WO2017118293A1 - 可降解骨植入物及其制备方法 - Google Patents

可降解骨植入物及其制备方法 Download PDF

Info

Publication number
WO2017118293A1
WO2017118293A1 PCT/CN2016/111416 CN2016111416W WO2017118293A1 WO 2017118293 A1 WO2017118293 A1 WO 2017118293A1 CN 2016111416 W CN2016111416 W CN 2016111416W WO 2017118293 A1 WO2017118293 A1 WO 2017118293A1
Authority
WO
WIPO (PCT)
Prior art keywords
degradable
bone implant
powder
phosphate
implant according
Prior art date
Application number
PCT/CN2016/111416
Other languages
English (en)
French (fr)
Inventor
吕世文
毛克亚
卓清山
张鹏云
Original Assignee
宁波华科润生物科技有限公司
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 宁波华科润生物科技有限公司 filed Critical 宁波华科润生物科技有限公司
Publication of WO2017118293A1 publication Critical patent/WO2017118293A1/zh

Links

Images

Classifications

    • 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
    • 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
    • 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
    • A61L27/025—Other specific inorganic materials not covered by A61L27/04 - A61L27/12
    • 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
    • A61L27/12—Phosphorus-containing materials, e.g. apatite
    • 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
    • A61L27/14—Macromolecular materials
    • A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • 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
    • A61L27/14—Macromolecular materials
    • A61L27/20—Polysaccharides
    • 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
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • 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
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
    • A61L27/3608—Bone, e.g. demineralised bone matrix [DBM], bone powder
    • 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
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3641—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the site of application in the body
    • A61L27/3645—Connective tissue
    • A61L27/365—Bones
    • 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
    • A61L27/56—Porous materials, e.g. foams or sponges
    • 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
    • A61L2400/18—Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
    • 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
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
    • 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
    • A61L27/52—Hydrogels or hydrocolloids

Definitions

  • the invention relates to the field of medical bone implant instruments, in particular to a novel degradable bone implant and a preparation method thereof.
  • Bone implants mainly include autologous bone implants, allogeneic bone implants, and biomaterial bone implants.
  • the first two are limited in clinical applications due to their limited number.
  • bone implants made of biological materials are commonly used clinically, and such biological materials include non-degradable and degradable materials.
  • Bone implants made of non-degradable materials such as stainless steel, titanium alloy, PEEK, etc., require secondary surgery for removal due to non-degradability in the body.
  • metal bone implants are prone to stress shielding problems.
  • PEEK materials are similar in mechanics to bone tissue, grinding particles that fall off is prone to complications such as inflammation.
  • biodegradable bioceramic bone implants have been limited in clinical applications due to their shortness of brittleness and insufficient bending strength.
  • the cage is a kind of bone implant commonly found in clinical practice.
  • the fusion cages are mainly made of pure magnesium, magnesium alloy, polylactic acid or its copolymer, bioceramics, etc. to make.
  • Chinese Patent 201310388513.X discloses an interbody fusion cage made of poly-DL-lactic acid, poly-L-lactic acid/glycolic acid copolymer, hydroxyapatite and tricalcium phosphate, which has high strength and good
  • the osteoinductive activity can be completely degraded and absorbed in the body, but the degradation rate is still slow and the degradation products are acidic.
  • Chinese Patent 201410073104.5 discloses a spine fusion cage with controllable degradation rate, the composition and weight percentage of which are: inorganic bioceramics 1%-10%, magnesium or magnesium alloy 10%-80%, and the rest are degradable polymer polymerization The degradable polymer material is coated on the surface to control the degradation rate.
  • the object of the present invention is to provide a novel degradable bone implant and a preparation method thereof, which are prepared by pressurization, placed in a constant temperature and humidity chamber, and added with a degradable metal in the bone implant.
  • the degradable bone implant of the present invention further comprises a degradable polymer coating that controls the rate of degradation of the bone implant by adjusting the thickness of the coating.
  • the bone implant has a high bone fusion rate and can be completely degraded and absorbed.
  • the degradable bone implant of the present invention comprises a silicon-containing compound which, upon degradation, produces a Si-O-Si rich porous gel layer on the surface of the bone implant.
  • the surface of the silicon gel layer will produce a large number of Si-OH negatively charged, and different types of protein through hydrogen bonding and ionic amine linkage (-Si-OH + 3 N - ) to form a high density of protein adsorption to Promotes extracellular response.
  • the silicone gel layer can chelate with metal ions formed by degradation, reduce the freeness of metal ions in body fluids, reduce the toxicity caused by the abnormal increase of these ions, thereby improving biocompatibility and promoting bone fusion.
  • a novel degradable bone implant prepared by mixing and pressing a powder and a liquid agent, the powder consisting of the following components: 32-70 wt% phosphate, 28-65 wt%
  • the metal oxide and 1 to 15% by weight of the silicon-containing compound have a liquid to solid ratio of 0.1 to 0.5 ml/g.
  • the phosphate comprises potassium dihydrogen phosphate, sodium dihydrogen phosphate, calcium dihydrogen phosphate, one of ammonium dihydrogen phosphate or a mixture thereof.
  • the metal oxide comprises at least one of magnesium oxide, aluminum oxide, iron oxide, ferric oxide, triiron tetroxide, zinc oxide, and zirconium oxide.
  • the powder further comprises a degradable adhesion promoting material.
  • the degradable adhesion promoting material comprises at least one of beeswax, sodium hyaluronate, bone glue, sugars and derivatives thereof.
  • the silicon-containing compound comprises silica and/or silicate.
  • the phosphate further comprises calcium phosphate
  • the calcium phosphate comprises one of ⁇ -tricalcium phosphate, ⁇ -tricalcium phosphate or a mixture thereof.
  • the liquid agent comprises one of deionized water, sodium chloride solution, phosphoric acid solution or a mixture thereof.
  • the bone implant further comprises a degradable metal frame or a metal inner support, the degradable metal comprising pure magnesium or a magnesium alloy.
  • the bone implant further comprises a degradable polymer material, and the degradable polymer material comprises at least one of polyglycolic acid, polylactic acid and a copolymer thereof.
  • a method for preparing a novel degradable bone implant the steps are as follows:
  • the degradable metal is processed into a wire, strip, frame or mesh and placed in a mold.
  • steps c and d are further included between the steps c and d:
  • the solution A is applied to the surface of the bone implant by spraying or dip coating, and the surface thickness of the bone implant is about 0.01-2 mm.
  • the degradable polymer material is preliminarily added to the powder and uniformly mixed.
  • a porous gel layer is formed on the surface, and a high density protein adsorption is formed on the surface of the silicone gel layer, thereby promoting the extracellular response.
  • the silicone gel layer can chelate with metal ions, reduce the freeness of metal ions in body fluids, reduce the toxicity caused by the abnormal increase of these ions, thereby improving biocompatibility and promoting bone fusion.
  • the degradable bone implant of the present invention adopts a compression measure during the injection molding process, and the demolded bone implant is placed in a constant temperature and humidity cabinet to process the degradable bone implant obtained. Has good mechanical properties.
  • the degradable bone implant of the present invention further comprises a degradable metal which is processed into a filament, strip, frame or mesh uniformly distributed in the bone implant, which further enhances the degradable bone implant.
  • Mechanical properties are provided.
  • the degradable bone implant of the present invention generates an appropriate amount of magnesium ions during the degradation process, and can promote bone tissue growth.
  • the degradable bone implant of the present invention can also control the rate of degradation of the bone implant to control bone tissue growth by controlling the content or thickness of the polymer coating.
  • Figure 1 is a schematic view of a ⁇ 3x3 degradable bone-filled particle of the present invention
  • FIG. 2 is a schematic structural view of a degradable fuser of a magnesium alloy-containing frame according to the present invention
  • FIG. 3 is a schematic structural view of a degradable fusion cage containing pure magnesium strip of the present invention.
  • Figure 4 is a schematic view showing the structure of a polylactic acid-coated degradable fuser of the present invention.
  • Figure 5 is a schematic view showing the structure of a degradable bone rod containing a polyglycolic acid filler of the present invention.
  • 1-degradable fuser 2-metal frame; 3-metal inner support; 4-polylactic acid coating; 5-degradable bone rod; 6-polyglycolic acid filler.
  • Exemplary formulations of the powders and solutions of the present invention are as follows:
  • the liquid agent is deionized water, and the liquid-solid ratio of the powder and the liquid agent is 0.2 ml/g.
  • the liquid agent is physiological saline, and the liquid-solid ratio of the powder and the liquid agent is 0.22 ml/g.
  • the liquid agent is a phosphoric acid solution, and the liquid-solid ratio of the powder and the liquid agent is 0.25 ml/g.
  • the liquid agent is deionized water, and the liquid-solid ratio of the powder and the liquid agent is 0.16 ml/g.
  • the liquid agent is physiological saline, and the liquid-solid ratio of the powder and the liquid agent is 0.32 ml/g.
  • FIG. 1 is a schematic view of the degradable bone-filled particles prepared by the present invention, and the specific preparation steps are as follows:
  • the powder and the liquid agent are mixed and stirred to obtain a paste
  • the bone-filled particles were placed in a constant temperature and humidity cabinet at a temperature of 37 ° C and a humidity of 60% for 28 hours.
  • the prepared degradable bone-filled particles can be used for filling the bone defect site.
  • FIG. 2 is a schematic structural view of a degradable fuser 1 of a metal frame 2 containing a magnesium alloy prepared according to the present invention, and the specific preparation steps are as follows:
  • the paste is injected into the mold with the magnesium alloy frame, and the injection pressure is maintained at 15 atm;
  • the degradable cage was placed in a constant temperature and humidity cabinet at a temperature of 37 ° C and a humidity of 80% for 48 hours.
  • the prepared degradation cage can be used for various fusion operations.
  • FIG. 3 is a schematic structural view of a degradable fuse 1 of a metal inner support 3 containing pure magnesium strip prepared according to the present invention, and the specific preparation steps are as follows:
  • the prepared degradation cage can be used for various fusion operations.
  • FIG. 4 is a schematic structural view of a degradable fuser 1 containing a polylactic acid coating 4 prepared according to the present invention, and the specific preparation steps are as follows:
  • the surface coating thickness is about 0.05 mm;
  • the degradable cage was placed in a constant temperature and humidity cabinet at a temperature of 37 ° C and a humidity of 90% for 36 hours.
  • the prepared degradation cage can be used for various fusion operations.
  • FIG. 5 is a schematic view showing the structure of the degradable bone rod 5 containing the polyglycolic acid filler 6 prepared by the present invention, and the specific preparation steps are as follows:
  • the polyglycolic acid powder is added to the powder described in Formula 5, the mass ratio is 0.1:1, and the mixture is uniformly mixed;
  • the prepared degradable bone rod can be used for filling of nail holes and the like.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Inorganic Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Botany (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Dispersion Chemistry (AREA)
  • Materials For Medical Uses (AREA)
  • Vascular Medicine (AREA)
  • Molecular Biology (AREA)
  • Urology & Nephrology (AREA)
  • Zoology (AREA)

Abstract

一种可降解骨植入物及其制备方法。骨植入物由粉剂和液剂混合加压后凝固制成，粉剂由以下组分组成：32-70wt%的磷酸盐，28-65wt%的金属氧化物和1-15wt%的含硅化合物，液剂与粉剂的液固比为0.1-0.5ml/g。制备方法的步骤如下：首先，将粉剂和液剂按比例混合搅拌后得到糊状物；其次，将糊状物注入模具中，并保持压力不低于5个大气压；再次，待糊状物固化后脱模，得到骨植入物；最后，将骨植入物放置在温度37℃，湿度50-100%的恒温恒湿柜中不低于24小时。骨植入物具有高强度、可降解、降解速率可控、高骨性融合率等优点。

Description

可降解骨植入物及其制备方法
相关申请
本发明申请要求2016年1月6日申请的，申请号为201610003199.2，名称为“一种新型可降解骨植入物及其制备方法”的中国专利申请的优先权，在此将其全文引入作为参考。
技术领域
本发明涉及医用骨植入器械领域，尤其涉及一种新型可降解骨植入物及其制备方法。
背景技术
当骨组织出现骨折、疾病等损伤时，需要进行骨植入。骨植入物主要有自体骨植入物、同种异体骨植入物和生物材料骨植入物。前两者因为数量有限，临床应用受到限制。目前，临床上常用生物材料制成的骨植入物，这种生物材料包括不可降解和可降解材料。不可降解材料如不锈钢、钛合金、PEEK等制成的骨植入物，因在体内不可降解而需二次手术取出。另外金属骨植入物容易造成应力遮挡等问题，PEEK材料虽然力学与骨组织差不多，但磨削掉落的颗粒容易造成炎症等并发症。可降解材料如PGA、PLLA、镁合金等制成的骨植入物，其植入后的降解产物均对组织产生不良影响。另外，可降解的生物陶瓷骨植入物，因其脆性大，弯曲强度不足等缺点，在临床应用上受到了一定的限制。
融合器是临床上常见的一种骨植入物，近年来关于可降解融合器的研究非常多，该类融合器主要是用纯镁、镁合金、聚乳酸或其共聚物、生物陶瓷等制成。例如，中国专利201310388513.X公布了一种椎间融合器，由聚-DL-乳酸、聚-L-乳酸/乙醇酸共聚物、羟基磷灰石和磷酸三钙制成，具有高强度、良好的骨诱导活性，能在体内完全降解吸收，但仍存降解速率偏慢、降解产物呈酸性等问题。
中国专利201410073104.5公开了一种降解速率可控的脊柱融合器，其组分及重量百分比为：无机生物陶瓷1％-10％，镁或镁合金10％-80％，其余为可降解高分子聚合物，可降解高分子材料涂覆在表面，使其降解速率可控。
基于此，设计开发出一种力学性能良好、可完全降解吸收且降解速率与新骨生长匹配、高骨性融合率的骨植入物，是近年来研究追求的目标之一。
发明内容
为此，本发明的目的在于提供一种新型可降解骨植入物及其制备方法,采取了加压制备后放置在恒温恒湿柜处理，并在骨植入物中加入可降解金属。本发明的可降解骨植入物还包括 可降解高分子涂层，通过调节涂层的厚度来控制骨植入物的降解速率。使骨植入物拥有高骨性融合率，能够完全降解吸收。本发明的可降解骨植入物包括含硅化合物，在降解过程中，骨植入物表面会产生富Si-O-Si的多孔凝胶层。在硅凝胶层表面会产生大量带负电荷的Si－OH，与不同种类的蛋白质通过氢键和离子胺键(－Si－O－H3N+－)结合形成高密度的蛋白吸附，从而促进细胞外响应。此外，硅凝胶层能够与降解形成的金属离子产生螯合作用，降低金属离子在体液中的游离度，减轻这些离子异常增多产生的毒性，从而提高生物相容性，促进骨性融合。
所采用技术方案如下所述：
一种新型可降解骨植入物，所述骨植入物由粉剂和液剂混合加压后凝固制成，所述粉剂由以下组分组成：32-70wt％的磷酸盐、28-65wt％的金属氧化物和1-15wt％的含硅化合物，所述液剂与粉剂的液固比为0.1-0.5ml/g。
本发明的目的还可以通过以下的技术方案来进一步实现：
优选的，所述磷酸盐包括磷酸二氢钾、磷酸二氢钠、磷酸二氢钙、磷酸二氢铵的一种或其混合物。
优选的，所述金属氧化物包括氧化镁、三氧化二铝、氧化铁、三氧化二铁、四氧化三铁、氧化锌及氧化锆中的至少一种。
优选的，所述的粉剂还包括可降解促粘接材料。
优选的，所述可降解促粘接材料包括蜂蜡、透明质酸钠、骨胶、糖类及其衍生物中的至少一种。
优选的，所述含硅化合物包括二氧化硅和/或硅酸盐。
优选的，所述磷酸盐还包括磷酸钙，所述的磷酸钙包括α-磷酸三钙、β-磷酸三钙的一种或其混合物。
优选的，所述液剂包括去离子水、氯化钠溶液、磷酸溶液的一种或其混合物。
优选的，所述骨植入物还包括可降解的金属框架或金属内支撑，所述可降解的金属包括纯镁或镁合金。
优选的，所述骨植入物还包括可降解高分子材料，所述可降解高分子材料包括聚乙醇酸、聚乳酸及其共聚物中的至少一种。
一种新型可降解骨植入物的制备方法，步骤如下：
a.将所述粉剂和液剂按0.1-0.5ml/g比例混合搅拌后得到糊状物；
b.将糊状物注入模具中，并保持注射压力≥5atm；
c.待糊状物固化后脱模，得到骨植入物；
d.将骨植入物放置在温度37℃、湿度50-100％的恒温恒湿柜中≥24h。
优选的，在所述步骤a之前，先将所述可降解的金属加工成丝、条、框或网状，并放入模具。
优选的，在所述步骤c和d之间还包括以下步骤：
(1)将所述的可降解高分子材料溶于有机溶剂中获得溶液A；
(2)采用喷涂法或者浸涂法将溶液A涂覆于骨植入物表面，骨植入物表面涂层厚度约0.01-2mm。
优选的，在所述步骤a之前，先将可降解高分子材料预先加入粉剂中，并混合均匀。
本发明相对于现有技术具有如下有益效果：
1.本发明的可降解骨植入物在降解过程中，表面会产生多孔凝胶层，在硅凝胶层表面会形成高密度的蛋白吸附，从而促进细胞外响应。此外，硅凝胶层能够与金属离子产生螯合作用，降低金属离子在体液中的游离度，减轻这些离子异常增多产生的毒性，从而提高生物相容性，促进骨性融合。
2.本发明的可降解骨植入物在注入模具过程中采取了加压措施，并将脱模后的骨植入物放置在恒温恒湿柜处理，使得所获得的可降解骨植入物具有良好的力学性能。
3.本发明的可降解骨植入物还包括可降解金属，可降解金属被加工成丝、条、框或网状均匀分布于骨植入物中，可进一步提升可降解骨植入物的力学性能。
4.本发明的可降解骨植入物在降解过程中，会产生适量的镁离子，可以促进骨组织生长。此外，本发明的可降解骨植入物还可通过控制高分子涂层的含量或厚度，控制骨植入物的降解速率，以匹配骨组织生长。
附图说明
为了使本发明的内容更容易被清楚的理解，下面根据本发明的具体实施例并结合附图，对本发明作进一步详细的说明，其中
图1为本发明的φ3x3可降解骨填充颗粒示意图；
图2为本发明的含镁合金框架的可降解融合器的结构示意图；
图3为本发明的含纯镁条的可降解融合器的结构示意图；
图4为本发明的含聚乳酸涂层的可降解融合器的结构示意图；
图5为本发明的含聚乙醇酸填料的可降解骨棒的结构示意图。
图中：1-可降解融合器；2-金属框架；3-金属内支撑；4-聚乳酸涂层；5-可降解骨棒；6-聚乙醇酸填料。
具体实施方式
为使本发明的目的、技术方案和优点更加清楚，下面将结合附图对本发明实施方式作进一步地详细描述。
本发明的粉剂和液剂示例性配方如下：
配方①：
按以下重量百分比(wt％)配制粉剂：
Figure PCTCN2016111416-appb-000001
液剂为去离子水，粉剂和液剂的液固比为0.2ml/g。
配方②：
按以下重量百分比(wt％)配制粉剂：
Figure PCTCN2016111416-appb-000002
液剂为生理盐水，粉剂和液剂的液固比为0.22ml/g。
配方③：
按以下重量百分比(wt％)配制粉剂：
Figure PCTCN2016111416-appb-000003
液剂为磷酸溶液，粉剂和液剂的液固比为0.25ml/g。
配方④：
按以下重量百分比(wt％)配制粉剂：
Figure PCTCN2016111416-appb-000004
Figure PCTCN2016111416-appb-000005
液剂为去离子水，粉剂和液剂的液固比为0.16ml/g。
配方⑤：
按以下重量百分比(wt％)配制粉剂：
Figure PCTCN2016111416-appb-000006
液剂为生理盐水，粉剂和液剂的液固比为0.32ml/g。
以上示例性配方为本发明的一些优选配方比例，并不用于限制本发明。
实施例1
图1为本发明制备的可降解骨填充颗粒示意图，具体制备步骤如下：
a.按配方①将所述粉剂和液剂混合搅拌后得到糊状物；
b.将糊状物注入φ3x3的模具中，并保持注射压力8atm；
c.待糊状物固化后脱模，得到骨填充颗粒；
d.将骨填充颗粒放置在温度37℃、湿度60％的恒温恒湿柜中28h。
所制备的可降解骨填充颗粒可用于骨缺损部位填充。
实施例2
图2为本发明制备的含镁合金的金属框架2的可降解融合器1的结构示意图，具体制备步骤如下：
a.将镁合金加工成框架，并放入模具；
b.按配方②将所述粉剂和液剂混合搅拌后得到糊状物；
c.将糊状物注入带有镁合金框架的模具中，并保持注射压力15atm；
d.待糊状物固化后脱模，得到可降解融合器；
e.将可降解融合器放置在温度37℃、湿度80％的恒温恒湿柜中48h。
所制备的可将降解融合器可用于各种融合手术。
实施例3
图3为本发明制备的含纯镁条的金属内支撑3的可降解融合器1的结构示意图，具体制备步骤如下：
a.将纯镁加工成条状，并放入模具；
b.按配方③将所述粉剂和液剂混合搅拌后得到糊状物；
c.将糊状物注入带有纯镁条架的模具中，并保持注射压力12atm；
d.待糊状物固化后脱模，得到可降解融合器；
e.将可降解融合器放置在温度37℃、湿度90％的恒温恒湿柜中36h。
所制备的可将降解融合器可用于各种融合手术。
实施例4
图4为本发明制备的含聚乳酸涂层4的可降解融合器1的结构示意图，具体制备步骤如下：
a.按配方④将所述粉剂和液剂混合搅拌后得到糊状物；
b.将糊状物注入融合器模具中，并保持注射压力10atm；
c.待糊状物固化后脱模，得到可降解融合器；
d.将聚乳酸溶于丙酮中形成0.1g/ml的溶液A；
e.采用浸涂法将溶液A涂覆于可降解融合器表面，表面涂层厚度约0.05mm；
f.将可降解融合器放置在温度37℃、湿度90％的恒温恒湿柜中36h。
所制备的可将降解融合器可用于各种融合手术。
实施例5
图5为本发明制备的含聚乙醇酸填料6的可降解骨棒5的结构示意图，具体制备步骤如下：
a.将聚乙醇酸粉末加入配方⑤所述的粉剂，其质量比为0.1:1，并混合均匀；
b.将粉剂和液剂混合搅拌后得到糊状物；
c.将糊状物注入融合器模具中，并保持注射压力6atm；
d.待糊状物固化后脱模，得到可降解骨棒；
e.将可降解骨棒放置在温度37℃、湿度100％的恒温恒湿柜中24h。
所制备的可降解骨棒可用于钉孔的填充等。
显然，上述实施例仅仅是为清楚地说明所作的举例，而并非对实施方式的限定。对于所属领域的普通技术人员来说，在上述说明的基础上还可以做出其它不同形式的变化或变动。这里无需也无法对所有的实施方式予以穷举。而由此所引伸出的显而易见的变化或变动仍处于本发明的保护范围之中。

Claims (11)

  1. 一种可降解骨植入物，其特征在于，所述骨植入物由粉剂和液剂混合加压后凝固制成，所述粉剂由以下组分组成：32-70wt％的磷酸盐、28-65wt％的金属氧化物和1-15wt％的含硅化合物，所述液剂与粉剂的液固比为0.1-0.5ml/g。
  2. 根据权利要求1所述的一种可降解骨植入物，其特征在于，所述磷酸盐包括磷酸二氢钾、磷酸二氢钠、磷酸二氢钙、磷酸二氢铵的一种或其混合物。
  3. 根据权利要求1所述的一种可降解骨植入物，其特征在于，所述金属氧化物包括氧化镁、三氧化二铝、氧化铁、三氧化二铁、四氧化三铁、氧化锌及氧化锆中的至少一种。
  4. 根据权利要求1所述的一种可降解骨植入物，其特征在于，所述粉剂还包括可降解促粘接材料，所述可降解促粘接材料包括蜂蜡、透明质酸钠、骨胶、糖类及其衍生物中的至少一种。
  5. 根据权利要求1所述的一种可降解骨植入物，其特征在于，所述含硅化合物包括二氧化硅和/或硅酸盐。
  6. 根据权利要求1所述的一种可降解骨植入物，其特征在于，所述磷酸盐还包括磷酸钙，所述磷酸钙包括α-磷酸三钙、β-磷酸三钙的一种或其混合物。
  7. 根据权利要求1所述的一种可降解骨植入物，其特征在于，所述骨植入物还包括可降解的金属框架或金属内支撑，所述可降解的金属包括纯镁或镁合金。
  8. 根据权利要求1所述的一种可降解骨植入物，其特征在于，所述骨植入物还包括可降解高分子材料，所述可降解高分子材料包括聚乙醇酸、聚乳酸及其共聚物中的至少一种。
  9. 一种如权利要求1～8任一项所述的可降解骨植入物的制备方法，步骤如下：
    a.将所述粉剂和液剂按0.1-0.5ml/g比例混合搅拌后得到糊状物；
    b.将所述糊状物注入模具中，并保持压力≥5atm；
    c.待所述糊状物固化后脱模，得到骨植入物；
    d.将所述骨植入物放置在温度37℃、湿度50-100％的恒温恒湿柜中≥24h。
  10. 根据权利要求9所述的一种可降解骨植入物的制备方法，其特征在于，在所述步骤a之前，先将所述可降解的金属加工成丝、条、框或网状，并放入模具。
  11. 根据权利要求9所述的一种可降解骨植入物及其制备方法，其特征在于，在所述步骤c和d之间还包括以下步骤：
    (1)将所述的可降解高分子材料溶于有机溶剂中获得溶液A；
    (2)采用喷涂法或者浸涂法将所述溶液A涂覆于所述骨植入物表面，所述骨植入物表面涂层厚度为0.01-2mm。
PCT/CN2016/111416 2016-01-06 2016-12-22 可降解骨植入物及其制备方法 WO2017118293A1 (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201610003199.2A CN105536048B (zh) 2016-01-06 2016-01-06 一种新型可降解骨植入物及其制备方法
CN201610003199.2 2016-01-06

Publications (1)

Publication Number Publication Date
WO2017118293A1 true WO2017118293A1 (zh) 2017-07-13

Family

ID=55815919

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2016/111416 WO2017118293A1 (zh) 2016-01-06 2016-12-22 可降解骨植入物及其制备方法

Country Status (2)

Country Link
CN (1) CN105536048B (zh)
WO (1) WO2017118293A1 (zh)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112773931A (zh) * 2021-01-04 2021-05-11 北京华钽生物科技开发有限公司 一种可吸收的增强骨植入物材料及其制备方法
CN113171211A (zh) * 2021-06-02 2021-07-27 上海凯利泰医疗科技股份有限公司 一种融合器持取装置

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105536048B (zh) * 2016-01-06 2019-04-02 宁波华科润生物科技有限公司 一种新型可降解骨植入物及其制备方法
SE1651271A1 (en) * 2016-09-27 2018-03-28 Gpbio Ltd Composition of alfa-tcp, silicate and phosphorylated amino acid
CN107213528A (zh) * 2017-05-31 2017-09-29 苏州蔻美新材料有限公司 一种可降解骨植入物的制备方法
CN114533950A (zh) * 2022-02-24 2022-05-27 上海市第六人民医院 一种用于骨缺损修复的生物陶瓷-金属组合体及其制备方法
CN115252229B (zh) * 2022-06-28 2024-03-19 香港中文大学 骨内植物

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101124178A (zh) * 2005-03-25 2008-02-13 创新生物陶瓷公司 水硬水泥组合物和制备及使用其的方法
CN101330934A (zh) * 2005-12-14 2008-12-24 Scil技术有限公司 一种用于骨再生的可模压的生物材料
CN103893829A (zh) * 2014-03-27 2014-07-02 西安理工大学 一种可注射型多孔复合骨水泥的制备方法
WO2015044401A2 (en) * 2013-09-27 2015-04-02 Vita Zahnfabrik H. Rauter Gmbh & Co. Kg Implants having a degradable coating for the prophylaxis of peri-implanitis
CN105536048A (zh) * 2016-01-06 2016-05-04 宁波华科润生物科技有限公司 一种新型可降解骨植入物及其制备方法

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2316383B1 (en) * 2009-10-30 2013-04-17 DePuy Products, Inc. Prosthesis with surfaces having different textures
CN102824657B (zh) * 2011-07-29 2014-05-21 深圳先进技术研究院 骨修复材料及其制备方法
CN103007340A (zh) * 2013-01-15 2013-04-03 河南理工大学 一种用于人体硬组织修复的自固化复合骨修复材料及应用
CN103845760A (zh) * 2014-02-25 2014-06-11 天津市镁胜生物技术有限公司 一种降解速率可控的体内降解脊柱融合器及其制备方法

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101124178A (zh) * 2005-03-25 2008-02-13 创新生物陶瓷公司 水硬水泥组合物和制备及使用其的方法
CN101330934A (zh) * 2005-12-14 2008-12-24 Scil技术有限公司 一种用于骨再生的可模压的生物材料
WO2015044401A2 (en) * 2013-09-27 2015-04-02 Vita Zahnfabrik H. Rauter Gmbh & Co. Kg Implants having a degradable coating for the prophylaxis of peri-implanitis
CN103893829A (zh) * 2014-03-27 2014-07-02 西安理工大学 一种可注射型多孔复合骨水泥的制备方法
CN105536048A (zh) * 2016-01-06 2016-05-04 宁波华科润生物科技有限公司 一种新型可降解骨植入物及其制备方法

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112773931A (zh) * 2021-01-04 2021-05-11 北京华钽生物科技开发有限公司 一种可吸收的增强骨植入物材料及其制备方法
CN112773931B (zh) * 2021-01-04 2022-06-21 北京华钽生物科技开发有限公司 一种可吸收的增强骨植入物材料及其制备方法
CN113171211A (zh) * 2021-06-02 2021-07-27 上海凯利泰医疗科技股份有限公司 一种融合器持取装置

Also Published As

Publication number Publication date
CN105536048A (zh) 2016-05-04
CN105536048B (zh) 2019-04-02

Similar Documents

Publication Publication Date Title
WO2017118293A1 (zh) 可降解骨植入物及其制备方法
Gu et al. Effects of incorporation of HA/ZrO2 into glass ionomer cement (GIC)
EP3401289B1 (en) Magnesium phosphate bone cement
EP2771041B1 (en) Compositions and their use in bone healing
JP5049119B2 (ja) 生体適合性骨インプラント組成物及び骨欠損の修復のための方法
US5840290A (en) Injectable bio-active glass in a dextran suspension
DE102006041023A1 (de) Strukturierte Beschichtungen für Implantate sowie Verfahren zu deren Herstellung
JP6289708B2 (ja) 生体インプラント
Li et al. In vitro and in vivo evaluation on the bioactivity of ZnO containing nano‐hydroxyapatite/chitosan cement
US20110142790A1 (en) Polyol Based - Bioceramic Composites
EP3031478B1 (en) Bone regeneration material kit, paste-like bone regeneration material, bone regeneration material, and bone bonding material
Lima et al. Injectable bone substitute based on chitosan with polyethylene glycol polymeric solution and biphasic calcium phosphate microspheres
JP2022088628A (ja) 骨移植片代用品
CN110180030B (zh) 复合胶原蛋白的磷酸钙生物陶瓷及其制备和使用方法
EP2839849A1 (en) BIOMATERIAL COATED WITH HAp/Col COMPOSITE
US9351812B2 (en) Calcium aluminate based paste for stabilizing dental implants and restoring tissue attachment after surgery and methods therefor
KR101654600B1 (ko) 주입형 자가-경화 인회석 시멘트를 포함하는 조성물
Wang et al. Enhanced biocompatibility and osseointegration of calcium titanate coating on titanium screws in rabbit femur
WO2023216069A1 (zh) 抗冲刷能力的可塑型的骨科组合物
CN107899088B (zh) 一种用于预防去除内固定物后再骨折的多孔生物支架及其制备
CN105731990A (zh) 一种可控降解磷酸镁骨水泥及其制备方法和应用
RU2617050C1 (ru) Биоактивный композиционный материал для замещения костных дефектов и способ его получения
KR100388074B1 (ko) 칼슘 포스페이트 초박막 코팅된 임플란트
TWI805355B (zh) 抗沖刷能力之可塑型的骨科組合物
CN117065088A (zh) 抗冲刷能力的可塑型的骨科组合物

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: 16883419

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: 16883419

Country of ref document: EP

Kind code of ref document: A1