WO2019148554A1 - Boron and phosphorus-based bioactive glass and preparation method thereof - Google Patents

Abstract

Disclosed are a boron and phosphorus-based bioactive glass and a preparation method thereof. The method comprises the steps of preparing a boron-based glass by melt-quenching method, wherein the raw materials includes B 2O 3, MgO, CaO, Na 2O, K 2O和SrO and SrO in a mass ratio of (45-60):(2-10):(15-25):(3-10):(10-15):(1-8); and then impregnating in a solution containing phosphorus ions to yield a double-layer bioactive glass with a porous phosphate shell and a borate core. The degradation rate of the borate glass structure in an organism can be controlled, and the biocompatibility of the biological material can be improved by the porous shell; and therefore, the repairing speed of an injured body surface tissue is significantly increased.

Description

Boron phosphorus bioactive glass and preparation method thereof Technical field

The invention belongs to the field of biomedical technology, and in particular relates to a bioactive glass for surface tissue damage repair and a preparation method thereof.

Background technique

With the rapid development of science and technology in today's society, the types and quantity of vehicles are increasing. Traffic congestion has occurred in every major and second-tier cities. These changes have directly led to frequent traffic accidents, resulting in a sharp increase in the number of deaths and injuries. Among the major traffic accidents, the majority of patients with surface diseases are suffering from the disease, and accelerating the repair of surface tissue damage has become a demand.

On the other hand, accelerating the surface tissue repair when the body surface is damaged can reduce the time of restoring and create more social value. The international research on bioglass has been carried out extensively. From the silicate system bioglass proposed by Professor Hench to the commercial 45S5 bioactive glass in 1971, the performance of the material has been continuously improved (Zhong Jipin, Journal of Inorganic Materials, 1995), and a large number of patents have emerged, such as CN201210518111.2. A method for preparing a cerium-containing bioglass powder by a sol-gel method is provided, and a preparation method for preparing a ruthenium-containing porous bioglass stent, such as CN201710198500.4, which provides a bacterium for healing a cervical wound, is further provided. Glass dressing and its drug delivery device.

technical problem

However, most of the current disclosed technologies are concentrated in the bio-glass system of phosphate and silicate systems. The disadvantage is that the degradation rate of the two in the human body is too slow, affecting the growth of the tissue, thereby affecting wound healing.

Technical solution

The object of the present invention is to prepare a core-shell structured borophosphate bioactive glass by a simple impregnation method to obtain excellent tissue repair ability and biocompatibility. The present invention is implemented by the following technical solutions:

A boron-phosphorus bioactive glass and a preparation method thereof, the selected initial glass is a boron-based glass, and the raw material composition is B ₂ O ₃ , MgO, CaO, Na ₂ O, K ₂ O and SrO, and the mass ratio thereof is 45 ~60:2~10:15~25:3~10:10~15:1~8. The initial glass is obtained by high-temperature melt cooling to obtain a glass frit, which is sieved to obtain a glass powder. The melting temperature is 1000-1350 ° C, the holding time is 0.5-4 hours, preferably 1100-1300 ° C, and the temperature is 0.5-2 hours. The specific steps are as follows:

(1) The experimental instruments used in the method, such as a beaker, a stir bar, a measuring cylinder, etc., are washed with ultrapure water and subjected to sterilization and sterilization;

(2) grinding the boron-based glass through a sieve to obtain a glass powder having a particle size of 30 to 45 μm, and disinfecting and sterilizing the glass powder;

(3) The raw materials required for the impregnation solution are arranged according to the ratio, and are stirred and dissolved for use; the components of the impregnated solution are CaCl ₂ , (NH ₄ ) ₂ HPO ₄ , K ₂ HPO ₄ × 3H ₂ O, HCl, dissolved in 1 L. In ultrapure water, the mass ratio is 5~20:15~25:60~70:0.1~2; the CaCl ₂ , (NH ₄ ) ₂ HPO ₄ , K ₂ HPO ₄ ×3H ₂ O are analyzed. Pure, HCl concentration is 0.1mol / L;

(4) Weigh 100 g glass powder, put into 1L impregnation solution, stirring for 1~8h, preferably 3-6h;

(5) performing solid-liquid separation of the impregnated glass powder by vacuum filtration;

(6) The separated glass powder is washed with ultrapure water in a vacuum filtration device, and dried for use;

(7) A medical solvent is added to the glass frit to prepare a bioglass coating material.

In the step (1), the appliance is disinfected and sterilized, and the operator and the environment are also required to maintain a high degree of sterility to ensure that no harmful substances are introduced during the experiment;

In the step (2), the grinding medium used for the polishing of the bioglass is an agate mortar; the sieve used is a food grade stainless steel sieve, the sieve is a 325 mesh, 270 mesh sieve, and the intermediate layer glass powder is used after sieving. .

In the step (3), the main purpose of the hydrochloric acid used is to adjust the pH value of the solution, and after the solution is prepared, the pH of the solution is weakly acidic.

In the step (4), it is necessary to confirm the uniform dispersion of the glass powder during the stirring process, and there is no agglomeration or agglomerate to ensure sufficient contact between the glass powder and the immersion liquid.

In the step (5), vacuum filtration uses a filter paper having a pore diameter of less than 30 μm to control the dropping rate and the degree of vacuum of the solution to prevent pore clogging and damage of the filter paper.

In the step (6), the ultrapure water washing is carried out for 3 cycles to ensure that the glass powder is cleaned comprehensively.

The medical solvent used in the step (7) is a mixture of liquid paraffin, polyethylene glycol, carboxymethyl chitosan, sodium hyaluronate or the like;

The steps (1) to (7) need to be carried out in a biomedical laboratory with high cleanliness to ensure the accuracy of the experimental process.

Beneficial effect

(1) preparing a boron-based glass by a melt-cooling method, and then impregnating it with a solution containing phosphorus ions to obtain a porous phosphate glass as a shell, and a borate glass as a core double-layer bioactive glass;

(2) The porous phosphate shell can not only control the degradation rate of the borate glass structure in the living body, but also improve the biocompatibility of the biomaterial and significantly improve the repair speed of the damaged surface tissue;

(3) By adjusting the concentration of calcium ions in the immersion liquid, an appropriate amount of hydroxyapatite can be formed on the surface of the bioactive glass to effectively promote the complexation of the bioglass dressing with the human tissue;

(4) The raw material of the invention is simple and easy to obtain, the preparation method is simple, the process is stable, and the conditions of practicalization and industrialization are achieved.

DRAWINGS

Figure 1 shows the wound healing of a control sample;

Figure 2 is a view of wound healing after use of borophosphorus glass;

Figure 3 is a comparison of in vitro cell culture of the respective examples.

Embodiments of the invention

A boron-phosphorus bioactive glass and a preparation method thereof, the initial bioglass selected is boron-based glass, and the raw material composition is B ₂ O ₃ , MgO, CaO, Na ₂ O, K ₂ O and SrO, and the mass ratio thereof is 45~60:2~10:15~25:3~10:10~15:1~8. The initial glass has a melting temperature of 1000 to 1350 ° C, a holding time of 0.5 to 4 hours, preferably 1100 to 1300 ° C, and a holding temperature of 0.5 to 2 hours. The impregnated solution components are CaCl ₂ , (NH ₄ ) ₂ HPO ₄ , K ₂ HPO ₄ × 3H ₂ O, HCl, dissolved in 1 L of ultrapure water, and the mass ratio is 5-20:15~25:60~ 70: 0.1~2. The specific steps are as follows:

(1) The experimental instruments used in the method, such as a beaker, a stir bar, a measuring cylinder, etc., are washed with ultrapure water and subjected to sterilization and sterilization;

(2) grinding the boron-based glass through a sieve to obtain a glass powder having a particle size of 30 to 45 μm, and disinfecting and sterilizing the glass powder;

(3) The raw materials required for the impregnation solution are arranged according to the ratio, and are stirred and dissolved for use;

(4) Weigh 100 g glass powder, put into 1L impregnation solution, stirring for 1~8h, preferably 3-6h;

(5) performing solid-liquid separation of the impregnated glass powder by vacuum filtration;

(6) The separated glass powder is washed with ultrapure water in a vacuum filtration device, and dried for use;

(7) A medical solvent is added to the glass frit to prepare a bioglass coating material.

In the step (1), the appliance is disinfected and sterilized, and the operator and the environment are also required to maintain a high degree of sterility to ensure that no harmful substances are introduced during the experiment;

In the step (2), the grinding medium used for the polishing of the bioglass is an agate mortar; the sieve used is a food grade stainless steel sieve, the sieve is a 325 mesh, 270 mesh sieve, and the intermediate layer glass powder is used after sieving. .

In the step (3), the main purpose of the hydrochloric acid used is to adjust the pH value of the solution, and after the solution is prepared, the pH of the solution is weakly acidic.

In the step (4), it is necessary to confirm the uniform dispersion of the glass powder during the stirring process, and there is no agglomeration or agglomerate to ensure sufficient contact between the glass powder and the immersion liquid.

In the step (5), vacuum filtration uses a filter paper having a pore diameter of less than 30 μm to control the dropping rate and the degree of vacuum of the solution to prevent pore clogging and damage of the filter paper.

In the step (6), the ultrapure water washing is carried out for 3 cycles to ensure that the glass powder is cleaned comprehensively.

The medical solvent used in the step (7) is a mixture of liquid paraffin, polyethylene glycol, carboxymethyl chitosan, sodium hyaluronate or the like;

The steps (1) to (7) need to be carried out in a biomedical laboratory with high cleanliness to ensure the accuracy of the experimental process.

Table 1 is a table of initial glass components (in mass percent) in Examples 1-4

Example 1: Preparation and performance test results of materials

According to the ratio of each component in Table 1, weigh a certain amount of analytically pure raw materials (B ₂ O ₃ , MgO, CaO, Na ₂ O, K ₂ O and SrO), mix them evenly and put the powder into platinum. It is placed in a box-type resistance furnace for melting (melting temperature is 1350 ° C, holding time is 2 hours). The melt is then poured into deionized water to be quenched, dried to obtain a glass frit, and after ball milling, a glass frit is obtained. A certain amount of CaCl ₂ , (NH ₄ ) ₂ HPO ₄ , K ₂ HPO ₄ × 3H ₂ O, HCl (mass ratio: 5:23:70:2) was weighed and dissolved in 1 L of ultrapure water. 100 g of glass powder was weighed and placed in 1 L of the impregnation solution, and stirring was continued for 6 hours. After the stirring is completed, the impregnated glass powder is separated by vacuum filtration, dried and made into a bioglass dressing. The dressings were used for wound healing and in vitro cell culture experiments in mice. The wound healing experiments were taken for 1, 3, 5, and 7 days, respectively. The in vitro cell cultures were compared with the samples after 7 days of culture. Figure 3 is a comparison of in vitro cell culture of the respective examples. As can be seen from the figure, the bioglass cell survival amount of Example 1 (8.9*10 ⁴ ) was higher than that of the untreated control sample (8.6*10 ⁴ ).

Example 2: Preparation and performance test results of materials

According to the ratio of each component in Table 1, weigh a certain amount of analytically pure raw materials (B ₂ O ₃ , MgO, CaO, Na ₂ O, K ₂ O and SrO), mix them evenly and put the powder into platinum. It is placed in a box-type resistance furnace for melting (melting temperature is 1300 ° C, holding time is 2 hours). The melt is then poured into deionized water to be quenched, dried to obtain a glass frit, and after ball milling, a glass frit is obtained. A certain amount of CaCl ₂ , (NH ₄ ) ₂ HPO ₄ , K ₂ HPO ₄ × 3H ₂ O, HCl (mass ratio: 10:20:68.5:1.5) was weighed and dissolved in 1 L of ultrapure water. 100 g of glass powder was weighed and placed in 1 L of the impregnation solution, and stirring was continued for 6 hours. After the stirring is completed, the impregnated glass powder is separated by vacuum filtration, dried and made into a bioglass dressing. The dressings were used for wound healing and in vitro cell culture experiments in mice. The wound healing experiments were taken for 1, 3, 5, and 7 days, respectively. The in vitro cell cultures were compared with the samples after 7 days of culture. Figure 3 is a comparison of in vitro cell culture of the respective examples. As can be seen from the figure, the bioglass cell survival of Example 2 (9.1*10 ⁴ ) was significantly higher than that of the untreated control sample.

Example 3: Preparation and performance test results of materials

According to the ratio of each component in Table 1, weigh a certain amount of analytically pure raw materials (B ₂ O ₃ , MgO, CaO, Na ₂ O, K ₂ O and SrO), mix them evenly and put the powder into platinum. It is placed in a box-type resistance furnace for melting (melting temperature is 1200 ° C, holding time is 2 hours). The melt is then poured into deionized water to be quenched, dried to obtain a glass frit, and after ball milling, a glass frit is obtained. A certain amount of CaCl ₂ , (NH ₄ ) ₂ HPO ₄ , K ₂ HPO ₄ × 3H ₂ O, HCl (mass ratio: 15:15:69:1) was weighed and dissolved in 1 L of ultrapure water. 100 g of glass powder was weighed and placed in 1 L of the impregnation solution, and stirring was continued for 6 hours. After the stirring is completed, the impregnated glass powder is separated by vacuum filtration, dried and made into a bioglass dressing. The dressings were used for wound healing and in vitro cell culture experiments in mice. The wound healing experiments were taken for 1, 3, 5, and 7 days, respectively. The in vitro cell cultures were compared with the samples after 7 days of culture. Figure 3 is a comparison of in vitro cell culture of the respective examples. As can be seen from the figure, the bioglass cell survival of Example 3 was as high as 9.6*10 ⁴ , which is a preferred embodiment. In addition, FIGS. 1 to 2 are graphs of wound healing of the control sample glass and Example 3, and it can be seen from the figure that Example 3 can effectively promote wound healing.

Example 4: Preparation and performance test results of materials

According to the ratio of each component in Table 1, weigh a certain amount of analytically pure raw materials (B ₂ O ₃ , MgO, CaO, Na ₂ O, K ₂ O and SrO), mix them evenly and put the powder into platinum. It is placed in a box-type resistance furnace for melting (melting temperature is 1100 ° C, holding time is 2 hours). The melt is then poured into deionized water to be quenched, dried to obtain a glass frit, and after ball milling, a glass frit is obtained. A certain amount of CaCl ₂ , (NH ₄ ) ₂ HPO ₄ , K ₂ HPO ₄ × 3H ₂ O, HCl (mass ratio: 20:19.9:60:0.1) was weighed and dissolved in 1 L of ultrapure water. 100 g of glass powder was weighed and placed in 1 L of the impregnation solution, and stirring was continued for 6 hours. After the stirring is completed, the impregnated glass powder is separated by vacuum filtration, dried and made into a bioglass dressing. The dressings were used for wound healing and in vitro cell culture experiments in mice. The wound healing experiments were taken for 1, 3, 5, and 7 days, respectively. The in vitro cell cultures were compared with the samples after 7 days of culture. Figure 3 is a comparison of in vitro cell culture of the respective examples. As can be seen from the figure, the bioglass cell survival rate of Example 4 (9.3*10 ⁴ ) was significantly higher than that of the control sample.

The present invention realizes a boron phosphorus bioactive glass and a preparation method thereof by the above embodiments. Its remarkable effects are concentrated in excellent biocompatibility and ability to promote tissue repair.

The above are only the preferred embodiments of the present invention, and all changes and modifications made to the scope of the present invention should fall within the scope of the present invention.

Claims (10)

A method for preparing a boron-phosphorus bioactive glass, characterized in that boron-based glass is prepared by a melt-cooling method, and the raw material composition thereof is B ₂ O ₃ , MgO, CaO, Na ₂ O, K ₂ O and SrO, and then passed The impregnation solution containing phosphorus ions is impregnated to obtain a double-layer bioactive glass in which a porous phosphate is an outer shell and a borate is an inner core. The method for preparing a boron-phosphorus bioactive glass according to claim 1, wherein the boron-based glass has a raw material composition of B ₂ O ₃ , MgO, CaO, Na ₂ O, K ₂ O, and SrO, the mass ratio is 45~60:2~10:15~25:3~10:10~15:1~8. The method for preparing a boron-phosphorus bioactive glass according to claim 2, wherein the boron-based glass has a raw material composition of B ₂ O ₃ , MgO, CaO, Na ₂ O, K ₂ O, and SrO, the mass ratio is 50~58:3~8:15~20:3~10:10~15:2~7. The method for preparing a boron-phosphorus bioactive glass according to claim 1, wherein: The composition of the impregnation solution is CaCl ₂ , (NH ₄ ) ₂ HPO ₄ , K ₂ HPO ₄ × 3H ₂ O, HCl, and the mass ratio thereof is 5-20:15~25:60~70:0.1~2, dissolved in 1L of ultrapure water. The method for preparing a boron-phosphorus bioactive glass according to claim 1, wherein: The specific steps are as follows: (1) Washing the required experimental instruments, such as beakers, stir bars, and measuring cylinders, with ultrapure water, and performing sterilization treatment; (2) The boron-based initial glass frit is obtained by melt cooling, and the boron-based glass is ground and sieved to obtain a glass powder having a particle size of 30 to 45 μm, and the glass powder is disinfected and sterilized; (3) The raw materials required for the impregnation solution are arranged according to the ratio, and are stirred and dissolved for use; (4) Weigh 100 g glass powder, put into 1L impregnation solution, and continue to stir for 1~8h; (5) performing solid-liquid separation of the impregnated glass powder by vacuum filtration; (6) The separated glass powder is washed with ultrapure water in a vacuum filtration device, and dried for use; (7) A medical solvent is added to the treated boron-based glass frit to prepare a bioglass coating material. The method for preparing a boron-phosphorus bioactive glass according to claim 5, wherein: In the step (2), the boron-based initial glass has a melting temperature of 1000 to 1350 ° C and a holding time of 0.5 to 4 hours. The method for preparing a boron-phosphorus bioactive glass according to claim 6, wherein: The melting temperature is 1100-1300 ° C and the temperature is maintained for 0.5-2 hours. The method for preparing a boron-phosphorus bioactive glass according to claim 5, wherein: The continuous stirring time in the step (4) is 3-6 hours. The method for preparing a boron-phosphorus bioactive glass according to claim 5, wherein: The medical solvent used in the step (7) is a mixture of liquid paraffin, polyethylene glycol, carboxymethyl chitosan, and sodium hyaluronate. A boron-phosphorus bioactive glass prepared by the method of claim 1.