WO2024012411A1 - Medical composite polymer material and preparation method therefor - Google Patents

Medical composite polymer material and preparation method therefor Download PDF

Info

Publication number
WO2024012411A1
WO2024012411A1 PCT/CN2023/106599 CN2023106599W WO2024012411A1 WO 2024012411 A1 WO2024012411 A1 WO 2024012411A1 CN 2023106599 W CN2023106599 W CN 2023106599W WO 2024012411 A1 WO2024012411 A1 WO 2024012411A1
Authority
WO
WIPO (PCT)
Prior art keywords
composite polymer
medical composite
calcium
preparing
ether ketone
Prior art date
Application number
PCT/CN2023/106599
Other languages
French (fr)
Chinese (zh)
Inventor
付家鹏
刘继强
赵学东
吕心建
张明振
陈峥嵘
Original Assignee
运怡（北京）医疗器械有限公司
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 运怡（北京）医疗器械有限公司 filed Critical 运怡（北京）医疗器械有限公司
Publication of WO2024012411A1 publication Critical patent/WO2024012411A1/en

Links

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
    • A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
    • A61L27/46—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with phosphorus-containing inorganic fillers
    • 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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29B—PREPARATION OR PRETREATMENT OF THE MATERIAL TO BE SHAPED; MAKING GRANULES OR PREFORMS; RECOVERY OF PLASTICS OR OTHER CONSTITUENTS OF WASTE MATERIAL CONTAINING PLASTICS
    • B29B13/00—Conditioning or physical treatment of the material to be shaped
    • B29B13/04—Conditioning or physical treatment of the material to be shaped by cooling
    • B29B13/045—Conditioning or physical treatment of the material to be shaped by cooling of powders or pellets
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29B—PREPARATION OR PRETREATMENT OF THE MATERIAL TO BE SHAPED; MAKING GRANULES OR PREFORMS; RECOVERY OF PLASTICS OR OTHER CONSTITUENTS OF WASTE MATERIAL CONTAINING PLASTICS
    • B29B13/00—Conditioning or physical treatment of the material to be shaped
    • B29B13/10—Conditioning or physical treatment of the material to be shaped by grinding, e.g. by triturating; by sieving; by filtering
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29B—PREPARATION OR PRETREATMENT OF THE MATERIAL TO BE SHAPED; MAKING GRANULES OR PREFORMS; RECOVERY OF PLASTICS OR OTHER CONSTITUENTS OF WASTE MATERIAL CONTAINING PLASTICS
    • B29B9/00—Making granules
    • B29B9/02—Making granules by dividing preformed material
    • B29B9/06—Making granules by dividing preformed material in the form of filamentary material, e.g. combined with extrusion

Definitions

  • the present invention relates to a method for preparing a medical composite polymer material, in particular to a method for preparing a medical composite polymer material containing polyaryletherketone and calcium-phosphorus materials.
  • thermoplastic special engineering plastic polyetheretherketone PEEK
  • CFR-PEEK carbon fiber reinforced PEEK
  • This close or matching elastic modulus weakens or eliminates the stress shielding effect to a certain extent, thereby reducing or avoiding bone absorption, thereby facilitating osseointegration between the implant and bone tissue. Therefore, since the 1980s, PEEK has received increasing attention from materials researchers and orthopedic researchers, and has the potential to replace metal materials in the field of hard tissue repair and replacement.
  • PEEK is transparent to X-rays and does not produce artifacts during CT or MRI scans, making it easier to monitor bone growth and healing processes.
  • PEEK also has good biocompatibility, wear resistance, fatigue resistance, corrosion resistance, and easy processing. The above advantages make PEEK widely used in the fields of trauma, spine and joints.
  • PEEK itself does not have biological activity and cannot form osseointegration with bone tissue, which limits its application in the field of tissue repair and replacement to a certain extent.
  • Hydroxyapatite [Ca 10 (PO 4 ) 6 (OH) 2 ] is the most well-known CaP material, with a Ca/P ratio of 1.67.
  • the hydroxyapatite crystal is a hexagonal crystal system, and when the OH - vacancies on the surface of the microcrystal are Adsorbs PO 43 - or phosphate groups or hydroxyl groups on macromolecules.
  • the Ca ion position is vacant, it can adsorb cations such as Sr 3 + and K + and protein molecular groups.
  • PO 43 - is located on the surface of the crystal, H 2 O can Combined with PO 43 - ions through hydrogen bonds.
  • Tricalcium phosphate [Ca 3 (PO4) 2 ] has a Ca/P ratio of 1.5, has a calcium-phosphorus ratio close to that of hydroxyapatite, and has higher solubility under physiological conditions. They themselves are also the main components of the inorganic components of natural bone. Research has found that it can also serve as a carrier for drug or ion delivery and promote the regeneration of new bone and new blood vessels, making it one of the first choice materials for repairing bone defects. In addition to its excellent biological performance, hydroxyapatite is easy and cheap to produce and can be relatively easily implemented in clinical applications, bringing great hope for the further development of bone tissue engineering.
  • Other useful calcium-phosphorus materials include tetracalcium phosphate and calcium oxide, among others.
  • Hydroxyapatite powder can be prepared by dry method, chemical precipitation method, sol-gel method, hydrothermal synthesis method, bionic solution growth synthesis method, etc.
  • PEEK mainly appears in the form of powder and pellets in the production and processing process.
  • Commercially available medical grade PEEK only exists in pellet products, which are mixed with hydroxyapatite for extrusion or injection molding. It is difficult to solve the problem of hydroxyapatite.
  • the uniform dispersion of particles in the PEEK matrix causes a large number of particles to agglomerate in the matrix.
  • the mechanical properties of the composite material, especially the tensile strength are seriously reduced, which poses safety risks in clinical applications and makes it difficult to meet the actual needs of clinical applications. Require.
  • commercially available PEEK powder is industrial grade and cannot meet the needs of medical devices.
  • CN 080814638A provides a preparation method and application of nanomaterial/polyetheretherketone composite material, which adopts the process of first solution dispersion, then grinding and dispersion, then high-speed dispersion, and then injection blending.
  • the nanomaterials and polyether ether ketone are uniformly dispersed through the dispersion liquid to obtain a blend, and then dried and ground and dispersed by grinding equipment, and then mixed evenly with the remaining polyether ether ketone through a high-speed mixer, and then extrusion processing is obtained.
  • New polyetheretherketone composite plastic particles introduces substances such as coupling agents in the solution dispersion step, thereby increasing the risk of materials and being unfavorable for application in the field of medical devices. The process is complex and time-consuming.
  • CN 110152068A provides a ball milling pretreatment to uniformly disperse nano-hydroxyapatite in polyether ether ketone, and then, after mixing, the mixture of nano-hydroxyapatite and polyether ether ketone is melted in a twin-screw extruder. mixed to further improve the concentration of nano-hydroxyapatite in polyetheretherketone Dispersion.
  • this method uses the ball milling method to grind and mix PEEK and hydroxyapatite.
  • the ball milling method is difficult to fully reduce the particle size of PEEK and achieve the purpose of fully mixing with hydroxyapatite. There is still uneven dispersion during the extrusion process. problem; on the other hand, the ball milling process will cause the temperature of PEEK to rise significantly, and the color and mechanical properties of the material will change to a certain extent.
  • the present invention provides a method for preparing a medical composite polymer material.
  • the medical composite polymer material includes polyaryletherketone and calcium-phosphorus materials.
  • the preparation method includes the following steps:
  • Polyaryl ether ketone powder and calcium-phosphorus material powder are co-extruded to form the medical composite polymer material.
  • the present invention uses freezing grinding technology to well maintain the The appearance and performance of the polyaryl ether ketone material itself can effectively reduce the particle size of polyaryl ether ketone, facilitate full mixing with calcium phosphorus material powder, and avoid problems such as impurity contamination caused by normal temperature grinding.
  • the polyaryl ether ketone is polyether ether ketone (PEEK).
  • PEEK polyether ether ketone
  • the embrittlement temperature of polyetheretherketone is usually, for example, between -80°C and -60°C.
  • the calcium-phosphorus material includes one or more of hydroxyapatite, ⁇ -tricalcium phosphate, ⁇ -tricalcium phosphate, tetracalcium phosphate and calcium oxide.
  • the calcium-phosphorus material is hydroxyapatite, or tricalcium phosphate, or a mixture of hydroxyapatite and tricalcium phosphate, or ⁇ -tricalcium phosphate, ⁇ -tricalcium phosphate, tetracalcium phosphate and calcium oxide A mixture of one or more of them and hydroxyapatite.
  • the mass percentage of hydroxyapatite in the mixture accounts for more than 80%. More preferably, the calcium-phosphorus ratio of the calcium-phosphorus material is within the range of 1.65 to 1.82 specified in ISO 13779-3.
  • the mass percentage of the calcium-phosphorus material in the total mass of the polyaryl ether ketone and the calcium-phosphorus material is 10% to 30%, preferably 15% to 20%.
  • the polyaryl ether ketone may also be polyether ketone (PEK), polyether ketone ketone (PEKK), polyether ether ketone ketone (PEEKK) and polyether ketone ether ketone ketone (PEKEKK).
  • the refining treatment under freezing conditions is freeze grinding.
  • the grinding speed of freeze grinding is 15000rpm-20000rpm, and the grinding time is 2-5 minutes.
  • the particle size of the calcium-phosphorus material used for mixing with the polyaryl ether ketone powder is 0.5 to 50 microns.
  • Low-temperature cooling of polyaryl ether ketone raw materials is preferably carried out using a cooling medium that is volatile, residue-free, and harmless to the human body.
  • the cooling medium is liquid nitrogen
  • the polyaryl ether ketone raw material is cooled in the liquid nitrogen for 1 to 5 minutes, so that the polyaryl ether ketone raw material is cooled to the embrittlement temperature.
  • refinement treatment is performed under freezing conditions in a temperature range of -150°C to -110°C (preferably -130°C). Polyaryl ether ketone powder is obtained through refinement treatment.
  • the cooling medium it may be considered to vacuum dry the polyaryletherketone powder obtained by the refinement treatment to remove the cooling medium and moisture. Vacuum drying is carried out at a temperature of 120°C to 180°C and a time of 4 to 8 hours.
  • the polyaryl ether ketone powder and the calcium phosphorus material powder are co-extruded through an extruder, and the polyaryl ether ketone powder and the calcium phosphorus material powder pass through different The feeding port enters the extruder.
  • twin-screw extruders use a single feeding port.
  • the mixed powder is difficult to mix evenly when entering the feeding port.
  • Calcium-phosphorus materials with small particle sizes often enter first, resulting in the agglomeration of calcium-phosphorus materials on the surface of the resulting calcium-phosphorus material-polyaryl ether ketone particles, which affects the appearance and reduces the mechanical properties.
  • the polyaryl ether ketone raw material in the present invention has been refined under freezing conditions.
  • the polyaryl ether ketone powder and the calcium phosphorus material powder enter the extruder through different feeding ports, which is beneficial to the calcium phosphorus material.
  • the dispersion uniformity of the material in polyaryl ether ketone and the obtaining of calcium phosphorus material-polyaryl ether ketone particles with stable and consistent performance.
  • This composite modification process enables hydroxyapatite to be evenly dispersed in polyetheretherketone, thus solving the technical problem of stress concentration due to the agglomeration effect of hydroxyapatite and ultimately resulting in a reduction in the mechanical properties of composite materials. It can improve biological activity. At the same time, the mechanical properties of polyetheretherketone/hydroxyapatite composite materials are further improved.
  • suitable particle size can be obtained Polyaryl ether ketone powder and calcium phosphorus material powder, so they can be directly injection molded.
  • hydroxyapatite and polyetheretherketone are used as raw materials, they are uniformly mixed while exposing the hydroxyapatite powder to
  • the surface of hydroxyapatite-polyetheretherketone (HA-PEEK) composite particles avoids the formation of a hydrophobic layer on the surface of products obtained by direct injection molding of hydroxyapatite (HA) and polyetheretherketone (PEEK). This hydrophobic layer limits Hydroxyapatite plays a biologically active role on the surface.
  • a medical composite polymer material prepared by the above preparation method of a medical composite polymer material is also provided.
  • Figure 1 schematically shows a flow chart of an implementation form of a method for preparing a medical composite polymer material according to the present invention.
  • PEEK polyetheretherketone
  • a calcium-phosphorus ratio of 1.65 to 1.82 containing hydroxyapatite (HA) and/or ⁇ -tricalcium phosphate ( ⁇ -TCP) and/or ⁇ -tricalcium phosphate and/or tetracalcium phosphate and/or oxidized Calcium calcium phosphorus material powder the calcium phosphorus material powder has a particle size of 0.5 to 50 microns. Then, the above-mentioned calcium-phosphorus material powder and PEEK powder are co-extruded through an extruder to form a medical composite polymer material.
  • the cutting tools used in the grinding process are all made of 316 stainless steel, and liquid nitrogen is used to control the temperature during the grinding process, no new substances will be produced or introduced during the grinding process, and no additives or other substances are introduced in other production processes, so in the The biocompatibility of the raw materials will not be changed during the entire production process of the above-mentioned medical composite polymer materials. Therefore, the biocompatibility of the medical-grade HA-PEEK materials produced accordingly fully complies with the national standard GB/T 16886.1-2011 "Biological Evaluation of Medical Devices Part 1: Risk Management Evaluation and Testing" provides regulations and requirements for cytotoxicity, sensitization, irritation or intradermal reaction, acute systemic toxicity, subchronic toxicity, genotoxicity and implantation testing.
  • PAEK raw material pellets are cooled to below the embrittlement temperature using liquid nitrogen as the cooling medium.
  • liquid nitrogen as the cooling medium.
  • the PAEK raw material is cooled to below the embrittlement temperature using liquid nitrogen as the cooling medium.
  • the obtained PAEK powder is vacuum-dried at a temperature of 120°C to 180°C for 4 to 8 hours.
  • calcium-phosphorus material powder with a calcium-phosphorus ratio of 1.65 to 1.82 and a particle size of 0.5-50 microns is provided, and the calcium-phosphorus material powder and PAEK powder are co-extruded through an extruder to form a medical composite polymer material.
  • PEEK polyetheretherketone
  • calcium-phosphorus material powder with a calcium-phosphorus ratio of 1.65 to 1.82 and a particle size of 0.5-50 microns is provided, and the calcium-phosphorus material powder and PEEK powder are co-extruded through an extruder to form a medical composite polymer material.
  • PEEK raw material pellets are cooled to below the embrittlement temperature using liquid nitrogen as the cooling medium. Then, using dry ice as the cooling medium, the PEEK raw material is freeze-ground at a temperature of -78.5°C to -57°C to obtain PEEK powder with a particle size of 50-800 microns. Then, the obtained PEEK powder is vacuum-dried at a temperature of 120°C to 180°C for 4 to 8 hours.
  • a calcium-phosphorus ratio of 1.65 to 1.82 containing hydroxyapatite (HA) and/or ⁇ -tricalcium phosphate ( ⁇ -TCP) and/or ⁇ -tricalcium phosphate and/or tetracalcium phosphate and/or oxidized Calcium calcium phosphorus material powder the calcium phosphorus material powder has a particle size of 0.5 to 50 microns. Then, the above-mentioned calcium-phosphorus material powder and PEEK powder are co-extruded through an extruder to form a medical composite polymer material.
  • PEEK polyetheretherketone
  • the calcium-phosphorus material powder and the PAEK powder are each supplied to the extruder through a feeding port and co-extruded by the extruder.
  • cryo-grinding process requires heat preservation. Both cryogenic cooling and freezing grinding are performed in a sealed container, and the input amount of the cooling medium used is controlled based on the real-time monitoring results of the temperature in the sealed container to ensure temperature conditions.
  • the above embodiments can also be implemented in a modified manner without adding cooling medium during the cryo-grinding process.
  • this may result in insufficient freezing of the material during the grinding process, which may cause the color of the resulting grinding powder to turn gray due to friction and heat generated between the polyaryletherketone material and the grinding tool, thereby affecting the appearance of the product.

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Mechanical Engineering (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Dermatology (AREA)
  • Medicinal Chemistry (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Epidemiology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Composite Materials (AREA)
  • Materials Engineering (AREA)
  • Inorganic Chemistry (AREA)
  • Materials For Medical Uses (AREA)

Abstract

The present invention relates to a preparation method for a medical composite polymer material. The medical composite polymer material comprises polyaryletherketone and a calcium phosphate material. The preparation method comprises the following steps: cooling a polyaryletherketone raw material to a temperature below a brittle temperature; performing fine treatment on the polyaryletherketone raw material under a freezing condition to obtain polyaryletherketone powder; and performing co-extrusion molding on the polyaryletherketone powder and calcium phosphate material powder to form the medical composite polymer material.

Description

医用复合高分子材料及其制备方法Medical composite polymer materials and preparation methods thereof 技术领域Technical field
本发明涉及一种医用复合高分子材料的制备方法，尤其是一种包含聚芳醚酮和钙磷材料的医用复合高分子材料的制备方法。The present invention relates to a method for preparing a medical composite polymer material, in particular to a method for preparing a medical composite polymer material containing polyaryletherketone and calcium-phosphorus materials.
背景技术Background technique
热塑性特种工程塑料聚醚醚酮(PEEK)的弹性模量与皮质骨弹性模量接近，尤其是碳纤维增强PEEK(CFR-PEEK)的弹性模量与皮质骨弹性模量更为匹配。这种接近或匹配的弹性模量一定程度上减弱或消除了应力屏蔽效应，进而减轻或避免了骨吸收，从而有利于植入体与骨组织之间的骨整合。因此，从20世纪80年代开始，PEEK受到材料学研究者和骨科学研究者越来越高的重视，有可能替代金属材料应用在硬组织修复与替换领域。PEEK可透过X射线，CT或MRI扫描时不产生伪影，因而较容易监控骨生长和愈合过程。此外，PEEK还具有良好的生物相容性、耐磨损、耐疲劳、耐腐蚀、易加工等特点。上述优点使PEEK广泛应用于创伤、脊柱和关节等领域。但PEEK本身不具备生物活性，不能与骨组织形成骨整合，这在一定程度上限制了其在组织修复与替换领域的应用。The elastic modulus of thermoplastic special engineering plastic polyetheretherketone (PEEK) is close to the elastic modulus of cortical bone, especially the elastic modulus of carbon fiber reinforced PEEK (CFR-PEEK) is more consistent with the elastic modulus of cortical bone. This close or matching elastic modulus weakens or eliminates the stress shielding effect to a certain extent, thereby reducing or avoiding bone absorption, thereby facilitating osseointegration between the implant and bone tissue. Therefore, since the 1980s, PEEK has received increasing attention from materials researchers and orthopedic researchers, and has the potential to replace metal materials in the field of hard tissue repair and replacement. PEEK is transparent to X-rays and does not produce artifacts during CT or MRI scans, making it easier to monitor bone growth and healing processes. In addition, PEEK also has good biocompatibility, wear resistance, fatigue resistance, corrosion resistance, and easy processing. The above advantages make PEEK widely used in the fields of trauma, spine and joints. However, PEEK itself does not have biological activity and cannot form osseointegration with bone tissue, which limits its application in the field of tissue repair and replacement to a certain extent.
面对这种不足，研究主要集中在通过改变PEEK表面结构或者是添加活性材料(如羟基磷灰石、生物活性玻璃等)来提高PEEK的生物活性及生物相容性，从而为植入体提供符合生物性能要求较好的材料。Faced with this shortcoming, research mainly focuses on improving the bioactivity and biocompatibility of PEEK by changing the surface structure of PEEK or adding active materials (such as hydroxyapatite, bioactive glass, etc.), thereby providing implants with Materials that meet better biological performance requirements.
羟基磷灰石[Ca10(PO4)6(OH)2]是最熟知的CaP材料，Ca/P比为1.67，羟基磷灰石晶体为六方晶系，微晶表面的OH-空缺时能够吸附PO43 -或大分子上的磷酸根基团或羟基基团，Ca离子位置空缺时能够吸附Sr3 +、K+等阳离子及蛋白质分子基团，PO43 -位于晶体表面时则H2O能够通过氢键与PO43 -离子结合。磷酸三钙[Ca3(PO4)2]的Ca/P比为1.5，具有接近于羟基磷灰石的钙磷比，在生理条件下溶解度较高。它们本身也是天然骨无机成分中的主要组成部分， 研究发现其还具有为药物或离子传递的载体，促进新骨、新生血管的再生的作用，这使其成为修复骨缺损的首选材料之一。除了出色的生物学表现外，羟基磷灰石较容易且廉价地生产，可以相对容易地开展于临床应用中，为骨组织工程的进一步发展带来了巨大希望。其他可用钙磷材料包括磷酸四钙和氧化钙等。Hydroxyapatite [Ca 10 (PO 4 ) 6 (OH) 2 ] is the most well-known CaP material, with a Ca/P ratio of 1.67. The hydroxyapatite crystal is a hexagonal crystal system, and when the OH - vacancies on the surface of the microcrystal are Adsorbs PO 43 - or phosphate groups or hydroxyl groups on macromolecules. When the Ca ion position is vacant, it can adsorb cations such as Sr 3 + and K + and protein molecular groups. When PO 43 - is located on the surface of the crystal, H 2 O can Combined with PO 43 - ions through hydrogen bonds. Tricalcium phosphate [Ca 3 (PO4) 2 ] has a Ca/P ratio of 1.5, has a calcium-phosphorus ratio close to that of hydroxyapatite, and has higher solubility under physiological conditions. They themselves are also the main components of the inorganic components of natural bone. Research has found that it can also serve as a carrier for drug or ion delivery and promote the regeneration of new bone and new blood vessels, making it one of the first choice materials for repairing bone defects. In addition to its excellent biological performance, hydroxyapatite is easy and cheap to produce and can be relatively easily implemented in clinical applications, bringing great hope for the further development of bone tissue engineering. Other useful calcium-phosphorus materials include tetracalcium phosphate and calcium oxide, among others.
羟基磷灰石粉末可以通过干法、化学沉淀法、溶胶-凝胶法、水热合成法、仿生溶液生长合成法等制备。Hydroxyapatite powder can be prepared by dry method, chemical precipitation method, sol-gel method, hydrothermal synthesis method, bionic solution growth synthesis method, etc.
目前PEEK在生产加工过程中主要是以粉料和粒料形式出现，市售的医用级PEEK仅存在粒料产品，与羟基磷灰石混合进行挤出或注塑，很难解决羟基磷灰石的粒子在PEEK基体中的均匀分散性问题，导致粒子在基体中大量团聚，其结果造成复合材料的力学性能尤其是拉伸强度严重降低，在临床应用中存在安全隐患，因而难以满足临床应用的实际要求。同时，市售PEEK粉料为工业级，不能满足医疗器械的需要。At present, PEEK mainly appears in the form of powder and pellets in the production and processing process. Commercially available medical grade PEEK only exists in pellet products, which are mixed with hydroxyapatite for extrusion or injection molding. It is difficult to solve the problem of hydroxyapatite. The uniform dispersion of particles in the PEEK matrix causes a large number of particles to agglomerate in the matrix. As a result, the mechanical properties of the composite material, especially the tensile strength, are seriously reduced, which poses safety risks in clinical applications and makes it difficult to meet the actual needs of clinical applications. Require. At the same time, commercially available PEEK powder is industrial grade and cannot meet the needs of medical devices.
目前业内生产出了含20％羟基磷灰石的PEEK棒材，线径约16mm，需要机加工切削才能使其中的羟基磷灰石暴露出来，因此，其产品线径和加工手段限制了其进入运动医学领域。At present, the industry has produced PEEK rods containing 20% hydroxyapatite, with a wire diameter of about 16mm. It requires machining and cutting to expose the hydroxyapatite. Therefore, its product wire diameter and processing methods limit its entry. The field of sports medicine.
CN 080814638A提供了一种纳米材料/聚醚醚酮复合材料的制备方法和应用，采用先溶液分散、再研磨分散、再高速分散、后注射共混的工艺。首先，通过分散液均匀分散纳米材料和聚醚醚酮得到共混物，然后烘干后经研磨设备研磨分散，再与其余聚醚醚酮通过高速搅拌机混合均匀，即可进行挤出加工，得到新型聚醚醚酮复合材料的塑料颗粒。该方法在溶液分散步骤引入了偶联剂等物质，因而增加了材料的风险，不利于在医疗器械领域的应用，并且流程复杂，时间成本高。CN 080814638A provides a preparation method and application of nanomaterial/polyetheretherketone composite material, which adopts the process of first solution dispersion, then grinding and dispersion, then high-speed dispersion, and then injection blending. First, the nanomaterials and polyether ether ketone are uniformly dispersed through the dispersion liquid to obtain a blend, and then dried and ground and dispersed by grinding equipment, and then mixed evenly with the remaining polyether ether ketone through a high-speed mixer, and then extrusion processing is obtained. New polyetheretherketone composite plastic particles. This method introduces substances such as coupling agents in the solution dispersion step, thereby increasing the risk of materials and being unfavorable for application in the field of medical devices. The process is complex and time-consuming.
CN 110152068A提供了通过球磨预处理使得纳米羟基磷灰石在聚醚醚酮中均匀分散，然后，混匀后纳米羟基磷灰石和聚醚醚酮混合物在双螺杆挤出机中通过熔融进行二次混合，进一步提高纳米羟基磷灰石在聚醚醚酮中的 分散性。然而，该方法利用球磨方法研磨混合PEEK和羟基磷灰石，一方面球磨方法很难充分降低PEEK的粒径，达到与羟基磷灰石混合充分的目的，在挤出过程中仍然存在分散不匀的问题；另一方面，球磨过程会导致PEEK温度显著升高，材料的颜色和力学性能等发生一定程度的改变。CN 110152068A provides a ball milling pretreatment to uniformly disperse nano-hydroxyapatite in polyether ether ketone, and then, after mixing, the mixture of nano-hydroxyapatite and polyether ether ketone is melted in a twin-screw extruder. mixed to further improve the concentration of nano-hydroxyapatite in polyetheretherketone Dispersion. However, this method uses the ball milling method to grind and mix PEEK and hydroxyapatite. On the one hand, the ball milling method is difficult to fully reduce the particle size of PEEK and achieve the purpose of fully mixing with hydroxyapatite. There is still uneven dispersion during the extrusion process. problem; on the other hand, the ball milling process will cause the temperature of PEEK to rise significantly, and the color and mechanical properties of the material will change to a certain extent.
因此，希望能够提供一种能够将市售的医用级PEEK粒料产品和羟基磷灰石精细化并充分混合、实现均匀分散、表面暴露充分，且不引入其他杂质、因而产品性能优良的医用复合高分子材料制备方法。Therefore, it is hoped to provide a medical composite product that can refine and fully mix commercially available medical-grade PEEK granular products and hydroxyapatite, achieve uniform dispersion, fully expose the surface, and do not introduce other impurities, so the product performance is excellent. Polymer material preparation methods.
发明内容Contents of the invention
为此，本发明提供了一种医用复合高分子材料的制备方法，所述医用复合高分子材料包含聚芳醚酮和钙磷材料，该制备方法包括以下步骤：To this end, the present invention provides a method for preparing a medical composite polymer material. The medical composite polymer material includes polyaryletherketone and calcium-phosphorus materials. The preparation method includes the following steps:
将聚芳醚酮原料低温冷却至脆化温度以下；Cool the polyaryl ether ketone raw material at low temperature to below the embrittlement temperature;
对聚芳醚酮原料进行冷冻条件下的精细化处理，以得到聚芳醚酮粉末；Perform refinement treatment on polyaryl ether ketone raw materials under freezing conditions to obtain polyaryl ether ketone powder;
将聚芳醚酮粉末与钙磷材料粉末共挤出成型，形成所述医用复合高分子材料。Polyaryl ether ketone powder and calcium-phosphorus material powder are co-extruded to form the medical composite polymer material.
由于在冷冻条件下对聚芳醚酮原料进行精细化处理，因此能够在市售的聚芳醚酮粒料产品的基础上首先得到符合精细尺寸要求的聚芳醚酮粉末，然后使聚芳醚酮粉末和钙磷材料粉末通过挤出机的两个喂料口分别进入挤出机，在挤出机内混合后共挤出成型。Due to the fine processing of the polyaryl ether ketone raw materials under freezing conditions, it is possible to first obtain polyaryl ether ketone powder that meets the fine size requirements based on commercially available polyaryl ether ketone pellet products, and then make the polyaryl ether ketone Ketone powder and calcium-phosphorus material powder enter the extruder respectively through the two feeding ports of the extruder, are mixed in the extruder and then co-extruded.
若研磨过程中不对材料进行冷冻，由于聚芳醚酮材料与刀具之间摩擦生热，所得研磨粉料颜色会变成灰色，影响产品的外观，而本发明利用冷冻研磨技术很好地保持了聚芳醚酮材料本身的外观与性能，有效降低聚芳醚酮的粒径，便于与钙磷材料粉末的充分混合，且能避免常温研磨导致的杂质污染等问题。If the material is not frozen during the grinding process, due to the friction and heat generated between the polyaryl ether ketone material and the cutter, the color of the resulting grinding powder will turn gray, affecting the appearance of the product. However, the present invention uses freezing grinding technology to well maintain the The appearance and performance of the polyaryl ether ketone material itself can effectively reduce the particle size of polyaryl ether ketone, facilitate full mixing with calcium phosphorus material powder, and avoid problems such as impurity contamination caused by normal temperature grinding.
优选的是，所述聚芳醚酮是聚醚醚酮(PEEK)。聚醚醚酮的脆化温度通常在例如-80℃～-60℃之间。进一步优选的是，所述钙磷材料包含羟基磷灰石、α-磷酸三钙、β-磷酸三钙、磷酸四钙和氧化钙中的一种或几种。优选的是， 所述钙磷材料是羟基磷灰石、或者是磷酸三钙、或者是羟基磷灰石和磷酸三钙的混合物、或者是α-磷酸三钙、β-磷酸三钙、磷酸四钙和氧化钙中的一种或几种与羟基磷灰石的混合物。在混合物含有羟基磷灰石时，羟基磷灰石在混合物中的质量百分比占比80％以上。更优选的是，钙磷材料的钙磷比优选在ISO 13779-3所规定的1.65～1.82的范围内。还优选的是，钙磷材料占聚芳醚酮与钙磷材料的总质量的质量百分比为10％～30％，优选15％～20％。作为替代或补充，所述聚芳醚酮是也可以是聚醚酮(PEK)、聚醚酮酮(PEKK)、聚醚醚酮酮(PEEKK)和聚醚酮醚酮酮(PEKEKK)。Preferably, the polyaryl ether ketone is polyether ether ketone (PEEK). The embrittlement temperature of polyetheretherketone is usually, for example, between -80°C and -60°C. It is further preferred that the calcium-phosphorus material includes one or more of hydroxyapatite, α-tricalcium phosphate, β-tricalcium phosphate, tetracalcium phosphate and calcium oxide. Preferably, The calcium-phosphorus material is hydroxyapatite, or tricalcium phosphate, or a mixture of hydroxyapatite and tricalcium phosphate, or α-tricalcium phosphate, β-tricalcium phosphate, tetracalcium phosphate and calcium oxide A mixture of one or more of them and hydroxyapatite. When the mixture contains hydroxyapatite, the mass percentage of hydroxyapatite in the mixture accounts for more than 80%. More preferably, the calcium-phosphorus ratio of the calcium-phosphorus material is within the range of 1.65 to 1.82 specified in ISO 13779-3. It is also preferred that the mass percentage of the calcium-phosphorus material in the total mass of the polyaryl ether ketone and the calcium-phosphorus material is 10% to 30%, preferably 15% to 20%. Alternatively or additionally, the polyaryl ether ketone may also be polyether ketone (PEK), polyether ketone ketone (PEKK), polyether ether ketone ketone (PEEKK) and polyether ketone ether ketone ketone (PEKEKK).
优选的是，冷冻条件下的精细化处理是冷冻研磨。例如，冷冻研磨的研磨转速为15000rpm-20000rpm，研磨时间为2-5分钟。Preferably, the refining treatment under freezing conditions is freeze grinding. For example, the grinding speed of freeze grinding is 15000rpm-20000rpm, and the grinding time is 2-5 minutes.
优选的是，用于与聚芳醚酮粉末混合的钙磷材料的粒径为0.5～50微米。Preferably, the particle size of the calcium-phosphorus material used for mixing with the polyaryl ether ketone powder is 0.5 to 50 microns.
聚芳醚酮原料的低温冷却优选采用易挥发、无残留、对人体无害的冷却介质进行。根据本发明的一种优选实施形式，冷却介质为液氮，聚芳醚酮原料在液氮内冷却1～5分钟，使聚芳醚酮原料冷却到脆化温度下。然后，在-150℃～-110℃(优选-130℃)的温度范围的冷冻条件下进行精细化处理。精细化处理得到聚芳醚酮粉末。此时，根据所用冷却介质的特性，可以考虑对精细化处理所得到的聚芳醚酮粉末进行真空干燥，去除其中的冷却介质及水分。真空干燥在温度120℃～180℃进行，时间4～8小时。Low-temperature cooling of polyaryl ether ketone raw materials is preferably carried out using a cooling medium that is volatile, residue-free, and harmless to the human body. According to a preferred embodiment of the present invention, the cooling medium is liquid nitrogen, and the polyaryl ether ketone raw material is cooled in the liquid nitrogen for 1 to 5 minutes, so that the polyaryl ether ketone raw material is cooled to the embrittlement temperature. Then, refinement treatment is performed under freezing conditions in a temperature range of -150°C to -110°C (preferably -130°C). Polyaryl ether ketone powder is obtained through refinement treatment. At this time, depending on the characteristics of the cooling medium used, it may be considered to vacuum dry the polyaryletherketone powder obtained by the refinement treatment to remove the cooling medium and moisture. Vacuum drying is carried out at a temperature of 120°C to 180°C and a time of 4 to 8 hours.
作为替代或补充，还可以在下列表1所列常见实验室冷浴所采用的物质中选择无残留且对人体无害的组合将聚芳醚酮原料冷却到其例如-80℃～-60℃之间的脆化温度下：As an alternative or supplement, you can also choose a residue-free and harmless combination from the substances used in common laboratory cold baths listed in Table 1 below to cool the polyaryl ether ketone raw material to a temperature between -80°C and -60°C, for example. At the embrittlement temperature between:
表1:常见实验室冷浴的冷却温度

Table 1: Cooling temperatures for common laboratory cold baths

根据本发明的医用复合高分子材料的制备方法的一种优选实施形式，聚芳醚酮粉末与钙磷材料粉末通过挤出机共挤出成型，聚芳醚酮粉末与钙磷材料粉末通过不同的喂料口进入挤出机。现有技术下，双螺杆挤出机采用单一的喂料口。但是由于钙磷材料和研磨的聚芳醚酮粉末粒径差异极大(钙磷材料约10微米，聚芳醚酮粉末约400微米)，其混合粉末很难均匀混合，在进入喂料口时往往粒径小的钙磷材料先进入，导致所得钙磷材料-聚芳醚酮的颗粒表面存在钙磷材料团聚现象，影响外观并降低力学性能。相比之下，本发明中的聚芳醚酮原料在冷冻条件下经过精细化处理得到的聚芳醚酮粉末与钙磷材料粉末通过不同的喂料口进入挤出机，这有利于钙磷材料在聚芳醚酮中的分散均匀性和获得性能稳定一致的钙磷材料-聚芳醚酮颗粒。这种复合改性工艺使羟基磷灰石均匀分散在聚醚醚酮中，从而解决了由于羟基磷灰石的团聚效应造成应力集中并最终导致复合材料力学性能降低的技术难题，在提升生物活性的同时进一步提高了聚醚醚酮/羟基磷灰石复合材料的力学性能。According to a preferred implementation form of the preparation method of the medical composite polymer material of the present invention, the polyaryl ether ketone powder and the calcium phosphorus material powder are co-extruded through an extruder, and the polyaryl ether ketone powder and the calcium phosphorus material powder pass through different The feeding port enters the extruder. Under the existing technology, twin-screw extruders use a single feeding port. However, due to the huge difference in particle size between calcium phosphorus material and ground polyaryl ether ketone powder (calcium phosphorus material is about 10 microns, polyaryl ether ketone powder is about 400 microns), the mixed powder is difficult to mix evenly when entering the feeding port. Calcium-phosphorus materials with small particle sizes often enter first, resulting in the agglomeration of calcium-phosphorus materials on the surface of the resulting calcium-phosphorus material-polyaryl ether ketone particles, which affects the appearance and reduces the mechanical properties. In contrast, the polyaryl ether ketone raw material in the present invention has been refined under freezing conditions. The polyaryl ether ketone powder and the calcium phosphorus material powder enter the extruder through different feeding ports, which is beneficial to the calcium phosphorus material. The dispersion uniformity of the material in polyaryl ether ketone and the obtaining of calcium phosphorus material-polyaryl ether ketone particles with stable and consistent performance. This composite modification process enables hydroxyapatite to be evenly dispersed in polyetheretherketone, thus solving the technical problem of stress concentration due to the agglomeration effect of hydroxyapatite and ultimately resulting in a reduction in the mechanical properties of composite materials. It can improve biological activity. At the same time, the mechanical properties of polyetheretherketone/hydroxyapatite composite materials are further improved.
使用本发明的医用复合高分子材料的制备方法，可以获得合适粒径尺寸 的聚芳醚酮粉末与钙磷材料粉末，因而可以以它们直接注塑，当以羟基磷灰石和聚醚醚酮为原料时，在使它们均匀混合的同时，使羟基磷灰石粉末暴露于羟基磷灰石-聚醚醚酮(HA-PEEK)复合颗粒表面，因而避免了羟基磷灰石(HA)与聚醚醚酮(PEEK)直接注塑所得制品在表面形成疏水层，该疏水层限制了羟基磷灰石在表面发挥生物活性的作用。Using the preparation method of the medical composite polymer material of the present invention, suitable particle size can be obtained Polyaryl ether ketone powder and calcium phosphorus material powder, so they can be directly injection molded. When hydroxyapatite and polyetheretherketone are used as raw materials, they are uniformly mixed while exposing the hydroxyapatite powder to The surface of hydroxyapatite-polyetheretherketone (HA-PEEK) composite particles avoids the formation of a hydrophobic layer on the surface of products obtained by direct injection molding of hydroxyapatite (HA) and polyetheretherketone (PEEK). This hydrophobic layer limits Hydroxyapatite plays a biologically active role on the surface.
根据本发明的另一方面，还提供了一种以上述医用复合高分子材料的制备方法制备的医用复合高分子材料。According to another aspect of the present invention, a medical composite polymer material prepared by the above preparation method of a medical composite polymer material is also provided.
附图说明Description of drawings
图1示意地示出了根据本发明的医用复合高分子材料的制备方法的一种实施形式的流程图。Figure 1 schematically shows a flow chart of an implementation form of a method for preparing a medical composite polymer material according to the present invention.
具体实施方式Detailed ways
下面结合附图对本发明进行详细说明，附图仅用于解释本发明，不能理解为对本发明的限制。The present invention will be described in detail below with reference to the accompanying drawings, which are only used to explain the present invention and cannot be understood as limiting the present invention.
实施例一Embodiment 1
如图1所示，首先，以液氮作为冷却介质，将市售的医用级聚醚醚酮(PEEK)原料粒料颗粒低温冷却至脆化温度以下。继续以液氮作为冷却介质，在-150℃～-110℃的温度条件下，通过对PEEK原料进行冷冻研磨，实现精细化处理，以得到粒径在50-800微米的PEEK粉末。然后，在温度120℃～180℃的温度条件下对所得到的PEEK粉末进行4～8小时的真空干燥。同时，提供钙磷比为1.65～1.82的包含羟基磷灰石(HA)和/或β-磷酸三钙(β-TCP)和/或α-磷酸三钙和/或磷酸四钙和/或氧化钙的钙磷材料粉末，钙磷材料粉末具有0.5～50微米的粒径。然后，通过挤出机将上述钙磷材料粉末与PEEK粉末共挤出成型，形成医用复合高分子材料。As shown in Figure 1, first, commercially available medical-grade polyetheretherketone (PEEK) raw material pellets are cooled to below the embrittlement temperature using liquid nitrogen as the cooling medium. Continue to use liquid nitrogen as the cooling medium and freeze-grind the PEEK raw material at a temperature of -150°C to -110°C to achieve refinement to obtain PEEK powder with a particle size of 50-800 microns. Then, the obtained PEEK powder is vacuum-dried at a temperature of 120°C to 180°C for 4 to 8 hours. At the same time, provide a calcium-phosphorus ratio of 1.65 to 1.82 containing hydroxyapatite (HA) and/or β-tricalcium phosphate (β-TCP) and/or α-tricalcium phosphate and/or tetracalcium phosphate and/or oxidized Calcium calcium phosphorus material powder, the calcium phosphorus material powder has a particle size of 0.5 to 50 microns. Then, the above-mentioned calcium-phosphorus material powder and PEEK powder are co-extruded through an extruder to form a medical composite polymer material.
经检验证明，根据本发明的方法所制备的医用复合高分子材料(HA-PEEK)的性能参数完全达到PEEK的有关材料标准，详见表2: It has been proved by inspection that the performance parameters of the medical composite polymer material (HA-PEEK) prepared according to the method of the present invention fully meet the relevant material standards of PEEK. See Table 2 for details:
表2:HA-PEEK实测数据
Table 2: HA-PEEK measured data
在此，由于研磨工序所用刀具均为316不锈钢材质，研磨过程中又采用液氮控制温度，因而研磨过程不会产生或引入新的物质，并且其它生产工序没有助剂或其他物质引入，因此在上述医用复合高分子材料的整个生产过程中不会对原材料的生物相容性进行改变，因此，据此生产的医用级HA-PEEK材料的生物相容性完全符合国家标准GB/T 16886.1-2011《医疗器械生物学评价第1部分：风险管理评价与试验》有关细胞毒性、致敏、刺激或皮内反应、急性全身毒性、亚慢性毒性、遗传毒性和植入试验的规定和要求。Here, since the cutting tools used in the grinding process are all made of 316 stainless steel, and liquid nitrogen is used to control the temperature during the grinding process, no new substances will be produced or introduced during the grinding process, and no additives or other substances are introduced in other production processes, so in the The biocompatibility of the raw materials will not be changed during the entire production process of the above-mentioned medical composite polymer materials. Therefore, the biocompatibility of the medical-grade HA-PEEK materials produced accordingly fully complies with the national standard GB/T 16886.1-2011 "Biological Evaluation of Medical Devices Part 1: Risk Management Evaluation and Testing" provides regulations and requirements for cytotoxicity, sensitization, irritation or intradermal reaction, acute systemic toxicity, subchronic toxicity, genotoxicity and implantation testing.
实施例二Embodiment 2
首先，以液氮作为冷却介质，将市售的医用级聚芳醚酮(PAEK)原料粒料颗粒低温冷却至脆化温度以下。继续以液氮作为冷却介质，在-130℃的温度条件下，对PAEK原料进行冷冻研磨，以得到粒径在50-800微米的PAEK粉末。然后，在温度120℃～180℃的温度条件下对所得到的PAEK粉末进行4～8小时的真空干燥。然后，提供钙磷比为1.65～1.82、粒径为0.5～50微米的钙磷材料粉末，通过挤出机将上述钙磷材料粉末与PAEK粉末共挤出成型，形成医用复合高分子材料。First, commercially available medical-grade polyaryl ether ketone (PAEK) raw material pellets are cooled to below the embrittlement temperature using liquid nitrogen as the cooling medium. Continue to use liquid nitrogen as the cooling medium and freeze-grind the PAEK raw material at a temperature of -130°C to obtain PAEK powder with a particle size of 50-800 microns. Then, the obtained PAEK powder is vacuum-dried at a temperature of 120°C to 180°C for 4 to 8 hours. Then, calcium-phosphorus material powder with a calcium-phosphorus ratio of 1.65 to 1.82 and a particle size of 0.5-50 microns is provided, and the calcium-phosphorus material powder and PAEK powder are co-extruded through an extruder to form a medical composite polymer material.
实施例三Embodiment 3
首先，以干冰作为冷却介质，将市售的医用级聚醚醚酮(PEEK)原料粒料颗粒低温冷却至脆化温度以下。继续以干冰作为冷却介质，在 -78.5℃～-57℃的温度条件下，通过对PEEK原料进行冷冻研磨，实现精细化处理，以得到粒径在50-800微米的PEEK粉末。然后，在温度120℃～180℃的温度条件下对所得到的PEEK粉末进行4～8小时的真空干燥。然后，提供钙磷比为1.65～1.82、粒径为0.5～50微米的钙磷材料粉末，通过挤出机将上述钙磷材料粉末与PEEK粉末共挤出成型，形成医用复合高分子材料。First, commercially available medical-grade polyetheretherketone (PEEK) raw material pellets are cooled to below the embrittlement temperature using dry ice as the cooling medium. Continue to use dry ice as the cooling medium. Under temperature conditions of -78.5°C to -57°C, the PEEK raw material is frozen and ground to achieve refinement to obtain PEEK powder with a particle size of 50-800 microns. Then, the obtained PEEK powder is vacuum-dried at a temperature of 120°C to 180°C for 4 to 8 hours. Then, calcium-phosphorus material powder with a calcium-phosphorus ratio of 1.65 to 1.82 and a particle size of 0.5-50 microns is provided, and the calcium-phosphorus material powder and PEEK powder are co-extruded through an extruder to form a medical composite polymer material.
实施例四Embodiment 4
首先，以液氮作为冷却介质，将市售的医用级聚醚醚酮(PEEK)原料粒料颗粒低温冷却至脆化温度以下。然后，以干冰作为冷却介质，在-78.5℃～-57℃的温度条件下，对PEEK原料进行冷冻研磨，以得到粒径在50-800微米的PEEK粉末。然后，在温度120℃～180℃的温度条件下对所得到的PEEK粉末进行4～8小时的真空干燥。同时，提供钙磷比为1.65～1.82的包含羟基磷灰石(HA)和/或β-磷酸三钙(β-TCP)和/或α-磷酸三钙和/或磷酸四钙和/或氧化钙的钙磷材料粉末，钙磷材料粉末具有0.5～50微米的粒径。然后，通过挤出机将上述钙磷材料粉末与PEEK粉末共挤出成型，形成医用复合高分子材料。First, commercially available medical-grade polyetheretherketone (PEEK) raw material pellets are cooled to below the embrittlement temperature using liquid nitrogen as the cooling medium. Then, using dry ice as the cooling medium, the PEEK raw material is freeze-ground at a temperature of -78.5°C to -57°C to obtain PEEK powder with a particle size of 50-800 microns. Then, the obtained PEEK powder is vacuum-dried at a temperature of 120°C to 180°C for 4 to 8 hours. At the same time, provide a calcium-phosphorus ratio of 1.65 to 1.82 containing hydroxyapatite (HA) and/or β-tricalcium phosphate (β-TCP) and/or α-tricalcium phosphate and/or tetracalcium phosphate and/or oxidized Calcium calcium phosphorus material powder, the calcium phosphorus material powder has a particle size of 0.5 to 50 microns. Then, the above-mentioned calcium-phosphorus material powder and PEEK powder are co-extruded through an extruder to form a medical composite polymer material.
实施例五Embodiment 5
首先，以干冰作为冷却介质，将市售的医用级聚醚醚酮(PEEK)原料粒料颗粒低温冷却至脆化温度以下。然后，以液氮作为冷却介质，在-150℃～-110℃的温度条件下，对PEEK原料进行冷冻研磨，以得到粒径在50-800微米的PEEK粉末。然后，在温度120℃～180℃的温度条件下对所得到的PEEK粉末进行4～8小时的真空干燥。然后，提供钙磷比为1.65～1.82、粒径为0.5～50微米的钙磷材料粉末，形成医用复合高分子材料。First, commercially available medical-grade polyetheretherketone (PEEK) raw material pellets are cooled to below the embrittlement temperature using dry ice as the cooling medium. Then, using liquid nitrogen as the cooling medium, the PEEK raw material is freeze-ground at a temperature of -150°C to -110°C to obtain PEEK powder with a particle size of 50-800 microns. Then, the obtained PEEK powder is vacuum-dried at a temperature of 120°C to 180°C for 4 to 8 hours. Then, calcium-phosphorus material powder with a calcium-phosphorus ratio of 1.65 to 1.82 and a particle size of 0.5 to 50 microns is provided to form a medical composite polymer material.
在上述各实施例中，将钙磷材料粉末与PAEK粉末分别各通过一个喂料口提供到挤出机内并由挤出机共挤出成型。这避免了单一喂料口的挤出机结构中因粒径相对较小的钙磷材料更易于进入挤出机而造成的团聚现象，从而有利于钙磷材料在聚芳醚酮中的分散均匀性，确保获得性能稳定一致的钙磷材料-聚芳醚酮颗粒 In each of the above embodiments, the calcium-phosphorus material powder and the PAEK powder are each supplied to the extruder through a feeding port and co-extruded by the extruder. This avoids the agglomeration phenomenon caused by the relatively small particle size of calcium and phosphorus materials in the extruder structure with a single feeding port, which is easier to enter the extruder, thereby facilitating the uniform dispersion of calcium and phosphorus materials in polyaryl ether ketone. properties to ensure the availability of calcium-phosphorus materials with stable and consistent performance - polyaryl ether ketone particles
在上述各实施例中，冷冻研磨过程需保温。低温冷却及冷冻研磨均在密封容器中进行，并根据对密封容器内温度的实时监测结果控制所使用的冷却介质的输入量，以确保温度条件。In each of the above embodiments, the cryo-grinding process requires heat preservation. Both cryogenic cooling and freezing grinding are performed in a sealed container, and the input amount of the cooling medium used is controlled based on the real-time monitoring results of the temperature in the sealed container to ensure temperature conditions.
亦可以变化地实施上述各实施例而在冷冻研磨过程中不再添加冷却介质。但由此或导致研磨过程中材料冷冻不充分，从而可能由于聚芳醚酮材料与研磨刀具之间的摩擦生热而使所得研磨粉料颜色变成灰色，从而影响产品的外观。The above embodiments can also be implemented in a modified manner without adding cooling medium during the cryo-grinding process. However, this may result in insufficient freezing of the material during the grinding process, which may cause the color of the resulting grinding powder to turn gray due to friction and heat generated between the polyaryletherketone material and the grinding tool, thereby affecting the appearance of the product.
以上记载了本发明的优选实施例，但是本发明的精神和范围不限于这里所公开的具体内容。本领域技术人员能够根据本发明的教导任意组合和扩展上述各实施例而在本发明的精神和范围内做出更多的实施方式和应用。本发明的精神和范围不由具体实施例来限定，而由权利要求来限定。 The preferred embodiments of the present invention have been described above, but the spirit and scope of the present invention are not limited to the specific contents disclosed here. Those skilled in the art can arbitrarily combine and expand the above-described embodiments based on the teachings of the present invention to make more implementations and applications within the spirit and scope of the present invention. The spirit and scope of the present invention are not limited by the specific embodiments, but by the claims.

Claims (24)

  1. 一种医用复合高分子材料的制备方法，所述医用复合高分子材料包含聚芳醚酮和钙磷材料，所述制备方法包括以下步骤：A method for preparing a medical composite polymer material. The medical composite polymer material contains polyaryl ether ketone and calcium phosphorus material. The preparation method includes the following steps:
    将所述聚芳醚酮原料低温冷却至脆化温度以下；Low-temperature cooling of the polyaryl ether ketone raw material to below the embrittlement temperature;
    对所述聚芳醚酮原料进行冷冻条件下的精细化处理，以得到聚芳醚酮粉末；The polyaryl ether ketone raw material is subjected to refinement treatment under freezing conditions to obtain polyaryl ether ketone powder;
    将所述聚芳醚酮粉末与钙磷材料粉末共挤出成型，形成所述医用复合高分子材料。The polyaryl ether ketone powder and the calcium phosphorus material powder are co-extruded to form the medical composite polymer material.
  2. 根据权利要求1所述的医用复合高分子材料的制备方法，其特征在于，所述聚芳醚酮是聚醚醚酮。The method for preparing medical composite polymer materials according to claim 1, wherein the polyaryl ether ketone is polyether ether ketone.
  3. 根据权利要求2所述的医用复合高分子材料的制备方法，其特征在于，所述钙磷材料包含羟基磷灰石、α-磷酸三钙、β-磷酸三钙、磷酸四钙和氧化钙中的一种或几种。The method for preparing medical composite polymer materials according to claim 2, wherein the calcium-phosphorus material contains hydroxyapatite, α-tricalcium phosphate, β-tricalcium phosphate, tetracalcium phosphate and calcium oxide. one or more types.
  4. 根据权利要求3所述的医用复合高分子材料的制备方法，其特征在于，所述钙磷材料是羟基磷灰石或β-磷酸三钙。The method for preparing medical composite polymer materials according to claim 3, wherein the calcium-phosphorus material is hydroxyapatite or β-tricalcium phosphate.
  5. 根据权利要求3所述的医用复合高分子材料的制备方法，其特征在于，所述钙磷材料是α-磷酸三钙、β-磷酸三钙、磷酸四钙和氧化钙中的一种或几种与羟基磷灰石的混合物。The method for preparing medical composite polymer materials according to claim 3, wherein the calcium-phosphorus material is one or more of α-tricalcium phosphate, β-tricalcium phosphate, tetracalcium phosphate and calcium oxide. A mixture of hydroxyapatite and hydroxyapatite.
  6. 根据权利要求5所述的医用复合高分子材料的制备方法，其特征在于，所述钙磷材料是羟基磷灰石和β-磷酸三钙的混合物。The method for preparing a medical composite polymer material according to claim 5, wherein the calcium-phosphorus material is a mixture of hydroxyapatite and β-tricalcium phosphate.
  7. 根据权利要求5或6所述的医用复合高分子材料的制备方法，其特征在于，羟基磷灰石在所述混合物中的质量百分比占比80％以上。The method for preparing a medical composite polymer material according to claim 5 or 6, wherein the mass percentage of hydroxyapatite in the mixture is more than 80%.
  8. 根据权利要求1至3中任一项所述的医用复合高分子材料的制备方 法，其特征在于，对精细化处理所得到的所述聚芳醚酮粉末进行真空干燥。Preparation method of medical composite polymer material according to any one of claims 1 to 3 The method is characterized in that the polyaryl ether ketone powder obtained by the refinement treatment is vacuum dried.
  9. 根据权利要求8所述的医用复合高分子材料的制备方法，其特征在于，所述真空干燥在温度120℃～180℃进行，时间4～8小时。The method for preparing medical composite polymer materials according to claim 8, characterized in that the vacuum drying is performed at a temperature of 120°C to 180°C and a time of 4 to 8 hours.
  10. 根据权利要求8或9所述的医用复合高分子材料的制备方法，其特征在于，聚芳醚酮粉末与钙磷材料粉末通过挤出机共挤出成型，聚芳醚酮粉末与钙磷材料粉末通过不同的喂料口进入所述挤出机。The method for preparing medical composite polymer materials according to claim 8 or 9, characterized in that the polyaryl ether ketone powder and the calcium phosphorus material powder are co-extruded through an extruder, and the polyaryl ether ketone powder and the calcium phosphorus material Powder enters the extruder through different feed ports.
  11. 根据权利要求1至3中任一项所述的医用复合高分子材料的制备方法，其特征在于，在低温冷却和精细化处理聚芳醚酮原料的步骤中，采用易挥发、无残留、对人体无害的冷却介质。The method for preparing medical composite polymer materials according to any one of claims 1 to 3, characterized in that in the steps of low-temperature cooling and fine processing of polyaryl ether ketone raw materials, volatile, residue-free, and A harmless cooling medium for the human body.
  12. 根据权利要求11所述的医用复合高分子材料的制备方法，其特征在于，所述冷却介质是液氮或干冰，聚芳醚酮原料在所述冷却介质内低温冷却至脆化温度以下的冷却时间为1～5分钟。The method for preparing medical composite polymer materials according to claim 11, wherein the cooling medium is liquid nitrogen or dry ice, and the polyaryl ether ketone raw material is cooled in the cooling medium to a temperature below the embrittlement temperature. The time is 1 to 5 minutes.
  13. 根据权利要求12所述的医用复合高分子材料的制备方法，其特征在于，所述冷却介质是液氮，冷冻条件下的精细化处理在-150℃～-110℃的温度范围内进行。The method for preparing medical composite polymer materials according to claim 12, wherein the cooling medium is liquid nitrogen, and the refining treatment under freezing conditions is performed in the temperature range of -150°C to -110°C.
  14. 根据权利要求13所述的医用复合高分子材料的制备方法，其特征在于，冷冻条件下的精细化处理在-130℃的温度进行。The method for preparing medical composite polymer materials according to claim 13, characterized in that the refining treatment under freezing conditions is performed at a temperature of -130°C.
  15. 根据权利要求12所述的医用复合高分子材料的制备方法，其特征在于，所述冷却介质是干冰，冷冻条件下的精细化处理在-78.5℃～-57℃的温度范围内进行。The method for preparing medical composite polymer materials according to claim 12, wherein the cooling medium is dry ice, and the refining treatment under freezing conditions is carried out in a temperature range of -78.5°C to -57°C.
  16. 根据权利要求1至3中任一项所述的医用复合高分子材料的制备方法，其特征在于，所述精细化处理是冷冻研磨。 The method for preparing medical composite polymer materials according to any one of claims 1 to 3, wherein the refining treatment is freeze grinding.
  17. 根据权利要求16所述的医用复合高分子材料的制备方法，其特征在于，所述冷冻研磨的研磨转速为15000rpm-20000rpm，研磨时间为2-5分钟。The method for preparing medical composite polymer materials according to claim 16, characterized in that the grinding speed of the freeze grinding is 15000rpm-20000rpm, and the grinding time is 2-5 minutes.
  18. 根据权利要求1至3中任一项所述的医用复合高分子材料的制备方法，其特征在于，所述钙磷材料粉末的粒径为0.5～50微米。The method for preparing medical composite polymer materials according to any one of claims 1 to 3, wherein the particle size of the calcium-phosphorus material powder is 0.5 to 50 microns.
  19. 根据权利要求1至3中任一项所述的医用复合高分子材料的制备方法，其特征在于，所述钙磷材料占聚芳醚酮与钙磷材料的总质量的质量百分比为10％～30％。The method for preparing a medical composite polymer material according to any one of claims 1 to 3, wherein the mass percentage of the calcium-phosphorus material to the total mass of the polyaryl ether ketone and the calcium-phosphorus material is 10% to 30%.
  20. 根据权利要求19所述的医用复合高分子材料的制备方法，其特征在于，所述钙磷材料占聚芳醚酮与钙磷材料的总质量的质量百分比为15％～20％。The method for preparing a medical composite polymer material according to claim 19, wherein the mass percentage of the calcium-phosphorus material to the total mass of the polyaryl ether ketone and the calcium-phosphorus material is 15% to 20%.
  21. 根据权利要求1至3中任一项所述的医用复合高分子材料的制备方法，其特征在于，所述钙磷材料的钙磷比在1.65～1.82的范围。The method for preparing a medical composite polymer material according to any one of claims 1 to 3, wherein the calcium to phosphorus material has a calcium to phosphorus ratio in the range of 1.65 to 1.82.
  22. 根据权利要求1至3中任一项所述的医用复合高分子材料的制备方法，其特征在于，冷冻条件下的精细化处理在保温条件下进行。The method for preparing medical composite polymer materials according to any one of claims 1 to 3, characterized in that the refinement treatment under freezing conditions is carried out under heat preservation conditions.
  23. 根据权利要求22所述的医用复合高分子材料的制备方法，其特征在于，低温冷却及冷冻条件下的精细化处理均在密封容器中进行，并根据对所述密封容器内温度的实时监测结果控制所使用的冷却介质的输入量。The method for preparing medical composite polymer materials according to claim 22, characterized in that the refining treatment under low-temperature cooling and freezing conditions is performed in a sealed container, and based on the real-time monitoring results of the temperature inside the sealed container Controls the input amount of cooling medium used.
  24. 一种医用复合高分子材料，其特征在于，所述医用复合高分子材料以根据权利要求1-23中任一项所述的医用复合高分子材料的制备方法制备。 A medical composite polymer material, characterized in that the medical composite polymer material is prepared by the method for preparing a medical composite polymer material according to any one of claims 1-23.
PCT/CN2023/106599 2022-07-11 2023-07-10 Medical composite polymer material and preparation method therefor WO2024012411A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN202210812783.8A CN115120781A (en) 2022-07-11 2022-07-11 Medical composite high polymer material and preparation method thereof
CN202210812783.8 2022-07-11

Publications (1)

Publication Number Publication Date
WO2024012411A1 true WO2024012411A1 (en) 2024-01-18

Family

ID=83384647

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2023/106599 WO2024012411A1 (en) 2022-07-11 2023-07-10 Medical composite polymer material and preparation method therefor

Country Status (2)

Country Link
CN (1) CN115120781A (en)
WO (1) WO2024012411A1 (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115120781A (en) * 2022-07-11 2022-09-30 运怡（北京）医疗器械有限公司 Medical composite high polymer material and preparation method thereof
CN116021790A (en) * 2022-12-12 2023-04-28 花沐医疗科技(上海)有限公司 Preparation method of absorbable internal fixation system
CN115737920B (en) * 2022-12-19 2024-02-23 北京德益达美医疗科技有限公司 Medical composite material and preparation method and application thereof
CN117736566B (en) * 2024-02-19 2024-05-10 上海珀利医用材料有限公司 Carbon fiber reinforced polyaryletherketone medical composite material and preparation method and application thereof

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20140236299A1 (en) * 2007-02-28 2014-08-21 Ryan K. Roeder Porous composite biomaterials and related methods
CN110152068A (en) * 2019-05-31 2019-08-23 武汉理工大学 A kind of polyether-ether-ketone/nano hydroxyapatite composite material and its preparation method and application
CN110624136A (en) * 2019-10-08 2019-12-31 威高集团有限公司 Degradable medical composite material and preparation method and application thereof
CN112852249A (en) * 2021-01-22 2021-05-28 江苏江南烯元石墨烯科技有限公司 Preparation and use methods of graphene polyether-ether-ketone anticorrosive high-temperature-resistant powder coating
CN115120781A (en) * 2022-07-11 2022-09-30 运怡（北京）医疗器械有限公司 Medical composite high polymer material and preparation method thereof

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20140236299A1 (en) * 2007-02-28 2014-08-21 Ryan K. Roeder Porous composite biomaterials and related methods
CN110152068A (en) * 2019-05-31 2019-08-23 武汉理工大学 A kind of polyether-ether-ketone/nano hydroxyapatite composite material and its preparation method and application
CN110624136A (en) * 2019-10-08 2019-12-31 威高集团有限公司 Degradable medical composite material and preparation method and application thereof
CN112852249A (en) * 2021-01-22 2021-05-28 江苏江南烯元石墨烯科技有限公司 Preparation and use methods of graphene polyether-ether-ketone anticorrosive high-temperature-resistant powder coating
CN115120781A (en) * 2022-07-11 2022-09-30 运怡（北京）医疗器械有限公司 Medical composite high polymer material and preparation method thereof

Also Published As

Publication number Publication date
CN115120781A (en) 2022-09-30

Similar Documents

Publication Publication Date Title
WO2024012411A1 (en) Medical composite polymer material and preparation method therefor
CN101695584B (en) Injectable composite material capable of promoting bone regeneration and repair and preparation method thereof
CN107303397B (en) A kind of biologically active Injectable compound bone cement and its preparation method and application
Deng et al. Nano-hydroxyapatite reinforced polyphenylene sulfide biocomposite with superior cytocompatibility and in vivo osteogenesis as a novel orthopedic implant
CN101309708A (en) Bone-repairing material
Lin et al. Anti-washout carboxymethyl chitosan modified tricalcium silicate bone cement: preparation, mechanical properties and in vitro bioactivity
CN106421929A (en) Injectable calcium phosphate/natural polymer composite material and preparation method and application thereof
CN102488927B (en) Bone repairing material and preparation method thereof
Chen et al. A new injectable quick hardening anti-collapse bone cement allows for improving biodegradation and bone repair
CN113511811A (en) Multifunctional mesoporous biomaterial, preparation method and application
Do Amaral et al. In vitro and in vivo response of composites based on chitosan, hydroxyapatite and collagen
Dziadek et al. Novel whey protein isolate-based highly porous scaffolds modified with therapeutic ion-releasing bioactive glasses
CA2351105A1 (en) Orthopedic filling material and method of use thereof
Albalwi et al. Medical applications of ternary nanocomposites based on hydroxyapatite/ytterbium oxide/graphene oxide: potential bone tissue engineering and antibacterial properties
EP2501754B1 (en) Novel formulation of physiological chitosan-inorganic salt solution/blood mixtures for tissue repair
Chernykh et al. Using enzymatic synthesis of hydroxyapatite as a technique to develop materials for biomedical applications
US11890392B2 (en) Absorbable bone wax and preparation method thereof
JP2004244291A (en) Calcium hydrogen phosphate powder, powder for calcium phosphate based paste, calcium phosphate based paste kneader unit and method of manufacturing calcium hydrogen phosphate powder
CN116942909A (en) Collagen-biological ceramic composite artificial bone and preparation method thereof
CN106620843A (en) Composite bone cement with bioactivity and antibacterial activity as well as preparation method and application
Mohammed et al. Synthesis of bio-Composite hybrid materials from natural waste
RU2617050C1 (en) Bioactive composite material for bone defect replacement and method for its manufacture
Gelli et al. Alendronate-loaded gelatin microparticles as templating agents for macroporous magnesium phosphate-based bone cements
Xu et al. Application of new bone cement biomaterials in osteoporotic compression fractures
CN106276835A (en) A kind of nano beta tricalcium phosphate and preparation method thereof

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: 23838903

Country of ref document: EP

Kind code of ref document: A1