An antibacterial hollow mesoporous silica sphere injectable hydrogel dressing and a preparation method thereof

Abstract

The application discloses an antibacterial hollow mesoporous silica ball injectable hydrogel dressing and a preparation method thereof, and belongs to the technical field of hydrogel dressing preparation. The antibacterial hollow mesoporous silica ball injectable hydrogel dressing provided by the application is obtained by self-crosslinking of a four-arm polyethylene glycol modified by o-phthaldehyde as a crosslinking agent and a hollow mesoporous silica ball loaded with tannic acid in a solvent. Compared with the prior art, the antibacterial hollow mesoporous silica ball injectable hydrogel dressing provided by the application can be gelled without the participation of catalase, has a better gelation time, and can be injected and in-situ formed, so that deep wounds can be treated (the existing hydrogel is too fast or too slow in gelation, and can only be directly made into a gel for use in shallow wounds); moreover, the mechanical strength of the gel can be improved; and the hydrogel dressing has good biocompatibility, degradability, antibacterial property and good repair promoting capacity.

Description

Technical Field

[0001] This invention belongs to the field of hydrogel dressing preparation technology, and more specifically relates to an antibacterial hollow mesoporous silica sphere injectable hydrogel dressing and its preparation method. Background Technology

[0002] In the clinical care of complex wounds such as chronic wound infections, burns, and deep trauma, traditional dressings generally suffer from limitations such as insufficient antibacterial properties, difficulty in adhering to irregular wound surfaces, secondary damage during dressing changes, and inability to provide active repair factors. Therefore, injectable hydrogel dressings have become a research hotspot due to their excellent in-situ molding ability, superior tissue compatibility, and three-dimensional microporous structure. They can fill wound cavities of any shape and maintain a moist environment. However, existing products still face challenges such as weak mechanical strength, limited functionality, and a lack of long-lasting antibacterial mechanisms, especially poor efficacy against multidrug-resistant bacteria, and most systems only provide limited antibacterial properties. Passive physical barriers cannot achieve synergistic effects of antibacterial and repair-promoting functions. Although some studies have attempted to load inorganic nano-antibacterial agents (such as silver nanoparticles and zinc oxide) into hydrogels, problems such as easy burst release, high biotoxicity, and poor stability exist. Hollow mesoporous silica spheres have shown potential as drug carriers in the field of controlled release due to their high specific surface area, adjustable pore size, and good biocompatibility. However, current technologies have not yet been able to intelligently integrate them with injectable hydrogels to construct an integrated dressing system with multiple functions such as rapid in-situ gelation, long-lasting antibacterial effect, controlled drug release, and active promotion of tissue regeneration.

[0003] Furthermore, existing hydrogels either gelle too quickly or too slowly, limiting their use to superficial wounds. Therefore, developing a hydrogel dressing with an optimal gelation time—neither too slow nor too fast—that can be injected and molded in situ, and is suitable for treating deep wounds, is of great significance. Summary of the Invention

[0004] The purpose of this invention is to provide an antibacterial hollow mesoporous silica ball injectable hydrogel dressing and its preparation method, so as to solve the problems existing in the prior art. The antibacterial hollow mesoporous silica ball injectable hydrogel dressing provided by this invention can form gel without the participation of catalase, and has high gel strength. It is also injectable and has a good effect on promoting the repair of deep wounds.

[0005] To achieve the above objectives, the present invention provides the following solution:

[0006] One of the technical solutions of this invention is to provide a method for preparing an antibacterial hollow mesoporous silica sphere injectable hydrogel dressing, comprising the following steps:

[0007] Hollow mesoporous silica spheres were dispersed in water, mixed with tannic acid solution, and collected to obtain hollow mesoporous silica spheres loaded with tannic acid.

[0008] The o-phthalaldehyde-terminated four-arm polyethylene glycol was dissolved in a solvent to obtain solution A;

[0009] The hollow mesoporous silica spheres loaded with tannic acid were dissolved in a solvent to obtain solution B;

[0010] Ciprofloxacin hydrochloride was dissolved in a solvent to obtain solution C;

[0011] After mixing and reacting the solutions A, B and C, the antibacterial hollow mesoporous silica sphere injectable hydrogel dressing is obtained.

[0012] The structural formula of the o-phthalaldehyde-terminated four-arm polyethylene glycol is:

[0013] Where n is the degree of aggregation, and its value ranges from 25 to n to 100.

[0014] If the degree of polymerization is too low or too high, it will adversely affect the gelation time and mechanical strength of the hydrogel dressing. Only by controlling the degree of polymerization within the specified range can ideal gelation time and high mechanical strength be achieved. This is because too low a degree of polymerization will result in prolonged gelation time, difficulty in gelation, poor mechanical strength, and easy disintegration; while too high a degree of polymerization will cause gelation to be too rapid (poor workability), and although the mechanical strength is high, the material becomes brittle and its toughness decreases. Therefore, a moderate degree of polymerization is the ideal choice for hydrogel dressing design, achieving a balance between controllable gelation and strength.

[0015] The present invention does not impose any special restrictions on the source of the o-phthalaldehyde-terminated four-arm polyethylene glycol, which can be a commercially available product or prepared according to methods known in the art.

[0016] Preferably, the loading rate of the hollow mesoporous silica spheres loaded with tannic acid is 3.5 to 4 wt%.

[0017] Furthermore, the specific preparation steps of the hollow mesoporous silica spheres loaded with tannic acid include: dispersing the hollow mesoporous silica spheres in water, mixing them evenly with the tannic acid solution, placing them in a shaker at 37°C overnight, centrifuging, drying, and collecting the hollow mesoporous silica spheres loaded with tannic acid.

[0018] Preferably, the solvent independently includes one or more of water, physiological saline, buffer solution, bacterial culture medium, tissue culture medium, and body fluid; the buffer solution includes PBS buffer solution; the pH value of the PBS buffer solution is preferably 7.4.

[0019] Preferably, the pH value of solution A is 4-9, more preferably 5-8, more preferably 6-7.6, and most preferably 7.4; the mass fraction of o-phthalaldehyde-terminated tetra-arm polyethylene glycol in solution A is 5-10%.

[0020] Preferably, the pH value of solution B is 4-9, more preferably 5-8, more preferably 6-7.6, and most preferably 7.4; the mass fraction of hollow mesoporous silica spheres carrying tannic acid in solution B is 5-10%.

[0021] Furthermore, the reagent used to adjust the pH values ​​of solutions A and B includes sodium hydroxide.

[0022] Preferably, the mass fraction of ciprofloxacin hydrochloride in solution C is 5-10%.

[0023] Preferably, the mass ratio of the hollow mesoporous silica spheres loaded with tannic acid, the four-arm polyethylene glycol with o-phthalaldehyde end caps, and the ciprofloxacin hydrochloride is 1 to 3:1:1, and more preferably 2:1:1.

[0024] Preferably, the melting temperature is 10–60°C, more preferably 25–40°C, and even more preferably 37°C.

[0025] Preferably, the reaction temperature is 10–60°C, more preferably 25–40°C, and even more preferably 37°C.

[0026] Furthermore, the reaction is preferably carried out using a vortex apparatus; the reaction time is 2–10 s, more preferably 5 s. During the above reaction process, the hollow mesoporous silica spheres and the four-arm polyethylene glycol with o-phthalaldehyde end-capped cross-links spontaneously. The aldehyde group of o-phthalaldehyde at the end of the polyethylene glycol reacts with the amino group on the hollow mesoporous silica spheres to generate a nitrogen-containing five-membered heterocycle. After mixing, the resulting injectable hydrogel dressing is initially a yellow suspension. When injected into the wound using a syringe, it adapts to the size of the wound. As time progresses, the system gradually changes from a yellow suspension to a yellow gel.

[0027] The second technical solution of the present invention provides an injectable hydrogel dressing of antibacterial hollow mesoporous silica spheres prepared by the above preparation method.

[0028] The antibacterial hollow mesoporous silica ball injectable hydrogel dressing provided by this invention can be applied to wounds to treat superficial wounds, and can also be injected in situ to treat deep wounds. Compared with the functions of existing dressings, the antibacterial hollow mesoporous silica ball injectable hydrogel dressing provided by this invention has different effects at different stages of wound healing. During the hemostasis stage, it adapts to the size of the wound, reduces pain, and quickly stops bleeding; during the inflammatory stage, it maintains wound moisture and shortens healing time; during the proliferation stage, it causes no secondary damage; and during the maturation stage, it promotes granulation tissue growth. The antibacterial hollow mesoporous silica ball injectable hydrogel dressing has the advantages of rapid hemostasis, infection prevention, no secondary damage, and promotion of granulation tissue growth when treating infected wounds, and has good practical value in the dressing industry. At the same time, the antibacterial hollow mesoporous silica ball injectable hydrogel dressing provided by this invention can improve the mechanical strength of the gel; it also has good biocompatibility, biodegradability, antibacterial properties, and good repair promotion ability.

[0029] The present invention discloses the following technical effects:

[0030] The present invention provides an antibacterial hollow mesoporous silica ball injectable hydrogel dressing. The hydrogel is obtained by self-crosslinking tannic acid-loaded hollow mesoporous silica balls with tetra-arm polyethylene glycol modified with o-phthalaldehyde end groups as a crosslinking agent in a solvent. Compared with the prior art, the antibacterial hollow mesoporous silica ball injectable hydrogel dressing provided by the present invention can form a gel without the participation of catalase, and the resulting antibacterial hollow mesoporous silica ball injectable hydrogel dressing has a better gelation time, which is neither too slow nor too fast, and can be injected in situ to treat deep wounds (existing hydrogels form too quickly or too slowly and can only be used directly as a gel for shallow wounds); it can also improve the mechanical strength of the gel; and it also has good biocompatibility, degradability, antibacterial properties, and good healing promotion ability.

[0031] Experimental results show that the antibacterial hollow mesoporous silica sphere injectable hydrogel dressing provided by the present invention has a gelation time of 180-330s, which is neither too fast nor too slow, and can be injected in situ for use in deep wounds; the mechanical strength (elastic modulus) is above 6000Pa; cytotoxicity experiments show that the gel has good biocompatibility; wound test results show that the gel has the ability to promote repair. Attached Figure Description

[0032] Figure 1 The mechanical properties of the antibacterial hollow mesoporous silica sphere injectable hydrogel dressing obtained in Example 1 are shown in the figure.

[0033] Figure 2 This is a diagram illustrating the in vitro degradation effect of the antibacterial hollow mesoporous silica sphere injectable hydrogel dressing obtained in Example 1.

[0034] Figure 3The image shows the antibacterial effect of the antibacterial hollow mesoporous silica ball injectable hydrogel dressing obtained in Example 1 against Staphylococcus aureus and Escherichia coli.

[0035] Figure 4 The image shows the inhibition zone effect of the antibacterial hollow mesoporous silica ball injectable hydrogel dressing obtained in Example 1 against Staphylococcus aureus and Escherichia coli.

[0036] Figure 5 This is a live / dead fluorescence staining effect image of the antibacterial hollow mesoporous silica ball injectable hydrogel dressing obtained in Example 1 after it interacts with Staphylococcus aureus and Escherichia coli.

[0037] Figure 6 This is a scanning electron microscope image showing the effect of the antibacterial hollow mesoporous silica ball injectable hydrogel dressing obtained in Example 1 after interaction with Staphylococcus aureus and Escherichia coli.

[0038] Figure 7 Graphs showing the cytotoxicity test results of tetra-arm polyethylene glycol with different concentrations of o-phthalaldehyde capping;

[0039] Figure 8 The image shows the effect of cytotoxicity testing on hollow mesoporous silica spheres loaded with tannic acid at different concentrations.

[0040] Figure 9 This is a graph showing the effect of cytotoxicity testing on the antibacterial hollow mesoporous silica sphere injectable hydrogel dressing in Example 1;

[0041] Figure 10 This is a diagram showing the effect of the antibacterial hollow mesoporous silica ball injectable hydrogel dressing described in Example 1 in a wound repair test. Detailed Implementation

[0042] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0043] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Any stated value or intermediate value within a stated range, as well as each smaller range between any other stated value or intermediate value within said range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0044] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0045] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be readily apparent to those skilled in the art. This specification and embodiments are merely exemplary.

[0046] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0047] It should be noted that any aspects not described in detail in this invention are conventional practices in the field and are not the focus of this invention.

[0048] The hollow mesoporous silica spheres used in the following embodiments and comparative examples of this invention were purchased from Nanjing Jike Biotechnology Co., Ltd.; the o-phthalaldehyde-terminated four-arm polyethylene glycol was purchased from Chongqing Yusi Pharmaceutical Technology Co., Ltd.; and all other raw materials used, unless otherwise specified, are commercially available products, and the source of commercially available products does not affect the technical effect of this invention.

[0049] The specific preparation steps of the hollow mesoporous silica spheres loaded with tannic acid involved in this invention are as follows: the hollow mesoporous silica spheres are dispersed in water, mixed evenly with tannic acid solution, placed in a shaker at 37°C overnight, centrifuged, dried, and the hollow mesoporous silica spheres loaded with tannic acid with a loading rate of 3.85 wt% are collected.

[0050] Example 1

[0051] S1. At 37°C, o-phthalaldehyde-terminated tetra-arm polyethylene glycol (n=63) was dissolved in PBS buffer at pH=7.4 to prepare a 5% (w / w) solution; then, the pH of the system was adjusted to 7.4 with NaOH solution to obtain solution A.

[0052] S2. At 37°C, hollow mesoporous silica spheres loaded with tannic acid were dispersed in PBS buffer solution with pH = 7.4 to prepare a 5% (w / w) solution; then, the pH of the system was adjusted to 7.4 with NaOH solution to obtain solution B.

[0053] S3. At 37°C, ciprofloxacin hydrochloride was dissolved in PBS buffer at pH 7.4 to prepare a 5% (w / w) solution, which is solution C.

[0054] S4. Using hollow mesoporous silica spheres loaded with tannic acid, tetra-arm polyethylene glycol with o-phthalaldehyde end-capping, and ciprofloxacin hydrochloride in a mass ratio of 2:1:1, solutions A, B, and C are mixed at 37°C and vortexed for 5 seconds to obtain an antibacterial hollow mesoporous silica sphere injectable hydrogel dressing.

[0055] Sample performance testing:

[0056] The antibacterial hollow mesoporous silica sphere injectable hydrogel dressing obtained in Example 1 was tested as follows.

[0057] (1) Gel formation time:

[0058] The gelation time of the samples at 37℃ was determined by the inverted test tube method. The results showed that the gelation time of the samples was 180-330 s.

[0059] (2) Mechanical strength:

[0060] The hydrogel dressing, after being mixed in a vortex apparatus, was rapidly transferred to a rotational rheometer to determine its mechanical properties (specifically, the elastic modulus). The results are as follows: Figure 1 As shown. Figure 1 The graph shows the mechanical properties of the antibacterial hollow mesoporous silica sphere injectable hydrogel dressing obtained in Example 1. One curve represents the energy loss G”, and the other curve represents the energy storage modulus G’. When G’ is greater than G”, gelation begins. The graph shows the gelation point measured by the instrument and the stable mechanical strength after gelation. Specifically, the elastic modulus is stable at 6130 Pa.

[0061] (3) Degradability:

[0062] After mixing the hydrogel dressing in a vortex mixer, 100 μL was pipetted into a pre-weighed dish. After 30 minutes, the dish was weighed using an analytical balance. 3 mL of pH 7.4 PBS buffer was added, and the dish was placed in a 37°C constant-temperature shaking incubator. The PBS buffer was changed periodically, and the weight was recorded. The results are shown in [reference needed]. Figure 2 . Figure 2 The image shows the in vitro degradation effect of the antibacterial hollow mesoporous silica ball injectable hydrogel dressing obtained in Example 1. It can be seen that the degradation time of the obtained antibacterial hollow mesoporous silica ball injectable hydrogel dressing is 16 days.

[0063] (4) Antibacterial properties:

[0064] After mixing the hydrogel dressing in a vortex mixer, transfer 300 μL to a test tube and let it stand for 30 minutes. Then, add 300 μL of the mixture to 10 test tubes. 8CFU / mL Staphylococcus aureus suspension and 300 μL 10 8 Add a CFU / mL E. coli suspension to a test tube, seal the tube opening with kraft paper, and incubate at 37°C for 12 hours. See attached results. Figure 3 . Figure 3 This image shows the antibacterial effect of the injectable hydrogel dressing made of antibacterial hollow mesoporous silica spheres obtained in Example 1 against Staphylococcus aureus and Escherichia coli. The left tube represents the blank control group (with an equal volume of PBS added), and the right tube represents the experimental group. It can be seen that the solution on the antibacterial hollow mesoporous silica sphere gel is clear, indicating a very low bacterial count and excellent antibacterial effect.

[0065] 100 μL of 10 6 CFU / mL suspensions of Staphylococcus aureus and Escherichia coli were evenly spread on LB agar medium (the agar medium has a small well with a diameter of 1 cm and a depth of 3 mm on the surface). Then, the hydrogel dressing obtained in Example 1 was transferred to the wells of the LB agar medium and incubated at 37°C for 12 h. The results are shown in [link to results]. Figure 4 . Figure 4 The image shows the antibacterial effect of the antibacterial hollow mesoporous silica ball injectable hydrogel dressing obtained in Example 1 against Staphylococcus aureus and Escherichia coli. It can be seen that the inhibition zones of the hydrogel dressing against Staphylococcus aureus and Escherichia coli are 16.5 mm and 18 mm, respectively, showing good antibacterial effect.

[0066] The antibacterial live-death test results showed that all Staphylococcus aureus and Escherichia coli were killed. (See attached results). Figure 5 . Figure 5 The image shows the live and dead fluorescence staining effect of the antibacterial hollow mesoporous silica ball injectable hydrogel dressing obtained in Example 1 after it interacts with Staphylococcus aureus and Escherichia coli.

[0067] Scanning electron microscopy results showed that the morphology of Staphylococcus aureus and Escherichia coli was significantly disrupted. (See attached image for details.) Figure 6 . Figure 6 The image shows the scanning electron microscope (SEM) results of the antibacterial hollow mesoporous silica ball injectable hydrogel dressing obtained in Example 1 after interaction with Staphylococcus aureus and Escherichia coli.

[0068] (5) Cytotoxicity test:

[0069] Mouse fibroblast 3T3 cells were seeded at a density of 5000 cells per well in 96-well plates, with 200 μL of complete culture medium (90% DMEM + 10% fetal bovine serum) per well, and incubated for 24 h. After 24 h, the culture plates were removed, and 20 μL of PBS buffer (pH 7.4) and different concentrations of o-phthalaldehyde-terminated tetra-arm polyethylene glycol were added to each plate, and incubated for another 24 h. After 24 h, the culture plates were removed, the culture medium was aspirated, and the plates were washed 2-3 times with PBS buffer. 10% CCK-8 solution was added in the dark, and the plates were incubated for 1 h. The absorbance at 450 nm was measured using a microplate reader. For the cytotoxicity of different concentrations of the material to 3T3 cells, see [link to microplate reading]. Figure 7 . Figure 7 The image shows the cytotoxicity test results of tetra-armed polyethylene glycol (PEG) with different concentrations of phthalaldehyde-terminated. The experimental results indicate that phthalaldehyde-terminated tetra-armed PEG has no cytotoxicity to normal fibroblasts.

[0070] Mouse fibroblast 3T3 cells were seeded at a density of 5000 cells per well in 96-well plates, with 200 μL of complete culture medium (90% DMEM + 10% fetal bovine serum) per well, and incubated for 24 h. After 24 h, the culture plates were removed, and 20 μL of PBS buffer (pH 7.4) and different concentrations of hollow mesoporous silica spheres loaded with tannic acid (prepared in Example 1) were added to the plates, and incubated for another 24 h. After 24 h, the culture plates were removed, the culture medium was aspirated, and the plates were washed 2-3 times with PBS buffer. 10% CCK-8 solution was added in the dark, and the plates were incubated for 1 h. The absorbance at 450 nm was measured using a microplate reader. For the cytotoxicity of different concentrations of the materials to 3T3 cells, see [link to microplate reading]. Figure 8 , Figure 8 The image shows the cytotoxicity test results of hollow mesoporous silica spheres loaded with tannic acid at different concentrations. The experimental results show that the hollow mesoporous silica sphere solution loaded with tannic acid has no cytotoxicity to normal fibroblasts.

[0071] Mouse fibroblast 3T3 cells were seeded at a density of 5000 cells per well in 96-well plates, with 200 μL of complete culture medium (90% DMEM + 10% fetal bovine serum) per well, and incubated for 24 h. After 24 h, the culture plates were removed, and 20 μL of PBS buffer (pH 7.4) and 20 μL of extract of antibacterial hollow mesoporous silica injectable hydrogel dressing were added to each plate, respectively, and incubated for 24 h, 48 h, and 72 h. After 24 h, 48 h, and 72 h, the culture plates were removed, the culture medium was aspirated, and the plates were washed 2–3 times with PBS buffer. 10% CCK-8 solution was added in the dark, and the plates were incubated for 1 h. The absorbance at 450 nm was measured using a microplate reader. For the cytotoxicity of different concentrations of the material to 3T3 cells, see [link to microplate reader]. Figure 9 , Figure 9 This is a graph showing the effect of cytotoxicity testing of the antibacterial hollow mesoporous silica ball injectable hydrogel dressing in Example 1. The experimental results show that the antibacterial hollow mesoporous silica ball injectable hydrogel dressing provided by the present invention has no cytotoxicity to normal fibroblasts.

[0072] (6) Wound healing test:

[0073] 200 μL of the antibacterial hollow mesoporous silica sphere injectable hydrogel dressing prepared in Example 1 was added to the wound. A blank control group and a 3M dressing group (purchased from Minnesota Mining Manufacturing Co., Ltd.) were used as controls. Photos were taken and recorded every 4–6 days. Results are shown in [link to relevant documentation]. Figure 10 , Figure 10 This image shows the effect of wound repair testing on the antibacterial hollow mesoporous silica ball injectable hydrogel dressing described in Example 1. The rightmost column, representing the hydrogel group, shows the test group using the antibacterial hollow mesoporous silica ball injectable hydrogel dressing of Example 1. It can be seen that the antibacterial hollow mesoporous silica ball injectable hydrogel dressing provided by this invention has a good effect on promoting wound repair.

[0074] The test results above show that the antibacterial hollow mesoporous silica ball injectable hydrogel dressing provided by the present invention can produce a better gelation time, improve mechanical strength and antibacterial properties, and has good biocompatibility and wound healing ability.

[0075] In the figures above, "Gel" represents the injectable hydrogel dressing assembly using antibacterial hollow mesoporous silica spheres prepared in Example 1.

[0076] Example 2

[0077] S1. At 37°C, o-phenylenedialdehyde-terminated four-arm polyethylene glycol (n=30) was dissolved in PBS buffer at pH=7.4 to prepare a 5% (w / w) solution; then, the pH of the system was adjusted to 7.4 with NaOH solution to obtain solution A.

[0078] S2. At 37°C, hollow mesoporous silica spheres loaded with tannic acid were dispersed in PBS buffer solution with pH = 7.4 to prepare a 5% (w / w) solution; then, the pH of the system was adjusted to 7.4 with NaOH solution to obtain solution B.

[0079] S3. At 37°C, ciprofloxacin hydrochloride was dissolved in PBS buffer at pH 7.4 to prepare a 5% (w / w) solution, which is solution C.

[0080] S4. Using hollow mesoporous silica spheres loaded with tannic acid, tetra-arm polyethylene glycol with o-phthalaldehyde end-capping, and ciprofloxacin hydrochloride in a mass ratio of 2:1:1, solutions A, B, and C are mixed at 37°C and vortexed for 5 seconds to obtain an antibacterial hollow mesoporous silica sphere injectable hydrogel dressing.

[0081] Example 3

[0082] S1. At 37°C, o-phenylenedialdehyde-terminated tetra-arm polyethylene glycol (n=90) was dissolved in PBS buffer at pH=7.4 to prepare a 5% (w / w) solution; then, the pH of the system was adjusted to 7.4 with NaOH solution to obtain solution A.

[0083] S2. At 37°C, hollow mesoporous silica spheres loaded with tannic acid were dispersed in PBS buffer solution with pH = 7.4 to prepare a 5% (w / w) solution; then, the pH of the system was adjusted to 7.4 with NaOH solution to obtain solution B.

[0084] S3. At 37°C, ciprofloxacin hydrochloride was dissolved in PBS buffer at pH 7.4 to prepare a 5% (w / w) solution, which is solution C.

[0085] S4. Using hollow mesoporous silica spheres loaded with tannic acid, tetra-arm polyethylene glycol with o-phthalaldehyde end-capping, and ciprofloxacin hydrochloride in a mass ratio of 2:1:1, solutions A, B, and C are mixed at 37°C and vortexed for 5 seconds to obtain an antibacterial hollow mesoporous silica sphere injectable hydrogel dressing.

[0086] Comparative Example 1

[0087] Same as Example 1, except that a four-arm polyethylene glycol with a degree of polymerization n=20 and phthalaldehyde-terminated is used.

[0088] Comparative Example 2

[0089] Same as Example 1, except that a four-arm polyethylene glycol with a degree of polymerization n=150 and phthalaldehyde-terminated is used.

[0090] The gelation time and mechanical strength (elastic modulus) of the antibacterial hollow mesoporous silica ball injectable hydrogel dressings obtained in Comparative Example 1 and Comparative Example 2 were tested according to the test method for the obtained antibacterial hollow mesoporous silica ball injectable hydrogel dressings in Example 1. The results are shown in Table 1. Table 1: Gelation time and mechanical strength (elastic modulus) of the antibacterial hollow mesoporous silica ball injectable hydrogel dressings obtained in Example 1, Comparative Example 1, and Comparative Example 2

[0091]

[0092] As shown in Table 1, excessively low or high degree of polymerization (n) will adversely affect the gelation time and mechanical strength of the hydrogel dressing. This invention controls the degree of polymerization within the range of 25 ≤ n ≤ 100 to obtain a hydrogel dressing with ideal gelation time and high mechanical strength. If the degree of polymerization is too low, the hydrogel gelation time will be prolonged, making it difficult to gel, and the mechanical strength will be poor and it will be easy to disintegrate. If the degree of polymerization is too high, the gelation will be too fast (poor operability), and although the mechanical strength is high, the material will become brittle and the toughness will decrease.

[0093] The various embodiments in this specification are described in a progressive manner, with each embodiment focusing on the differences from other embodiments. The same or similar parts between the various embodiments can be referred to each other.

[0094] The above description of the disclosed embodiments enables those skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the invention is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A method for preparing an injectable hydrogel dressing with antibacterial hollow mesoporous silica spheres, characterized in that, Includes the following steps: Hollow mesoporous silica spheres were dispersed in water, mixed with tannic acid solution, and collected to obtain hollow mesoporous silica spheres loaded with tannic acid. The o-phthalaldehyde-terminated four-arm polyethylene glycol was dissolved in a solvent to obtain solution A; The hollow mesoporous silica spheres loaded with tannic acid were dissolved in a solvent to obtain solution B; Ciprofloxacin hydrochloride was dissolved in a solvent to obtain solution C; After mixing and reacting the solutions A, B and C, the antibacterial hollow mesoporous silica sphere injectable hydrogel dressing is obtained. The structural formula of the o-phthalaldehyde-terminated four-arm polyethylene glycol is: Where n is the degree of aggregation, and its value ranges from 25 to n to 100. During the preparation process, hollow mesoporous silica spheres and four-arm polyethylene glycol with o-phthalaldehyde end caps cross-link spontaneously. The aldehyde groups of o-phthalaldehyde at the end of the polyethylene glycol react with the amino groups on the hollow mesoporous silica spheres to generate nitrogen-containing five-membered heterocycles.

2. The preparation method according to claim 1, characterized in that, The loading rate of the hollow mesoporous silica spheres loaded with tannic acid is 3.5~4 wt%.

3. The preparation method according to claim 1, characterized in that, The solvent independently includes one or more of water, physiological saline, buffer solution, bacterial culture medium, tissue culture medium, and body fluid.

4. The preparation method according to claim 1, characterized in that, The pH value of solution A is 4 to 9; and / or, the mass fraction of o-phthalaldehyde-terminated tetra-arm polyethylene glycol in solution A is 5 to 10%.

5. The preparation method according to claim 1, characterized in that, The pH value of solution B is 4 to 9; and / or the mass fraction of hollow mesoporous silica spheres containing tannic acid in solution B is 5 to 10%.

6. The preparation method according to claim 1, characterized in that, The mass fraction of ciprofloxacin hydrochloride in solution C is 5-10%.

7. The preparation method according to claim 1, characterized in that, The mass ratio of the hollow mesoporous silica spheres loaded with tannic acid, the four-arm polyethylene glycol with o-phthalaldehyde end caps, and the ciprofloxacin hydrochloride is 1~3:1:

1.

8. The preparation method according to claim 1, characterized in that, The melting temperature is independently 10~60℃.

9. The preparation method according to claim 1, characterized in that, The reaction temperature is 10~60℃.

10. An antibacterial hollow mesoporous silica sphere injectable hydrogel dressing prepared by the preparation method according to any one of claims 1 to 9.

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