Micron-scale polyetheretherketone microspheres, their preparation method and applications

Abstract

The present invention relates to the technical field of polymer microspheres, and specifically relates to micron-sized polyether ether ketone microspheres and their preparation methods and applications, including the following steps: S1. Dispersing a nano-bio-ceramic material into a mixed solution of polyol and water to form a suspension, and then adding an azo-based bubble generator to form a dispersed mixture; at the same time, dissolving polyether ether ketone in an oxidizing inorganic acid to form a PEEK solution; S2. Heating the dispersed mixture to within the thermal decomposition temperature range of the bubble generator. After the foam starts to form, immediately atomizing and dispersing the PEEK solution into the dispersed mixture where the foam has formed. After the two come into contact, they solidify to form microspheres. After post-treatment, micron-sized polyether ether ketone microspheres are obtained. The microspheres obtained by the method of the present invention have a smaller particle size and a concave-pit type porous structure on the surface. The nano-bio-ceramic material is uniformly dispersed on its surface and inside, ensuring that the microspheres have good long-term stable physical and chemical properties after being made into implants for use.

Description

Technical Field

[0001] The present invention relates to the technical field of polymer microspheres, and particularly to micron-sized polyetheretherketone microspheres, a preparation method thereof, and an application thereof. Background Art

[0002] As a high-performance thermoplastic polymer, polyetheretherketone (PEEK) has made remarkable progress in the application in the field of medical implants since its development. PEEK has excellent chemical stability in implantation, and can resist the erosion of body fluids and tissues. In addition, PEEK has good biocompatibility and will not cause obvious inflammatory reactions or foreign body reactions when implanted into the body. At the same time, the strength, modulus and fatigue resistance of PEEK make it an ideal material for mimicking human bones and soft tissues.

[0003] The PEEK material has various applications in the field of implantation. For example, in spinal implants, PEEK is used to manufacture spinal fusion cages and artificial intervertebral discs. Due to its elastic modulus similar to that of bone, it helps to reduce the stress shielding effect. In joint replacement, PEEK is used as the material for some implant components, such as tibial spacers or joint heads. In bone defect repair, bone repair scaffolds or filling materials made of PEEK are used to repair bone defects and promote bone tissue regeneration.

[0004] Hydroxyapatite (HA) and tricalcium phosphate (β-TCP) are two commonly used bioceramic materials, which have good osteoconductivity and osteoinductivity. Combining these materials with PEEK can improve the bioactivity of PEEK and promote the growth and repair of bone tissue. However, the uniform dispersion of inorganic fillers in the polymer matrix has always been a difficult problem to be solved in this field.

[0005] In addition, 3D printing is a common preparation method for implants, but the particle size of 3D printing consumables for medical implants has an important impact on the product performance. Generally speaking, smaller particle size microspheres can print finer and more uniform structures, improve the printing resolution and detail performance, and may have better mechanical properties; in the application of medical implants that require a specific pore structure, the particle size of microspheres directly affects the pore size and distribution of the product, thereby affecting behaviors such as permeability, growth of biological tissues, and biocompatibility. Therefore, how to make the microspheres have a smaller particle size while combining the uniform dispersion of fillers is a technical problem to be urgently solved by the present invention. Summary of the Invention

[0006] To solve the above technical problems, provided are polyetheretherketone microspheres, a preparation method thereof, and an application thereof. The micron-sized polyetheretherketone microspheres of the present invention have uniformly dispersed bioceramic materials on the surface and inside, and the microspheres have a small particle size. The surface of the microspheres has pits, showing a porous microstructure; the microspheres of the present invention have a small and controllable particle size and also have a porous microstructure, which is beneficial to cell adhesion and proliferation, and is beneficial to improving the accuracy, structural uniformity, mechanical properties, biocompatibility, etc. of 3D printing products.

[0007] To achieve the above object, the present invention is realized through the following technical solutions:

[0008] A preparation method of micron-sized polyetheretherketone microspheres, comprising the following steps:

[0009] S1. Dispersing the nano-bioceramic material into a mixed solution of polyol and water to form a suspension, and then adding an azo-based bubble generator to form a dispersed mixture;

[0010] Meanwhile, dissolving polyetheretherketone in an oxidizing inorganic acid to form a PEEK solution;

[0011] S2. Heating the dispersed mixture to within the thermal decomposition temperature range of the bubble generator to form a foamy structure, and then immediately atomizing and dispersing the PEEK solution into the formed foamy structure. The atomization process enables the PEEK solution to uniformly cover the foamy structure in the form of small droplets. When the small droplets of the PEEK solution come into contact with the foamy structure, the PEEK will quickly solidify. This solidification effect causes the foamy structure to break, and the nano-bioceramic material is loaded on the solidified PEEK to form microspheres. After post-treatment, micron-sized polyetheretherketone microspheres loaded with nano-bioceramic materials are obtained, and the median particle size of the microspheres is less than 5 μm.

[0012] Further, the azo-based bubble generator is azodicarbonamide, and the range of the thermal decomposition temperature is 180 - 225 °C.

[0013] Further, the average particle size of the nano-bioceramic material is 20 - 200 nm, and the nano-bioceramic material is selected from nano-hydroxyapatite and / or nano-tricalcium phosphate; the mixed solution of polyol and water is a mixed solution of glycerol and water, wherein the mass percentage of glycerol is 80 - 95%.

[0014] Further, the mass percentage of the nano-bioceramic material in the suspension is 1 - 10%; the dosage of the bubble generator is in the range of 0.5 - 4.5% of the weight of the suspension, and preferably the dosage of the bubble generator is 1 - 3% of the weight of the suspension.

[0015] Furthermore, the oxidizing inorganic acid is selected from concentrated sulfuric acid or concentrated nitric acid, and the mass percentage content of the oxidizing inorganic acid is greater than or equal to 70%; the mass percentage content of the PEEK solution is 20 - 35%; the mass ratio of the PEEK solution to the suspension is 1:4 - 8, and preferably the mass ratio of the PEEK solution to the suspension is 1:5.

[0016] Furthermore, an air - flow type sprayer is used to atomize and disperse the PEEK solution into the dispersion - mixed liquid that forms foam, and the air - flow pressure is 0.05 - 0.1 MPa.

[0017] Furthermore, the post - treatment includes conventional operations such as washing, filtering, and drying.

[0018] On the other hand, the present invention provides micron - sized polyetheretherketone microspheres prepared by the above - mentioned preparation method.

[0019] Finally, the present invention provides the application of the micron - sized polyetheretherketone microspheres prepared by the above - mentioned preparation method in 3D printing consumables for medical implants.

[0020] Beneficial technical effects:

[0021] PEEK microsphere design: Developed brand - new polyetheretherketone (PEEK) microspheres with hydroxyapatite (HA) or tricalcium phosphate (β - TCP) loaded on the surface, combining the advantages of high - performance polymers and bioactive ceramics;

[0022] Innovation in the preparation method: Introduced a technology that combines solvent spraying and foaming. Through a gas - bubble generator, a uniform foam - like structure is formed to ensure that the microspheres have controllable porosity and particle size;

[0023] Enhanced bioactivity: By loading nano - sized HA or β - TCP on the surface, the osteoconductivity and osteoinductivity of the microspheres are improved, promoting the growth and repair of the surrounding bone tissue;

[0024] Advantages of the porous structure: The porous structure of the microspheres is beneficial to cell adhesion and proliferation, enhancing the biocompatibility of the material and contributing to the stability of long - term implants;

[0025] Synergistic effect of the composite material: The combination of PEEK and bio - ceramic materials improves the overall performance of the material, including mechanical strength, biocompatibility, and bone integration ability;

[0026] Customized microsphere properties: The physical and chemical properties of the microspheres can be customized by adjusting the loading amount of bio - ceramic materials, particle size, and its distribution to meet different clinical needs and application scenarios;

[0027] Reduced risk of immune response: As a material with good biocompatibility, PEEK further reduces the risk of immune response after implantation by loading bio - ceramics on the surface;

[0028] Long-term stability and persistent effect: The surface-loaded bioceramic material ensures the long-term stable physical and chemical properties of the microspheres in vivo, ensuring a long-lasting and effective therapeutic effect. Description of the Drawings

[0029] Figure 1 SEM image of the polyetheretherketone microspheres loaded with nano-bioceramic material prepared in Example 1, with the scale bar length in the figure being 1 μm;

[0030] Figure 2 SEM image of the polyetheretherketone microspheres loaded with nano-bioceramic material prepared in Example 5, with the scale bar length in the figure being 1 μm;

[0031] Figure 3 SEM image of the polyetheretherketone microspheres loaded with nano-bioceramic material prepared in Comparative Example 2, with the scale bar length in the figure being 2 μm. Detailed Description of the Invention

[0032] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the embodiments and drawings of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments. The description of at least one exemplary embodiment below is actually only illustrative and in no way limits the present invention and its application or use. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts belong to the scope of protection of the present invention.

[0033] Unless otherwise specifically stated, the numerical values set forth in these embodiments do not limit the scope of the present invention. Technologies and methods known to those of ordinary skill in the relevant art may not be discussed in detail, but where appropriate, such technologies and methods should be regarded as part of the specification. In all examples shown and discussed herein, any specific value should be construed as merely exemplary and not as a limitation. Therefore, other examples of the exemplary embodiments may have different values.

[0034] The experimental methods without specific conditions noted in the following examples are generally determined according to national standards; if there are no corresponding national standards, they are carried out according to general standard requirements or general methods.

[0035] The polyetheretherketone powder model PEEK5600P used below is provided by Shandong Junhao High-Performance Polymer Co., Ltd.

[0036] Example 1

[0037] A method for preparing micron-sized polyetheretherketone microspheres loaded with nano-bioceramic material, comprising the following steps:

[0038] S1. Disperse 5 g of nano-hydroxyapatite (HA) with an average particle size of 50 nm into 95 g of a glycerol-water mixed solution (mass percentage content is 90%) to form a suspension with a mass percentage content of 5%. Then add 2 g of azodicarbonamide as a gas bubble generator to form a dispersed mixture. The dosage of azodicarbonamide is 2% of the weight of the suspension.

[0039] Meanwhile, dissolve 6 g of polyetheretherketone powder in 14 g of concentrated sulfuric acid (concentration 98 wt%) to form a PEEK solution with a mass percentage content of 30%.

[0040] S2. Heat the dispersed mixture to 200 °C. After forming a foamy structure, immediately atomize the PEEK solution using an air-atomizing sprayer. Disperse the generated atomized droplets into the formed foamy structure at an air pressure of 0.05 Mpa. After they come into contact, they solidify to form microspheres. After washing, filtering, and drying, the micron-sized polyetheretherketone microspheres loaded with HA are obtained.

[0041] The microsphere size of this case is shown in Table 1 and Figure 1 .

[0042] Example 2

[0043] A method for preparing micron-sized polyetheretherketone microspheres loaded with nano-bio-ceramic materials, comprising the following steps:

[0044] S1. Disperse 5 g of nano-hydroxyapatite (HA) with an average particle size of 50 nm into 95 g of a glycerol-water mixed solution (mass percentage content is 90%) to form a suspension with a mass percentage content of 5%. Then add 2 g of azodicarbonamide as a gas bubble generator to form a dispersed mixture. The dosage of azodicarbonamide is 2% of the weight of the suspension.

[0045] Meanwhile, dissolve 6 g of polyetheretherketone powder in 14 g of concentrated sulfuric acid (concentration 98 wt%) to form a PEEK solution with a mass percentage content of 30%.

[0046] S2. Heat the dispersed mixture to 210 °C. After forming a foamy structure, immediately atomize the PEEK solution using an air-atomizing sprayer. Disperse the generated atomized droplets into the formed foamy structure at an air pressure of 0.05 Mpa. After they come into contact, they solidify to form microspheres. After washing, filtering, and drying, the micron-sized polyetheretherketone microspheres loaded with HA are obtained.

[0047] The microsphere size of this case is shown in Table 1.

[0048] Example 3

[0049] A method for preparing micron-sized polyetheretherketone microspheres loaded with nano-bio-ceramic materials, comprising the following steps:

[0050] S1. Disperse 5 g of nano-hydroxyapatite (HA) with an average particle size of 50 nm into 95 g of a glycerol-water mixed solution (mass percentage content is 90%) to form a suspension with a mass percentage content of 5%. Then add 2 g of azodicarbonamide as a gas bubble generator to form a dispersed mixture. The dosage of azodicarbonamide is 2% of the weight of the suspension.

[0051] Meanwhile, dissolve 6 g of polyetheretherketone powder in 14 g of concentrated sulfuric acid (concentration 98 wt%) to form a PEEK solution with a mass percentage content of 30%.

[0052] S2. Heat the dispersed mixture to 220 °C. After forming a foamy structure, immediately atomize the PEEK solution using an air atomizer. Disperse the generated atomized droplets into the formed foamy structure at an air pressure of 0.05 Mpa. After they come into contact and solidify, microspheres are formed. After washing, filtering, and drying, microspheres of polyetheretherketone loaded with HA are obtained.

[0053] The microsphere size of this case is shown in Table 1.

[0054] Example 4

[0055] A method for preparing microspheres of polyetheretherketone loaded with nano-biological ceramic materials, comprising the following steps:

[0056] S1. Disperse 7 g of nano-tricalcium phosphate (β-TCP) with an average particle size of 100 nm into 93 g of a glycerol-water mixed solution (mass percentage content is 95%) to form a suspension with a mass percentage content of 7%. Then add 1.5 g of azodicarbonamide as a gas bubble generator to form a dispersed mixture. The dosage of azodicarbonamide is 1.5% of the weight of the suspension.

[0057] Meanwhile, dissolve 5 g of polyetheretherketone powder in 15 g of concentrated sulfuric acid (concentration 98 wt%) to form a PEEK solution with a mass percentage content of 25%.

[0058] S2. Heat the dispersed mixture to 195 °C. After forming a foamy structure, immediately atomize the PEEK solution using an air atomizer. Disperse the generated atomized droplets into the formed foamy structure at an air pressure of 0.05 Mpa. After they come into contact and solidify, microspheres are formed. After washing, filtering, and drying, microspheres of polyetheretherketone loaded with β-TCP are obtained.

[0059] The microsphere size of this case is shown in Table 1.

[0060] Example 5

[0061] Preparation method of micron-sized polyetheretherketone microspheres loaded with nano-bioceramic materials, comprising the following steps:

[0062] S1. Disperse 7 g of nano-tricalcium phosphate (β-TCP) with an average particle size of 20 nm into 93 g of a glycerol-water mixed solution (mass percentage content of 95%) to form a suspension with a mass percentage content of 7%. Then, add 1.5 g of azodicarbonamide as a gas bubble generator to form a dispersion mixture. The dosage of azodicarbonamide is 1.5% of the weight of the suspension;

[0063] Meanwhile, dissolve 5 g of polyetheretherketone powder in 15 g of concentrated sulfuric acid (concentration 98 wt%) to form a PEEK solution with a mass percentage content of 25%;

[0064] S2. Heat the dispersion mixture to 205 °C. After forming a foam-like structure, immediately atomize the PEEK solution using an air-flow type sprayer, and disperse the generated atomized droplets into the formed foam-like structure at an air-flow pressure of 0.05 Mpa. After contact, they solidify to form microspheres. After washing, filtering, and drying, micron-sized polyetheretherketone microspheres loaded with β-TCP are obtained.

[0065] The microsphere size of this example is shown in Table 1 and Figure 2 .

[0066] Comparative example 1

[0067] The microsphere preparation process of this example is the same as that of Example 1, except that azodicarbonamide is not added. The microsphere size of this example is shown in Table 1.

[0068] Comparative example 2

[0069] The microsphere preparation process of this example is the same as that of Example 1, except that 5.3 g of azodicarbonamide is added to form a dispersion mixture. The dosage of azodicarbonamide is 5.3% of the weight of the suspension. The microsphere size of this example is shown in Table 1 and Figure 3 .

[0070] The microsphere sizes of each example are shown in Table 1.

[0071] Table 1 Microsphere sizes of each example

[0072]

[0073] As can be seen from Table 1 and Figure 1 it can be known that the median particle size of the microspheres prepared by the method of the present invention is in the range of 0.5 - 5 μm, and the microspheres have a surface pit-type porous structure, and a small amount of uniformly loaded bioceramic materials can be seen on the surface.

[0074] The microspheres of the present invention have a small particle size and can be controllably adjusted. They also have a porous microstructure, which is beneficial to cell adhesion and proliferation, and is conducive to improving the accuracy, structural uniformity, mechanical properties, biocompatibility, etc. of 3D printing products.

[0075] As described above, the above are only the preferred specific embodiments of the present invention, but the protection scope of the present invention is not limited thereto. Any person skilled in the art within the technical scope disclosed by the present invention, according to the technical solution and inventive concept of the present invention, makes equivalent substitutions or changes, and should be covered within the protection scope of the present invention.

Claims

1. A method for preparing micron-sized polyetheretherketone microspheres, characterized in that: The steps include: S1, dispersing the nano-bioceramic material into a mixed solution of polyol and water to form a suspension, and then adding an azo bubble generator to form a dispersed mixed solution; the amount of the bubble generator is in the range of 0.5-4.5% by weight of the suspension; Meanwhile, polyetheretherketone is dissolved in an oxidizing inorganic acid to form a PEEK solution; the mass percentage of the PEEK solution is 20-35%; S2. The dispersed mixed liquid is heated to a temperature within the thermal decomposition temperature range of the bubble generating agent. After forming foam, the PEEK solution is atomized and dispersed into the dispersed mixed liquid forming the foam. The mass ratio of the PEEK solution to the suspension is 1:4-8. The two solidify to form microspheres after contact. After post-treatment, micron-sized polyetheretherketone microspheres loaded with nano-bioceramic materials are obtained, and the median particle size of the microspheres is less than 5 μm.

2. The method for preparing micron-sized polyetheretherketone microspheres according to claim 1, characterized in that: The azo bubble generator is azodicarbonamide, and the thermal decomposition temperature ranges from 180 to 225°C.

3. The method for preparing micron-sized polyetheretherketone microspheres according to claim 2, characterized in that: The average particle size of the nano bioceramic material is 20-200 nm, and the nano bioceramic material is selected from nano hydroxyapatite and / or nano tricalcium phosphate; the mixed solution of polyol and water is a mixed solution of glycerol and water, wherein the mass percentage of glycerol is 80-95%.

4. The method for preparing micron-sized polyetheretherketone microspheres according to claim 2, characterized in that: The mass percentage of the nano bioceramic material in the suspension is 1-10%.

5. The method for preparing micron-sized polyetheretherketone microspheres according to claim 2, characterized in that: The oxidizing inorganic acid is selected from concentrated sulfuric acid or concentrated nitric acid, and the mass percentage of the oxidizing inorganic acid is greater than or equal to 70%.

6. The method for preparing micron-sized polyetheretherketone microspheres according to any one of claims 1 to 5, characterized in that: The PEEK solution is atomized and dispersed into the dispersed mixed liquid forming the foam by using an airflow sprayer, and the airflow pressure is 0.05-0.1 MPa.

7. Micron-sized polyetheretherketone microspheres prepared by the preparation method according to any one of claims 1 to 6.

8. Use of micron-sized polyetheretherketone microspheres prepared by the preparation method according to any one of claims 1 to 6 in the preparation of medical implant 3D printing consumables.

Images