A method for increasing the degradation rate of bioactive glass nanoparticles

Abstract

The application discloses a method for improving the degradation rate of bioactive glass nanoparticles, and adopts ion exchange treatment of bioactive glass nanoparticles by using molten metal salt and then water cooling. The method of the application promotes the rearrangement of bioactive glass nanoparticle molecules and makes the structure of the bioactive glass nanoparticles more loose by using ion exchange treatment of bioactive glass nanoparticles by using molten metal salt, significantly improves the degradation efficiency of the bioactive glass nanoparticles, effectively promotes the early dissociation of the Si-O-Si structure of the bioactive glass nanoparticles, and is suitable for the field of degradable biomedical materials.

Description

Technical Field

[0001] This invention belongs to the field of biodegradable biomedical materials, and in particular relates to a method for improving the degradation rate of bioactive glass nanoparticles. Background Technology

[0002] In the early 1970s, Professor Hench developed the first generation of bioactive glass materials (BG, 46.1SiO2-2.6P2O5-24.4Na2O-26.9CaO). Bioactive glass is a class of materials capable of repairing, replacing, and regenerating body tissues, and possessing the ability to form bonds between tissues and materials. It has long been studied for its application in the regeneration of mineralized tissues, but recently its application in soft tissue repair, particularly in skin wound repair, has been gradually expanded. Bioactive glass nanoparticles (BGN) generally stimulate tissue healing by releasing ions, such as promoting hemostasis, antibacterial activity, promoting epithelial cell migration, angiogenesis, and fibroblast proliferation, thus involving all stages of wound healing.

[0003] However, BGN degrades slowly and releases relatively few ions, making it difficult to meet the high requirements of repairing complex skin wounds. Therefore, how to effectively improve the degradation rate of BGN and fully utilize its ionic biological functions has become a key issue in the application of BGN in complex wounds. Summary of the Invention

[0004] The purpose of this invention is to overcome the shortcomings of the prior art and provide a method for improving the degradation rate of bioactive glass nanoparticles. This method involves ion exchange treatment of bioactive glass nanoparticles with molten metal salts, which induces molecular rearrangement and makes the structure more loosely dispersed, significantly improving the degradation efficiency of the bioactive glass nanoparticles and effectively promoting the early dissociation of Si-O-Si, thus solving the problems of slow degradation and low ion dissolution of bioactive glass nanoparticles.

[0005] To achieve the above objectives, the technical solution adopted by the present invention is: a method for improving the degradation rate of bioactive glass nanoparticles, characterized in that the bioactive glass nanoparticles are subjected to ion exchange treatment with molten metal salts and then water-cooled.

[0006] The above-mentioned method for improving the degradation rate of bioactive glass nanoparticles is characterized in that the metal salt is rubidium nitrate or rubidium chloride.

[0007] This invention uses rubidium nitrate or rubidium chloride as a molten metal salt. Because rubidium ions have a large ionic radius (0.152 nm), they can replace metal ions with smaller ionic radii in bioactive glass nanoparticles, thereby expanding their network structure, further increasing the disorder and chemical potential of the structure, which is beneficial for ion dissolution and improving the degradation rate of bioactive glass nanoparticles. In addition, rubidium ions have the potential to promote angiogenesis and are an essential trace element for the human body, and are expected to be applied in the field of tissue repair.

[0008] The above-mentioned method for improving the degradation rate of bioactive glass nanoparticles is characterized in that the mass ratio of the metal salt to the bioactive glass nanoparticles is not less than 10:1.

[0009] This invention controls the mass ratio of metal salt to bioactive glass nanoparticles to ensure that the molten salt can cover the bioactive glass nanoparticles, thereby achieving sufficient ion exchange.

[0010] The above-mentioned method for improving the degradation rate of bioactive glass nanoparticles is characterized in that the temperature of the ion exchange treatment is 400℃~500℃ and the duration of the ion exchange treatment is 1h~3h.

[0011] This invention enables ion exchange in bioactive glass nanoparticles below their glass transition temperature by controlling the ion exchange treatment temperature, thus avoiding alteration of the nanoparticles' state. By controlling the ion exchange treatment time, it ensures sufficient ion exchange occurs within the bioactive glass nanoparticles, preventing insufficient exchange due to too short a time or excessive ion release from the nanoparticles due to too long a time, which could negatively impact subsequent biological functions. Furthermore, by controlling the temperature and duration of the ion exchange treatment, the amount of Rb ions penetrating into the bioactive glass nanoparticles can be controlled, allowing for flexible adjustment to meet different degradation rate requirements.

[0012] The above-mentioned method for improving the degradation rate of bioactive glass nanoparticles is characterized in that the bioactive glass nanoparticles are mesoporous or spherical in shape, and the bioactive glass nanoparticles are Mn ion-doped or Na ion-doped bioactive glass nanoparticles.

[0013] Compared with the prior art, the present invention has the following advantages:

[0014] 1. This invention places bioactive glass nanoparticles in molten metal salts and achieves the exchange of alkaline ions in the molten metal salts with ions in the bioactive glass nanoparticles based on a chemical concentration gradient. This breaks the inherent molecular structural stability of the bioactive glass nanoparticles, promotes the rearrangement of the bioactive glass nanoparticle molecules, and makes their structure more loose, thereby accelerating the degradation rate of the bioactive glass nanoparticles.

[0015] 2. The ion exchange process of the present invention is simple to operate and can be completed without complex equipment or harsh conditions. It can realize batch processing of bioactive glass nanoparticles and reduce processing costs, opening up new avenues for the further application and research of bioactive glass nanoparticles.

[0016] 3. The method of the present invention can prepare bioactive glass nanoparticle materials with adjustable composition and controllable biological properties by controlling the temperature and time of ion exchange treatment and the type of bioactive glass nanoparticles, opening up broad space for the application of bioactive glass nanoparticles in diverse medical scenarios.

[0017] The technical solution of the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. Attached Figure Description

[0018] Figure 1 These are microscopic morphology images of MnBGN, MnRbBGN-400, and MnRbBGN-500 in Embodiments 1 and 2 of the present invention.

[0019] Figure 2 The Fourier transform infrared spectra of MnBGN, MnRbBGN-400 and MnRbBGN-500 in Embodiments 1 and 2 of the present invention are shown.

[0020] Figure 3 The graph shows the Rb ion content detection results of MnBGN, MnRbBGN-400 and MnRbBGN-500 in Examples 1 and 2 of this invention.

[0021] Figure 4 The thermogravimetric results of MnBGN, MnRbBGN-400 and MnRbBGN-500 in Embodiments 1 and 2 of the present invention are shown.

[0022] Figure 5 The differential scanning calorimetry results of MnBGN, MnRbBGN-400 and MnRbBGN-500 in Embodiments 1 and 2 of the present invention are shown.

[0023] Figure 6The images show the microstructures of MnBGN, MnRbBGN-400, and MnRbBGN-500 after soaking in Tris buffer for different durations in Examples 1 and 2 of this invention.

[0024] Figure 7 The graph shows the cumulative release of Si ions from MnBGN, MnRbBGN-400, and MnRbBGN-500 after immersion in Tris buffer for different durations in Examples 1 and 2 of this invention.

[0025] Figure 8 The images show the microstructure of NaBGN and NaRbBGN-500 in Example 3 of this invention.

[0026] Figure 9 The Fourier transform infrared spectra of NaBGN and NaRbBGN-500 in Example 3 of this invention are shown.

[0027] Figure 10 The images show the microstructures of NaBGN and NaRbBGN-500 after soaking in Tris buffer for different durations in Example 3 of this invention.

[0028] Figure 11 This is a graph showing the cumulative release of Si ions from NaBGN and NaRbBGN-500 after soaking in Tris buffer for different durations in Example 3 of the present invention. Detailed Implementation

[0029] Example 1

[0030] The method for improving the degradation rate of bioactive glass nanoparticles in this embodiment is as follows:

[0031] Mn-doped mesoporous bioactive glass nanoparticles (MnBGN) were prepared using a microemulsion-assisted sol-gel method. 10 g of rubidium nitrate was placed in an Al2O3 crucible and heated to melt, resulting in molten rubidium nitrate. 100 mg of MnBGN was added, and the mixture was kept at 400 °C for 1 h. It was then cooled in deionized water, washed by centrifugation, and freeze-dried for later use. This mixture was designated MnRbBGN-400.

[0032] The specific process for preparing MnBGN using the microemulsion-assisted sol-gel method is as follows: 0.25 g of hexadecylpyridine bromide and 0.15 g of urea were placed in 7.5 mL of deionized water and stirred in a water bath at 25 °C; then 7.5 mL of cyclohexane and 0.23 g of isopropanol were added and reacted for 2 h, followed by the dropwise addition of 0.669 mL of tetraethyl orthosilicate, and the temperature was raised to 70 °C and reacted for 7.5 h; subsequently, 68.2 μL of triethyl phosphate was added and reacted for 30 min, followed by the addition of 330.5 mg of calcium nitrate tetrahydrate and reacted for 15 min, and then 63.3 mg of manganese nitrate hexahydrate was added and stirred for 16 h. The mixture was centrifuged at 10,000 rpm for 15 min to obtain a precipitate; the precipitate was washed sequentially with acetone, ethanol, and deionized water and then freeze-dried; finally, it was calcined in a muffle furnace at 600 °C for 5 h, and after natural cooling, MnBGN was obtained.

[0033] Example 2

[0034] The difference between this embodiment and Example 1 is that: molten rubidium nitrate and MnBGN are kept at 500°C for 1 hour, then cooled in deionized water, washed by centrifugation, and freeze-dried for later use, and are denoted as MnRbBGN-500.

[0035] Morphological analysis was performed on MnBGN, MnRbBGN-400, and MnRbBGN-500, such as... Figure 1 As shown, MnBGN consists of mesoporous nanoparticles with a particle size of approximately 200 nm. After Rb ion exchange treatment at 400℃ and 500℃, its morphology did not change significantly. Fourier transform infrared spectroscopy analysis was performed on MnBGN, MnRbBGN-400, and MnRbBGN-500, as shown... Figure 2 As shown, MnRbBGN-400 and MnRbBGN-500 still possess the Si-O-Si molecular structure of bioglass.

[0036] The Rb ion content of MnBGN, MnRbBGN-400, and MnRbBGN-500 was detected, such as... Figure 3 As shown, MnRbBGN-500 has a higher Rb ion content than MnRbBGN-400, indicating that increasing the treatment temperature is beneficial for Rb ion penetration.

[0037] Thermogravimetric and differential scanning calorimetric analyses were performed on MnBGN, MnRbBGN-400, and MnRbBGN-500. The results are as follows: Figure 4 and Figure 5 As shown, at temperatures below 560℃, each sample experienced approximately a 15% weight loss due to water evaporation and nitrate decomposition; when the temperature exceeded 560℃, the weight of each sample remained stable, but a phase transition might occur. Figure 5It can be seen that MnRbBGN-400 and MnRbBGN-500 exhibit a weak glass transition in the temperature range of 223℃ to 263℃, while MnBGN does not show this phenomenon, indicating that ion exchange weakens the glass network structure; when the temperature rises to 850℃, MnRbBGN-400 and MnRbBGN-500 exhibit crystallization, indicating that internal molecules rearrange.

[0038] MnBGN, MnRbBGN-400, and MnRbBGN-500 were immersed in Tris buffer, and the supernatant and nanoparticles were collected. The Si content in the supernatant was determined, and the morphology of the nanoparticles was observed. The morphologies of MnBGN, MnRbBGN-400, and MnRbBGN-500 after immersion for different durations are shown in the figures. Figure 6 As shown, when the immersion time was 4 weeks, MnRbBGN-500 exhibited a more porous structure compared to MnRbBGN-400 and MnBGN; when the immersion time was 8 weeks, the diameters of MnRbBGN-400 and MnRbBGN-500 were significantly reduced, and their structures remained porous; this indicates that the method of the present invention can effectively improve the degradation rate of bioactive glass nanoparticles. The cumulative release of Si ions from MnBGN, MnRbBGN-400, and MnRbBGN-500 after immersion for different durations is shown in the figure. Figure 7 As shown, both MnRbBGN-400 and MnRbBGN-500 have higher Si ion release rates than MnBGN, and MnRbBGN-500 releases more Si ions than MnRbBGN-400. This indicates that ion exchange treatment can effectively promote the early dissociation of Si-O-Si, and the higher the temperature of the ion exchange treatment, the better the promoting effect.

[0039] Example 3

[0040] The method for improving the degradation rate of bioactive glass nanoparticles in this embodiment is as follows:

[0041] Na-doped mesoporous bioactive glass nanoparticles (NaBGN) were prepared using a microemulsion-assisted sol-gel method. 10 g of rubidium nitrate was placed in an Al2O3 crucible and heated to melt, resulting in molten rubidium nitrate. 100 mg of NaBGN was added, and the mixture was kept at 500 °C for 1 h. Then, it was cooled in deionized water, washed by centrifugation, and freeze-dried for later use. This mixture was designated as NaRbBGN-500.

[0042] The specific process for preparing NaBGN using the microemulsion-assisted sol-gel method is as follows: 10g of DDA is dissolved in 62.5mL of deionized water and 200mL of anhydrous ethanol, then 5mL of tetraethyl orthosilicate, 510μL of triethyl phosphate and 3.18g of calcium nitrate tetrahydrate are added. After magnetic treatment for 3 hours, the mixture is filtered to obtain a precipitate. The precipitate is washed with anhydrous ethanol and deionized water and then freeze-dried. Finally, it is calcined in a muffle furnace at 650℃ for 3 hours and then naturally cooled to obtain NaBGN.

[0043] Morphological analysis was performed on NaBGN and NaRbBGN-500, such as... Figure 8 As shown, NaBGN consists of spherical particles with a diameter of approximately 150 nm. After Rb ion exchange treatment at 500℃, its morphology did not change significantly. Fourier transform infrared spectroscopy analysis was performed on NaBGN and NaRbBGN-500, as shown... Figure 9 As shown, NaRbBGN-500 still possesses the Si-O-Si molecular structure of bioglass.

[0044] NaBGN and NaRbBGN-500 were immersed in Tris buffer, and the supernatant and nanoparticles were collected. The Si content in the supernatant was determined, and the morphology of the nanoparticles was observed. The morphologies of NaBGN and NaRbBGN-500 after immersion for different durations are shown in the figures below. Figure 10 As shown, in the early stage of immersion, NaRbBGN-500 exhibits a more porous structure compared to NaBGN, indicating that the method of this invention can effectively improve the degradation rate of bioactive glass nanoparticles. The cumulative release of Si ions from NaBGN and NaRbBGN-500 after immersion for different durations is shown in the figure. Figure 11 As shown, NaRbBGN-500 releases more Si ions than NaBGN, indicating that ion exchange treatment can effectively promote the early dissociation of Si-O-Si.

[0045] Example 4

[0046] The difference between this embodiment and Example 3 is that 10g of rubidium chloride was placed in an Al2O3 crucible and heated to melt, resulting in molten rubidium chloride. After adding 100mg of MnBGN, the mixture was kept at 450℃ for 2 hours, then cooled in deionized water, and after centrifugation and washing, it was freeze-dried for later use and designated as NaRbBGN-450.

[0047] In this embodiment, NaRbBGN-450, after being soaked in Tris buffer for 4 weeks, exhibited a more porous structure compared to NaBGN soaked for the same period.

[0048] The above description is merely a preferred embodiment of the present invention and does not constitute any limitation on the present invention. Any simple modifications, alterations, or equivalent structural transformations made to the above embodiments based on the technical essence of the present invention shall still fall within the protection scope of the present invention.

Claims

1. A method for improving the degradation rate of bioactive glass nanoparticles, characterized in that, The bioactive glass nanoparticles are subjected to ion exchange treatment with molten metal salts followed by water cooling. The metal salts are rubidium nitrate or rubidium chloride. The bioactive glass nanoparticles are mesoporous or spherical in shape and are Mn-doped or Na-doped.

2. The method for improving the degradation rate of bioactive glass nanoparticles according to claim 1, characterized in that, The mass ratio of the metal salt to the bioactive glass nanoparticles is not less than 10:

1.

3. The method for improving the degradation rate of bioactive glass nanoparticles according to claim 1, characterized in that, The ion exchange treatment is performed at a temperature of 400℃ to 500℃ for a duration of 1 hour to 3 hours.

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