Foam hydrogel dressing and preparation method and application thereof

Abstract

A foam hydrogel dressing comprising 20-50% by mass of SBMA (sulfobetaine methacrylate), 0.5-5% of a cross-linking agent, and 5-30% of a foaming agent. Chemical foaming forms a three-dimensional framework with internal Class I and Class II pores, where the Class I pores have a pore size of 1000-2000 μm and the Class II pores have a pore size of 10-30 μm. This novel foam hydrogel dressing, obtained through a one-pot chemical foaming process, possesses the properties of both a hydrogel dressing and a foam dressing, effectively promoting the healing of pressure ulcer wounds.

Description

Technical Field

[0001] The present invention relates to the technical field of foam hydrogel dressings, in particular to a foam hydrogel dressing and its preparation method and application. Background Art

[0002] As the world's population ages, the incidence of pressure ulcers is increasing year by year. For bedridden patients, pressure ulcers not only increase their pain, but also the financial burden on their families and the difficulty of care. They can also lead to life-threatening complications such as infection and sepsis.

[0003] Jointly prepared by the European Commission on Pressure Ulcer Prevention, the American Commission on Pressure Ulcer Prevention, and the Pan Pacific Pressure Injury Council Prevention and Treatment of Pressure Ulcers / Injuries: Clinical Practice Guideline (The International Guideline 2019) It points out that for uninfected stage III and IV pressure injuries with low exudate, hydrogel dressings are recommended; for pressure injuries with moderate or severe exudate covering a large area, foam dressings are recommended. The American College of Physicians (ACP) recommends that clinicians use foam dressings to reduce the size of wounds in patients with pressure ulcers, and they are more effective than gauze dressings. Compared with other dressings, foam dressings can provide an insulating, warm, and breathable healing environment, support autolytic debridement, absorb moderate to large amounts of exudate to reduce the impact of exudate on the wound surface, and are soft, comfortable, and well-compliant, which can effectively buffer local pressure on the wound surface. However, existing foam dressings generally do not have sticky edges, require an outer dressing to fix them, and are opaque, making it impossible to directly observe the wound surface. Summary of the Invention

[0004] The purpose of the present invention is to solve the defects of existing foam dressings and provide a foam hydrogel dressing prepared by chemical foaming.

[0005] The present invention provides a foam hydrogel dressing, comprising 20-50% by mass of SBMA, 0.5-5% by mass of a cross-linking agent, 5-30% by mass of a foaming agent, an initiator, and a catalyst, wherein the SBMA is sulfobetaine methacrylate. The foam hydrogel dressing is chemically foamed to form a three-dimensional skeleton having type I pores and type II pores therein, wherein the pore diameter of the type I pores is 1000-2000 μm, and the pore diameter of the type II pores is 10-30 μm.

[0006] Specifically, the first type of pores and the second type of pores are partially connected.

[0007] Preferably, the water vapor permeability of the foam hydrogel is 211-579 g·m -2 ·h -1 .

[0008] Preferably, the foaming agent is ammonium bicarbonate (NH4HCO3), and the cross-linking agent is polyethylene glycol dimethacrylate (PEGDMA).

[0009] Furthermore, the foam hydrogel dressing comprises 20-40% by mass of SBMA, 0.5-2% by mass of polyethylene glycol dimethacrylate, and 10-30% by mass of ammonium bicarbonate.

[0010] Furthermore, the foam hydrogel dressing comprises 30% by mass of SBMA, 1% by mass of polyethylene glycol dimethacrylate, and 20% by mass of ammonium bicarbonate; the density of the obtained foam hydrogel is 0.61 ± 0.03 g / cm 3 .

[0011] Preferably, the catalyst is N,N-dimethylethylenediamine (TEMED), and the initiator is ammonium persulfate (APS).

[0012] Specifically, the mass ratio of ammonium persulfate (APS) to polyethylene glycol dimethacrylate (PEGDMA) in the reaction solution is 1:1.

[0013] Preferably, the foam hydrogel dressing comprises 20-40% by mass of SBMA, 1% of polyethylene glycol dimethacrylate, 20% of ammonium bicarbonate, 1% of ammonium persulfate and 0.5% of N,N-dimethylethylenediamine; the swelling rate of the obtained foam hydrogel in physiological saline is ≥200%.

[0014] The present invention provides a method for preparing a foam hydrogel dressing, comprising the following steps:

[0015] Step (1): adding an initiator and a cross-linking agent to the SBMA solution and mixing to obtain a mixed solution;

[0016] Step (2): adding a foaming agent and a catalyst to the mixed solution obtained in step (1) to obtain a reaction solution; and foaming the reaction solution in a water bath at 30-60° C. to obtain the foam hydrogel dressing.

[0017] The invention provides an application of the foam hydrogel dressing in preparing a dressing for treating pressure sores.

[0018] The beneficial effects of the present invention are:

[0019] The present invention prepares a novel foam hydrogel dressing having the characteristics of both hydrogel dressing and foam dressing through a one-pot method, which can effectively promote the healing of pressure ulcer wounds.

[0020] The foam hydrogel dressing prepared by the present invention has the following advantages: (1) SBMA is used as a monomer, which has a certain anti-bacterial adhesion ability and can effectively block the invasion of external bacteria in pressure sore exposed wounds; (2) The simultaneous existence of interconnected macropores and micropores makes the foam hydrogel dressing have appropriate air permeability, thereby realizing moisture exchange and connection between skin and air, thereby promoting wound healing; (3) The swollen foam hydrogel dressing can provide a moist healing environment, soften eschar, and promote autolysis and debridement; (4) Due to the presence of SBMA, the dressing can establish adhesion with the skin through dipole-dipole interaction, and can also be quickly separated without secondary damage after adding physiological saline through rapid hydration; (5) Good application prospects: The combination of hydrogel properties and foam dressing properties enables the dressing to achieve better effects in the healing of pressure sores. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 These are visible light micrographs, polarizing microscope micrographs, and SEM micrographs of the cross section of FSBH obtained by chemical foaming of Formula 2 before swelling and after swelling in normal saline for 3 days. The scale bars in the visible light micrographs and polarizing microscope micrographs are 500 μm; the scale bar in the SEM micrographs is 50 μm.

[0022] Figure 2 The density of FSBH obtained by chemical foaming of formulas 1-4 in Example 1 and the density of NFSBH obtained by formulas 13-16.

[0023] Figure 3 These are the WVTR test results of the FSBH obtained by chemical foaming of formulations 1-12 in Example 3.

[0024] Figure 4 These are photos of the foam hydrogel dressings prepared by foaming in a water bath at 30, 40, 50, and 60°C, respectively, using Formula 2 in Example 2. The scale bar is 1 cm.

[0025] Figure 5 The volume changes of FSBH obtained by chemical foaming of formula 1-4 in Example 4 before swelling and after swelling in normal saline for 3 days.

[0026] Figure 6 The swelling ratio statistics of FSBH obtained by chemical foaming of formula 1-4 in Example 4 are shown.

[0027] Figure 7 Figures 6A and 6B show the results of the antibacterial adhesion test of the foam hydrogel dressing. 6A shows the images of colonies of active adherent bacteria (Escherichia coli and Staphylococcus aureus) on the surface of each matrix in Example 5, and 6B shows the SEM images of the cross-section and surface of each matrix infected with Escherichia coli. The scale bar is 30 μm.

[0028] Figure 8 These are the appearance photos of the pressure ulcer wounds in each group in Example 6 on days 0, 3, 7, 14, and 18. The scale bar is 0.5 cm.

[0029] Figure 9 These are the statistical results of the unhealed rates of pressure ulcer wounds in each group in Example 6.

[0030] Figure 10 Graphs showing the wound healing process of each group simulated using Image J software in Example 6. DETAILED DESCRIPTION

[0031] The technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments.

[0032] Reagents and materials used in the following examples: SBMA (537284, Sigma-Aldrich (Shanghai) Trading Co., Ltd.); NH4HCO3 (1066-33-7, Xilong Scientific Co., Ltd.); PEGDMA (409510, Sigma-Aldrich (Shanghai) Trading Co., Ltd.); TEMED (T105497, Shanghai Aladdin Biochemical Technology Co., Ltd.); APS (A6295, Sinopharm Chemical Reagent Co., Ltd.); Staphylococcus aureus (ATCC 29213); Escherichia coli (ATCC 25922); TCPS (BS-90-D, Hefei White Shark Biotechnology Co., Ltd.).

[0033] Example 1 Preparation of Foam Hydrogel Dressing

[0034] A method for preparing a foam hydrogel dressing, comprising the following steps:

[0035] Step (0): dissolving SBMA in pure water to prepare an SBMA solution;

[0036] Step (1): adding an initiator and a cross-linking agent to the SBMA solution obtained in step (0), mixing them evenly, and obtaining a mixed solution; the initiator is ammonium persulfate (APS), and the cross-linking agent is polyethylene glycol dimethacrylate (PEGDMA);

[0037] Step (2): adding a foaming agent and a catalyst to the mixed solution obtained in step (1) to obtain a reaction solution; the reaction solution is foamed in a 60°C water bath to obtain the foam hydrogel dressing, and the reaction is terminated when the foaming agent reacts fully and the foam gel no longer expands; the foaming agent is ammonium bicarbonate (NH4HCO3), and the catalyst is N,N-dimethylethylenediamine (TEMED); the mass ratio of APS to PEGDMA in the reaction solution is 1:1.

[0038] Among them, formulas 1-12 were prepared according to the reaction liquid ratio described in Table 1, and foamed in a 60°C water bath to prepare foamed hydrogel dressings (FSBH); formulas 13-16 were prepared according to the reaction liquid ratio described in Table 1, and fully reacted in a 60°C water bath to prepare non-foamed hydrogel dressings (NFSBH); the amount of TEMED added in the above formulas was 5 μL.

[0039] Table 1 Reaction liquid content (mass fraction, the balance is water)

[0040]

[0041] Example 2 Surface Characteristics of Foam Hydrogel Dressing

[0042] like Figure 1 As shown in the figure, the prepared FSBH was observed to have a type of pores under a white light / polarized light microscope, the pore size of the type of pores was 1000-2000 μm, and they were macroscopic pores; under SEM, the FSBH was observed to have a type of pores, the pore size of the type of pores was 10-30 μm, and they were microscopic pores.

[0043] like Figure 2 As shown, the FSBH density obtained by formula 1-4 is 0.6-0.8 g / cm 3 , which is generally lower than the density of NFSBH prepared by formulas 13-16, which is 0.78-0.9 g / cm 3 , indicating that the prepared FSBH has lightweight properties, among which the density of the foam hydrogel prepared by formula 2 is only 0.61 ± 0.03 g / cm 3 , the lowest among all formulas.

[0044] like Figure 3 As shown in the figure, according to the ratio of formula 2, foam hydrogel dressings were prepared by foaming in a water bath at 30, 40, 50, and 60 °C, respectively. Each group of products had macropores and micropores.

[0045] Example 3 Air Permeability Test of Foam Hydrogel Dressing

[0046] The present invention examines the air permeability of the foam hydrogel dressing by testing the water vapor transmission rate (WVTR).

[0047] The specific procedure is as follows: Weigh the upper glass bottle, denoted as W1. Add 100°C hot water to the lower glass bottle (the effective area of ​​the lower glass bottle opening is A). Place a FSBH sealant at the bottle opening. Place the upper glass bottle on top of the FSBH, and seal all three with tape. Observe the upper glass bottle for the appearance of water droplets / mist. After a time t (t is calculated based on the time it takes for a water droplet to fall in the group with the best air permeability), weigh the upper glass bottle, denoted as W2. Measure at least three identical hydrogel samples in each group.

[0048] The water vapor transmission rate (WVTR) is calculated as follows: WVTR = (W2-W1) / (A × t), where A is the effective area of ​​the sample in m²; t is the test time in h.

[0049] If WVTR is too low, it will easily lead to the accumulation of exudate and be detrimental to the interaction of oxygen, while if WVTR is too high, it may lead to wound dehydration. Figure 4 As shown in FIG, the WVTR of the foam hydrogel dressing obtained by formula 1-12 is 211-579 g·m -2 ·h -1 , which meets the application requirements of pressure ulcers. Among them, the average WVTR of FSBH prepared by formulas 2, 7 and 10 is 355.41 ± 50 g·m -2 ·h -1 .

[0050] Example 4 Swelling rate test of foam hydrogel dressing

[0051] The foam hydrogel dressings prepared according to Formulas 1-4 were soaked in physiological saline to test their ability to absorb exudate.

[0052] The specific procedure is as follows: Weigh the unswollen foam hydrogel dressing, recorded as M0; after swelling in saline for three days, weigh the foam hydrogel dressing again, recorded as M1. At least three identical hydrogel samples were measured in each group. Surface imaging of each group was performed to observe changes in hydrogel volume, transparency, and morphology before and after swelling.

[0053] The swelling rate is calculated as follows: Swelling rate (%) = ((M1-M0) / M0) × 100%

[0054] like Figure 5-6 As shown, the foam hydrogel dressing can absorb liquid greater than twice its own weight until it reaches swelling equilibrium; the mechanical properties of the swollen FSBH were tested, and the test results showed that the tensile properties of the FSBH prepared by Formula 1 were much weaker than those of the FSBH prepared by Formula 2.

[0055] Example 5 Antibacterial Adhesion Performance Test of Foam Hydrogel Dressing

[0056] Staphylococcus aureus and Escherichia coli were used as test objects. The experimental group used FSBH formulas prepared by formulas 1-4 and NFSBH prepared by formula 14 as matrices, and the control group used TCPS (polystyrene) as the matrix.

[0057] The specific operation method is as follows:

[0058] Inoculate Staphylococcus aureus / Escherichia coli into LB broth and incubate overnight at 37°C. Place several 6 mm diameter, 1 mm thick circular matrices in groups into a centrifuge tube and submerge each matrix in a 1% penicillin-streptomycin mixture. Incubate overnight.

[0059] On the next day, the LB broth was centrifuged at 10,000 rpm and 25°C for 5 min in a clean bench to collect Staphylococcus aureus / Escherichia coli, and the bacterial pellet was plated at 1 x 10 7 Colony-forming units (CFU) / mL were obtained to obtain a suspension. Each matrix was washed three times with PBS and the sterilized matrix was placed in a 5-mL centrifuge tube. 3 mL of the Staphylococcus aureus / Escherichia coli suspension was added to each centrifuge tube and incubated at 37°C on a shaker (150 rpm) for 24 h.

[0060] After the incubation is complete, the matrix is ​​removed and washed three times with sterile PBS (placed on a shaker), then added to 10 mL of PBS, sonicated for 8 min, 50 μL is taken and spread on a plate, and cultured at 37 °C for 12 h. The matrix is ​​recorded using a camera. Figure 7 As shown in A.

[0061] After incubation with E. coli for 24 h, the matrix was fractured in liquid nitrogen, the cross section and surface were recorded, and the sample was freeze-dried under vacuum for 48 h. After freeze-drying, the hydrogel was coated with Au and the distribution of bacteria on the cross section and surface of the sample was observed by SEM at an accelerating voltage of 5 kV. Figure 7 As shown in B.

[0062] Due to the coexistence of macropores and micropores, some bacteria are easily retained in the pores, weakening the anti-bacterial adhesion ability of SBMA. However, compared with the control group (TCPS), the FSBH foamed hydrogel prepared by formula 1-3 still has a certain anti-bacterial adhesion ability, which can effectively block the invasion of external bacteria in exposed wounds of pressure ulcers.

[0063] Example 6 Application of Foam Hydrogel Dressing

[0064] This example was applied to a pressure ulcer healing animal model. The NFSBH prepared in Formula 14 and the swollen FSBH in Formula 2 (the swelling matrix was water) were used as the experimental groups, a foam dressing (soft silicone wound dressing, pressure ulcer patch, Haishi Hainuo) was used as the positive control group, and a self-healing group was used as the negative control group.

[0065] A pressure ulcer healing model was established in SD rats (300-340 g, male), with three rats per group. Ischemia (I) and reperfusion (R) cycles (I / R cycles) were performed on the bilateral gracilis muscles of the rats. Specifically, the rats' hind legs were placed within two mutually attractive permanent magnets (disc-shaped, 8 mm diameter, 4 mm thickness, 3500 g) for 12 hours to induce Ischemia (I). Thereafter, the magnets were removed for 12 hours to induce reperfusion (R). The I / R cycles were repeated four times to confirm successful modeling in all groups.

[0066] The wounds of the rats in each group were treated with the corresponding dressings according to the aforementioned grouping. The dressings were used to cover the wounds and were changed every two days. The pressure ulcer wounds were photographed and recorded on days 0, 3, 7, 14, and 18. The wound healing process was simulated and analyzed using Image J software. The results are shown in the figure below. Figure 8-10 As shown in the results, the FSBH group had a significantly better effect on promoting the healing of pressure ulcer wounds than the other groups. On the 18th day, the wound non-healing rate was only 2%-10%, while the wound non-healing rate of the positive control group remained at 15%-35% on the 18th day.

[0067] The above description is only a preferred specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any technician familiar with the technical field, within the technical scope disclosed by the present invention, who makes equivalent replacements or changes based on the technical solution and inventive concept of the present invention, should be covered by the scope of protection of the present invention.

Claims

1. A foam hydrogel dressing, characterized in that: The foam hydrogel dressing comprises 20-50% by mass of SBMA, 0.5-5% by mass of a cross-linking agent, 5-30% by mass of a foaming agent, an initiator, and a catalyst, wherein the SBMA is sulfobetaine methacrylate; the foam hydrogel dressing is chemically foamed to form a three-dimensional skeleton having type I pores and type II pores therein, wherein the pore diameter of the type I pores is 1000-2000 μm, and the pore diameter of the type II pores is 10-30 μm; The water vapor permeability of the foam hydrogel is 211-579 g·m -2 ·h -1 .

2. The foam hydrogel dressing according to claim 1, characterized in that The foaming agent is ammonium bicarbonate, and the cross-linking agent is polyethylene glycol dimethacrylate.

3. The foam hydrogel dressing according to claim 2, characterized in that The foam hydrogel dressing comprises 20-40% by mass of SBMA, 0.5-2% by mass of polyethylene glycol dimethacrylate and 10-30% by mass of ammonium bicarbonate.

4. The foam hydrogel dressing according to claim 3, characterized in that The foam hydrogel dressing comprises 30% by mass of SBMA, 1% by mass of polyethylene glycol dimethacrylate, and 20% by mass of ammonium bicarbonate; the density of the obtained foam hydrogel is 0.61 ± 0.03 g / cm 3 .

5. The foam hydrogel dressing according to claim 2, characterized in that The catalyst is N,N-dimethylethylenediamine, and the initiator is ammonium persulfate.

6. The foam hydrogel dressing according to claim 5, characterized in that The foam hydrogel dressing comprises 20-40% by mass of SBMA, 1% of polyethylene glycol dimethacrylate, 20% of ammonium bicarbonate, 1% of ammonium persulfate and 0.5% of N,N-dimethylethylenediamine; the swelling rate of the obtained foam hydrogel in physiological saline is ≥200%.

7. The method for preparing the foam hydrogel dressing according to any one of claims 1 to 6, characterized in that: The preparation method comprises the following steps: Step (1): adding an initiator and a cross-linking agent to the SBMA solution and mixing to obtain a mixed solution; Step (2): adding a foaming agent and a catalyst to the mixed solution obtained in step (1) to obtain a reaction solution; and foaming the reaction solution in a water bath at 30-60° C. to obtain the foam hydrogel dressing.

8. Use of the foam hydrogel dressing according to any one of claims 1 to 6 in preparing a dressing for treating pressure sores.

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