrix, and an outer layer 13 of the matrix. Among them, the pore diameter and gap of the inner layer 11 of the matrix are smaller than those of the intermediate layer 12 of the matrix, and the pore diameter and gap of the intermediate layer 12 of the matrix are smaller than those of the outer layer 13 of the matrix.

[0035] As Figure 2 shown, the pore diameter of the inner layer 11 of the matrix is set to 50-100 μm, and the porosity ≥ 80%. The pore diameter and porosity in the inner layer 11 of the matrix are the smallest in the foam matrix 1. It directly contacts the wound surface. The small pore diameter provides high capillary force, which can quickly absorb the exudate from the wound, and can also reduce the frictional pressure on the wound to prevent secondary damage. The 80% porosity ensures sufficient liquid storage space to avoid the backflow of exudate.

[0036] As Figure 2 and Figure 7As shown, inner hollow silver-loaded fibers 5 are randomly dispersed in the pores of the inner layer 11 of the matrix. The inner diameter of the fibers is 5-10 μm, the wall thickness is 5-10 μm, and the distribution density is 5-8%. The inner cavity of the fibers is filled with nano-silver gel, and micropores are also provided on their outer surfaces to sustainably release silver ions through the slow-release micropores, maintaining the antibacterial concentration on the wound contact surface. The small inner diameter of the inner hollow silver-loaded fibers 5 can extend the dwell time of exudate, enhance the long-term release of silver ions, and the relatively thick wall thickness compared to the overall fiber can also enhance the compressive strength of the inner layer 11 of the matrix, preventing the foam matrix 1 from deforming.

[0037] As Figure 3 and Figure 4 As shown, the pore diameter of the middle layer 12 of the matrix is set to 100-300 μm, and the porosity is ≥85%. The pore diameter and porosity of the middle layer 12 of the matrix are larger than those of the inner layer 11 of the matrix. The middle layer 12 of the matrix is used to guide exudate to flow from the inner layer to the outer layer, temporarily storing part of the liquid to avoid instantaneous overload of the outer layer. The transition pore diameter balances the requirements of diversion and temporary storage, and the porosity is slightly higher than that of the inner layer to promote the diffusion of exudate.

[0038] pH-responsive microcapsules 4 are provided in the middle layer 12 of the matrix. The particle size of the microcapsules is 10-20 μm, and they are fixed on the inner wall of the pores. The shell layer of the microcapsules is made of a pH-sensitive methacrylic acid copolymer, and the inner core encapsulates antibacterial peptides. The middle layer is the necessary passage for exudate to flow from the wound (inner layer) to the storage area (outer layer), and the probability of its pH increase is the highest (the area where bacteria proliferate actively). By setting pH-responsive microcapsules 4 here, it is ensured that the antibacterial components are released in the core area of infection. When the pH of the exudate is >7.0 due to bacterial metabolism, the shell layer of the microcapsules dissolves and releases antibacterial peptides, synergistically targeting and killing drug-resistant bacteria with silver ions.

[0039] In contrast, if only relying on the silver ion slow-release mechanism of hollow fibers, not only is the antibacterial rate insufficient for some drug-resistant bacteria, but it is also difficult to cope with mixed infection scenarios (such as bacterial and fungal co-infection). By using microcapsules to carry antibacterial peptides, it can respond to changes in the environmental pH value, reducing the dosage of silver ions, reducing the risk of toxicity accumulation, while expanding the antibacterial spectrum and inhibiting the expression of drug-resistant genes.

[0040] As Figure 4 As shown, the pore diameter of the outer layer 13 of the matrix is set to 300-500 μm, and the porosity is ≥90%. The pore diameter and porosity of the outer layer 13 of the matrix are the largest. The large pore diameter can reduce the flow resistance of the exudate, and the high porosity maximizes the storage capacity.

[0041] As Figure 4 and Figure 7As shown, an outer hollow silver-loaded fiber 3 is disposed within the outer layer 13 of the matrix. Its inner diameter is 10 - 50 μm, the wall thickness is 5 - 15 μm, and the hollow cavity is also filled with nano-silver gel. Micropores are also provided on the outer surface, arranged radially, extending from the middle layer 12 of the matrix to the outer layer 13 of the matrix, forming a directional flow channel. A larger inner diameter and a thinner wall thickness are used relative to the overall fiber to promote rapid liquid flow. When exudate diffuses from the inner layer 11 of the matrix to the middle layer 12 of the matrix, the outer hollow silver-loaded fiber 3 accelerates the liquid flow from the middle layer 12 of the matrix to the outer layer 13 of the matrix through capillary action and stores it in the pore network of the outer layer 13 of the matrix. At the same time, silver ions are released from the micropores on the fiber surface to inhibit bacterial growth.

[0042] As Figure 5 and Figure 6 shown, the temperature-sensitive hydrogel layer 2 is composed of a composite of poly(N-isopropylacrylamide) and sodium alginate, with a thickness set at 50 - 100 μm and a phase transition temperature of 32 - 37 °C. When the wound temperature rises above 32 °C due to infection, the hydrogel swells to expand the pores of the outer layer 13 of the matrix, accelerating the evaporation of exudate. After the temperature returns to normal, the hydrogel shrinks to close the pores, reducing water loss.

[0043] Preparation process: The original one-step foaming method is optimized by using a segmented temperature-controlled foaming technique. The bubble expansion speed is regulated through the temperature gradient of the mold to form a three-layer different pore size gradient structure. The outer layer maintains a high-temperature environment of 60 °C. After the polyurethane prepolymer is mixed with the foaming agent, it rapidly expands under the action of high temperature to form a macroporous structure with a pore size of 300 - 500 microns and a porosity exceeding 90%; the middle layer is controlled at a medium temperature of 45 °C, and 100 - 200 micron transition pores are generated by adjusting the diffusion speed of the foaming agent; the inner layer maintains a low temperature of 30 °C to inhibit bubble expansion to form 50 - 100 micron high-density small pores with a porosity of over 80%. This gradient structure enables the foam to have both a high liquid absorption capacity and mechanical support.

[0044] A mixed solution with a mass ratio of poly(N-isopropylacrylamide) to sodium alginate of 7:3 is sprayed on the surface of the outer layer of the gradient foam, and a 50 - 100 micron temperature-sensitive hydrogel layer 2 is formed by using ultraviolet light curing technology. This coating can dynamically shrink the pores by 50% above 32 °C, effectively preventing the backflow of exudate.

[0045] 5 - 10 wt% of pH-responsive microcapsules 4 are premixed in the middle layer. The antimicrobial peptide LL-37 is encapsulated in the Eudragit S100 shell material by spray drying. The inlet temperature is controlled at 150 - 180 degrees Celsius and the atomization pressure is 0.2 - 0.4 MPa to prepare complete microcapsules with a particle size of 10 - 20 microns, ensuring the accurate release of antibacterial components in the alkaline environment of the wound.

[0046] The hollow silver-loaded fiber is prepared by electrospinning technology to produce hollow polyester fibers with an inner diameter of 10-50 microns at a voltage of 15-20 kV and a spinning solution flow rate of 0.5-1.0 ml / hour. Nano-silver gel with a concentration of 2-5% is injected into the inner cavity of the fiber through microfluidics technology, achieving a 30% increase in the silver loading. The outer layer fibers are arranged radially with a density of 10-15%, and the inner layer is randomly dispersed with a density of 5-8%. They are naturally embedded in the foam matrix 1 during the foaming and expansion stage, and the interfacial bonding strength exceeds 1.5 MPa. Finally, γ-ray irradiation sterilization is used to ensure the sterility of the material while maintaining the stability of the functional components.

[0047] Working principle: The dressing made of the foam matrix 1 is applied to the wound. When the exudate contacts the inner layer 11 of the matrix, its small pore diameter structure quickly absorbs the exudate through capillary action. When the inner layer of hollow silver-loaded fibers 5 contacts the exudate, its micropores start to continuously release silver ions, and the slender cavity of the fiber prolongs the contact time between the silver gel and the exudate. The exudate then enters the transition pores of the middle layer 12 of the matrix. When the pH value of the exudate rises above 7.0 due to bacterial metabolism, the shell layer of the pH-responsive microcapsules 4 fixed on the pore wall gradually dissolves, releasing the antibacterial peptide components encapsulated inside.

[0048] After that, the exudate diffuses to the large pore diameter structure of the outer layer 13 of the matrix. The inner cavity of the outer layer of hollow silver-loaded fibers 3 forms a directional diversion channel, accelerating the migration of the exudate to the outer layer through the radially arranged micropores and starting to release silver ions. At this time, the temperature-sensitive hydrogel layer 2 senses the change in the surface temperature of the material. When the temperature exceeds 32°C, the molecular chains undergo conformational changes, and the hydrogel network starts to dynamically adjust the pore opening and closing state of the outer layer 13 of the matrix, accelerating the evaporation of the exudate to reduce the risk of infection. After the temperature returns to normal, the hydrogel shrinks and closes the pores, reducing water loss and maintaining the wet balance of the wound surface. The exudate is finally stored in the 90% high porosity structure of the outer layer 13 of the matrix, and the outer layer of hollow silver-loaded fibers 3 continuously releases silver ions to inhibit the growth of bacteria in the exudate storage area, forming a multi-level antibacterial barrier.

[0049] The above shows and describes the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited by the above embodiments. The above embodiments and the descriptions in the specification are only preferred examples of the present invention and are not used to limit the present invention. Without departing from the spirit and scope of the present invention, the present invention will have various changes and improvements, and these changes and improvements all fall within the scope of the present invention claimed. The scope of the present invention claimed is defined by the appended claims and their equivalents.

Claims

1. A medical silver-containing porous polyurethane foam, comprising a foam matrix (1), characterized in that: The foam matrix (1) adopts a gradient layered design, including an inner matrix layer (11), a middle matrix layer (12), and an outer matrix layer (13), where: The pore size of the inner matrix layer (11) is smaller than that of the middle matrix layer (12), and the pore size of the middle matrix layer (12) is smaller than that of the outer matrix layer (13); Inner hollow silver-loaded fibers (5) are arranged in the inner matrix layer (11), and the inner hollow silver-loaded fibers (5) are randomly dispersed in the pores of the inner matrix layer (11); pH-responsive microcapsules (4) are arranged in the middle matrix layer (12), and the pH-responsive microcapsules (4) are fixed on the inner wall of the pores of the middle matrix layer (12); Outer hollow silver-loaded fibers (3) are arranged in the outer matrix layer (13), and the outer hollow silver-loaded fibers (3) are arranged radially along the outer matrix layer (13).

2. The silver-containing porous polyurethane foam for medical use according to claim 1, wherein: The pore structures of the inner matrix layer (11), the middle matrix layer (12), and the outer matrix layer (13) are naturally connected through a pore size gradient, and the porosity increases layer by layer from the inner matrix layer (11) to the outer matrix layer (13).

3. The medical silver-containing porous polyurethane foam according to claim 2, wherein: The pore network of the inner matrix layer (11) directly adheres to the wound surface, the pore network of the middle layer (12) balances the diversion and temporary storage requirements through a transition pore size, and the pore network of the outer matrix layer (13) forms a leachate storage area.

4. The silver-containing porous polyurethane foam for medical use according to claim 3, wherein: The outer hollow silver-loaded fibers (3) penetrate through the pore network of the middle matrix layer (12) to the outer matrix layer (13), forming a continuous diversion channel from the middle matrix layer (12) to the outer matrix layer (13).

5. The medical silver-containing porous polyurethane foam according to claim 4, characterized in that: The inner cavity size of the outer hollow silver-loaded fibers (3) is larger than that of the inner hollow silver-loaded fibers (5), and the wall thickness is smaller than that of the inner hollow silver-loaded fibers (5).

6. The silver-containing porous polyurethane foam for medical use according to claim 5, characterized in that: The distribution density and pore size of the micropores on the outer surface of the inner hollow silver-loaded fibers (5) are smaller than those of the outer hollow silver-loaded fibers (3).

7. The medical silver-containing porous polyurethane foam according to claim 1, characterized in that: The pH-responsive microcapsules (4) are linearly distributed on the inner wall of the pores of the middle matrix layer (12) along the leachate flow direction, the shell layer of the pH-responsive microcapsules (4) is exposed to the leachate contact surface, and dissolves in an alkaline environment to release antibacterial components.

8. The medical silver-containing porous polyurethane foam according to claim 1, wherein: The surface of the outer matrix layer (13) is covered with a temperature-sensitive hydrogel layer (2), and the temperature-sensitive hydrogel layer (2) fits with the pore openings of the outer matrix layer (13) to adjust the pore size through temperature changes.

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