Method for improving degradation rate of bioactive glass nanoparticles

Abstract

The invention discloses a method for improving the degradation rate of bioactive glass nano-particles. The bioactive glass nano-particles are subjected to ion exchange treatment by adopting molten metal salt and then are subjected to water cooling. According to the method, the metal salt in the molten state is adopted for conducting ion exchange treatment on the bioactive glass nanoparticles, molecules of the bioactive glass nanoparticles are promoted to be rearranged, the structures of the bioactive glass nanoparticles become looser, the degradation efficiency of the bioactive glass nanoparticles is remarkably improved, and the bioactivity of the bioactive glass nanoparticles is improved. The method effectively promotes early dissociation of Si-O-Si structures of bioactive glass nanoparticles, and is suitable for the field of degradable biomedical materials.

Description

Technical Field

[0001] The present invention belongs to the field of biodegradable biomedical materials, and particularly relates to a method for improving the degradation rate of bioactive glass nanoparticles. Background Art

[0002] In the early 1970s, Professor Hench developed the first generation of bioactive glass materials (Bioactive Glass, abbreviated as BG, 46.1SiO 2 -2.6P 2 O 5 -24.4Na 2 O-26.9CaO). Bioactive glass is a kind of material that can repair, replace and regenerate body tissues and has the ability to form a bonding effect between tissues and materials. It has been studied for mineralized tissue regeneration for a long time, but recently it has been gradually applied in soft tissue repair, especially in skin wound repair. Among them, bioactive glass nanoparticles (abbreviated as BGN) generally stimulate tissue healing by releasing ions, such as promoting hemostasis, antibacterial, promoting epithelial cell migration, angiogenesis and fibroblast proliferation, etc., and have been involved in all stages of wound healing.

[0003] However, BGN degrades slowly and relatively few ions are dissolved out, making it difficult to meet the high requirements of complex skin wound repair. Therefore, how to effectively improve the degradation rate of BGN itself and give full play to the ionic biological function has become a key issue in the application of BGN in complex wounds. Summary of the Invention

[0004] The purpose of the present invention is to overcome the deficiencies in the above-mentioned prior art and provide a method for improving the degradation rate of bioactive glass nanoparticles. This method uses molten metal salts to perform ion exchange treatment on bioactive glass nanoparticles, promotes the rearrangement of bioactive glass nanoparticle molecules, and makes their structure become looser, significantly improving the degradation efficiency of bioactive glass nanoparticles, effectively promoting the early dissociation of Si-O-Si, and solving the problems of slow degradation and less ion dissolution of bioactive glass nanoparticles.

[0005] To achieve the above purpose, the technical solution adopted by the present invention is: a method for improving the degradation rate of bioactive glass nanoparticles, characterized in that molten metal salts are used to perform ion exchange treatment on bioactive glass nanoparticles 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] The present invention uses rubidium nitrate or rubidium chloride as molten metal salts. Since rubidium ions have a large ionic radius (0.152 nm), they are used to replace metal ions with smaller ionic radii in bioactive glass nanoparticles, which can expand their network structure, further increase the disorder and chemical potential of the structure, facilitate ion dissolution, and improve the degradation rate of bioactive glass nanoparticles. Moreover, rubidium ions have a potential role in promoting angiogenesis and are essential trace elements in the human body, and are expected to be applied in the field of tissue repair.

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

[0009] The present invention controls the mass ratio of the metal salt to the bioactive glass nanoparticles to ensure that the molten salt can cover the bioactive glass nanoparticles and achieve sufficient ion exchange.

[0010] For the above method for improving the degradation rate of bioactive glass nanoparticles, it is characterized in that the temperature of the ion exchange treatment is 400°C to 500°C, and the duration of the ion exchange treatment is 1 h to 3 h.

[0011] The present invention controls the temperature of the ion exchange treatment to enable the bioactive glass nanoparticles to undergo ion exchange under conditions below the glass transition temperature, avoiding changing the state of the bioactive glass nanoparticles. By controlling the time of the ion exchange treatment, it can ensure that the bioactive glass nanoparticles undergo sufficient ion exchange, avoiding insufficient ion exchange when the time is too short and excessive ion release in the bioactive glass nanoparticles when the time is too long, which affects subsequent biological functions. At the same time, by controlling the temperature and duration of the ion exchange treatment, the infiltration amount of Rb ions in the bioactive glass nanoparticles can be controlled, and flexible regulation can be carried out according to the requirements of different degradation rates.

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

[0013] The present invention has the following advantages compared with the prior art:

[0014] 1. In the present invention, by placing bioactive glass nanoparticles in molten metal salts, the exchange of alkaline ions in the molten metal salts with the ions of the bioactive glass nanoparticles is achieved based on the chemical concentration gradient, breaking the inherent molecular structure stability inside the bioactive glass nanoparticles, promoting the rearrangement of the bioactive glass nanoparticle molecules, and making their structure become looser, 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 achieve batch processing of bioactive glass nanoparticles, and can reduce the processing cost, opening up a new way 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 components and controllable biological properties by regulating the temperature and time of the ion exchange treatment and the type of bioactive glass nanoparticles, opening up a 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 drawings and embodiments. Description of the Drawings

[0018] Figure 1 It is the micrograph of MnBGN, MnRbBGN - 400 and MnRbBGN - 500 in Example 1 and Example 2 of the present invention.

[0019] Figure 2 It is the Fourier transform infrared spectrum of MnBGN, MnRbBGN - 400 and MnRbBGN - 500 in Example 1 and Example 2 of the present invention.

[0020] Figure 3 It is the detection result graph of the Rb ion content of MnBGN, MnRbBGN - 400 and MnRbBGN - 500 in Example 1 and Example 2 of the present invention.

[0021] Figure 4 It is the thermogravimetric result graph of MnBGN, MnRbBGN - 400 and MnRbBGN - 500 in Example 1 and Example 2 of the present invention.

[0022] Figure 5 It is the differential scanning calorimetry result graph of MnBGN, MnRbBGN - 400 and MnRbBGN - 500 in Example 1 and Example 2 of the present invention.

[0023] Figure 6Microscopic morphology diagrams of MnBGN, MnRbBGN-400, and MnRbBGN-500 in Tris buffer solution soaked for different durations in Example 1 and Example 2 of the present invention.

[0024] Figure 7 Results diagrams of cumulative Si ion release amounts of MnBGN, MnRbBGN-400, and MnRbBGN-500 in Tris buffer solution soaked for different durations in Example 1 and Example 2 of the present invention.

[0025] Figure 8 Microscopic morphology diagrams of NaBGN and NaRbBGN-500 in Example 3 of the present invention.

[0026] Figure 9 Fourier transform infrared spectroscopy diagrams of NaBGN and NaRbBGN-500 in Example 3 of the present invention.

[0027] Figure 10 Microscopic morphology diagrams of NaBGN and NaRbBGN-500 in Tris buffer solution soaked for different durations in Example 3 of the present invention.

[0028] Figure 11 Results diagrams of cumulative Si ion release amounts of NaBGN and NaRbBGN-500 in Tris buffer solution soaked for different durations in Example 3 of the present invention. Detailed implementation manners

[0029] Example 1

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

[0031] Using the microemulsion-assisted sol-gel method to prepare Mn-doped mesoporous bioactive glass nanoparticles (MnBGN); placing 10 g of rubidium nitrate in an Al 2 O 3 crucible and heating it to melt to obtain molten rubidium nitrate, adding 100 mg of MnBGN, keeping it at 400 °C for 1 h, then cooling it in deionized water, and freeze-drying it after centrifugal washing for standby, denoted as MnRbBGN-400;

[0032] The specific process of preparing MnBGN by the microemulsion-assisted sol-gel method is as follows: 0.25 g of cetylpyridinium bromide and 0.15 g of urea are 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 are added and reacted for 2 h, and then 0.669 mL of tetraethyl orthosilicate is added dropwise and the temperature is raised to 70 °C and reacted for 7.5 h; subsequently, 68.2 μL of triethyl phosphate is added and reacted for 30 min, 330.5 mg of calcium nitrate tetrahydrate is added and reacted for 15 min, 63.3 mg of manganese nitrate hexahydrate is added and stirred for 16 h, and centrifuged at 10,000 rpm for 15 min to obtain a precipitate; the precipitate is washed successively with acetone, ethanol, and deionized water and then freeze-dried; finally, it is calcined in a muffle furnace at 600 °C for 5 h and naturally cooled to obtain MnBGN.

[0033] Example 2

[0034] The difference between this example and Example 1 is that molten rubidium nitrate and MnBGN are kept at 500 °C for 1 h, then put into deionized water to cool, and after centrifugal washing, they are freeze-dried for standby, denoted as MnRbBGN-500.

[0035] Morphological analysis was performed on MnBGN, MnRbBGN-400, and MnRbBGN-500. As Figure 1 shown, MnBGN is mesoporous nanoparticles with a particle size of about 200 nm. After Rb ion exchange treatment at 400 °C and 500 °C, its morphology did not change significantly; Fourier transform infrared spectroscopy analysis was performed on MnBGN, MnRbBGN-400, and MnRbBGN-500. As Figure 2 shown, MnRbBGN-400 and MnRbBGN-500 still have the Si-O-Si molecular structure of bioactive glass.

[0036] Rb ion content detection was performed on MnBGN, MnRbBGN-400, and MnRbBGN-500. As Figure 3 shown, the Rb ion content of MnRbBGN-500 is higher than that of MnRbBGN-400, indicating that increasing the treatment temperature is beneficial to the infiltration of Rb ions.

[0037] Thermogravimetric and differential scanning calorimetric analyses were performed on MnBGN, MnRbBGN-400, and MnRbBGN-500. The results are as Figure 4 and Figure 5 shown. Below 560 °C, due to the evaporation of water and the decomposition of nitrate, each sample has a weight loss of about 15%; when the temperature is greater than 560 °C, the weight of each sample remains stable, but a phase change may occur. Combining Figure 5It can be seen that in the range of 223°C to 263°C, MnRbBGN-400 and MnRbBGN-500 have a weak glass transition, while this phenomenon is not observed in MnBGN, indicating that ion exchange weakens the glass network structure; when the temperature rises to 850°C, MnRbBGN-400 and MnRbBGN-500 exhibit crystallization phenomena, indicating that internal molecular rearrangement occurs.

[0038] MnBGN, MnRbBGN-400, and MnRbBGN-500 were respectively immersed in Tris buffer solution. The supernatant and nanoparticles were collected, the Si element content in the supernatant was detected, and the morphology of the nanoparticles was observed. The morphologies of MnBGN, MnRbBGN-400, and MnRbBGN-500 after being immersed for different durations are as Figure 6 shown. When the immersion duration was 4 weeks, MnRbBGN-500 showed a relatively loose structure compared with MnRbBGN-400 and MnBGN; when the immersion duration was 8 weeks, the diameters of MnRbBGN-400 and MnRbBGN-500 decreased significantly and the structures were loose; indicating that the method of the present invention can effectively improve the degradation rate of bioactive glass nanoparticles. The cumulative Si ion release amounts of MnBGN, MnRbBGN-400, and MnRbBGN-500 after being immersed for different durations are as Figure 7 shown. The Si ion release amounts of both MnRbBGN-400 and MnRbBGN-500 are higher than that of MnBGN, and MnRbBGN-500 releases more Si ions than MnRbBGN-400, indicating that ion exchange treatment can effectively promote the early dissociation of Si-O-Si, and the higher the temperature of ion exchange treatment, the better the promotion effect.

[0039] Example 3

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

[0041] The microemulsion-assisted sol-gel method was used to prepare Na-doped mesoporous bioactive glass nanoparticles (NaBGN); 10 g of rubidium nitrate was placed in an Al 2 O 3 crucible and heated to melting to obtain molten rubidium nitrate. After adding 100 mg of NaBGN, it was kept at 500°C for 1 h, then cooled in deionized water, and freeze-dried after centrifugal washing for standby, denoted as NaRbBGN-500;

[0042] The specific process for preparing NaBGN by the microemulsion-assisted sol-gel method is as follows: Dissolve 10 g of DDA in 62.5 mL of deionized water and 200 mL of absolute ethanol, then add 5 mL of tetraethyl orthosilicate, 510 μL of triethyl phosphate, and 3.18 g of calcium nitrate tetrahydrate, magnetically stir for 3 h and then filter to obtain a precipitate; rinse the precipitate with absolute ethanol and deionized water and then freeze-dry; finally, place it in a muffle furnace and calcine at 650 °C for 3 h, and naturally cool to obtain NaBGN.

[0043] Morphological analysis was performed on NaBGN and NaRbBGN-500. As Figure 8 shown, NaBGN is spherical particles with a particle size of about 150 nm. After being treated by Rb ion exchange at 500 °C, its morphology did not change significantly; Fourier transform infrared spectroscopy analysis was performed on NaBGN and NaRbBGN-500. As Figure 9 shown, NaRbBGN-500 still has the Si-O-Si molecular structure of bioactive glass.

[0044] NaBGN and NaRbBGN-500 were respectively immersed in Tris buffer solution, the supernatant and nanoparticles were collected, the Si element content in the supernatant was detected, and the morphology of the nanoparticles was observed. The morphologies of NaBGN and NaRbBGN-500 immersed for different durations are as Figure 10 shown. In the early stage of immersion, NaRbBGN-500 already showed a relatively loose structure compared with NaBGN, indicating that the method of the present invention can effectively improve the degradation rate of bioactive glass nanoparticles. The cumulative Si ion release amounts of NaBGN and NaRbBGN-500 immersed for different durations are as Figure 11 shown. The Si ion release amount of NaRbBGN-500 is higher than that of NaBGN, indicating that ion exchange treatment can effectively promote the early dissociation of Si-O-Si.

[0045] Example 4

[0046] The difference between this example and Example 3 is that 10 g of rubidium chloride is placed in an Al 2 O 3 crucible and heated to melt to obtain molten rubidium chloride. After adding 100 mg of MnBGN, keep it at 450 °C for 2 h, then put it into deionized water to cool, and freeze-dry after centrifugal washing for standby, denoted as NaRbBGN-450.

[0047] After NaRbBGN-450 in this example was immersed in Tris buffer solution for 4 weeks, compared with NaBGN immersed for the same time, it showed a more loose structure.

[0048] The above are only the preferred embodiments of the present invention, and do not impose any limitations on the present invention. Any simple modifications, changes, and equivalent structural transformations made to the above embodiments based on the technical essence of the present invention still fall within the scope of protection of the technical solution of the present invention.

Claims

1. A method for increasing the degradation rate of bioactive glass nanoparticles, characterized in that: The bioactive glass nanoparticles are treated with ion exchange by using molten metal salts and then water-cooled.

2. A method for increasing the degradation rate of bioactive glass nanoparticles according to claim 1, characterized in that: The metal salt is rubidium nitrate or rubidium chloride.

3. The method for increasing 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.

4. The method for increasing the degradation rate of bioactive glass nanoparticles according to claim 1, characterized in that: The temperature of the ion exchange treatment is 400° C. to 500° C., and the duration of the ion exchange treatment is 1 hour to 3 hours.

5. The method for increasing the degradation rate of bioactive glass nanoparticles according to claim 1, characterized in that: The bioactive glass nanoparticles are in a mesoporous or spherical shape, and are Mn ion-doped or Na ion-doped bioactive glass nanoparticles.

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