Foam hydrogel dressing as well as preparation method and application thereof

Abstract

The foam hydrogel dressing is prepared from the following components in percentage by mass: 20 to 50 percent of SBMA (Styrene-Butadiene-Methacrylate), 0.5 to 5 percent of a cross-linking agent and 5 to 30 percent of a foaming agent, and the SBMA is sulfobetaine methacrylate; the foam hydrogel dressing is chemically foamed to form a three-dimensional skeleton internally provided with first-class holes and second-class holes, the hole diameter of the first-class holes is 1000-2000 microns, and the hole diameter of the second-class holes is 10-30 microns. The novel foam hydrogel dressing which has the characteristics of hydrogel dressing and foam dressing at the same time is obtained through chemical foaming with a one-pot method, and healing of pressure sore wounds can be effectively promoted.

Description

Technical Field

[0001] This invention patent relates to the technical field of foam hydrogel dressings, and particularly to a foam hydrogel dressing, its preparation method and application. Background Art

[0002] With the accelerating aging process of the world's population, the incidence of pressure ulcers has been increasing year by year. For long-term bedridden patients, pressure ulcers not only increase the patients' pain, the economic burden on their families, and the difficulty of nursing, but also can lead to serious complications such as infection and sepsis, endangering their lives.

[0003] Jointly compiled by the European Pressure Ulcer Advisory Panel, the National Pressure Ulcer Advisory Panel, and the Pan-Pacific Pressure Injury Alliance Prevention and Treatment of Pressure Ulcers / Injuries: Clinical Practice Guideline(The International Guideline 2019) It is pointed out in [reference] that for un-infected stage III and IV pressure injuries with little exudate, hydrogel dressings are recommended; for pressure injuries with large areas and moderate or severe exudate, foam dressings are recommended. The American College of Physicians (ACP) recommends that clinicians use foam dressings in patients with pressure ulcers to reduce wound size, and their effects are better than those of gauze dressings. Compared with other dressings, foam dressings can provide a heat-insulating, warm-keeping, 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 have good compliance, which can effectively buffer the local pressure on the wound surface. However, existing foam dressings generally do not have an adhesive edge and need an outer dressing for fixation, and they are opaque and cannot 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] A foam hydrogel dressing provided by the present invention, the foam hydrogel dressing comprises 20 - 50% by mass of SBMA, 0.5 - 5% of a cross-linking agent, 5 - 30% of a foaming agent, an initiator and a catalyst, wherein the SBMA is sulfobetaine methacrylate; the foam hydrogel dressing is formed into a three-dimensional skeleton with type I pores and type II pores inside through chemical foaming, 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 type I pores and the type II pores are partially connected.

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

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

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

[0010] Furthermore, the foam hydrogel dressing comprises 30% by mass of SBMA, 1% of polyethylene glycol dimethacrylate, and 20% 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 ratio of the obtained foam hydrogel in physiological saline is ≥200%.

[0014] The preparation method of the foam hydrogel dressing provided by the present invention comprises the following steps: Step (1): Add the initiator and the crosslinking agent into the SBMA solution, mix well to obtain a mixed solution; Step (2): Add the foaming agent and the catalyst into the mixed solution obtained in step (1) to obtain a reaction solution; the reaction solution is foamed in a water bath at 30 - 60 °C to prepare the foam hydrogel dressing.

[0015] The application of the foam hydrogel dressing provided by the present invention in the preparation of a pressure ulcer treatment dressing.

[0016] The beneficial effects of the present invention are: The present invention prepares a novel foam hydrogel dressing with the characteristics of both a hydrogel dressing and a foam dressing by a one - pot method, which can effectively promote the healing of pressure ulcer wounds.

[0017] The foam hydrogel dressing prepared by the present invention has the following advantages: (1) Using SBMA as a monomer, it has certain antibacterial adhesion ability and can effectively block the invasion of external bacteria in the exposed pressure ulcer wounds; (2) The simultaneous presence of interconnected macropores and micropores enables the foam hydrogel dressing to have appropriate air permeability, thereby realizing the moisture exchange and connection between the skin and the air, and promoting wound healing; (3) The swollen foam hydrogel dressing can provide a moist healing environment, soften the eschar, and promote autolytic debridement; (4) Due to the presence of SBMA, the dressing can establish adhesion with the skin through dipole-dipole interaction and can be quickly separated without secondary damage after dropping physiological saline through rapid hydration; (5) Good application prospects: The combination of hydrogel characteristics and foam dressing characteristics enables the dressing to achieve better results in the healing of pressure ulcers. Description of the Drawings

[0018] Figure 1 It is the cross-sectional visible light micrograph, polarized light microscope micrograph and SEM micrograph of FSBH before swelling and after swelling in physiological saline for 3 days obtained by chemical foaming of Formula 2, wherein the scale in the visible light micrograph and polarized light microscope micrograph is 500 μm; the scale of the SEM micrograph is 50 μm.

[0019] Figure 2 It is the density of FSBH obtained by chemical foaming of Formulas 1-4 and NFSBH obtained by Formulas 13-16 in Example 1.

[0020] Figure 3 It is the photo of the foam hydrogel dressing prepared by foaming Formula 2 in a water bath at 30, 40, 50, and 60 °C in Example 2, and the scale is 1 cm.

[0021] Figure 4 It is the WVTR test result of FSBH obtained by chemical foaming of Formulas 1-12 in Example 3.

[0022] Figure 5 It is the volume change of FSBH obtained by chemical foaming of Formulas 1-4 before swelling and after swelling in physiological saline for 3 days in Example 4.

[0023] Figure 6 It is the statistical result of the swelling rate of FSBH obtained by chemical foaming of Formulas 1-4 in Example 4.

[0024] Figure 7 It is the test result graph of the antibacterial adhesion performance of the foam hydrogel dressing. Among them, 6A is the image of the colonies of active adherent bacteria (Escherichia coli and Staphylococcus aureus) on the surface of each group of substrates in Example 5, and 6B is the SEM image of the cross-section and surface of each group of substrates infected with Escherichia coli, and the scale is 30 μm.

[0025] Figure 8 Apparent photos of pressure ulcer wounds in each group on days 0, 3, 7, 14, and 18 in Example 6, with a scale of 0.5 cm.

[0026] Figure 9 Statistical results of the non - healing rate of pressure ulcer wounds in each group in Example 6.

[0027] Figure 10 Graphs of the wound healing process simulated by Image J software for each group in Example 6. Detailed implementation mode

[0028] Next, in combination with the embodiments of the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments.

[0029] Reagents and materials used in the following embodiments: 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 Baisha Biotechnology Co., Ltd.).

[0030] Example 1 Preparation of foam hydrogel dressing A preparation method of a foam hydrogel dressing, the preparation method comprising the following steps: Step (0): Dissolve SBMA in pure water to prepare an SBMA solution; Step (1): Add an initiator and a cross - linker to the SBMA solution obtained in step (0), and mix evenly to obtain a mixed solution; the initiator is ammonium persulfate (APS), and the cross - linker is polyethylene glycol dimethacrylate (PEGDMA); Step (2): Add 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 water bath at 60 °C to prepare the foam hydrogel dressing. When the foaming agent reacts sufficiently and the foam gel no longer swells, the reaction ends; 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.

[0031] Table 1 Content table of the reaction solution (by mass fraction, the balance is water) Among them, formula 1-12 was prepared according to the reaction liquid ratio described in Table 1, and foamed in a 60°C water bath to obtain foamed hydrogel dressing (FSBH); formula 13-16 was prepared according to the reaction liquid ratio described in Table 1, and fully reacted in a 60°C water bath to obtain non-foamed hydrogel dressing (NFSBH); the amount of TEMED added in the above formula was 5 μL.

[0032] Example 2 Surface characteristics of the foam hydrogel dressing like Figure 1 As shown, under white light / polarized light microscopy, it was observed that the prepared FSBH had a type of pores, the pore size of which was 1000–2000 μm, which were macroscopic pores; under SEM, it was observed that the FSBH had a type of pores, the pore size of which was 10-30 μm, which were microscopic pores.

[0033] like Figure 2 As shown, the density of FSBH prepared by formula 1-4 is 0.6-0.8 g / cm 3 , which is generally lower than the density of NFSBH prepared by formula 13-16, which is 0.78-0.9 g / cm 3 , indicating that the prepared FSBH has lightweight characteristics, 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 formulations.

[0034] like Figure 3 As shown, 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 macroscopic pores and microscopic pores.

[0035] Example 3 Air Permeability Test of Foam Hydrogel Dressing The present invention examines the air permeability of the foam hydrogel dressing by testing the water vapor transmission rate (WVTR).

[0036] The specific operation method is as follows: weigh the weight of the upper glass bottle, record it as W1. Add 100 ℃ hot water into the lower glass bottle, the effective area of the lower glass bottle mouth is A, put FSBH on the bottle mouth to seal, then put the upper glass bottle on the FSBH, and seal the three with tape. Observe whether there are water droplets / water mist in the upper glass bottle, weigh the weight of the upper glass bottle after t time (t is calculated based on the time when the water droplets are about to fall in the group with the best air permeability), record it as W2, and measure at least three identical hydrogel samples in each group.

[0037] 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.

[0038] Too low WVTR is likely to cause the accumulation of exudate and is not conducive to oxygen interaction, while too high WVTR may lead to wound dehydration. As Figure 4 shown, the WVTR of the foam hydrogel dressings obtained from Formulas 1 - 12 is 211 - 579 g·m -2 ·h -1 , meeting the application requirements for pressure ulcer wounds. Among them, the average WVTR of the FSBHs prepared from Formulas 2, 7, and 10 is 355.41 ± 50 g·m -2 ·h -1 .

[0039] Example 4 Swelling ratio test of the foam hydrogel dressing The foam hydrogel dressings prepared from Formulas 1 - 4 were immersed in physiological saline to detect their ability to absorb exudate.

[0040] The specific operation method is as follows: Weigh the unswollen foam hydrogel dressing and record it as M0; after swelling in physiological saline for three days, weigh the foam hydrogel dressing again and record it as M1; measure at least three identical hydrogel samples in each group. Take apparent photographs of each group to observe the changes in the volume, transparency, and morphology of the hydrogel before and after swelling.

[0041] The swelling ratio is calculated as follows: Swelling ratio (%) = ((M1 - M0) / M0) × 100% As Figures 5 - 6 shown, the foam hydrogel dressings can absorb more than twice their own weight of liquid until they reach swelling equilibrium; mechanical property tests were carried out on the swollen FSBH, and the test results showed that the tensile property of the FSBH prepared from Formula 1 was much weaker than that of the FSBH prepared from Formula 2.

[0042] Example 5 Anti - bacterial adhesion property test of the foam hydrogel dressing Staphylococcus aureus and Escherichia coli were used as the detection objects. The experimental group used the FSBH formulas prepared from Formulas 1 - 4 and the NFSBH prepared from Formula 14 as the matrix, and the control group used TCPS (polystyrene) as the matrix.

[0043] The specific operation method is as follows: Inoculate Staphylococcus aureus / Escherichia coli in LB broth and incubate overnight at 37 °C. Divide several circular matrices with a diameter of 6 mm and a thickness of 1 mm into groups and place them in centrifuge tubes. Immerse each matrix with 1% penicillin - streptomycin mixture and incubate overnight.

[0044] On the second day, in the laminar flow hood, centrifuge the LB broth at 10,000 rpm and 25 °C for 5 min to collect Staphylococcus aureus / Escherichia coli, and resuspend the bacterial pellet at 1 x 10 7 colony forming units (CFU) / mL to obtain a suspension. Wash each group of substrates 3 times with PBS, place the sterilized substrates in 5 mL centrifuge tubes, add 3 mL of the Staphylococcus aureus / Escherichia coli suspension to each centrifuge tube, and incubate at 37 °C on a shaker (150 rpm) for 24 h.

[0045] After incubation, take out the substrates, wash the substrates (placed on the shaker) three times with sterile PBS, add them to 10 mL of PBS, sonicate for 8 min, take 50 μL and spread it on a plate, culture at 37 °C for 12 h, and use a camera to take pictures and record as Figure 7 shown in A.

[0046] Fracture the substrates co-incubated with Escherichia coli for 24 h brittly in liquid nitrogen, record the cross-section and surface, and freeze-dry the samples under vacuum for 48 h. After freeze-drying, coat the hydrogel with Au, and observe the distribution of bacteria on the cross-section and surface of the samples by SEM at an acceleration voltage of 5 kV as Figure 7 shown in B.

[0047] Due to the coexistence of macro-pores and micro-pores, some bacteria are likely to be retained in the pores, weakening the antibacterial adhesion ability of SBMA. However, compared with the control group (TCPS), the FSBH foamed hydrogels prepared by Formulas 1-3 still possess a certain antibacterial adhesion ability and can effectively block the invasion of external bacteria in the exposed wounds of pressure ulcers.

[0048] Example 6 Application of the Foamed Hydrogel Dressing This example is applied to the pressure ulcer animal healing model. The NFSBH prepared by Formula 14 and the FSBH (the swollen matrix is water) after swelling with Formula 2 are used as the experimental groups, the foam dressing (soft silicone wound dressing, bedsore patch, Haisi Hainuo) is used as the positive control group, and the self-healing group is used as the negative control group.

[0049] The modeling object is SD rats (300 - 340 g, male). Establish the pressure ulcer animal healing model with 3 rats in each group: Perform ischemia (I) and reperfusion (R) cycles (I / R cycles) at the bilateral gracilis muscles of the rats. Specifically, place the two hind legs of the rats in two mutually attracting permanent magnets (disk-shaped, diameter 8 mm, thickness 4 mm, 3500 g) for 12 h to induce the ischemia (I) process. Thereafter, remove the magnets for 12 h to induce the reperfusion (R) process. Repeat the I / R cycle four times to confirm that the modeling of each group of rats is successful.

[0050] Apply the corresponding dressings to the wounds of rats in each group as described above. The amount of dressing used should cover the wound, and it should be changed every two days. Take pictures of the pressure ulcer wounds on days 0, 3, 7, 14, and 18 respectively, and use Image J image software to simulate the wound healing process and analyze it. The results are as Figures 8 - 10 shown. The wound-healing promotion effect of the FSBH group on pressure ulcer wounds is significantly better than that of other groups. At day 18, the non-healing rate of the wounds in the FSBH group is only 2%-10%, while the non-healing rate of the wounds in the positive control group still remains at 15%-35% at day 18.

[0051] As mentioned above, the above are only the preferred specific embodiments of the present invention, but the protection scope of the present invention is not limited thereto. Any person skilled in the art within the technical scope disclosed by the present invention, according to the technical solution of the present invention and its inventive concept, makes equivalent substitutions or changes, and all should be covered by the protection scope of the present invention.

Claims

1. A foam hydrogel dressing, characterized in that, The foam hydrogel dressing comprises sulfobetaine methacrylate (SBMA) with a mass fraction of 20 - 50%, a crosslinking agent with a mass fraction of 0.5 - 5%, a foaming agent with a mass fraction of 5 - 30%, an initiator and a catalyst, wherein the SBMA is sulfobetaine methacrylate; the foam hydrogel dressing is formed by chemical foaming to form a three-dimensional skeleton with type-I pores and type-II pores inside, 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.

2. The foam hydrogel dressing according to claim 1, wherein The water vapor transmission rate of the foam hydrogel is 211 - 579 g·m -2 ·h -1 .

3. The foam hydrogel dressing according to claim 2, characterized in that, The foaming agent is ammonium bicarbonate, and the crosslinking agent is polyethylene glycol dimethacrylate.

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

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

6. The foam hydrogel dressing according to claim 3, characterized in that The catalyst is N,N-dimethylethylenediamine, and the initiator is ammonium persulfate.

7. The foam hydrogel dressing according to claim 6, wherein The foam hydrogel dressing comprises SBMA with a mass fraction of 20 - 40%, 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%.

8. The preparation method of the foam hydrogel dressing according to any one of claims 1-7, characterized in that, The preparation method comprises the following steps: Step (1): Add the initiator and the crosslinking agent into the SBMA solution, and mix well to obtain a mixed solution. Step (2): Add the foaming agent and the catalyst into the mixed solution obtained in step (1) to obtain a reaction solution; the reaction solution is foamed in a water bath at 30 - 60 °C to prepare the foam hydrogel dressing.

9. Use of the foam hydrogel dressing according to any one of claims 1 - 7 in the preparation of a pressure ulcer treatment dressing.

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