WO2020224261A1 - 掺硼生物活性玻璃微球及其制备方法与应用 - Google Patents

掺硼生物活性玻璃微球及其制备方法与应用 Download PDF

Info

Publication number
WO2020224261A1
WO2020224261A1 PCT/CN2019/124797 CN2019124797W WO2020224261A1 WO 2020224261 A1 WO2020224261 A1 WO 2020224261A1 CN 2019124797 W CN2019124797 W CN 2019124797W WO 2020224261 A1 WO2020224261 A1 WO 2020224261A1
Authority
WO
WIPO (PCT)
Prior art keywords
boron
bioactive glass
doped
preparation
source
Prior art date
Application number
PCT/CN2019/124797
Other languages
English (en)
French (fr)
Inventor
潘浩波
王聿栋
崔旭
Original Assignee
深圳先进技术研究院
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 深圳先进技术研究院 filed Critical 深圳先进技术研究院
Publication of WO2020224261A1 publication Critical patent/WO2020224261A1/zh

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • 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
    • 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
    • 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
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/12—Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces

Definitions

  • the invention belongs to the field of biomedical materials, and specifically relates to a boron-doped bioactive glass microsphere and a preparation method and application thereof.
  • bioactive glass is a silicate glass material with a special composition and structure. It is an important type of bioactive material and is widely used in the medical field.
  • Bioactive glass has good osteoinduction and bone repair properties. So far, the bioactive glass used for hard tissue repair in clinical practice is made by the high-temperature melting method, but the bioactive glass prepared by the high-temperature melting method has many shortcomings: high preparation conditions, high energy High consumption; the prepared bioglass is dense particles with a small specific surface area, so the effect of ion release and in vivo degradation is not good.
  • the subsequent disclosed sol-gel method for preparing bioactive glass greatly improves the preparation process and increases the specific surface area of the particles; meanwhile, by introducing a template agent, bioactive glass powder particles with controllable morphology can be prepared.
  • the current bioactive glass prepared by the sol-gel method has a relatively high Si element content in its actual components, and the internal Si—O network system is relatively stable, which hinders the internal Ca and P plasmas.
  • the release of ions affects the long-term release of biologically active ions and limits its application.
  • boron is an essential trace element of the human body, which can affect the metabolism of calcium and magnesium, promote bone formation, and ultimately improve the physical and chemical properties and mechanical strength of bones.
  • boron is also closely related to bone immunology, which can inhibit the expression of RANKL and promote the expression of OPG, thereby regulating the bone loss caused by immune diseases. Studies have found that adding boron to the silicate glass matrix can effectively reduce the strong binding force of the Si—O network and promote the dissolution of biologically active ions.
  • the purpose of the present invention is to overcome the above-mentioned shortcomings of the prior art and provide a boron-doped bioactive glass microsphere and a preparation method thereof, so as to solve the problem that the existing boron-doped bioactive glass has irregular blocks, large particle size,
  • the unfavorable characteristics such as small specific surface area lead to technical problems such as hindered release of biologically active ions.
  • one aspect of the invention provides a method for preparing boron-doped bioactive glass microspheres.
  • the preparation method of the boron-doped bioactive glass microspheres includes the following steps:
  • the bioactive glass precursor is sintered, and boron-doped micro-nano boron-doped bioactive glass microspheres.
  • a boron-doped bioactive glass microsphere is provided.
  • the boron-doped bioactive glass microspheres are prepared by the preparation method of the present invention.
  • Another aspect of the present invention provides an application method of the boron-doped bioactive glass microspheres of the present invention.
  • the boron-doped bioactive glass microspheres are widely used in bone tissue repair, oral repair, skin repair, body immune regulation, and drug carriers.
  • the preparation method of the boron-doped bioactive glass microspheres of the present invention combines the sol-gel method and the template method preparation process, so that the prepared boron-doped bioactive glass microspheres present a good spherical morphology, and the particles The morphology and size are controllable, and the particle size is small, with high specific surface area and good dispersibility. It is precisely because the prepared boron-doped bioactive glass microspheres have the microscopic morphology and characteristics, they have excellent characteristics of releasing bioactive ions.
  • the boron-doped bioactive glass microspheres of the present invention are prepared by the preparation method of the boron-doped bioactive glass microspheres of the present invention, the boron-doped bioactive glass microspheres have spherical morphology, small particle size, and high The specific surface area and good dispersibility, which have excellent characteristics of releasing bioactive ions, effectively expand its applicability in the medical field.
  • FIG. 1 is a schematic diagram of the process flow of the preparation method of boron-doped bioactive glass microspheres according to an embodiment of the present invention
  • Example 2 is a scanning electron micrograph of the boron-doped bioactive glass microspheres provided in Example 1 of the present invention
  • Figure 3 is the energy spectrum analysis of the boron-doped bioactive glass microspheres provided in Example 1 of the present invention; among them, Figure 3-A is the EDS energy spectrum of the boron-doped bioactive glass microspheres provided in Example 1, Figure 3- B is a scanning electron micrograph of the energy spectrum collection area of the boron-doped bioactive glass microspheres provided in Example 1, and FIG. 3-C is a distribution diagram of element B in the boron-doped bioactive glass microspheres provided in Example 1.
  • each component mentioned in the description of the embodiment of the present invention can not only refer to the specific content of each component, but also the ratio of the mass between the components. Therefore, as long as each component is in accordance with the description of the embodiment of the present invention
  • the content of the components is scaled up or down within the scope disclosed in the specification of the embodiments of the present invention.
  • the mass described in the specification of the embodiment of the present invention may be a mass unit known in the chemical industry, such as ⁇ g, mg, g, and kg.
  • the embodiment of the present invention provides a method for preparing boron-doped bioactive glass microspheres.
  • the process flow of the preparation method of the boron-doped bioactive glass microspheres is shown in Figure 1, which includes the following steps:
  • bioactive glass gel solution to prepare a bioactive glass precursor: the bioactive glass gel solution in step S01 is subjected to precipitation treatment to obtain a wet gel, and the wet gel is dried to obtain a mixture Boron bioactive glass precursor;
  • the method for preparing the bioactive glass gel solution in step S01 can be prepared according to a conventional bioactive glass gel solution, except that the prepared bioactive glass gel solution contains a boron source.
  • the method for preparing a bioactive glass gel solution containing a boron source includes the following steps:
  • the template agent and the alcohol aqueous solution are prepared into a mixed solution, and then a silicon source, a boron source, a phosphorus source and a calcium source are sequentially added to the mixed solution for mixing treatment to obtain a bioactive glass gel solution.
  • the method for preparing bioactive glass gel can effectively uniformly disperse the boron source in the sol solution, and improve the dispersion uniformity of the boron source.
  • the molar ratio of the silicon source, boron source, phosphorous source and calcium source is (40-55):(40-10):8:36.
  • the concentration of the template in the bioactive glass gel solution is 0.08-0.32 mol/L.
  • the stability of the bioactive glass gel solution can be provided, which guarantees the final production of boron-doped bioactive glass microspheres with stable performance and stable morphology, and can make
  • the boron source is uniformly dispersed and the particle size of the precipitate is small.
  • the template is dodecylamine
  • the silicon source is ethyl orthosilicate
  • the phosphorus source is triethyl phosphate
  • the calcium source is calcium nitrate
  • the alcohol is ethanol.
  • the boron source is tributyl borate.
  • the precipitation treatment in step S02 preferably adopts centrifugal treatment, so that the bioactive glass gel solution prepared in step S01 is precipitated, and the precipitate is collected to obtain a wet gel.
  • it also includes the step of cleaning the wet gel.
  • clean water can be used to clean the wet gel to improve the purity of the wet gel.
  • the temperature for drying the wet gel is 50-100°C, and the time is 1-2 days.
  • the drying treatment can effectively remove moisture and residual solvents such as alcohol solvents, specifically ethanol; on the other hand, it can effectively retain the microscopic morphology of the precipitate to maintain stability.
  • the drying treatment may, but not only place the wet gel in an oven for drying treatment. After drying treatment, a precursor of boron-doped bioactive glass is obtained.
  • the sintering process in step S03 is to perform a sintering process on the boron-doped bioactive glass precursor obtained in step S02, so that the boron-doped bioactive glass precursor generates boron-doped bioactive glass microspheres.
  • the temperature of the sintering treatment is 600-700°C, and the time of the heat treatment is 2-5 hours.
  • the sintering treatment may be sintering the boron-doped bioactive glass precursor in a high-temperature furnace. Through sintering, the boron-doped bioactive glass precursor generates boron-doped bioactive glass microspheres.
  • the boron-doped bioactive glass microspheres prepared by the above method have a particle size of micro-nano scale, and their morphology is spherical, as shown in Figure 2.
  • the above-mentioned preparation method of boron-doped bioactive glass microspheres combined with the sol-gel method and template method preparation process can prepare boron-doped bioactive glass microspheres with good spherical morphology, and the boron-doped bioactive glass microspheres
  • the active glass microspheres are stable and small in size, with high specific surface area and good dispersibility.
  • the doped boron element can be evenly distributed. Specifically, it can be evenly distributed on the surface of the boron-doped bioactive glass microspheres, as shown in the figure 3 shown. Since the boron-doped bioactive glass microspheres are doped with boron, boron can effectively reduce the strong binding force of the Si—O network in the bioactive glass microspheres and promote the dissolution of bioactive ions, thereby giving the boron-doped biological activity Glass microspheres have excellent characteristics of releasing biologically active ions. Moreover, the preparation method can make the particle shape and size of the boron-doped bioactive glass microspheres controllable, and the generated boron-doped bioactive glass microspheres have stable performance and high efficiency, and are suitable for industrial production.
  • embodiments of the present invention also provide a boron-doped bioactive glass microsphere.
  • the boron-doped bioactive glass microspheres are prepared by the above-mentioned preparation method of boron-doped bioactive glass microspheres. Therefore, the boron-doped bioactive glass microspheres are spherical in appearance, and their particle size is micro Nanoscale, specifically, the particle size of the boron-doped bioactive glass microspheres is less than 1 micron. Therefore, the particle size is small, the particle size distribution is uniform, and the specific surface area is high and the dispersibility is good.
  • the boron-doped bioactive glass microspheres are doped with boron element, and the doped boron element is uniformly mixed and distributed in the boron-doped bioactive glass microspheres, as in the boron-doped bioactive glass microspheres.
  • the surface is evenly distributed.
  • boron can effectively reduce the strong binding force of the Si—O network in the boron-doped bioactive glass microspheres, and promote the dissolution of bioactive ions, thereby giving the boron-doped bioactive glass microspheres excellent release of bioactive ions.
  • the above-mentioned boron-doped bioactive glass microspheres have the spherical morphology, micro-nano particle size, high specific surface area and good dispersibility, as well as good bioactive ion dissolution, and effective expansion.
  • the application of the boron-doped bioactive glass microspheres in the field of biological materials is described.
  • the boron-doped bioactive glass microspheres are widely used in bone tissue repair, oral repair, skin repair, immune regulation, and drug carriers.
  • This Example 1 provides a boron-doped bioactive glass microsphere and a preparation method thereof.
  • the preparation method of the boron-doped bioactive glass microspheres includes the following steps:
  • the bioactive glass gel solution obtained in step S11 is centrifuged and cleaned to obtain a wet gel precipitate, and the wet gel precipitate is placed in an oven at 60°C for 2 days to dry to obtain boron-doped bioactive glass precursor powder ;
  • the boron-doped bioactive glass precursor powder obtained in step S12 is heat-treated in a high-temperature furnace at 650° C. for 3 hours to obtain micro-nano boron-doped bioactive glass microspheres.
  • Example 2 provides a boron-doped bioactive glass microsphere and a preparation method thereof.
  • the preparation method of the boron-doped bioactive glass microspheres includes the following steps:
  • step S11 Centrifuging the bioactive glass gel solution obtained in step S11, washing to obtain a wet gel precipitate, and then placing the wet gel precipitate in an oven at 50° C. for drying for 2 days to obtain a bioactive glass precursor powder;
  • the boron-doped bioactive glass precursor powder obtained in step S12 is heat-treated in a high-temperature furnace at 600° C. for 3 hours to obtain boron-doped micro/nano bioactive glass microspheres.
  • Example 2 Scanning electron microscopy and energy spectrum analysis and energy spectrum analysis were performed on the boron-doped bioactive glass microspheres prepared in Example 2, and the results were basically the same as those of Example 1.
  • the boron-doped micro/nano bioactive glass microspheres had a good spherical shape. Morphology and dispersion, and the boron element on the surface of the microspheres is evenly distributed.
  • Example 3 provides a boron-doped bioactive glass microsphere and a preparation method thereof.
  • the preparation method of the boron-doped bioactive glass microspheres includes the following steps:
  • step S11 Centrifuging the bioactive glass gel solution obtained in step S11, washing to obtain a wet gel precipitate, and then placing the wet gel precipitate in an oven at 80° C. for drying for 1 day to obtain a bioactive glass precursor powder;
  • the boron-doped bioactive glass precursor powder obtained in step S12 is heat-treated in a high-temperature furnace at 700° C. for 3 hours to obtain boron-doped micro/nano bioactive glass microspheres.
  • Example 3 Scanning electron microscopy and energy spectrum analysis and energy spectrum analysis were performed on the boron-doped bioactive glass microspheres prepared in Example 3, and the results were basically the same as those of Example 1.
  • the boron-doped micro/nano bioactive glass microspheres had a good spherical shape. Morphology and dispersion, and the boron element on the surface of the microspheres is evenly distributed.
  • Example 4 provides a boron-doped bioactive glass microsphere and a preparation method thereof.
  • the preparation method of the boron-doped bioactive glass microspheres includes the following steps:
  • step S11 Centrifuging the bioactive glass gel solution obtained in step S11, washing to obtain a wet gel precipitate, and then placing the wet gel precipitate in an oven at 60° C. for drying for 2 days to obtain a bioactive glass precursor powder;
  • the boron-doped bioactive glass precursor powder obtained in step S12 is heat-treated in a high-temperature furnace at 600° C. for 3 hours to obtain boron-doped micro/nano bioactive glass microspheres.
  • Example 4 Scanning electron microscopy and energy spectrum analysis and energy spectrum analysis were performed on the boron-doped bioactive glass microspheres prepared in Example 4, and the results were basically the same as those of Example 1.
  • the boron-doped micro/nano bioactive glass microspheres had a good spherical shape. Morphology and dispersion, and the boron element on the surface of the microspheres is evenly distributed.
  • Example 5 provides a boron-doped bioactive glass microsphere and a preparation method thereof.
  • the preparation method of the boron-doped bioactive glass microspheres includes the following steps:
  • step S11 Centrifuging the bioactive glass gel solution obtained in step S11, washing to obtain a wet gel precipitate, and then placing the wet gel precipitate in an oven at 50° C. for drying for 2 days to obtain a bioactive glass precursor powder;
  • the boron-doped bioactive glass precursor powder obtained in step S12 is heat-treated in a high temperature furnace at 650° C. for 3 hours to obtain boron-doped micro/nano bioactive glass microspheres.
  • Example 5 Scanning electron microscopy and energy spectrum analysis and energy spectrum analysis were performed on the boron-doped bioactive glass microspheres prepared in Example 5, and the results were basically the same as those of Example 1.
  • the boron-doped micro-nano bioactive glass microspheres had a good spherical shape. Morphology and dispersion, and the boron element on the surface of the microspheres is evenly distributed.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Inorganic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Dermatology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Ceramic Engineering (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Materials Engineering (AREA)
  • Geochemistry & Mineralogy (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Glass Compositions (AREA)
  • Materials For Medical Uses (AREA)

Abstract

一种掺硼生物活性玻璃微球及其制备方法与应用。所述掺硼生物活性玻璃微球的制备方法包括的步骤有：制备含有硼源的生物活性玻璃凝胶溶液；将所述生物活性玻璃凝胶溶液进行沉淀处理，获得湿态凝胶，并将所述湿态凝胶进行干燥处理，获得掺硼生物活性玻璃前驱体；将所述掺硼生物活性玻璃前驱体进行烧结处理。掺硼生物活性玻璃微球制备方法结合溶胶-凝胶法与模板法制备工艺，使得制备获得的掺硼生物活性玻璃微球呈现良好的球形形貌，而且颗粒形貌尺寸可控，且粒径小，具有较高的比表面积与良好的分散性。正是由于制备的掺硼生物活性玻璃微球具有该微观形貌和特性，其具有优异的释放生物活性离子特性。

Description

掺硼生物活性玻璃微球及其制备方法与应用 技术领域
本发明属于生物医用材料领域，具体涉及一种掺硼生物活性玻璃微球及其制备方法与应用。
背景技术
随着科学技术的发展，用于对生物体进行诊断、治疗、修复或者替换其病损组织、器官或者增进其功能的生物医用材料，得到了大力的推广应用。其中生物活性玻璃(bioactiveglass，BG)是一种具有特殊组成和结构的硅酸盐玻璃材料，是一类重要的生物活性材料，广泛的应用于医学领域。
生物活性玻璃具备良好的骨诱导和骨修复性能，至今临床上用于硬组织修复的生物活性玻璃是通过高温熔融法制得，但高温熔融法制备的生物活性玻璃具有诸多不足：制备条件高，能耗大；所制备的生物玻璃为致密的颗粒，比表面积小，从而离子释放和体内降解效果不佳。
随后公开的溶胶凝胶法制备生物活性玻璃的极大地改良了制备工艺，提高了颗粒的比表面积；同时通过引入模板剂可制备处形貌可控的生物活性玻璃粉体颗粒。然而，在以及生产和应用中发现，目前溶胶凝胶法制备的生物活性玻璃由于其实际组分中的Si元素含量较高，内部的Si—O网络体系较稳定，阻碍了内部Ca、P等离子的释放，影响了其生物活性离子长效释放的性能，限制了其应用。
随着生物活性玻璃的不断发展，逐渐引入了人体代谢所需的功能元素，如利用硅酸盐生物活性玻璃特有的网络结构使其能够同时引入多种人体代谢所需元素，如硼(B)。硼是人体的必须微量元素，能够影响钙和镁的代谢，促进成骨，并最终改善骨骼的理化性能与力学强度。同时硼还与骨免疫学密切相关，能够 抑制RANKL的表达，促进OPG的表达，从而调节免疫疾病导致的骨量流失。研究发现，在硅酸盐玻璃基体中加入硼可以有效降低Si—O网络的强结合力，促进生物活性离子的溶出。近年来，掺硼生物活性玻璃的研究得到了广泛的关注，但目前已有的掺硼生物活性玻璃多为无规则的块体，且粒径较大，比表面积较小，影响了生物活性离子的释放，限制了其应用。
发明内容
本发明的目的在于克服现有技术的上述不足，提供一种掺硼生物活性玻璃微球及其制备方法，以解决现有掺硼生物活性玻璃由于呈现无规则的块体、粒径较大、比表面积较小等不利特性而导致其生物活性离子的释放受阻等的技术问题。
为了实现上述发明目的，本发明的一方面，提供了一种掺硼生物活性玻璃微球的制备方法。所述掺硼生物活性玻璃微球制备方法包括以下步骤：
制备含有硼源的生物活性玻璃凝胶溶液；
将所述生物活性玻璃凝胶溶液进行沉淀处理，获得湿态凝胶，并将所述湿态凝胶进行干燥处理，获得掺硼生物活性玻璃前驱体；
将所述生物活性玻璃前驱体进行烧结处理，掺硼微纳米掺硼生物活性玻璃微球。
本发明的又一方面，提供了一种掺硼生物活性玻璃微球。所述掺硼生物活性玻璃微球由本发明制备方法制备获得。
本发明的再一方面，提供了本发明掺硼生物活性玻璃微球的应用方法。所述掺硼生物活性玻璃微球在骨组织修复、口腔修复、皮肤修复、机体免疫调控、药物载体方面应用广泛。
与现有技术相比，本发明掺硼生物活性玻璃微球制备方法结合溶胶-凝胶法与模板法制备工艺，使得制备获得的掺硼生物活性玻璃微球呈现良好的球形形貌，而且颗粒形貌尺寸可控，且粒径小，具有较高的比表面积与良好的分散性。 正是由于制备的掺硼生物活性玻璃微球具有该微观形貌和特性，其具有优异的释放生物活性离子特性。
本发明掺硼生物活性玻璃微球由于是利用本发明掺硼生物活性玻璃微球制备方法制备获得，因此，所述掺硼生物活性玻璃微球颗粒为球形形貌，粒径小，具有较高的比表面积与良好的分散性，从而具有优异的释放生物活性离子特性，有效扩展了其在医疗领域中的应用性。
附图说明
下面将结合附图及实施例对本发明作进一步说明，附图中：
图1为本发明实施例掺硼生物活性玻璃微球的制备方法工艺流程示意图；
图2是本发明实施例1提供的掺硼生物活性玻璃微球的扫面电镜照片；
图3是本发明实施例1提供的掺硼生物活性玻璃微球的能谱分析；其中，图3-A为实施例1提供的掺硼生物活性玻璃微球的EDS能谱图，图3-B为实施例1提供的掺硼生物活性玻璃微球的能谱采集区域扫面电镜照片，图3-C为实施例1提供的掺硼生物活性玻璃微球中的B元素分布图。
具体实施方式
为了使本发明要解决的技术问题、技术方案及有益效果更加清楚明白，以下结合实施例，对本发明进行进一步详细说明。应当理解，此处所描述的具体实施例仅仅用以解释本发明，并不用于限定本发明。
本发明实施例说明书中所提到的各组分的质量不仅仅可以指代各组分的具体含量，也可以表示各组分间质量的比例关系，因此，只要是按照本发明实施例说明书各组分的含量按比例放大或缩小均在本发明实施例说明书公开的范围之内。具体地，本发明实施例说明书中所述的质量可以是μg、mg、g、kg等化工领域公知的质量单位。
一方面，本发明实施例提供了一种掺硼生物活性玻璃微球的制备方法。所 述掺硼生物活性玻璃微球的制备方法的工艺流程如图1所示，其包括以下步骤：
S01：制备含有硼源的生物活性玻璃凝胶溶液；
S02.利用生物活性玻璃凝胶溶液制备生物活性玻璃前驱体：将步骤S01中生物活性玻璃凝胶溶液进行沉淀处理，获得湿态凝胶，并将所述湿态凝胶进行干燥处理，获得掺硼生物活性玻璃前驱体；
S03：将所述掺硼生物活性玻璃前驱体进行烧结处理。
其中，所述步骤S01的生物活性玻璃凝胶溶液制备方法可以按照常规的生物活性玻璃凝胶溶液进行配制，不同之处，在于配制的所述生物活性玻璃凝胶溶液中含有硼源。在一实施例中，所述制备含有硼源的生物活性玻璃凝胶溶液的方法包括如下步骤：
将模板剂与醇的水溶液配成混合溶液，再向所述混合溶液中依次加入硅源、硼源、磷源和钙源进行混合处理，得到生物活性玻璃凝胶溶液。
该配制生物活性玻璃凝胶的方法能够有效将硼源均匀分散在溶胶溶液中，提高了硼源的分散均匀性。其中，一实施例中，所述硅源、硼源、磷源和钙源的摩尔比为(40～55)：(40～10)：8：36。所述醇的水溶液中的水、醇与模板剂和硅源的摩尔比为水：醇：模板剂：硅源＝200：(100～200)：(1～4)：(5～10)。所述模板剂在所述生物活性玻璃凝胶溶液中的浓度为0.08～0.32mol/L。通过优化生物活性玻璃凝胶溶液中各成分的比例，能够提供生物活性玻璃凝胶溶液的稳定性，为最终生成性能稳定和形貌稳定的掺硼生物活性玻璃微球提供了保证，而且能够使得硼源均匀分散，并使得沉淀物的粒径小。在具体实施例中，所述模板剂为十二胺，所述硅源为正硅酸乙酯，所述磷源为磷酸三乙酯，所述钙源为硝酸钙，所述醇为乙醇。所述硼源为硼酸三丁酯。通过优化生物活性玻璃凝胶溶液各组分中的成分，以提高生成生物活性玻璃凝胶溶液的稳定性凝胶。
所述步骤S02的沉淀处理处理优选采用离心处理，使得步骤S01配制的所述生物活性玻璃凝胶溶液发生沉淀，并收集沉淀物，获得湿态凝胶。为了降低湿态凝胶的杂质，还包括对所述湿态凝胶进行清洗处理的步骤，如可以采用清 水等方式进行清洗湿态凝胶，以提高湿态凝胶的纯度。在一实施例中，对所述湿态凝胶进行干燥处理的温度为50～100℃，时间为1～2天。该干燥处理一方面能够有效除去水分和残留的溶剂如醇溶剂具体的如乙醇；另一方面有效保留沉淀物的微观形态保持稳定。具体的，所述干燥处理可以但不仅仅将所述湿态凝胶放置于烘箱内进行烘干处理。经过干燥处理，获得了掺硼生物活性玻璃前驱体。
所述步骤S03的烧结处理是对步骤S02获得的所述掺硼生物活性玻璃前驱体进行煅烧烧结处理，使得掺硼生物活性玻璃前驱体生成掺硼生物活性玻璃微球。在一实施例中，所述烧结处理的温度为600～700℃，所述热处理的时间为2-5h。在具体实施例中，所述烧结处理可以是将所述掺硼生物活性玻璃前驱体高温炉中进行烧结处理。通过烧结，所述掺硼生物活性玻璃前驱体生成掺硼生物活性玻璃微球。经检测，通过上述方法制备的掺硼生物活性玻璃微球粒径为微纳米级，而且其形貌为球形，如图2所示。另外，经测得，所述掺硼生物活性玻璃微球分散性好。因此，上文所述掺硼生物活性玻璃微球制备方法结合溶胶-凝胶法与模板法制备工艺，能够制备处具有良好球形形貌的掺硼生物活性玻璃微球，而且所述掺硼生物活性玻璃微球尺寸稳定且小，具有较高的比表面积与良好的分散性。另外，经过能谱分析得知，在制备的掺硼生物活性玻璃微球中，掺杂的硼元素能够均匀分布，具体的如能够在所述掺硼生物活性玻璃微球表面均匀分布，如图3所示。由于掺硼生物活性玻璃微球掺杂了硼元素，这样，硼可以有效降低生物活性玻璃微球中Si—O网络的强结合力，促进生物活性离子的溶出，从而赋予所述掺硼生物活性玻璃微球具有优异的释放生物活性离子特性。而且所述制备方法能够使得掺硼生物活性玻璃微球颗粒形貌尺寸可控，生成的掺硼生物活性玻璃微球性能稳定，而且效率高，适于工业化生产。
相应地，基于上述掺硼生物活性玻璃微球的制备方法，本发明实施例还提供了一种掺硼生物活性玻璃微球。所述掺硼生物活性玻璃微球是由上文所述掺硼生物活性玻璃微球的制备方法制备获得，因此，所述掺硼生物活性玻璃微球 形貌为球形，且其粒径为微纳米级，具体的如所述掺硼生物活性玻璃微球的粒径小于1微米。因此，其粒径尺寸小，粒径分布均匀，而且较高的比表面积与良好的分散性。而且在所述掺硼生物活性玻璃微球中掺杂有硼元素，而且掺杂的硼元素在所述掺硼生物活性玻璃微球中掺均匀分布，如在所述掺硼生物活性玻璃微球的表面均匀分布。这样，硼可以有效降低所述掺硼生物活性玻璃微球中Si—O网络的强结合力，促进生物活性离子的溶出，从而赋予所述掺硼生物活性玻璃微球具有优异的释放生物活性离子特性，而且安全和生物活性高。
正是由于上文所述掺硼生物活性玻璃微球具有如上文所述的球形形貌、微纳米级颗粒尺寸，较高的比表面积与良好的分散性以及生物活性离子溶出性良好，有效扩展了所述掺硼生物活性玻璃微球在生物材料领域中的应用。如一实施例中，所述掺硼生物活性玻璃微球在骨组织修复、口腔修复、皮肤修复、机体免疫调控、药物载体方面应用广泛。
以下通过多个具体实施例来举例说明本发明实施例掺硼生物活性玻璃微球及其制备方法等。
实施例1
本实施例1提供了一种掺硼生物活性玻璃微球及其制备方法。所述掺硼生物活性玻璃微球制备方法包括如下步骤：
S11.含有硼源的生物活性玻璃凝胶溶液的制备：
(1)将8.00g十二胺加入到70ml水和160ml乙醇中，搅拌均匀形成混合溶液；
(2)依次将29.12ml正硅酸乙酯、6.37ml硼酸三丁酯、3.24ml磷酸三乙酯及20.24g四水合硝酸钙加入到步骤(1)中所述混合溶液中，搅拌均匀得到生物活性玻璃凝胶溶液；
S12.掺硼生物活性玻璃前驱体：
将步骤S11中所得的生物活性玻璃凝胶溶液离心分离处理，清洗得到湿态凝胶沉淀，再将湿态凝胶沉淀放置于60℃烘箱中干燥2天，得到掺硼生物活性 玻璃前驱体粉末；
S13.将掺硼生物活性玻璃前驱体进行烧结处理：
将步骤S12中所得掺硼生物活性玻璃前驱体粉末在高温炉中650℃热处理3h，得到微纳米掺硼生物活性玻璃微球。
对本实施例1制备的所述掺硼生物活性玻璃微球进行扫描电镜及能谱分析和能谱分析，其中所述扫面电镜照片如图1所示，能谱分析数据如图2所示。由图1可知，所述掺硼生物活性玻璃微球具有良好的球形形貌与分散性，粒径尺寸小于1微米。由图2可知，所述掺硼生物活性玻璃微球的表面硼元素分布均匀。
实施例2
本实施例2提供了一种掺硼生物活性玻璃微球及其制备方法。所述掺硼生物活性玻璃微球制备方法包括如下步骤：
S11.含有硼源的生物活性玻璃凝胶溶液的制备：
(1)将6.00g十二胺加入到100ml水和100ml乙醇中，搅拌均匀形成混合溶液；
(2)依次将26.47ml正硅酸乙酯、12.74ml硼酸三丁酯、3.24ml磷酸三乙酯及20.24g四水合硝酸钙加入到所述混合溶液中，搅拌均匀得到生物活性玻璃凝胶溶液；
S12.掺硼生物活性玻璃前驱体：
将步骤S11中所得的生物活性玻璃凝胶溶液离心分离处理，清洗得到湿态凝胶沉淀，再将湿态凝胶沉淀放置于50℃烘箱中干燥2天，得到生物活性玻璃前驱体粉末；
S13.将掺硼生物活性玻璃前驱体进行烧结处理：
将步骤S12中所得掺硼生物活性玻璃前驱体粉末在高温炉中600℃热处理3h，得到掺硼微纳米生物活性玻璃微球。
对本实施例2制备的所述掺硼生物活性玻璃微球进行扫描电镜及能谱分析 和能谱分析，结果与实施例1基本相同，所述掺硼微纳米生物活性玻璃微球具有良好的球形形貌与分散性，且微球的表面硼元素分布均匀。
实施例3
本实施例3提供了一种掺硼生物活性玻璃微球及其制备方法。所述掺硼生物活性玻璃微球制备方法包括如下步骤：
S11.含有硼源的生物活性玻璃凝胶溶液的制备：
(1)将10.00g十二胺加入到60ml水和180ml乙醇中，搅拌均匀形成混合溶液；
(2)依次将29.12ml正硅酸乙酯、6.37ml硼酸三丁酯、3.24ml磷酸三乙酯及20.24g四水合硝酸钙加入到所述混合溶液中，搅拌均匀得到生物活性玻璃凝胶溶液；
S12.掺硼生物活性玻璃前驱体：
将步骤S11中所得的生物活性玻璃凝胶溶液离心分离处理，清洗得到湿态凝胶沉淀，再将湿态凝胶沉淀放置于80℃烘箱中干燥1天，得到生物活性玻璃前驱体粉末；
S13.将掺硼生物活性玻璃前驱体进行烧结处理：
将步骤S12中所得掺硼生物活性玻璃前驱体粉末在高温炉中700℃热处理3h，得到掺硼微纳米生物活性玻璃微球。
对本实施例3制备的所述掺硼生物活性玻璃微球进行扫描电镜及能谱分析和能谱分析，结果与实施例1基本相同，所述掺硼微纳米生物活性玻璃微球具有良好的球形形貌与分散性，且微球的表面硼元素分布均匀。
实施例4
本实施例4提供了一种掺硼生物活性玻璃微球及其制备方法。所述掺硼生物活性玻璃微球制备方法包括如下步骤：
S11.含有硼源的生物活性玻璃凝胶溶液的制备：
(1)将8.00g十二胺加入到50ml水和150ml乙醇中，搅拌均匀形成混合 溶液；
(2)依次将21.18ml正硅酸乙酯、25.48ml硼酸三丁酯、3.24ml磷酸三乙酯及20.24g四水合硝酸钙加入到所述混合溶液中，搅拌均匀得到生物活性玻璃凝胶溶液；
S12.掺硼生物活性玻璃前驱体：
将步骤S11中所得的生物活性玻璃凝胶溶液离心分离处理，清洗得到湿态凝胶沉淀，再将湿态凝胶沉淀放置于60℃烘箱中干燥2天，得到生物活性玻璃前驱体粉末；
S13.将掺硼生物活性玻璃前驱体进行烧结处理：
将步骤S12中所得掺硼生物活性玻璃前驱体粉末在高温炉中600℃热处理3h，得到掺硼微纳米生物活性玻璃微球。
对本实施例4制备的所述掺硼生物活性玻璃微球进行扫描电镜及能谱分析和能谱分析，结果与实施例1基本相同，所述掺硼微纳米生物活性玻璃微球具有良好的球形形貌与分散性，且微球的表面硼元素分布均匀。
实施例5
本实施例5提供了一种掺硼生物活性玻璃微球及其制备方法。所述掺硼生物活性玻璃微球制备方法包括如下步骤：
S11.含有硼源的生物活性玻璃凝胶溶液的制备：
(1)将12.00g十二胺加入到100ml水和150ml乙醇中，搅拌均匀形成混合溶液；
(2)依次将26.47ml正硅酸乙酯、12.74ml硼酸三丁酯、3.24ml磷酸三乙酯及20.24g四水合硝酸钙加入到所述混合溶液中，搅拌均匀得到生物活性玻璃凝胶溶液；
S12.掺硼生物活性玻璃前驱体：
将步骤S11中所得的生物活性玻璃凝胶溶液离心分离处理，清洗得到湿态凝胶沉淀，再将湿态凝胶沉淀放置于50℃烘箱中干燥2天，得到生物活性玻璃 前驱体粉末；
S13.将掺硼生物活性玻璃前驱体进行烧结处理：
将步骤S12中所得掺硼生物活性玻璃前驱体粉末在高温炉中650℃热处理3h，得到掺硼微纳米生物活性玻璃微球。
对本实施例5制备的所述掺硼生物活性玻璃微球进行扫描电镜及能谱分析和能谱分析，结果与实施例1基本相同，所述掺硼微纳米生物活性玻璃微球具有良好的球形形貌与分散性，且微球的表面硼元素分布均匀。
以上所述仅为本发明的较佳实施例而已，并不用以限制本发明，凡在本发明的精神和原则之内所作的任何修改、等同替换和改进等，均应包含在本发明的保护范围之内。

Claims (10)

  1. 一种掺硼生物活性玻璃微球的制备方法，其特征在于，包括以下步骤：
    制备含有硼源的生物活性玻璃凝胶溶液；
    将所述生物活性玻璃凝胶溶液进行沉淀处理，获得湿态凝胶，并将所述湿态凝胶进行干燥处理，获得掺硼生物活性玻璃前驱体；
    将所述掺硼生物活性玻璃前驱体进行烧结处理。
  2. 根据权利要求1所述的制备方法，其特征在于：制备含有硼源的所述生物活性玻璃凝胶溶液的方法包括如下步骤：
    将模板剂与醇的水溶液配成混合溶液，再向所述混合溶液中依次加入硅源、硼源、磷源和钙源进行混合处理，得到生物活性玻璃凝胶溶液。
  3. 根据权利要求2所述的制备方法，其特征在于：所述硅源、硼源、磷源和钙源的摩尔比为(40～55)：(40～10)：8：36；和/或
    所述醇的水溶液中的水、醇与模板剂和硅源的摩尔比为水：醇：模板剂：硅源＝200：(100～200)：(1～4)：(5～10)。
  4. 根据权利要求2-3任一项所述的制备方法，其特征在于：所述模板剂为十二胺；所述硅源为正硅酸乙酯；所述磷源为磷酸三乙酯；所述钙源为硝酸钙；所述醇为乙醇；所述模板剂在所述生物活性玻璃凝胶溶液中的浓度为0.08～0.32mol/L。
  5. 根据权利要求1-3任一项所述的制备方法，其特征在于：所述硼源为硼酸三丁酯。
  6. 根据权利要求1-3任一项所述的制备方法，其特征在于：所述烧结处理的温度为600～700℃，所述热处理的时间为2-5h。
  7. 根据权利要求1-3任一项所述的制备方法，其特征在于：所述干燥处理的温度为50～100℃，时间为1～2天。
  8. 一种掺硼生物活性玻璃微球，其特征在于：所述掺硼生物活性玻璃微球由权利要求1-8任一项所述的制备方法制备获得。
  9. 根据权利要求8所述的掺硼生物活性玻璃微球，其特征在于：所述掺硼生物活性玻璃微球为球形形貌，且直径为微纳米级。
  10. 根据权利要求8-9任一项所述的掺硼生物活性玻璃微球在骨组织修复、口腔修复、皮肤修复、机体免疫调控、药物载体方面应用广泛。
PCT/CN2019/124797 2019-05-06 2019-12-12 掺硼生物活性玻璃微球及其制备方法与应用 WO2020224261A1 (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201910371075.3A CN110272209A (zh) 2019-05-06 2019-05-06 掺硼生物活性玻璃微球及其制备方法与应用
CN201910371075.3 2019-05-06

Publications (1)

Publication Number Publication Date
WO2020224261A1 true WO2020224261A1 (zh) 2020-11-12

Family

ID=67960330

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2019/124797 WO2020224261A1 (zh) 2019-05-06 2019-12-12 掺硼生物活性玻璃微球及其制备方法与应用

Country Status (2)

Country Link
CN (1) CN110272209A (zh)
WO (1) WO2020224261A1 (zh)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110272209A (zh) * 2019-05-06 2019-09-24 深圳先进技术研究院 掺硼生物活性玻璃微球及其制备方法与应用
CN111268916B (zh) * 2020-03-18 2021-06-08 四川大学 一种硒掺杂硅钙磷生物活性介孔玻璃粉末制备方法
WO2022120768A1 (zh) * 2020-12-10 2022-06-16 深圳先进技术研究院 一种硼硅酸盐生物活性玻璃微纳米颗粒及制备方法和应用
CN114084898A (zh) * 2021-12-06 2022-02-25 景德镇陶瓷大学 一种耐高温、不团聚的超细γ-Ce2S3红色色料的制备方法及其制得的产品

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0153863B1 (en) * 1984-03-01 1989-03-01 Pfizer Hospital Products Group, Inc. Bonding of bioactive glass coatings
CN102557398A (zh) * 2011-12-31 2012-07-11 武汉大学 一种含硼纳米介孔大孔生物活性玻璃、其制备方法及应用
CN103143057A (zh) * 2011-12-06 2013-06-12 中国科学院上海微系统与信息技术研究所 石墨烯/生物活性干凝胶及其制备方法与应用
US20140271913A1 (en) * 2013-03-14 2014-09-18 Gregory J. Pomrink Compositions and methods for manufacturing sol-gel derived bioactive borophosphate glasses for medical applications
CN108892145A (zh) * 2018-07-17 2018-11-27 佛山今兰生物科技有限公司 一种SiO2基生物活性组织修复材料的量化生产方法
CN109336371A (zh) * 2018-09-03 2019-02-15 中国科学院深圳先进技术研究院 微纳米硼硅酸盐生物活性玻璃的制备方法
CN110272209A (zh) * 2019-05-06 2019-09-24 深圳先进技术研究院 掺硼生物活性玻璃微球及其制备方法与应用

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2338694T3 (es) * 2006-09-20 2010-05-11 Inion Oy Composiciones de vidrio bioactivo.

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0153863B1 (en) * 1984-03-01 1989-03-01 Pfizer Hospital Products Group, Inc. Bonding of bioactive glass coatings
CN103143057A (zh) * 2011-12-06 2013-06-12 中国科学院上海微系统与信息技术研究所 石墨烯/生物活性干凝胶及其制备方法与应用
CN102557398A (zh) * 2011-12-31 2012-07-11 武汉大学 一种含硼纳米介孔大孔生物活性玻璃、其制备方法及应用
US20140271913A1 (en) * 2013-03-14 2014-09-18 Gregory J. Pomrink Compositions and methods for manufacturing sol-gel derived bioactive borophosphate glasses for medical applications
CN108892145A (zh) * 2018-07-17 2018-11-27 佛山今兰生物科技有限公司 一种SiO2基生物活性组织修复材料的量化生产方法
CN109336371A (zh) * 2018-09-03 2019-02-15 中国科学院深圳先进技术研究院 微纳米硼硅酸盐生物活性玻璃的制备方法
CN110272209A (zh) * 2019-05-06 2019-09-24 深圳先进技术研究院 掺硼生物活性玻璃微球及其制备方法与应用

Also Published As

Publication number Publication date
CN110272209A (zh) 2019-09-24

Similar Documents

Publication Publication Date Title
WO2020224261A1 (zh) 掺硼生物活性玻璃微球及其制备方法与应用
Zheng et al. Porous bioactive glass micro-and nanospheres with controlled morphology: Developments, properties and emerging biomedical applications
CN113174080B (zh) 一种生物玻璃纳米纤维多孔支架及其制备和应用
CN108083618A (zh) 一种利用微乳液技术制备的微纳米生物活性玻璃微球及其制备方法
Yao et al. 3D interpenetrated graphene foam/58S bioactive glass scaffolds for electrical-stimulation-assisted differentiation of rabbit mesenchymal stem cells to enhance bone regeneration
CN111097068B (zh) 一种仿生的羟基磷灰石粉体/明胶/海藻酸钠复合3d打印支架及其制备方法
CN112899808B (zh) 一种多功能纳米纤维及其制备方法与应用
Dreanca et al. Bioactive glass-biopolymers‑gold nanoparticle based composites for tissue engineering applications
WO2020252957A1 (zh) 一种促进组织原位再生的可降解再生医学材料及其制备方法
CN108030956B (zh) 治疗肿瘤性骨缺损的生物活性玻璃陶瓷支架及其制备方法和应用
CN104288830A (zh) 一种微纳米棒状生物活性玻璃及其制备方法与应用
CN111228484B (zh) 铜硅钙石的应用以及含有铜硅钙石的复合生物材料
CN113398327B (zh) 一种高生物活性MXene/生物玻璃微球复合材料的制备方法
CN109336371A (zh) 微纳米硼硅酸盐生物活性玻璃的制备方法
WO2019148554A1 (zh) 一种硼磷系生物活性玻璃及其制备方法
US20230045516A1 (en) Bioactive glass as nucleic acid carriers with ph switch control-releasing
Wang et al. The effect of magnetic poly (lactic-co-glycolic acid) microsphere-gelatin hydrogel on the growth of pre-osteoblasts under static magnetic field
CN101215153B (zh) 一种非晶态生物活性超细粉体的制备方法
Wang et al. A bifunctional scaffold for tissue regeneration and photothermal therapy
CN114129727B (zh) 一种硼纳米片复合材料及其制备方法
CN107964533B (zh) 二硫化钼用于干细胞增殖和/或分化及干细胞增殖和/或分化用衬底及制备方法和应用
WO2022120902A1 (zh) 骨修复支架及其制备方法
Guan et al. Preparation and properties of nano silica-based bioactive glass/apatite/sodium alginate composite hydrogel
CN115010966A (zh) 一种过氧化氢酶启发的纳米复合水凝胶及其制备方法与应用
CN110668695B (zh) 一种生物活性玻璃微粒及其制备方法

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 19927908

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 19927908

Country of ref document: EP

Kind code of ref document: A1