WO2019148554A1 - 一种硼磷系生物活性玻璃及其制备方法 - Google Patents

一种硼磷系生物活性玻璃及其制备方法 Download PDF

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WO2019148554A1
WO2019148554A1 PCT/CN2018/077009 CN2018077009W WO2019148554A1 WO 2019148554 A1 WO2019148554 A1 WO 2019148554A1 CN 2018077009 W CN2018077009 W CN 2018077009W WO 2019148554 A1 WO2019148554 A1 WO 2019148554A1
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Prior art keywords
boron
glass
preparing
phosphorus
bioactive glass
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PCT/CN2018/077009
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English (en)
French (fr)
Inventor
刘鸿琳
陈瑞果
黄培琰
李倩
王俊峰
张腾
傅宇宏
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福州瑞克布朗医药科技有限公司
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Publication of WO2019148554A1 publication Critical patent/WO2019148554A1/zh

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    • C—CHEMISTRY; METALLURGY
    • C03—GLASS; MINERAL OR SLAG WOOL
    • C03C—CHEMICAL COMPOSITION OF GLASSES, GLAZES OR VITREOUS ENAMELS; SURFACE TREATMENT OF GLASS; SURFACE TREATMENT OF FIBRES OR FILAMENTS MADE FROM GLASS, MINERALS OR SLAGS; JOINING GLASS TO GLASS OR OTHER MATERIALS
    • C03C3/00—Glass compositions
    • C03C3/12—Silica-free oxide glass compositions
    • C03C3/14—Silica-free oxide glass compositions containing boron
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/18—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing inorganic materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02—Inorganic materials
    • A61L27/10—Ceramics or glasses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/58—Materials at least partially resorbable by the body
    • C—CHEMISTRY; METALLURGY
    • C03—GLASS; MINERAL OR SLAG WOOL
    • C03C—CHEMICAL COMPOSITION OF GLASSES, GLAZES OR VITREOUS ENAMELS; SURFACE TREATMENT OF GLASS; SURFACE TREATMENT OF FIBRES OR FILAMENTS MADE FROM GLASS, MINERALS OR SLAGS; JOINING GLASS TO GLASS OR OTHER MATERIALS
    • C03C12/00—Powdered glass; Bead compositions
    • C—CHEMISTRY; METALLURGY
    • C03—GLASS; MINERAL OR SLAG WOOL
    • C03C—CHEMICAL COMPOSITION OF GLASSES, GLAZES OR VITREOUS ENAMELS; SURFACE TREATMENT OF GLASS; SURFACE TREATMENT OF FIBRES OR FILAMENTS MADE FROM GLASS, MINERALS OR SLAGS; JOINING GLASS TO GLASS OR OTHER MATERIALS
    • C03C4/00—Compositions for glass with special properties
    • C03C4/0007—Compositions for glass with special properties for biologically-compatible glass
    • C—CHEMISTRY; METALLURGY
    • C03—GLASS; MINERAL OR SLAG WOOL
    • C03C—CHEMICAL COMPOSITION OF GLASSES, GLAZES OR VITREOUS ENAMELS; SURFACE TREATMENT OF GLASS; SURFACE TREATMENT OF FIBRES OR FILAMENTS MADE FROM GLASS, MINERALS OR SLAGS; JOINING GLASS TO GLASS OR OTHER MATERIALS
    • C03C4/00—Compositions for glass with special properties
    • C03C4/0007—Compositions for glass with special properties for biologically-compatible glass
    • C03C4/0014—Biodegradable glass
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
    • A61L2300/112—Phosphorus-containing compounds, e.g. phosphates, phosphonates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/412—Tissue-regenerating or healing or proliferative agents

Definitions

  • 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.
  • 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
  • the temperature is 0.5-2 hours.
  • 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;
  • 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.
  • 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;
  • a medical solvent is added to the glass frit to prepare a bioglass coating material.
  • 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;
  • 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. .
  • 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.
  • 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.
  • vacuum filtration uses a filter paper having a pore diameter of less than 30 ⁇ m to control the dropping rate and the degree of vacuum of the solution to prevent pore clogging and damage of the filter paper.
  • 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.
  • 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;
  • 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.
  • 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.
  • 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:
  • 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;
  • a medical solvent is added to the glass frit to prepare a bioglass coating material.
  • 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;
  • 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. .
  • 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.
  • 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.
  • vacuum filtration uses a filter paper having a pore diameter of less than 30 ⁇ m to control the dropping rate and the degree of vacuum of the solution to prevent pore clogging and damage of the filter paper.
  • 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
  • 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.
  • analytically pure raw materials B 2 O 3 , MgO, CaO, Na 2 O, K 2 O and SrO
  • 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.
  • analytically pure raw materials B 2 O 3 , MgO, CaO, Na 2 O, K 2 O and SrO
  • 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.
  • analytically pure raw materials B 2 O 3 , MgO, CaO, Na 2 O, K 2 O and SrO
  • 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.
  • 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.
  • analytically pure raw materials B 2 O 3 , MgO, CaO, Na 2 O, K 2 O and SrO
  • 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.

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Abstract

一种硼磷系生物活性玻璃及其制备方法，通过熔融冷却法制备硼系玻璃，原料组成为B 2O 3、MgO、CaO、Na 2O、K 2O和SrO，其质量比为45～60∶2～10∶15～25∶3～10∶10～15∶1～8。然后通过含磷离子的溶液浸渍，获得多孔的磷酸盐为外壳，硼酸盐为内核的双层生物活性玻璃。通过该多孔外壳，不仅能够控制硼酸盐玻璃结构在生物体内的降解速率，而且可以提高生物材料的生物相容性，从而显著提升受损体表组织的修复速度。

Description

一种硼磷系生物活性玻璃及其制备方法 技术领域
本发明属于生物医疗技术领域，具体涉及一种用于体表组织损伤修复的生物活性玻璃及其制备方法。
 背景技术
当今社会科技飞速发展，交通工具种类和数量都不断增多，各大一、二线城市都出现了交通过渡拥挤的情况，这些变化直接导致了交通事故频发，导致人员死亡及受伤人数剧增。各大交通事故中，体表受创病患者居多，加速体表组织损伤修复成为大家的需求。
另一方面，体表受损时加速体表组织修复可减少养伤时间，创造更多的社会价值，国际上对生物玻璃进行了大量研究。从Hench教授提出的硅酸盐体系生物玻璃到1971年商业化的45S5生物活性玻璃，材料的性能不断提升（钟吉品，无机材料学报，1995），也涌现了大量的专利，如CN201210518111.2，其提供了通过溶胶凝胶法制作含锶生物玻璃粉体制备的方法，还进一步提供了制作含锶多孔生物玻璃支架的制备方法，如CN201710198500.4，其提供了一种用于宫颈创面愈合的生物玻璃敷料及其给药装置。
 技术问题
但是目前公开技术大多集中在磷酸盐及硅酸盐体系生物玻璃体系，其缺点在于二者在人体内的降解速率过于缓慢，影响组织的生长，从而影响伤口愈合。
 技术解决方案
本发明的目的是通过一种简易的浸渍方法，制备核壳结构的硼磷酸盐生物活性玻璃，获得优异的组织修复能力和生物相容性。本发明是通过如下技术方案实施的：
一种硼磷系生物活性玻璃及其制备方法，所选的初始玻璃为硼系玻璃，原料组成为B 2O 3、MgO、CaO、Na 2O、K 2O和SrO，其质量比为45~60：2~10：15~25：3~10：10~15：1~8。初始玻璃采用高温熔融冷却的方法制得玻璃熔块，经球磨过筛后得到玻璃粉末。熔制温度为1000-1350℃，保温时间为0.5~4小时，优选为1100-1300℃，保温0.5-2小时。具体操作步骤如下：
（1）对该方法中所使用到的实验器具，如烧杯、搅拌棒、量筒等用超纯水清洗，并进行消毒杀菌处理；
（2）将硼系玻璃磨碎过筛，获得粒径30~45μm玻璃粉，并对玻璃粉进行消毒杀菌处理；
（3）将浸渍溶液所需原料按照配比配置，搅拌溶解后备用；浸渍的溶液成分为CaCl 2、(NH 4) 2HPO 4、K 2HPO 4×3H 2O、HCl，溶解在1L的超纯水中，其质量比为5~20：15~25：60~70：0.1~2；所述的CaCl 2、(NH 4) 2HPO 4、K 2HPO 4×3H 2O均为分析纯，HCl浓度为0.1mol/L；
（4）称取100 g玻璃粉末，放入1L浸渍溶液中，持续搅拌1~8h，优选3-6h；
（5）采用真空过滤法将浸渍后的玻璃粉进行固液分离；
（6）将分离后的玻璃粉用超纯水在真空过滤装置中进行清洗，烘干后备用；
（7）向玻璃粉中加入医用溶剂，制备成生物玻璃涂敷料。
    所述步骤（1）中，使用器具需进行消毒杀菌，操作人员及环境也要求保持高度的无菌状态，保证实验过程中不引入有害物质；
    所述步骤（2）中，生物玻璃的研磨使用的研磨介质为玛瑙研钵；使用的筛子为食用级的不锈钢筛，筛子采用325目、270目筛，过筛后取用中间层玻璃粉备用。
    所述步骤（3）中，所使用的盐酸主要目的为调节溶液的PH值，在溶液配制完成后加入，使溶液的酸碱度呈弱酸性。
    所述步骤（4）中，搅拌过程中需确认玻璃粉的均匀分散，不能有结块或团聚物，保证玻璃粉与浸渍液的充分接触。
    所述步骤（5）中，真空过滤使用孔径小于30微米的滤纸，控制溶液滴入速度及真空度，防止孔隙堵塞及滤纸破损。
    所述步骤（6）中，超纯水清洗进行3次循环，确保玻璃粉末清洗全面。
    所述步骤（7）中所使用的医用溶剂为液体石蜡、聚乙二醇、羧甲基壳聚糖、透明质酸钠等的混合物；
    所述步骤（1）~（7）都需在洁净度较高的生物医用实验室进行，保证实验过程的精确性。
 有益效果
（1）熔融冷却法制备硼系玻璃，然后通过含磷离子的溶液浸渍，获得多孔的磷酸盐玻璃为外壳，硼酸盐玻璃为内核的双层生物活性玻璃；
（2）利用多孔的磷酸盐外壳，不仅能够控制硼酸盐玻璃结构在生物体内的降解速率，而且可以提高生物材料的生物相容性，显著提升受损体表组织的修复速度；
（3）通过调节浸渍液中的钙离子浓度，还可以在生物活性玻璃表面形成适量的羟基磷灰石，有效促进生物玻璃敷料与人体组织的络合；
（4）本发明的原料简单易得，制备方法简便，工艺稳定，达到了实用化和工业化的条件。
 附图说明
图1为对照样品的伤口愈合情况；
图2为硼磷系玻璃使用后的伤口愈合情况；
图3为各实施例的体外细胞培养对比图。
 本发明的实施方式
一种硼磷系生物活性玻璃及其制备方法，所选初始的生物玻璃为硼系玻璃，原料组成为B 2O 3、MgO、CaO、Na 2O、K 2O和SrO，其质量比为45~60：2~10：15~25：3~10：10~15：1~8。初始玻璃的熔制温度为1000-1350℃，保温时间为0.5~4小时，优选为1100-1300℃，保温0.5-2小时。浸渍的溶液成分为CaCl 2、(NH 4) 2HPO 4、K 2HPO 4×3H 2O、HCl，溶解在1L的超纯水中，其质量比为5~20：15~25：60~70：0.1~2。具体操作步骤如下：
（1）对该方法中所使用到的实验器具，如烧杯、搅拌棒、量筒等用超纯水清洗，并进行消毒杀菌处理；
（2）将硼系玻璃磨碎过筛，获得粒径30~45μm玻璃粉，并对玻璃粉进行消毒杀菌处理；
（3）将浸渍溶液所需原料按照配比配置，搅拌溶解后备用；
（4）称取100 g玻璃粉末，放入1L浸渍溶液中，持续搅拌1~8h，优选3-6h；
（5）采用真空过滤法将浸渍后的玻璃粉进行固液分离；
（6）将分离后的玻璃粉用超纯水在真空过滤装置中进行清洗，烘干后备用；
（7）向玻璃粉中加入医用溶剂，制备成生物玻璃涂敷料。
    所述步骤（1）中，使用器具需进行消毒杀菌，操作人员及环境也要求保持高度的无菌状态，保证实验过程中不引入有害物质；
    所述步骤（2）中，生物玻璃的研磨使用的研磨介质为玛瑙研钵；使用的筛子为食用级的不锈钢筛，筛子采用325目、270目筛，过筛后取用中间层玻璃粉备用。
    所述步骤（3）中，所使用的盐酸主要目的为调节溶液的PH值，在溶液配制完成后加入，使溶液的酸碱度呈弱酸性。
    所述步骤（4）中，搅拌过程中需确认玻璃粉的均匀分散，不能有结块或团聚物，保证玻璃粉与浸渍液的充分接触。
    所述步骤（5）中，真空过滤使用孔径小于30微米的滤纸，控制溶液滴入速度及真空度，防止孔隙堵塞及滤纸破损。
    所述步骤（6）中，超纯水清洗进行3次循环，确保玻璃粉末清洗全面。
    所述步骤（7）中所使用的医用溶剂为液体石蜡、聚乙二醇、羧甲基壳聚糖、透明质酸钠等的混合物；
    所述步骤（1）~（7）都需在洁净度较高的生物医用实验室进行，保证实验过程的精确性。
表1为实施例1-4中的初始玻璃组分表（按质量百分数计）
Figure 326016dest_path_image001
实施例1：材料的制备与性能测试结果
按照表1的各组分的配比，称取一定量的分析纯原料（B 2O 3、MgO、CaO、Na 2O、K 2O和SrO），混合均匀后将粉料放入铂金坩埚，置于箱式电阻炉熔制（熔制温度为1350℃，保温时间为2小时）。随后将熔体倒入去离子水中急冷，干燥获得玻璃熔块，球磨后得到玻璃粉料。称取一定量的CaCl 2、(NH 4) 2HPO 4、K 2HPO 4×3H 2O、HCl（其质量比为5：23：70：2），溶解在1L的超纯水中。称取100g玻璃粉末，放入1L浸渍溶液中，持续搅拌6h。搅拌完成后采用真空过滤将浸渍后的玻璃粉分离出来，烘干并制成生物玻璃敷料备用。敷料分别用于小鼠表面创口愈合和体外细胞培养实验，创口愈合实验分别对1、3、5、7天后的伤口愈合情况拍照记录，体外细胞培养取用培养7天后的样品进行比对。图3为各实施例的体外细胞培养对比图。由图可看到，实施例1的生物玻璃细胞存活量（8.9*10 4）高于未处理的对照样品（8.6*10 4）。
实施例2：材料的制备与性能测试结果
按照表1的各组分的配比，称取一定量的分析纯原料（B 2O 3、MgO、CaO、Na 2O、K 2O和SrO），混合均匀后将粉料放入铂金坩埚，置于箱式电阻炉熔制（熔制温度为1300℃，保温时间为2小时）。随后将熔体倒入去离子水中急冷，干燥获得玻璃熔块，球磨后得到玻璃粉料。称取一定量的CaCl 2、(NH 4) 2HPO 4、K 2HPO 4×3H 2O、HCl（其质量比为10：20：68.5：1.5），溶解在1L的超纯水中。称取100g玻璃粉末，放入1L浸渍溶液中，持续搅拌6h。搅拌完成后采用真空过滤将浸渍后的玻璃粉分离出来，烘干并制成生物玻璃敷料备用。敷料分别用于小鼠表面创口愈合和体外细胞培养实验，创口愈合实验分别对1、3、5、7天后的伤口愈合情况拍照记录，体外细胞培养取用培养7天后的样品进行比对。图3为各实施例的体外细胞培养对比图。由图可看到，实施例2的生物玻璃细胞存活量（9.1*10 4）明显高于未处理的对照样品。
实施例3：材料的制备与性能测试结果
按照表1的各组分的配比，称取一定量的分析纯原料（B 2O 3、MgO、CaO、Na 2O、K 2O和SrO），混合均匀后将粉料放入铂金坩埚，置于箱式电阻炉熔制（熔制温度为1200℃，保温时间为2小时）。随后将熔体倒入去离子水中急冷，干燥获得玻璃熔块，球磨后得到玻璃粉料。称取一定量的CaCl 2、(NH 4) 2HPO 4、K 2HPO 4×3H 2O、HCl（其质量比为15：15：69：1），溶解在1L的超纯水中。称取100g玻璃粉末，放入1L浸渍溶液中，持续搅拌6h。搅拌完成后采用真空过滤将浸渍后的玻璃粉分离出来，烘干并制成生物玻璃敷料备用。敷料分别用于小鼠表面创口愈合和体外细胞培养实验，创口愈合实验分别对1、3、5、7天后的伤口愈合情况拍照记录，体外细胞培养取用培养7天后的样品进行比对。图3为各实施例的体外细胞培养对比图。由图可看到，实施例3的生物玻璃细胞存活量高达9.6*10 4，为最佳实施例。另外，图1~2为对照样品玻璃与实施例3的伤口愈合情况图，由图可知，实施例3可有效促进伤口愈合。
实施例4：材料的制备与性能测试结果
按照表1的各组分的配比，称取一定量的分析纯原料（B 2O 3、MgO、CaO、Na 2O、K 2O和SrO），混合均匀后将粉料放入铂金坩埚，置于箱式电阻炉熔制（熔制温度为1100℃，保温时间为2小时）。随后将熔体倒入去离子水中急冷，干燥获得玻璃熔块，球磨后得到玻璃粉料。称取一定量的CaCl 2、(NH 4) 2HPO 4、K 2HPO 4×3H 2O、HCl（其质量比为20：19.9：60：0.1），溶解在1L的超纯水中。称取100g玻璃粉末，放入1L浸渍溶液中，持续搅拌6h。搅拌完成后采用真空过滤将浸渍后的玻璃粉分离出来，烘干并制成生物玻璃敷料备用。敷料分别用于小鼠表面创口愈合和体外细胞培养实验，创口愈合实验分别对1、3、5、7天后的伤口愈合情况拍照记录，体外细胞培养取用培养7天后的样品进行比对。图3为各实施例的体外细胞培养对比图。由图可看到，实施例4的生物玻璃细胞存活量（9.3*10 4）明显高于对照样品。
本发明通过上述实施例实现一种硼磷系生物活性玻璃及其制备方法。其显著的效果集中体现在优异的生物相容性及促进组织修复的能力。
以上所述仅为本发明的较佳实施例，凡依本发明申请专利范围所做的均等变化与修饰，皆应属本发明的涵盖范围。

Claims (10)

  1. 一种硼磷系生物活性玻璃的制备方法，其特征在于：通过熔融冷却法制备硼系玻璃，其原料组成为B 2O 3、MgO、CaO、Na 2O、K 2O和SrO，然后通过含磷离子的浸渍溶液进行浸渍，获得多孔的磷酸盐为外壳，硼酸盐为内核的双层生物活性玻璃。
  2. 根据权利要求1所述的一种硼磷系生物活性玻璃的制备方法，其特征在于：所述硼系玻璃，其原料组成为B 2O 3、MgO、CaO、Na 2O、K 2O和SrO，其质量比为45~60：2~10：15~25：3~10：10~15：1~8。
  3. 根据权利要求2所述的一种硼磷系生物活性玻璃的制备方法，其特征在于：所述硼系玻璃，其原料组成为B 2O 3、MgO、CaO、Na 2O、K 2O和SrO，其质量比为50~58：3~8：15~20：3~10：10~15：2~7。
  4. 根据权利要求1所述的一种硼磷系生物活性玻璃的制备方法，其特征在于：
    所述浸渍溶液成分为CaCl 2、(NH 4) 2HPO 4、K 2HPO 4×3H 2O、HCl，其质量比为5~20：15~25：60~70：0.1~2，溶解在1L的超纯水中。
  5. 根据权利要求1所述的一种硼磷系生物活性玻璃的制备方法，其特征在于：
    具体操作步骤如下：
    （1）对所需的实验器具，如烧杯、搅拌棒、量筒用超纯水清洗，并进行消毒杀菌处理；
    （2）采用熔融冷却的方法制得硼系初始玻璃熔块，将硼系玻璃磨碎过筛，获得粒径30~45μm玻璃粉，并对玻璃粉进行消毒杀菌处理；
    （3）将浸渍溶液所需原料按照配比配置，搅拌溶解后备用；
    （4）称取100 g玻璃粉末，放入1L浸渍溶液中，持续搅拌1~8h；
    （5）采用真空过滤法将浸渍后的玻璃粉进行固液分离；
    （6）将分离后的玻璃粉用超纯水在真空过滤装置中进行清洗，烘干后备用；
    （7）在处理后的硼系玻璃粉中加入医用溶剂，制备成生物玻璃涂敷料。
  6. 根据权利要求5所述的一种硼磷系生物活性玻璃的制备方法，其特征在于：
    步骤（2）所述硼系初始玻璃的熔制温度为1000-1350℃，保温时间为0.5~4小时。
  7. 根据权利要求6所述的一种硼磷系生物活性玻璃的制备方法，其特征在于：
    熔制温度为1100-1300℃，保温0.5-2小时。
  8. 根据权利要求5所述的一种硼磷系生物活性玻璃的制备方法，其特征在于：
    步骤（4）所述持续搅拌时间为3-6h。
  9. 根据权利要求5所述的一种硼磷系生物活性玻璃的制备方法，其特征在于：
    所述步骤（7）中所使用的医用溶剂为液体石蜡、聚乙二醇、羧甲基壳聚糖、透明质酸钠的混合物。
  10. 一种如权利要求1所述方法制备的硼磷系生物活性玻璃。
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