WO2023174079A1 - Ceramic calcium phosphate bone cement and preparation method therefor - Google Patents

Ceramic calcium phosphate bone cement and preparation method therefor Download PDF

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Publication number
WO2023174079A1
WO2023174079A1 PCT/CN2023/079716 CN2023079716W WO2023174079A1 WO 2023174079 A1 WO2023174079 A1 WO 2023174079A1 CN 2023079716 W CN2023079716 W CN 2023079716W WO 2023174079 A1 WO2023174079 A1 WO 2023174079A1
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ceramic
bone cement
calcium phosphate
phosphate bone
tcp
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PCT/CN2023/079716
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French (fr)
Chinese (zh)
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卢霄
卢建熙
刘欣
莫秀梅
范存义
姚宸维
高旭
韦荣华
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卢霄
卢建熙
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Publication of WO2023174079A1 publication Critical patent/WO2023174079A1/en

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    • C—CHEMISTRY; METALLURGY
    • C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
    • C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
    • C04B28/00—Compositions of mortars, concrete or artificial stone, containing inorganic binders or the reaction product of an inorganic and an organic binder, e.g. polycarboxylate cements
    • C04B28/34—Compositions of mortars, concrete or artificial stone, containing inorganic binders or the reaction product of an inorganic and an organic binder, e.g. polycarboxylate cements containing cold phosphate binders
    • C04B28/344—Compositions of mortars, concrete or artificial stone, containing inorganic binders or the reaction product of an inorganic and an organic binder, e.g. polycarboxylate cements containing cold phosphate binders the phosphate binder being present in the starting composition solely as one or more phosphates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/28—Bones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds

Definitions

  • the invention relates to the field of biomedical materials, and in particular to a ceramic calcium phosphate bone cement and a preparation method thereof.
  • Bone cement is a member of bone repair biomaterials. It forms self-curing through physical, chemical and chemical reactions between solid and liquid phases. Bone cement can be delivered to the target treatment area through small surgical incisions or even percutaneous injection, making the treatment simple and minimally invasive and promoting the patient's recovery.
  • CPC calcium phosphate bone cement
  • a solid phase and a liquid phase composed of one or several calcium phosphate salt compounds. It is uniformly formed into a slurry, solidified through chemical reactions under physiological conditions, and finally bioconverted into hydroxyapatite (HA) in the body because of its good fluidity, low heat release during the solidification process, bone conduction and biocompatibility. It is good, has the advantages of degradability and drug loading, and has important application value in bone repair.
  • the solid phase used in the current preparation of calcium phosphate bone cement is powder.
  • the calcium phosphate bone cement formed by chemical reactions between powders will degrade and produce a lot of particles after being implanted into the human body. These particles Particles can trigger an inflammatory response that can cause damage to human tissue.
  • the object of the present invention is to provide a ceramic calcium phosphate bone cement and a preparation method thereof, the core of which lies in the self-curing reaction of ⁇ -tricalcium phosphate ( ⁇ -TCP) ceramic particles with dicalcium phosphate powder through the medium of distilled water.
  • ⁇ -TCP ⁇ -tricalcium phosphate
  • the present invention provides a preparation method of ceramic calcium phosphate bone cement, which includes:
  • Distilled water was selected as the liquid phase of ceramic calcium phosphate bone cement
  • the ceramic calcium phosphate bone cement is obtained by self-curing reaction of the ⁇ -TCP ceramic particles and calcium dihydrogen phosphate powder in the liquid phase.
  • the steps of preparing the ⁇ -TCP ceramic particles include:
  • the ceramic body is sintered at 1000°C ⁇ 1200°C, mechanically pulverized, uniformly ground and washed and sieved to form the required ⁇ -TCP ceramic particles.
  • the particle size range of the ⁇ -TCP ceramic particles is 10 ⁇ m ⁇ 1000 ⁇ m.
  • the morphology of the ⁇ -TCP ceramic particles includes regular particles, irregular particles or a mixture of regular particles and irregular particles.
  • the structure of the ⁇ -TCP ceramic particles is dense, porous, or a mixture of dense and porous.
  • a mixing method is used to prepare the plastic ceramic calcium phosphate bone cement, and the steps include:
  • the injection-type ceramic calcium phosphate bone cement is prepared using a blending method, and the steps include:
  • the ⁇ -TCP ceramic particles and calcium dihydrogen phosphate powder are mixed with the liquid phase respectively to obtain a first semi-solid mixture and a second semi-solid mixture respectively;
  • the first semi-solid mixture and the second semi-solid mixture are blended to obtain the ceramic calcium phosphate bone cement through a self-curing reaction.
  • the proportion of the ⁇ -TCP ceramic particles in the total weight of the solid phase and the first semi-solid mixture is 5% to 95%.
  • calcium sulfate is added to both the solid phase and the second semi-solid mixture.
  • the present invention also provides a ceramic calcium phosphate bone cement, which is prepared by the preparation method of ceramic calcium phosphate bone cement.
  • the core of the ceramic calcium phosphate bone cement and its preparation method of the present invention lies in the self-curing reaction between ⁇ -TCP ceramic particles and calcium dihydrogen phosphate powder through the medium of distilled water, so that the chemical properties of the bone cement It has higher stability, better operability, stronger mechanical properties, and more controllable degradation; especially after being implanted in the body, it can avoid or reduce the inflammatory reaction and tissue and organ damage caused by the generation of degraded particles.
  • Figure 1 is a flow chart of a method for preparing ceramic calcium phosphate bone cement according to an embodiment of the present invention.
  • FIG. 1 is a flow chart of a method for preparing ceramic calcium phosphate bone cement according to one embodiment of the present invention.
  • the ceramic phosphate Calcium bone cement preparation methods include:
  • Step S1 prepare ⁇ -TCP ceramic particles
  • Step S2 use distilled water as the liquid phase of ceramic calcium phosphate bone cement
  • Step S3 using the ⁇ -TCP ceramic particles and calcium dihydrogen phosphate powder to undergo a self-curing reaction in the liquid phase to obtain the ceramic calcium phosphate bone cement.
  • the steps for preparing the ⁇ -TCP ceramic particles include: first, prepare a ceramic body from the ⁇ -TCP powder through molding techniques such as extrusion, extrusion or grouting; then, sintering the ceramic body, mechanically Crush, homogeneously grind, wash and sieve with water to obtain the required ⁇ -TCP ceramic particles. This process is to ceramize the ⁇ -TCP powder to obtain the ⁇ -TCP ceramic particles, making the structure of the ⁇ -TCP ceramic particles more solid and stable.
  • the ⁇ -TCP ceramic particles are not in the human body. It is easy to collapse, thereby improving the stability of the ceramic calcium phosphate bone cement.
  • the sintering temperature may be 1000°C ⁇ 1200°C.
  • the prepared ⁇ -TCP ceramic particles meet biocompatibility and corresponding mechanical strength requirements, and the morphology of the ⁇ -TCP ceramic particles can include regular particles or irregular particles or a mixture of regular particles and irregular particles.
  • the regular particles can be spherical or regular polyhedron.
  • the structure of the ⁇ -TCP ceramic particles can be dense, porous, or a mixture of dense and porous.
  • the particle size range of the ⁇ -TCP ceramic particles is required for the preparation of ceramic calcium phosphate bone cement.
  • the screened ⁇ -TCP ceramic particles can be dried at a temperature of 60°C to 120°C, and the baking time can be 20h to 50h.
  • the particle size range of the selected ⁇ -TCP ceramic particles is 10 ⁇ m ⁇ 1000 ⁇ m.
  • step S2 distilled water is selected as the liquid phase of the ceramic calcium phosphate bone cement.
  • the ⁇ -TCP ceramic particles and calcium dihydrogen phosphate powder form a chemical reaction to achieve the goal of self-curing.
  • Step S3 using the ⁇ -TCP ceramic particles and calcium dihydrogen phosphate powder to undergo a self-curing reaction in the liquid phase to obtain the ceramic calcium phosphate bone cement.
  • a mixing method can be used to obtain the plastic ceramic calcium phosphate bone cement, and the steps can include:
  • Step S31 mix the ⁇ -TCP ceramic particles and calcium dihydrogen phosphate powder in corresponding proportions to obtain the solid phase of ceramic calcium phosphate bone cement; the solid phase is commercialized by long-term storage and transportation after dehydration. lay the foundation;
  • Step S32 the solid phase and the liquid phase are mixed and stirred in a certain proportion to form a pasty first intermediate of the ceramic calcium phosphate bone cement.
  • the first intermediate has good fluidity and can be used. Operability, providing corresponding operating time for clinical application; and, the first intermediate forms a paste-like second intermediate through a partial self-curing reaction, and the second intermediate has good plasticity and is convenient for clinical application; then , the second intermediate forms the solid ceramic calcium phosphate bone cement with strength through a complete self-curing reaction to achieve the ultimate clinical treatment goal.
  • calcium sulfate powder can also be added to the solid phase as a retarder, with an addition ratio of 0.1% to 30%, to slow down the self-curing reaction of the first intermediate and prevent the reaction from being too fast.
  • the resulting operating time is too short, making it possible to regulate the operating and curing time of the ceramic calcium phosphate bone cement.
  • the ⁇ -TCP ceramic particles, the calcium dihydrogen phosphate powder and the calcium sulfate powder can be mixed according to a certain proportion, and after drying at a temperature of 60°C to 80°C for 20h to 50h, the mixture can be Add to the mixing container and stir evenly to obtain a dry and evenly mixed solid phase.
  • the surface of the mixing container is smooth, so that no powder adheres to the surface of the mixing container during the mixing process, ensuring that the particle size distribution of each raw material in the solid phase is accurate and uniform.
  • the mixing container can be metal or glass.
  • the ⁇ -TCP ceramic particles may account for 5% to 95% of the total weight of the solid phase, and the calcium dihydrogen phosphate powder may account for 5% to 95% of the total weight of the solid phase. Moreover, the purity of the ⁇ -TCP ceramic particles, the calcium dihydrogen phosphate powder and the calcium sulfate powder are all greater than 95%.
  • disodium dihydrogen pyrophosphate and sodium hydroxide can also be added to the distilled water, that is, the liquid phase is a mixed solution of disodium dihydrogen pyrophosphate, sodium hydroxide and distilled water in a certain proportion.
  • disodium dihydrogen pyrophosphate is also used as a retarder to slow down the chemical reaction after the solid phase and the liquid phase are mixed, preventing the reaction from being too fast and causing the operating time to be too short, so that the ceramicization can be controlled.
  • the operation and curing time of calcium phosphate bone cement; sodium hydroxide is used to adjust the pH value so that the acidity of the prepared ceramic calcium phosphate bone cement will not be too strong and trigger a tissue reaction in the body.
  • the proportion of disodium dihydrogen pyrophosphate to the total weight of the liquid phase can be 0.1% to 30%, the proportion of sodium hydroxide to the total weight of the liquid phase is 0.1% to 30%, and the pyrophosphate
  • the purity of disodium dihydrogen and sodium hydroxide is both greater than 95%.
  • the blending method can be used in the step S3 to obtain the injection type of the ceramicized calcium phosphate bone cement, and the steps can include:
  • Step S31 mix the ⁇ -TCP ceramic particles and calcium dihydrogen phosphate powder with the liquid phase in corresponding proportions to obtain the first semi-solid mixture and the second semi-solid with good injectability respectively.
  • Mixture since the first semi-solid mixture and the second semi-solid mixture are in a physical mixing state, no chemical reaction occurs, which facilitates long-term storage and transportation, laying the foundation for commercialization;
  • Step S32 Mix the first semi-solid mixture and the second semi-solid mixture by stirring and mixing to form a pasty first intermediate of the ceramic calcium phosphate bone cement.
  • the first intermediate The body has good fluidity and injectability, providing corresponding operating time and convenience for clinical application; and, the first intermediate forms a paste-like second intermediate through a partial self-curing reaction, and the second intermediate has Very good plasticity, convenient for clinical application; Then, the second intermediate forms the solid ceramic calcium phosphate bone cement with strength through a complete self-curing reaction to achieve the final clinical treatment goal.
  • disodium dihydrogen pyrophosphate and sodium hydroxide can also be added to the distilled water, that is, the liquid phase is disodium dihydrogen pyrophosphate, sodium hydroxide and distilled water.
  • calcium sulfate powder as a retarder can also be added to the second semi-solid mixture to improve the operation and curing time of the ceramic calcium phosphate bone cement.
  • the first semi-solid mixture is a paste or paste-like semi-solid mixture containing the ⁇ -TCP ceramic particles
  • the second semi-solid mixture is a paste or paste containing the calcium dihydrogen phosphate powder.
  • the proportion of the ⁇ -TCP ceramic particles to the total weight of the first semi-solid mixture can be 5% to 95%
  • the proportion of the calcium dihydrogen phosphate powder to the total weight of the second semi-solid mixture can be is 5% to 95%
  • the proportion of the calcium sulfate powder to the total weight of the second semi-solid mixture can be 5% to 50%
  • the proportion of the disodium dihydrogen pyrophosphate to the total weight of the first semi-solid mixture and the second semi-solid mixture can be 0.1% to 30% respectively
  • the sodium hydroxide accounts for the first half of the total weight.
  • the proportion of the total weight of the solid mixture and the second semi-solid mixture can be 0.1% ⁇ 30% respectively.
  • the purity of the ⁇ -TCP ceramic particles, the calcium dihydrogen phosphate powder, the calcium sulfate powder, the disodium dihydrogen pyrophosphate and sodium hydroxide are all greater than 95%.
  • step S3 by adjusting the particle size, morphology and proportion of the ⁇ -TCP ceramic particles to the total weight of the solid phase and the first semi-solid mixture, the ceramic calcium phosphate can be regulated
  • the operating time of the bone cement i.e., in the early stage of the chemical reaction, the ceramic calcium phosphate bone cement has good fluidity and injectability, and the doctor has enough operating time
  • curing time mechanical properties and degradation properties after curing.
  • the solid phase and the described solid phase can be mixed according to the quality requirements of the ceramic calcium phosphate bone cement (i.e., operating time, curing time, mechanical properties and degradation properties after curing, etc.)
  • the liquid phase is mixed in a certain proportion and the first semi-solid mixture and the second semi-solid mixture are mixed in a certain proportion, and then the first intermediate of the ceramic calcium phosphate bone cement is obtained; then, in the After the first intermediate partially self-cures to form the second intermediate, the second intermediate is injected into the treatment target site to perform an in-situ solidification reaction until it is completely solidified into the ceramic calcium phosphate bone cement.
  • the surface of the ⁇ -TCP ceramic particles is mixed with the diphosphate
  • a chemical reaction occurs between hydrogen calcium powders to form calcium phosphate (DCPD).
  • DCPD calcium phosphate
  • the chemical reaction formula for the formation of calcium phosphate is as follows:
  • the particle size of the ⁇ -TCP ceramic particles is much larger than the particle size of the powder material, and the structure of the ⁇ -TCP ceramic particles is more stable than the powder material.
  • the ceramic calcium phosphate bone cement is stronger, has higher chemical stability, and has better controllability of degradation properties, thus making the ceramic Calcium phosphate bone cement will not be dispersed into small-sized (for example, 1.5 ⁇ m in diameter) particles during the degradation process of the treatment site, but will slowly dissolve and degrade, thereby reducing the inflammatory response.
  • the ceramic calcium phosphate bone cement will undergo a biological reaction, that is, the calcium phosphate bone cement will gradually transform into hydroxyapatite (HA), and the unreacted ⁇ -TCP wrapped by the calcium phosphate bone cement will gradually transform into hydroxyapatite (HA).
  • the ceramic particles gradually transform into biological hydroxyapatite.
  • the ceramic calcium phosphate bone cement releases calcium ions and phosphorus ions, which can promote and/or induce bone regeneration and provide a scaffold for blood vessel ingrowth and new bone formation, thereby achieving guidance. and/or induce new bone formation, while at the same time, the material can be completely degraded and absorbed.
  • the preparation method of ceramic calcium phosphate bone cement of the present invention provides a plastic or injectable self-curing bone repair material; and, due to the use of ⁇ -TCP ceramic particles and calcium dihydrogen phosphate powder in the ceramic
  • the ceramic calcium phosphate bone cement is obtained from the self-curing reaction in the liquid phase of the ceramic calcium phosphate bone cement, which makes the ceramic calcium phosphate bone cement have higher chemical stability, better operability, and stronger mechanical properties.
  • the degradation performance is more controllable; especially after implantation in the body, it can avoid or reduce the inflammatory response and tissue and organ damage caused by the generation of degradation particles.
  • One embodiment of the present invention provides a ceramic calcium phosphate bone cement, which is prepared by the preparation method of the ceramic calcium phosphate bone cement provided by the present invention, so that the chemical stability of the ceramic calcium phosphate bone cement is higher. It has better operability, stronger mechanical properties, and more controllable degradation performance; especially after being implanted in the body, it can avoid or reduce the inflammatory reaction and damage to tissues and organs caused by the generation of degraded particles.

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Abstract

The present invention provides a ceramic calcium phosphate bone cement and a preparation method therefor. The preparation method for the ceramic calcium phosphate bone cement comprises: preparing a β-TCP ceramic particle; selecting distilled water as a liquid phase of the ceramic calcium phosphate bone cement; and using the β-TCP ceramic particle and a calcium dihydrogen phosphate powder to carry out a self-curing reaction in the liquid phase to obtain the ceramic calcium phosphate bone cement. Using preparation processes such as a mixing method and a blending method, the moldable and the injection-type ceramic calcium phosphate bone cement are respectively formed. The technical solution of the present invention makes the chemical stability of the ceramic calcium phosphate bone cement higher, makes the operability better, makes the mechanical property higher, makes the degradability more controllable, and can avoid or reduce an inflammatory response and tissue organ damage caused by a degraded particle especially after the ceramic calcium phosphate bone cement is implanted in vivo.

Description

陶瓷化磷酸钙骨水泥及其制备方法Ceramic calcium phosphate bone cement and preparation method thereof 技术领域Technical field
本发明涉及生物医用材料领域，特别涉及一种陶瓷化磷酸钙骨水泥及其制备方法。The invention relates to the field of biomedical materials, and in particular to a ceramic calcium phosphate bone cement and a preparation method thereof.
背景技术Background technique
理想的骨修复材料应具有良好的生物相容性，对人体无毒无害，或低毒性；材料易 于成型满足不同移植部位的需要；合适的材料微结构来确保组织长入和营养供给；能够在 体内被逐步降解和新骨代替。骨水泥是骨修复生物材料的成员之一，它通过固相和液相的 理化和化学反应形成自固化。可以通过手术小切口，甚至经皮穿刺注射，将骨水泥送入治疗 目标部位，使得治疗简单化和微创化，促进患者的康复。The ideal bone repair material should have good biocompatibility, be non-toxic and harmless to the human body, or have low toxicity; the material should be easy to shape to meet the needs of different transplant sites; the material microstructure should be suitable to ensure tissue ingrowth and nutrient supply; It can be gradually degraded and replaced by new bone in the body. Bone cement is a member of bone repair biomaterials. It forms self-curing through physical, chemical and chemical reactions between solid and liquid phases. Bone cement can be delivered to the target treatment area through small surgical incisions or even percutaneous injection, making the treatment simple and minimally invasive and promoting the patient's recovery.
技术问题technical problem
上世纪80年代，Brown和Chow博士研究再矿化糊剂来修复早期龋齿病变，研发出磷 酸钙骨水泥(CPC)，通过一种或几种磷酸钙盐化合物组成的固相与液相调和均匀成浆体，在 生理条件下通过化学反应固化，最终在体内生物转化为羟基磷灰石(HA)，因其流动性佳、固 化过程中放热少且骨传导作用及生物相容性良好、具有可降解性及可载药性等优点，在骨 修复方面有重要应用价值。但是，现有制备磷酸钙骨水泥采用的固相均为粉体，粉体与粉体 之间发生化学反应形成的磷酸钙骨水泥在种植进入人体内后，会降解产生很多的颗粒，而 这些颗粒会引发炎症反应，导致对人体组织产生损害。In the 1980s, Dr. Brown and Dr. Chow studied remineralization paste to repair early caries lesions and developed calcium phosphate bone cement (CPC), which is blended with a solid phase and a liquid phase composed of one or several calcium phosphate salt compounds. It is uniformly formed into a slurry, solidified through chemical reactions under physiological conditions, and finally bioconverted into hydroxyapatite (HA) in the body because of its good fluidity, low heat release during the solidification process, bone conduction and biocompatibility. It is good, has the advantages of degradability and drug loading, and has important application value in bone repair. However, the solid phase used in the current preparation of calcium phosphate bone cement is powder. The calcium phosphate bone cement formed by chemical reactions between powders will degrade and produce a lot of particles after being implanted into the human body. These particles Particles can trigger an inflammatory response that can cause damage to human tissue.
因此，需要对现有的磷酸钙骨水泥的制备方法进行改进，以减少炎症反应。Therefore, there is a need to improve the existing preparation methods of calcium phosphate bone cement to reduce the inflammatory response.
技术解决方案Technical solutions
本发明的目的在于提供一种陶瓷化磷酸钙骨水泥及其制备方法，其核心在于β‑磷 酸三钙(β-TCP)陶瓷颗粒通过蒸馏水这个介质与磷酸二氢钙粉体产生自固化反应，使得骨 水泥的化学稳定性更高，可操作性更好，力学性能更强，降解性更可控；尤其植入体内后能 避免或减少降解颗粒产生引起的炎症反应和组织器官的损害。The object of the present invention is to provide a ceramic calcium phosphate bone cement and a preparation method thereof, the core of which lies in the self-curing reaction of β-tricalcium phosphate (β-TCP) ceramic particles with dicalcium phosphate powder through the medium of distilled water. , making the bone cement have higher chemical stability, better operability, stronger mechanical properties, and more controllable degradation; especially after implantation in the body, it can avoid or reduce the inflammatory reaction and damage to tissues and organs caused by the generation of degraded particles.
为实现上述目的，本发明提供了一种陶瓷化磷酸钙骨水泥的制备方法，包括：In order to achieve the above object, the present invention provides a preparation method of ceramic calcium phosphate bone cement, which includes:
制备β-TCP陶瓷颗粒；Preparation of β-TCP ceramic particles;
选用蒸馏水作为陶瓷化磷酸钙骨水泥的液相；Distilled water was selected as the liquid phase of ceramic calcium phosphate bone cement;
采用所述β-TCP陶瓷颗粒与磷酸二氢钙粉体在所述液相中自固化反应得到所述陶 瓷化磷酸钙骨水泥。The ceramic calcium phosphate bone cement is obtained by self-curing reaction of the β-TCP ceramic particles and calcium dihydrogen phosphate powder in the liquid phase.
可选地，制备所述β-TCP陶瓷颗粒的步骤包括：Optionally, the steps of preparing the β-TCP ceramic particles include:
将β-TCP粉体通过挤压、挤出或注浆成型技术制备出陶瓷坯体；Prepare a ceramic body from β-TCP powder through extrusion, extrusion or slip casting technology;
将所述陶瓷坯体经过1000℃~1200℃烧结、机械粉碎、均一化研磨和水洗过筛，形 成所需的所述β-TCP陶瓷颗粒。The ceramic body is sintered at 1000℃~1200℃, mechanically pulverized, uniformly ground and washed and sieved to form the required β-TCP ceramic particles.
可选地，所述β-TCP陶瓷颗粒的粒径范围为10μm~1000μm。Optionally, the particle size range of the β-TCP ceramic particles is 10 μm ~ 1000 μm.
可选地，所述β-TCP陶瓷颗粒的形态包括规则颗粒、非规则颗粒或规则颗粒与非规 则颗粒的混合物。Optionally, the morphology of the β-TCP ceramic particles includes regular particles, irregular particles or a mixture of regular particles and irregular particles.
可选地，所述β-TCP陶瓷颗粒的结构为密质、多孔或者密质和多孔的混合体。Optionally, the structure of the β-TCP ceramic particles is dense, porous, or a mixture of dense and porous.
可选地，采用混合法制备出可塑型的所述陶瓷化磷酸钙骨水泥，其步骤包括：Optionally, a mixing method is used to prepare the plastic ceramic calcium phosphate bone cement, and the steps include:
将所述β‑TCP陶瓷颗粒与磷酸二氢钙粉体混合，以得到陶瓷化磷酸钙骨水泥的固相；以及，Mix the β-TCP ceramic particles with calcium dihydrogen phosphate powder to obtain the solid phase of ceramic calcium phosphate bone cement; and,
将所述固相与所述液相混合，形成糊状混合物，并通过自固化反应得到所述陶瓷化磷酸钙骨水泥；Mix the solid phase and the liquid phase to form a paste mixture, and obtain the ceramic calcium phosphate bone cement through a self-curing reaction;
或者，采用调和法制备出注射型的所述陶瓷化磷酸钙骨水泥，其步骤包括：Alternatively, the injection-type ceramic calcium phosphate bone cement is prepared using a blending method, and the steps include:
将所述β-TCP陶瓷颗粒和磷酸二氢钙粉体分别与所述液相混合，以分别得到第一 半固体混合物和第二半固体混合物；以及，The β-TCP ceramic particles and calcium dihydrogen phosphate powder are mixed with the liquid phase respectively to obtain a first semi-solid mixture and a second semi-solid mixture respectively; and,
 将所述第一半固体混合物和所述第二半固体混合物进行调和，通过自固化反应得 到所述陶瓷化磷酸钙骨水泥。The first semi-solid mixture and the second semi-solid mixture are blended to obtain the ceramic calcium phosphate bone cement through a self-curing reaction.
 可选地，所述β-TCP陶瓷颗粒占所述固相和所述第一半固体混合物总重量的比例 均为5％~95％。Optionally, the proportion of the β-TCP ceramic particles in the total weight of the solid phase and the first semi-solid mixture is 5% to 95%.
 可选地，所述固相和所述第二半固体混合物中均添加有硫酸钙。Optionally, calcium sulfate is added to both the solid phase and the second semi-solid mixture.
   可选地，所述蒸馏水中添加焦磷酸二氢二钠和氢氧化钠。Optionally, add disodium dihydrogen pyrophosphate and sodium hydroxide to the distilled water.
本发明还提供一种陶瓷化磷酸钙骨水泥，采用所述的陶瓷化磷酸钙骨水泥的制备 方法制备。The present invention also provides a ceramic calcium phosphate bone cement, which is prepared by the preparation method of ceramic calcium phosphate bone cement.
有益效果beneficial effects
与现有技术相比，本发明的陶瓷化磷酸钙骨水泥及其制备方法，其核心在于β-TCP 陶瓷颗粒通过蒸馏水这个介质与磷酸二氢钙粉体产生自固化反应，使得骨水泥的化学稳定 性更高，可操作性更好，力学性能更强，降解性更可控；尤其植入体内后能避免或减少降解 颗粒产生引起的炎症反应和组织器官的损害。Compared with the existing technology, the core of the ceramic calcium phosphate bone cement and its preparation method of the present invention lies in the self-curing reaction between β-TCP ceramic particles and calcium dihydrogen phosphate powder through the medium of distilled water, so that the chemical properties of the bone cement It has higher stability, better operability, stronger mechanical properties, and more controllable degradation; especially after being implanted in the body, it can avoid or reduce the inflammatory reaction and tissue and organ damage caused by the generation of degraded particles.
附图说明Description of the drawings
图1是本发明一实施例的陶瓷化磷酸钙骨水泥的制备方法的流程图。Figure 1 is a flow chart of a method for preparing ceramic calcium phosphate bone cement according to an embodiment of the present invention.
本发明的实施方式Embodiments of the invention
为使本发明的目的、优点和特征更加清楚，以下对本发明提出的陶瓷化磷酸钙骨水泥及其制备方法作进一步详细说明。需说明的是，附图均采用非常简化的形式且均使用 非精准的比例，仅用以方便、明晰地辅助说明本发明实施例的目的。In order to make the purpose, advantages and characteristics of the present invention clearer, the ceramic calcium phosphate bone cement proposed by the present invention and its preparation method will be further described in detail below. It should be noted that the accompanying drawings are in a very simplified form and use imprecise proportions, and are only used to conveniently and clearly assist the purpose of explaining the embodiments of the present invention.
   本发明一实施例提供一种陶瓷化磷酸钙骨水泥的制备方法，参阅图1，图1是本发 明一实施例的陶瓷化磷酸钙骨水泥的制备方法的流程图，所述陶瓷化磷酸钙骨水泥的制备 方法包括：One embodiment of the present invention provides a method for preparing ceramic calcium phosphate bone cement. Refer to Figure 1. Figure 1 is a flow chart of a method for preparing ceramic calcium phosphate bone cement according to one embodiment of the present invention. The ceramic phosphate Calcium bone cement preparation methods include:
   步骤S1，制备β-TCP陶瓷颗粒；Step S1, prepare β-TCP ceramic particles;
   步骤S2，选用蒸馏水作为陶瓷化磷酸钙骨水泥的液相；Step S2, use distilled water as the liquid phase of ceramic calcium phosphate bone cement;
   步骤S3，采用所述β-TCP陶瓷颗粒与磷酸二氢钙粉体在所述液相中自固化反应得 到所述陶瓷化磷酸钙骨水泥。Step S3, using the β-TCP ceramic particles and calcium dihydrogen phosphate powder to undergo a self-curing reaction in the liquid phase to obtain the ceramic calcium phosphate bone cement.
   下面更为详细介绍本实施例提供的陶瓷化磷酸钙骨水泥的制备方法：The following is a more detailed introduction to the preparation method of the ceramic calcium phosphate bone cement provided in this embodiment:
   按照步骤S1，根据陶瓷化磷酸钙骨水泥的性能要求，制备β-TCP陶瓷颗粒。Follow step S1 and prepare β-TCP ceramic particles according to the performance requirements of ceramic calcium phosphate bone cement.
   制备所述β‑TCP陶瓷颗粒的步骤包括：首先，将β-TCP粉体通过挤压、挤出或注浆等成型技术制备出陶瓷坯体；然后，将所述陶瓷坯体经过烧结、机械粉碎、均一化研磨和水洗过筛，以得到所需的所述β-TCP陶瓷颗粒。此过程即为将β-TCP粉体进行陶瓷化处理后得到 所述β-TCP陶瓷颗粒，使得所述β-TCP陶瓷颗粒的结构更加坚固和稳定，所述β-TCP陶瓷颗粒 在人体内不容易溃散，进而能够提高所述陶瓷化磷酸钙骨水泥的稳定性。其中，所述烧结温 度可以为1000℃~1200℃。The steps for preparing the β-TCP ceramic particles include: first, prepare a ceramic body from the β-TCP powder through molding techniques such as extrusion, extrusion or grouting; then, sintering the ceramic body, mechanically Crush, homogeneously grind, wash and sieve with water to obtain the required β-TCP ceramic particles. This process is to ceramize the β-TCP powder to obtain the β-TCP ceramic particles, making the structure of the β-TCP ceramic particles more solid and stable. The β-TCP ceramic particles are not in the human body. It is easy to collapse, thereby improving the stability of the ceramic calcium phosphate bone cement. Wherein, the sintering temperature may be 1000℃~1200℃.
   制备得到的所述β-TCP陶瓷颗粒符合生物相容性和相应力学强度要求，且所述β-TCP陶瓷颗粒的形貌可以包括规则颗粒或非规则颗粒或规则颗粒与非规则颗粒的混合物。 其中，规则颗粒可为球形或者正多面体。The prepared β-TCP ceramic particles meet biocompatibility and corresponding mechanical strength requirements, and the morphology of the β-TCP ceramic particles can include regular particles or irregular particles or a mixture of regular particles and irregular particles. Among them, the regular particles can be spherical or regular polyhedron.
   所述β‑TCP陶瓷颗粒的结构可以为密质、多孔或者密质和多孔的混合体。The structure of the β-TCP ceramic particles can be dense, porous, or a mixture of dense and porous.
   其中，通过采用水洗过筛，能够去除粒径很小的微粒及其静电作用，使得所述β-TCP陶瓷颗粒的粒径范围为制备陶瓷化磷酸钙骨水泥所需。并且，筛选好之后，可以将筛选 好的所述β-TCP陶瓷颗粒在60℃~120℃的温度下烘干，烘烤时间可以为20h~50h。Among them, by using water washing and sieving, particles with very small particle sizes and their electrostatic effects can be removed, so that the particle size range of the β-TCP ceramic particles is required for the preparation of ceramic calcium phosphate bone cement. Moreover, after screening, the screened β-TCP ceramic particles can be dried at a temperature of 60°C to 120°C, and the baking time can be 20h to 50h.
   优选的，筛选出的所述β-TCP陶瓷颗粒的粒径范围为10μm~1000μm。Preferably, the particle size range of the selected β-TCP ceramic particles is 10 μm ~ 1000 μm.
   步骤S2，选用蒸馏水作为陶瓷化磷酸钙骨水泥的液相，通过所述液相使得所述β‑ TCP陶瓷颗粒与磷酸二氢钙粉体形成化学反应，实现自固化的目标。In step S2, distilled water is selected as the liquid phase of the ceramic calcium phosphate bone cement. Through the liquid phase, the β-TCP ceramic particles and calcium dihydrogen phosphate powder form a chemical reaction to achieve the goal of self-curing.
   步骤S3，采用所述β-TCP陶瓷颗粒与磷酸二氢钙粉体在所述液相中自固化反应得 到所述陶瓷化磷酸钙骨水泥。Step S3, using the β-TCP ceramic particles and calcium dihydrogen phosphate powder to undergo a self-curing reaction in the liquid phase to obtain the ceramic calcium phosphate bone cement.
   其中，在实施例一中，所述步骤S3中可以采用混合法得到可塑型的所述陶瓷化磷 酸钙骨水泥，其步骤可以包括：Wherein, in Embodiment 1, in the step S3, a mixing method can be used to obtain the plastic ceramic calcium phosphate bone cement, and the steps can include:
   步骤S31，将所述β-TCP陶瓷颗粒与磷酸二氢钙粉体按相应比例混合，以得到陶瓷 化磷酸钙骨水泥的固相；所述固相通过脱水后长期储存和运输，为商品化奠定基础；Step S31, mix the β-TCP ceramic particles and calcium dihydrogen phosphate powder in corresponding proportions to obtain the solid phase of ceramic calcium phosphate bone cement; the solid phase is commercialized by long-term storage and transportation after dehydration. lay the foundation;
   步骤S32，将所述固相与所述液相按一定比例进行混合搅拌，形成所述陶瓷化磷酸 钙骨水泥的糊状第一中间体，所述第一中间体具有良好的流动性和可操作性，为临床应用 提供相应的操作时间；并且，所述第一中间体通过部分自固化反应形成膏状第二中间体，所 述第二中间体具有很好的可塑性，便于临床应用；接着，所述第二中间体通过完全自固化反 应形成具有强度的固体状所述陶瓷化磷酸钙骨水泥，实现最终的临床治疗目标。Step S32, the solid phase and the liquid phase are mixed and stirred in a certain proportion to form a pasty first intermediate of the ceramic calcium phosphate bone cement. The first intermediate has good fluidity and can be used. Operability, providing corresponding operating time for clinical application; and, the first intermediate forms a paste-like second intermediate through a partial self-curing reaction, and the second intermediate has good plasticity and is convenient for clinical application; then , the second intermediate forms the solid ceramic calcium phosphate bone cement with strength through a complete self-curing reaction to achieve the ultimate clinical treatment goal.
   优选的，所述固相中还可添加硫酸钙粉体作为缓凝剂，添加比例为0 .1％~30％， 用于减缓所述第一中间体的自固化反应，防止反应过快而导致操作时间过短，使得能够调 控所述陶瓷化磷酸钙骨水泥的操作和固化时间。Preferably, calcium sulfate powder can also be added to the solid phase as a retarder, with an addition ratio of 0.1% to 30%, to slow down the self-curing reaction of the first intermediate and prevent the reaction from being too fast. The resulting operating time is too short, making it possible to regulate the operating and curing time of the ceramic calcium phosphate bone cement.
   并且，可以将所述β-TCP陶瓷颗粒、所述磷酸二氢钙粉体和硫酸钙粉体按照一定比 例混合，并在60℃~80℃的温度下烘干20h~50h后，将混合物添加至搅拌容器中搅拌均匀， 以得到干燥且混合均匀的所述固相。Moreover, the β-TCP ceramic particles, the calcium dihydrogen phosphate powder and the calcium sulfate powder can be mixed according to a certain proportion, and after drying at a temperature of 60°C to 80°C for 20h to 50h, the mixture can be Add to the mixing container and stir evenly to obtain a dry and evenly mixed solid phase.
   其中，搅拌容器的表面光滑，使得搅拌过程中无粉体粘附在搅拌容器的表面，确保 所述固相中的每种原料的粒径分布准确且均匀。搅拌容器可以为金属或玻璃容器。Among them, the surface of the mixing container is smooth, so that no powder adheres to the surface of the mixing container during the mixing process, ensuring that the particle size distribution of each raw material in the solid phase is accurate and uniform. The mixing container can be metal or glass.
   所述β-TCP陶瓷颗粒占所述固相总重量的比例可以为5％~95％，所述磷酸二氢钙 粉体占所述固相总重量的比例可以为5％~95％。并且，所述β-TCP陶瓷颗粒、所述磷酸二氢 钙粉体和所述硫酸钙粉体的纯度均大于95％。The β-TCP ceramic particles may account for 5% to 95% of the total weight of the solid phase, and the calcium dihydrogen phosphate powder may account for 5% to 95% of the total weight of the solid phase. Moreover, the purity of the β-TCP ceramic particles, the calcium dihydrogen phosphate powder and the calcium sulfate powder are all greater than 95%.
   优选的，所述蒸馏水中还可添加有焦磷酸二氢二钠和氢氧化钠，即所述液相为焦 磷酸二氢二钠、氢氧化钠和蒸馏水按一定比例配置成的混合溶液。其中，焦磷酸二氢二钠也作为缓凝剂，用于减缓所述固相与所述液相混合后的化学反应，防止反应过快而导致操作时间过短，使得能够调控所述陶瓷化磷酸钙骨水泥的操作和固化时间；氢氧化钠用于调节 pH值，使得制备的所述陶瓷化磷酸钙骨水泥的酸性不会太强，引发机体组织反应。Preferably, disodium dihydrogen pyrophosphate and sodium hydroxide can also be added to the distilled water, that is, the liquid phase is a mixed solution of disodium dihydrogen pyrophosphate, sodium hydroxide and distilled water in a certain proportion. Among them, disodium dihydrogen pyrophosphate is also used as a retarder to slow down the chemical reaction after the solid phase and the liquid phase are mixed, preventing the reaction from being too fast and causing the operating time to be too short, so that the ceramicization can be controlled. The operation and curing time of calcium phosphate bone cement; sodium hydroxide is used to adjust the pH value so that the acidity of the prepared ceramic calcium phosphate bone cement will not be too strong and trigger a tissue reaction in the body.
   其中，焦磷酸二氢二钠占所述液相的总重量的比例可以为0.1％~30％，氢氧化钠 占所述液相的总重量的比例为0 .1％~30％，焦磷酸二氢二钠和氢氧化钠的纯度均大于 95％。Wherein, the proportion of disodium dihydrogen pyrophosphate to the total weight of the liquid phase can be 0.1% to 30%, the proportion of sodium hydroxide to the total weight of the liquid phase is 0.1% to 30%, and the pyrophosphate The purity of disodium dihydrogen and sodium hydroxide is both greater than 95%.
   另外，在实施例二中，所述步骤S3中可以采用调和法得到注射型的所述陶瓷化磷 酸钙骨水泥，其步骤可以包括：In addition, in the second embodiment, the blending method can be used in the step S3 to obtain the injection type of the ceramicized calcium phosphate bone cement, and the steps can include:
   步骤S31，将所述β-TCP陶瓷颗粒和磷酸二氢钙粉体分别与所述液相按相应比例混 合，以分别得到具有很好可注射性的第一半固体混合物和第二半固体混合物，由于第一半 固体混合物和第二半固体混合物处于物理混合状态，不产生化学反应，便于长期储存和运 输，为商品化奠定基础；Step S31, mix the β-TCP ceramic particles and calcium dihydrogen phosphate powder with the liquid phase in corresponding proportions to obtain the first semi-solid mixture and the second semi-solid with good injectability respectively. Mixture, since the first semi-solid mixture and the second semi-solid mixture are in a physical mixing state, no chemical reaction occurs, which facilitates long-term storage and transportation, laying the foundation for commercialization;
   步骤S32，通过搅拌混合的方式将所述第一半固体混合物和所述第二半固体混合 物进行调和，形成所述陶瓷化磷酸钙骨水泥的糊状第一中间体，所述第一中间体具有良好 的流动性和可注射性，为临床应用提供相应的操作时间和便利；并且，所述第一中间体通过 部分自固化反应形成膏状第二中间体，所述第二中间体具有很好的可塑性，便于临床应用； 接着，所述第二中间体通过完全自固化反应形成具有强度的固体状所述陶瓷化磷酸钙骨水 泥，实现最终的临床治疗目标。其中，在本实施例中，优选的，所述蒸馏水中也可添加有焦磷 酸二氢二钠和氢氧化钠，即所述液相为焦磷酸二氢二钠、氢氧化钠和蒸馏水按一定比例配 置成的混合溶液。Step S32: Mix the first semi-solid mixture and the second semi-solid mixture by stirring and mixing to form a pasty first intermediate of the ceramic calcium phosphate bone cement. The first intermediate The body has good fluidity and injectability, providing corresponding operating time and convenience for clinical application; and, the first intermediate forms a paste-like second intermediate through a partial self-curing reaction, and the second intermediate has Very good plasticity, convenient for clinical application; Then, the second intermediate forms the solid ceramic calcium phosphate bone cement with strength through a complete self-curing reaction to achieve the final clinical treatment goal. Among them, in this embodiment, preferably, disodium dihydrogen pyrophosphate and sodium hydroxide can also be added to the distilled water, that is, the liquid phase is disodium dihydrogen pyrophosphate, sodium hydroxide and distilled water. A mixed solution prepared in a certain proportion.
   并且，优选的，所述第二半固体混合物中还可添加有作为缓凝剂的硫酸钙粉体，以 改善所述陶瓷化磷酸钙骨水泥的操作和固化时间。And, preferably, calcium sulfate powder as a retarder can also be added to the second semi-solid mixture to improve the operation and curing time of the ceramic calcium phosphate bone cement.
   所述第一半固体混合物为含有所述β-TCP陶瓷颗粒的糊状或者膏状的半固体混合 物，所述第二半固体混合物为含有所述磷酸二氢钙粉体的糊状或者膏状的半固体混合物， 使得所述第一半固体混合物与所述第二半固体混合物进行调和之后，反应初期得到的所述 第一中间体具有良好的流动性和可注射性。The first semi-solid mixture is a paste or paste-like semi-solid mixture containing the β-TCP ceramic particles, and the second semi-solid mixture is a paste or paste containing the calcium dihydrogen phosphate powder. A shape of semi-solid mixture, so that after the first semi-solid mixture and the second semi-solid mixture are reconciled, the first intermediate obtained in the early stage of the reaction has good fluidity and injectability.
   其中，所述β-TCP陶瓷颗粒占所述第一半固体混合物总重量的比例可以为5％~ 95％，所述磷酸二氢钙粉体占所述第二半固体混合物总重量的比例可以为5％~95％，所述 硫酸钙粉体占所述第二半固体混合物总重量的比例可以为5％~50％。所述焦磷酸二氢二 钠占所述第一半固体混合物和所述第二半固体混合物总重量的比例分别可以为0 .1％~ 30％，所述氢氧化钠占所述第一半固体混合物和所述第二半固体混合物总重量的比例分别 可以为0.1％~30％。并且，所述β-TCP陶瓷颗粒、所述磷酸二氢钙粉体、所述硫酸钙粉体、所 述焦磷酸二氢二钠和氢氧化钠的纯度均大于95％。Wherein, the proportion of the β-TCP ceramic particles to the total weight of the first semi-solid mixture can be 5% to 95%, and the proportion of the calcium dihydrogen phosphate powder to the total weight of the second semi-solid mixture can be is 5% to 95%, and the proportion of the calcium sulfate powder to the total weight of the second semi-solid mixture can be 5% to 50%. The proportion of the disodium dihydrogen pyrophosphate to the total weight of the first semi-solid mixture and the second semi-solid mixture can be 0.1% to 30% respectively, and the sodium hydroxide accounts for the first half of the total weight. The proportion of the total weight of the solid mixture and the second semi-solid mixture can be 0.1%~30% respectively. Moreover, the purity of the β-TCP ceramic particles, the calcium dihydrogen phosphate powder, the calcium sulfate powder, the disodium dihydrogen pyrophosphate and sodium hydroxide are all greater than 95%.
   在所述步骤S3中，通过调整所述β-TCP陶瓷颗粒的粒径、形貌以及占所述固相和所 述第一半固体混合物总重量的比例，使得能够调控所述陶瓷化磷酸钙骨水泥的操作时间(即化学反应初期，陶瓷化磷酸钙骨水泥具有好的流动性以及可注射性阶段，医生有足够的 操作时间)、固化时间、固化后的力学性能和降解性能。In step S3, by adjusting the particle size, morphology and proportion of the β-TCP ceramic particles to the total weight of the solid phase and the first semi-solid mixture, the ceramic calcium phosphate can be regulated The operating time of the bone cement (i.e., in the early stage of the chemical reaction, the ceramic calcium phosphate bone cement has good fluidity and injectability, and the doctor has enough operating time), curing time, mechanical properties and degradation properties after curing.
   并且，在所述步骤S3中，可以根据所述陶瓷化磷酸钙骨水泥的质量要求(即操作时 间、固化时间、固化后的力学性能和降解性能等)，将所述固相与所述液相按一定比例混合以及将所述第一半固体混合物和所述第二半固体混合物按一定比例调和，之后得到所述陶 瓷化磷酸钙骨水泥的第一中间体；然后，在所述第一中间体部分自固化反应形成所述第二 中间体之后，将所述第二中间体注射到治疗目标部位，进行原位凝固反应，直至完全固化成 为所述陶瓷化磷酸钙骨水泥。Moreover, in step S3, the solid phase and the described solid phase can be mixed according to the quality requirements of the ceramic calcium phosphate bone cement (i.e., operating time, curing time, mechanical properties and degradation properties after curing, etc.) The liquid phase is mixed in a certain proportion and the first semi-solid mixture and the second semi-solid mixture are mixed in a certain proportion, and then the first intermediate of the ceramic calcium phosphate bone cement is obtained; then, in the After the first intermediate partially self-cures to form the second intermediate, the second intermediate is injected into the treatment target site to perform an in-situ solidification reaction until it is completely solidified into the ceramic calcium phosphate bone cement.
   其中，在所述固相与所述液相混合以及在所述第一半固体混合物和所述第二半固 体混合物进行调和之后，在所述β-TCP陶瓷颗粒的表面与所述磷酸二氢钙粉体之间发生化 学反应，以形成钙磷石(DCPD)。并且，所述β‑TCP陶瓷颗粒的内部未与所述磷酸二氢钙粉体 之间发生化学反应，钙磷石仅形成在所述β-TCP陶瓷颗粒的表面，因此，制备获得的所述陶 瓷化磷酸钙骨水泥为钙磷石包裹未反应的β‑TCP陶瓷颗粒的结构，实现石子水泥增强目标。 形成钙磷石的化学反应式如下：Wherein, after the solid phase is mixed with the liquid phase and the first semi-solid mixture and the second semi-solid mixture are reconciled, the surface of the β-TCP ceramic particles is mixed with the diphosphate A chemical reaction occurs between hydrogen calcium powders to form calcium phosphate (DCPD). Moreover, there is no chemical reaction between the interior of the β-TCP ceramic particles and the calcium dihydrogen phosphate powder, and calcium phosphate is only formed on the surface of the β-TCP ceramic particles. Therefore, the preparation of the Ceramic calcium phosphate bone cement is a structure in which calcium phosphate encapsulates unreacted β-TCP ceramic particles to achieve the goal of stone cement reinforcement. The chemical reaction formula for the formation of calcium phosphate is as follows:
   β-Ca3 (PO4)2+Ca(H2PO4)2 ·H2O+7H2O→4CaHPO4 ·2H2Oβ-Ca3 (PO4)2+Ca(H2PO4)2 ·H2O+7H2O→4CaHPO4 ·2H2O
   在所述陶瓷化磷酸钙骨水泥中，由于钙磷石内部包裹有未反应的β-TCP陶瓷颗粒， 而所述β-TCP陶瓷颗粒是经陶瓷化处理得到，与现有制备磷酸钙骨水泥采用的固相均为粉 体材料相比，所述β-TCP陶瓷颗粒的粒径远大于粉体材料的粒径，且所述β-TCP陶瓷颗粒比 粉体材料的结构更加稳定，因此，与固相均为粉体材料反应得到的磷酸钙骨水泥相比，所述 陶瓷化磷酸钙骨水泥更加坚固且化学稳定性更高，降解性能的可控性更好，进而使得所述 陶瓷化磷酸钙骨水泥在治疗部位的降解过程中不会分散为小尺寸(例如直径1 .5μm)的颗 粒，而是慢慢溶化降解，从而减少炎症反应。In the ceramic calcium phosphate bone cement, since the calcium phosphate stone is internally wrapped with unreacted β-TCP ceramic particles, and the β-TCP ceramic particles are obtained by ceramic treatment, it is different from the existing calcium phosphate bone cement. Compared with the solid phase used in powder materials, the particle size of the β-TCP ceramic particles is much larger than the particle size of the powder material, and the structure of the β-TCP ceramic particles is more stable than the powder material. Therefore, Compared with calcium phosphate bone cement obtained by reacting solid phases with powder materials, the ceramic calcium phosphate bone cement is stronger, has higher chemical stability, and has better controllability of degradation properties, thus making the ceramic Calcium phosphate bone cement will not be dispersed into small-sized (for example, 1.5 μm in diameter) particles during the degradation process of the treatment site, but will slowly dissolve and degrade, thereby reducing the inflammatory response.
   在人体内治疗部位，所述陶瓷化磷酸钙骨水泥会发生生物反应，即钙磷石会逐渐 转化为羟基磷灰石(HA)，且被所述钙磷石包裹的未反应的β-TCP陶瓷颗粒逐渐转化为生物 羟基磷灰石。在上述生物反应的过程中，所述陶瓷化磷酸钙骨水泥中释放出钙离子和磷离 子，能够促进和/或诱导骨再生，并为血管长入和新骨形成提供支架，从而实现引导和/或诱 导新骨形成目标，同时，材料能被完全降解吸收。At the treatment site in the human body, the ceramic calcium phosphate bone cement will undergo a biological reaction, that is, the calcium phosphate bone cement will gradually transform into hydroxyapatite (HA), and the unreacted β-TCP wrapped by the calcium phosphate bone cement will gradually transform into hydroxyapatite (HA). The ceramic particles gradually transform into biological hydroxyapatite. During the above-mentioned biological reaction, the ceramic calcium phosphate bone cement releases calcium ions and phosphorus ions, which can promote and/or induce bone regeneration and provide a scaffold for blood vessel ingrowth and new bone formation, thereby achieving guidance. and/or induce new bone formation, while at the same time, the material can be completely degraded and absorbed.
   从上述内容可知，本发明的陶瓷化磷酸钙骨水泥的制备方法，提供了可塑性或可 注射性的自固化骨修复材料；并且，由于采用β-TCP陶瓷颗粒与磷酸二氢钙粉体在陶瓷化磷 酸钙骨水泥的液相中自固化反应得到所述陶瓷化磷酸钙骨水泥，使得所述陶瓷化磷酸钙骨 水泥的化学稳定性更高，可操作性更好，力学性能更强，降解性能更可控；尤其植入体内后 能避免或减少降解颗粒产生引起的炎症反应和组织器官的损害。It can be seen from the above that the preparation method of ceramic calcium phosphate bone cement of the present invention provides a plastic or injectable self-curing bone repair material; and, due to the use of β-TCP ceramic particles and calcium dihydrogen phosphate powder in the ceramic The ceramic calcium phosphate bone cement is obtained from the self-curing reaction in the liquid phase of the ceramic calcium phosphate bone cement, which makes the ceramic calcium phosphate bone cement have higher chemical stability, better operability, and stronger mechanical properties. The degradation performance is more controllable; especially after implantation in the body, it can avoid or reduce the inflammatory response and tissue and organ damage caused by the generation of degradation particles.
   本发明一实施例提供一种陶瓷化磷酸钙骨水泥，采用本发明提供的所述陶瓷化磷 酸钙骨水泥的制备方法制备，使得所述陶瓷化磷酸钙骨水泥的化学稳定性更高，可操作性 更好，力学性能更强，降解性能更可控；尤其植入体内后能避免或减少降解颗粒产生引起的 炎症反应和组织器官的损害。One embodiment of the present invention provides a ceramic calcium phosphate bone cement, which is prepared by the preparation method of the ceramic calcium phosphate bone cement provided by the present invention, so that the chemical stability of the ceramic calcium phosphate bone cement is higher. It has better operability, stronger mechanical properties, and more controllable degradation performance; especially after being implanted in the body, it can avoid or reduce the inflammatory reaction and damage to tissues and organs caused by the generation of degraded particles.
   上述描述仅是对本发明较佳实施例的描述，并非对本发明范围的任何限定，本发 明领域的普通技术人员根据上述揭示内容做的任何变更、修饰，均属于权利要求书的保护 范围。The above description is only a description of the preferred embodiments of the present invention, and does not limit the scope of the present invention in any way. Any changes or modifications made by those of ordinary skill in the field of the present invention based on the above disclosure shall fall within the scope of protection of the claims.

Claims (10)

  1. 一种陶瓷化磷酸钙骨水泥的制备方法，其特征在于，包括：制备β-TCP陶瓷颗粒；A method for preparing ceramic calcium phosphate bone cement, which is characterized in that it includes: preparing β-TCP ceramic particles;
    选用蒸馏水作为陶瓷化磷酸钙骨水泥的液相；Distilled water was selected as the liquid phase of ceramic calcium phosphate bone cement;
    采用所述β-TCP陶瓷颗粒与磷酸二氢钙粉体在所述液相中自固化反应得到所述陶瓷化 磷酸钙骨水泥。The ceramicized calcium phosphate bone cement is obtained by self-curing reaction of the β-TCP ceramic particles and calcium dihydrogen phosphate powder in the liquid phase.
  2. 如权利要求1所述的陶瓷化磷酸钙骨水泥的制备方法，其特征在于，制备所述β-TCP陶瓷颗粒的步骤包括：将β-TCP粉体通过挤压、挤出或注浆成型技术制备出陶瓷坯体；The method for preparing ceramic calcium phosphate bone cement according to claim 1, wherein the step of preparing the β-TCP ceramic particles includes: passing the β-TCP powder through extrusion, extrusion or slip molding technology. Prepare a ceramic body;
    将所述陶瓷坯体经过1000℃~1200℃烧结、机械粉碎、均一化研磨和水洗过筛，形成所 需的所述β-TCP陶瓷颗粒。The ceramic body is sintered at 1000°C to 1200°C, mechanically pulverized, uniformly ground and washed and sieved to form the required β-TCP ceramic particles.
  3. 如权利要求1所述的陶瓷化磷酸钙骨水泥的制备方法，其特征在于，所述β-TCP陶瓷 颗粒的粒径范围为10μm~1000μm。The preparation method of ceramic calcium phosphate bone cement according to claim 1, characterized in that the particle size range of the β-TCP ceramic particles is 10 μm ~ 1000 μm.
  4. 如权利要求1所述的陶瓷化磷酸钙骨水泥的制备方法，其特征在于，所述β-TCP陶瓷 颗粒的形态包括规则颗粒、非规则颗粒或规则颗粒与非规则颗粒的混合物。The preparation method of ceramic calcium phosphate bone cement according to claim 1, wherein the shape of the β-TCP ceramic particles includes regular particles, irregular particles or a mixture of regular particles and irregular particles.
  5. 如权利要求1所述的陶瓷化磷酸钙骨水泥的制备方法，其特征在于，所述β-TCP陶瓷 颗粒的结构为密质、多孔或者密质和多孔的混合体。The preparation method of ceramic calcium phosphate bone cement according to claim 1, characterized in that the structure of the β-TCP ceramic particles is dense, porous or a mixture of dense and porous.
  6. 如权利要求1所述的陶瓷化磷酸钙骨水泥的制备方法，其特征在于，采用混合法制备 出可塑型的所述陶瓷化磷酸钙骨水泥，其步骤包括：The preparation method of ceramic calcium phosphate bone cement as claimed in claim 1, characterized in that, a mixing method is used to prepare the plastic ceramic calcium phosphate bone cement, and the steps include:
    将所述β-TCP陶瓷颗粒与磷酸二氢钙粉体混合，以得到陶瓷化磷酸钙骨水泥的固相；以 及，Mix the β-TCP ceramic particles with calcium dihydrogen phosphate powder to obtain the solid phase of ceramic calcium phosphate bone cement; and,
    将所述固相与所述液相混合，形成糊状混合物，并通过自固化反应得到所述陶瓷化磷 酸钙骨水泥；或者，采用调和法制备出注射型的所述陶瓷化磷酸钙骨水泥，其步骤包括：The solid phase and the liquid phase are mixed to form a paste mixture, and the ceramic calcium phosphate bone cement is obtained through a self-curing reaction; or, an injection type of the ceramic calcium phosphate bone is prepared using a blending method Cement, the steps include:
    将所述β-TCP陶瓷颗粒和磷酸二氢钙粉体分别与所述液相混合，以分别得到第一半固 体混合物和第二半固体混合物；以及，The β-TCP ceramic particles and calcium dihydrogen phosphate powder are mixed with the liquid phase respectively to obtain a first semi-solid mixture and a second semi-solid mixture respectively; and,
    将所述第一半固体混合物和所述第二半固体混合物进行调和，通过自固化反应得到所 述陶瓷化磷酸钙骨水泥。The first semi-solid mixture and the second semi-solid mixture are blended to obtain the ceramic calcium phosphate bone cement through a self-curing reaction.
  7. 如权利要求6所述的陶瓷化磷酸钙骨水泥的制备方法，其特征在于，所述β-TCP陶瓷 颗粒占所述固相和所述第一半固体混合物总重量的比例均为5％~95％。The preparation method of ceramic calcium phosphate bone cement as claimed in claim 6, characterized in that the proportion of the β-TCP ceramic particles in the total weight of the solid phase and the first semi-solid mixture is 5%~ 95%.
  8. 如权利要求6所述的陶瓷化磷酸钙骨水泥的制备方法，其特征在于，所述固相和所述 第二半固体混合物中均添加有硫酸钙。The preparation method of ceramic calcium phosphate bone cement according to claim 6, wherein calcium sulfate is added to the solid phase and the second semi-solid mixture.
  9. 如权利要求1所述的陶瓷化磷酸钙骨水泥的制备方法，其特征在于，所述蒸馏水中添 加焦磷酸二氢二钠和氢氧化钠。The preparation method of ceramic calcium phosphate bone cement as claimed in claim 1, characterized in that, disodium dihydrogen pyrophosphate and sodium hydroxide are added to the distilled water.
  10. 一种陶瓷化磷酸钙骨水泥，其特征在于，采用如权利要求1至9中任一项所述的陶瓷 化磷酸钙骨水泥的制备方法制备。A kind of ceramic calcium phosphate bone cement is characterized in that it is prepared by the preparation method of ceramic calcium phosphate bone cement as described in any one of claims 1 to 9.
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CN114591066B (en) * 2022-03-14 2023-03-17 卢霄 Ceramic calcium phosphate bone cement and preparation method thereof
CN114956026A (en) * 2022-06-09 2022-08-30 卢霄 Method for synthesizing calcium phosphate powder by precise atom pairing suspension
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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1597590A (en) * 2004-07-27 2005-03-23 西南交通大学 Calcium phoshate bone cement powder containing traditional Chinese medicine and its preparation method
WO2006082442A1 (en) * 2005-02-07 2006-08-10 Orthogem Limited Bone cement
CN1919357A (en) * 2006-09-19 2007-02-28 天津大学 Premix plaster calcium phosphate bone cement
WO2009108934A2 (en) * 2008-02-28 2009-09-03 Osteotherapeutics, L.L.C. Injectable calcium phosphate cememts formulated with bioactive agents and methods for making same
CN102423504A (en) * 2011-12-22 2012-04-25 南京工业大学 Piezoelectric calcium phosphate cement composite material
CN103961741A (en) * 2014-05-14 2014-08-06 常州大学 Calcium phosphate bone repair material and preparation method thereof
CN114591066A (en) * 2022-03-14 2022-06-07 卢霄 Ceramic calcium phosphate bone cement and preparation method thereof

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100070049A1 (en) * 2008-05-06 2010-03-18 O'donnell Patrick Method and apparatus for treating compression fractures in vertebral bodies
CN105327395B (en) * 2015-11-19 2018-07-13 上海纳米技术及应用国家工程研究中心有限公司 A kind of preparation method of acid hydroxy group apatite catalytic curing bone cement
CN106563158A (en) * 2016-11-03 2017-04-19 上海纳米技术及应用国家工程研究中心有限公司 Preparation method of degradation rate adjustable injection bone cement
WO2020008558A1 (en) * 2018-07-04 2020-01-09 オリンパス株式会社 Bone substitute and method for producing bone substitute

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1597590A (en) * 2004-07-27 2005-03-23 西南交通大学 Calcium phoshate bone cement powder containing traditional Chinese medicine and its preparation method
WO2006082442A1 (en) * 2005-02-07 2006-08-10 Orthogem Limited Bone cement
CN1919357A (en) * 2006-09-19 2007-02-28 天津大学 Premix plaster calcium phosphate bone cement
WO2009108934A2 (en) * 2008-02-28 2009-09-03 Osteotherapeutics, L.L.C. Injectable calcium phosphate cememts formulated with bioactive agents and methods for making same
CN102423504A (en) * 2011-12-22 2012-04-25 南京工业大学 Piezoelectric calcium phosphate cement composite material
CN103961741A (en) * 2014-05-14 2014-08-06 常州大学 Calcium phosphate bone repair material and preparation method thereof
CN114591066A (en) * 2022-03-14 2022-06-07 卢霄 Ceramic calcium phosphate bone cement and preparation method thereof

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