RU2771017C1 - Method for producing bioactive ceramics based on zirconium dioxide - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention can be used in traumatology, orthopedics, regenerative medicine, dentistry and maxillofacial surgery to restore the functional integrity of bone tissue. A method for producing bioactive ceramics based on zirconium dioxide includes heat treatment of a mixture containing zirconium and glass components. A solution in organic solvents containing sodium oleate, tetraethoxysilane, calcium oleate, tributyl phosphate and zirconyl oleate is used as a mixture. Solvents are distilled from the initial mixture, then the precursor is pyrolyzed at 1300°C for 30 minutes. The resulting product is cooled to room temperature, crushed, pressed, calcined in a muffle furnace up to 1300°C and cooled in two stages: first in a separate annealing chamber at 550°C with an exposure for an hour, and then when cooled to room temperature in a switched-off annealing chamber.

EFFECT: invention makes it possible to increase the density and strength of bioactive ceramics based on zirconium dioxide.

1 cl, 4 ex

Description

The invention relates to methods for producing bioactive ceramics, which is used in medicine, in particular in traumatology, orthopedics, regenerative medicine, dentistry and maxillofacial surgery to restore the functional integrity of bone tissue.

One of the promising materials for the manufacture of porous structures for bone arthroplasty is zirconium dioxide, which is characterized by high strength, corrosion resistance, resistance to chemically active media, and the absence of exchange reactions with body structures. The main disadvantage of zirconia materials is their bioinertness. To solve this problem, such methods are used as applying bioactive layers to the surface of the material, or obtaining composite ceramics with a bioactive phase. Calcium phosphate compounds can serve as such a phase. Calcium phosphate-based materials have excellent biocompatibility, but they do not have sufficient strength and cannot be used independently as bone tissue substitutes.

A known method of obtaining a porous glass-ceramic material that can be used for the manufacture of implants [RU No. 2462272, publ. 09/27/2012]. This method includes the production of a semi-dry mass containing calcium phosphate glass powder and a 1-10% solution of a polymer selected from polyvinyl alcohol, gelatin, methylcellulose or carboxymethylcellulose, which is then molded in paper molds by pressing, dried, fired with an exposure of 0.5-1.5 hours at 900-1000°C. Pore-forming rods are also introduced into the semi-dry mass in the amount of 3-30 wt. %, representing nylon, lavsan or graphite, and starch in the amount of 1-10 wt. %. Calcium phosphate glass has the following composition 40-55 mol. % CaO, 4-10 mol. % Al ₂ O ₃ , 1-5 mol. % B ₂ O ₃ , 1-10 mol. % TiO ₂ , 1-10 mol. % ZrO ₂ and P ₂ O ₅ the rest. The method provides for the production of bioactive glass-ceramic materials for implantation with a channel and inter-channel pore structure.

The disadvantage of this method is the low compressive strength of the samples, equal to 3-50 MPa.

In [Narulkar VV et al. "Characteristics of porous zirconia coated with hydroxyapatite as human bones" // Bull. Mat. Sci., 2007, v.30, no. 4, pp. 309-314] proposed the use of a porous ceramic matrix to solve the problem of implant fragility. A porous matrix was prepared by pouring expanded polystyrene granules with a suspension of yttrium-stabilized zirconium dioxide or a suspension of zirconium dioxide and Al ₂ O ₃ in polymethyl methacrylate. This was followed by drying of the sample and mechanical knocking out of expanded polystyrene granules from the matrix, after which the matrix was calcined at 1500°C for 2 hours. Powders of hydroxyapatite and borosilicate glass were thoroughly crushed and dispersed. After that, the mixture was transferred into a suspension, into which a porous ceramic matrix with zirconium was immersed and fired at 1200°C. Uncoated porous structures had a high porosity of 51-69%, a high degree of pore interconnection, and rather large pore window sizes (300-500 µm). The average thickness of the bioactive coating layer was 50 μm. The porous ceramics had a compressive strength of 3–36.8 MPa, which is comparable to the mechanical properties of spongy bones.

The disadvantages of this method are, first of all, the duration of the process, the use of additional equipment, as well as manual extraction of expanded polystyrene granules from the matrix, which can affect the reproducibility of the properties of the material.

A known method of obtaining porous bioactive ceramics based on zirconium oxide [RU No. 2595703, publ. 08/27/2016], which provides for the following operations: zirconium dioxide is mixed with chemically resistant glass grade XC-2 No. 29 and magnesium oxide, which is used as a stabilizing component that prevents the transition of zirconium dioxide from a tetragonal structure to a monoclinic one when heated. Then add a mixture of ammonium phosphate 2-substituted (NH ₄ ) ₂ HPO ₄ and calcium carbonate CaCO ₃ . The initial mixture contains 72-73 wt. % ZrO ₂ , 4-5 wt. % MgO, 6-8 wt. % (NH ₄ ) ₂ HPO ₄ , 7-9 wt. % CaCO ₃ and 8-8.5 wt. % glass grade XC-2 No. 29. The mixture is triturated, after which 90% of the particles have a size of less than 50 μm, then pressed in a mold under a pressure of 100 MPa/cm ² and calcined in a muffle furnace at a temperature of 1300°C. As a result, a porous bioactive ceramic based on zirconium dioxide is obtained, in which the pores are lined from the inside with a bioactive layer (particles of calcium phosphates) with a compressive strength of at least 100 MPa.

The disadvantage of this method is the use of a mixture of (NH ₄ ) ₂ HPO ₄ and CaCO ₃ , which is both a blowing agent and a bioactive component. As a result of using such a mixture, the resulting bioactive calcium phosphates are predominantly locked inside closed pores, which hinders the process of their biodegradation, as a result of which ions should be released that form a chemical bond between ceramics and bone tissue components. At the same time, the surface layer of such ceramics, which should directly interact with bone tissue, consists of zirconium oxide particles inside chemically resistant glass, that is, it is bioinert. Thus, the ceramic obtained by this method has a low biological activity necessary for osseointegration.

As a prototype, the selected method for the synthesis of bioactive ceramics containing bioglass 45S5, zirconium dioxide and hydroxyapatite [Prasad S. et al. "Preparation, in-vitro bioactivity and mechanical properties of reinforced 45S5 bioglass composite with HA-ZrO ₂ powders" // Orient. J. Chem., 2017, V. 33, No. 3, pp. 1286-1296]. Bioglass 45S5 composition, wt. %: 45 SiO ₂ , 24.5 Na ₂ O, 24.5 CaO, 6 P ₂ O ₅ , prepared using quartz, calcium carbonate, sodium carbonate and ammonium dihydroorthophosphate, which were first melted at 1400-1410 ° C, and then annealed in a furnace at 500–550°C. Hydroxyapatite (HA) was obtained by the sol-gel method, for which an aqueous solution of H ₃ PO ₄ , the pH of which was adjusted to 10 with NH ₃ , was mixed with an aqueous solution of Ca(NO ₃ ) ₂ 4H ₂ O, the mixture was stirred for one hour , then kept for 24 hours, the resulting gel was dried at 65 ºС for 24 hours and calcined. Bioglass (45S5), powder of hydroxyapatite and ZrO ₂ in the following ratio, wt.%: 85-40 45S5, 10-40 GA, 5-20 ZrO ₂ , was crushed and mixed with a ball mill for about 4 hours. The samples were placed and sintered in a furnace at 1000, 1100, and 1200°C for 5 hours, the heating and cooling rate was 5°C/min. Using a uniaxial pressure of 100 MPa, rectangular rod-shaped samples were formed.

The disadvantage of the prototype is its multi-stage, duration of the process, as well as the low strength of the resulting glass ceramics, which does not exceed 109 MPa.

The objective of this invention is to create an easy-to-implement method for obtaining bioactive ceramics based on zirconium oxide, which has a higher density and strength relative to the prototype, which allows you to expand the range of possible use.

The technical result of the proposed method consists in increasing the amount of zirconium oxide uniformly distributed in the matrix of bioactive ceramics, which significantly increases the strength of bioceramics, as well as in using the re-sintering of the obtained ceramics alloyed with zirconium oxide after its pressing, which, in turn, increases material density.

The technical result is achieved by the proposed method for producing bioceramics based on zirconium dioxide using organic derivatives of silicon, phosphorus and zirconium as starting materials, namely sodium, calcium and zirconyl oleates, tributyl phosphate and tetraethylorthosilicate, the mixture of which is subjected to pyrolysis to obtain a product that is further crushed, pressed and additionally calcined to give greater strength to bioceramics.

The process is carried out as follows.

To a solution of sodium oleate with tetraethoxysilane in turpentine is added a solution of calcium oleate with tributyl phosphate in toluene, then a solution of zirconyl oleate in toluene. After mixing all the components in the calculated amounts, the solvents are distilled off at a temperature of 150-200°C. The resulting precursor is subjected to pyrolysis in a muffle furnace, heated to a temperature of 1300°C, and kept for 30 minutes. After cooling at room temperature, the obtained glass-ceramic is rubbed on a vibrating mill: 80% of the particles have a size of less than 50 μm. The powder is pressed under a pressure of 50 MPa by cold uniaxial pressing at a speed of 0.5 mm/sec, holding for 120 seconds, then calcined in a muffle furnace to a temperature of 1300°C. Cooling of ceramics is carried out in two stages in order to avoid cracking of the sample. The formation of 45S5 was ensured by transferring the sample to an annealing chamber at a temperature of 550°C, where it was kept at this temperature for an hour, and then cooling occurred slowly with the annealing chamber turned off to room temperature in a natural way. The result is bioactive ceramics, with a composition of 60-90 wt. % ZrO ₂ and 40-10 wt. % "Bioglass 45S5", in which bioglass is evenly distributed in the volume of the composite.

To confirm the formation of bioactive ceramics, the product was examined by X-ray phase analysis on a Bruker AXS, D8 ADVANCE diffractometer; the qualitative and quantitative elemental composition and surface morphology of the samples were determined by scanning electron microscopy. The samples obtained by the claimed method are opaque and consist of a glass phase, as well as particles of spherical and cubic shapes. The distribution maps of the elements obtained from the samples showed a uniform distribution of the elements in the ceramics.

The bioactivity of the samples was confirmed by in vitro studies using a model medium - SBF solution. The samples were placed in solution for 18 days at a temperature of 37°C, which was maintained by a thermostat. The solution was updated every 48 hours. All samples have hydroxyapatite coatings in the form of a dense cracked crust.

The possibility of carrying out the invention is confirmed by the following examples.

Example 1

_A solution _{of 4.683} g _of calcium _{oleate (C 36 H 66 O 4} Ca , 98%) with 0.400 g of tributyl phosphate (C ₁₂ H ₂₇ O ₄ P, 99%) in toluene, then a solution of 14.503 g of zirconyl oleate (C ₃₆ H ₆₆ O ₅ Zr) in toluene. The amount of zirconyl oleate corresponds to 60 wt. % ZrO ₂ in bioceramics. After mixing all the components, the solvents are distilled off at a temperature of 150-200°C. The resulting precursor is subjected to pyrolysis in a muffle furnace by heating to a temperature of 1300°C and kept at this temperature for 30 min. The resulting ceramic is cooled at room temperature. Glass ceramics are abraded on a vibrating mill. The powder is pressed under a pressure of 50 MPa and calcined in a muffle furnace to a temperature of 1300°C. The ceramics are cooled in a separate annealing chamber at a temperature of 550°C and held for an hour, followed by slow cooling to room temperature in the off annealing chamber.

The ceramic sample consists of a glass phase, as well as spherical particles corresponding to ZrO ₂ and cubic particles corresponding to Na ₄ Zr ₂ Si ₃ O ₁₂ . The average diameter of the spherical particles is 1 µm, the edge side of the cubic particles is about 1.5 µm. The glass phase is characterized by an increased content of calcium, phosphorus and silicon; it forms a phase that is bioactive. The bioactivity of the samples was confirmed by in vitro studies using a model medium - SBF solution. The thickness of the resulting coating of nanocrystalline hydroxyapatite, capable of supporting tissue regeneration, was about 0.3 μm. The coating is dense, uniform and occupies the entire surface of the sample. The compressive strength of the sample is (420 ± 15) MPa.

Example 2

_A solution _{of 3.513} g _of calcium _{oleate (C 36 H 66 O 4} Ca , 98%) with 0.300 g of tributyl phosphate (C ₁₂ H ₂₇ O ₄ P, 99%) in toluene, then a solution of 16.920 g of zirconyl oleate (C ₃₆ H ₆₆ O ₅ Zr) in toluene. The amount of zirconyl oleate corresponds to 70 wt. % ZrO ₂ in bioceramics. After mixing all the components, the solvents are distilled off at a temperature of 150-200°C. The resulting precursor is subjected to pyrolysis in a muffle furnace by heating to a temperature of 1300°C and kept at this temperature for 30 min. The resulting ceramic is cooled at room temperature. Glass ceramics are abraded on a vibrating mill. The powder is pressed under a pressure of 50 MPa and calcined in a muffle furnace to a temperature of 1300°C. The ceramics are cooled in a separate annealing chamber at a temperature of 550°C and held for an hour, followed by slow cooling to room temperature in the off annealing chamber.

The ceramic sample consists of a glass phase, as well as spherical particles corresponding to ZrO ₂ and cubic particles corresponding to Na ₄ Zr ₂ Si ₃ O ₁₂ . The average diameter of the spherical particles is 1 µm, the edge side of the cubic particles is about 1.5 µm. The glass phase is characterized by an increased content of calcium, phosphorus and silicon; it forms a phase that is bioactive. The bioactivity of the samples was confirmed by in vitro studies using a model medium - SBF solution. The thickness of the resulting coating of nanocrystalline hydroxyapatite, capable of supporting tissue regeneration, was about 0.25 µm. The coating is dense, uniform and occupies the entire surface of the sample. The compressive strength of the sample is (480 ± 20) MPa.

Example 3

_A solution _of 2.342 g _of calcium _{oleate (C 36 H 66 O 4 Ca} , 98%) with 0.200 g of tributyl phosphate (C ₁₂ H ₂₇ O ₄ P, 99%) in toluene, then a solution of 19.337 g of zirconyl oleate (C ₃₆ H ₆₆ O ₅ Zr) in toluene. The amount of zirconyl oleate corresponds to 80 wt.% ZrO ₂ in bioceramics. After mixing all the components, the solvents are distilled off at a temperature of 150 - 200 ºС. The resulting precursor is subjected to pyrolysis in a muffle furnace, heated to a temperature of 1300 ºС and kept at this temperature for 30 min. The resulting ceramic is cooled at room temperature. Glass ceramics are abraded on a vibrating mill. The powder is pressed under a pressure of 50 MPa and calcined in a muffle furnace to a temperature of 1300°C. The ceramics are cooled in a separate annealing chamber at a temperature of 550 °C and held for an hour, followed by slow cooling to room temperature in a switched off annealing chamber.

The ceramic sample consists of a glass phase and mainly particles of a spherical shape corresponding to ZrO₂. The average diameter of the spherical particles is 1 µm, the side of the edge of the particles is a cubic shape, occasionally found in the sample and corresponding to Na₄Zr₂Si₃O₁₂, about 1.5 µm. glass phase is bioactive.

The thickness of the resulting coating was about 0.2 µm. The coating is dense, uniform and covers the entire surface. The compressive strength of the sample is (600 ± 25) MPa.

Example 4

_A solution _of 1.171 g _of calcium _{oleate (C 36 H 66 O 4 Ca} , 98%) with 0.100 g of tributyl phosphate (C ₁₂ H ₂₇ O ₄ P, 99%) in toluene, then a solution of 21.754 g of zirconyl oleate (C ₃₆ H ₆₆ O ₅ Zr) in toluene. The amount of zirconyl oleate corresponds to 90 wt. % ZrO ₂ in bioceramics. After mixing all the components, the solvents are distilled off at a temperature of 150-200°C. The resulting precursor is subjected to pyrolysis in a muffle furnace by heating to a temperature of 1300°C and kept at this temperature for 30 min. The resulting ceramic is cooled at room temperature. Glass ceramics are abraded on a vibrating mill. The powder is pressed under a pressure of 50 MPa and calcined in a muffle furnace to a temperature of 1300°C. The ceramics are cooled in a separate annealing chamber at a temperature of 550°C and held for an hour, followed by slow cooling to room temperature in the off annealing chamber.

The ceramic sample consists of a glass phase and mainly particles of a spherical shape corresponding to ZrO₂. The average diameter of the spherical particles is 1 µm, the side of the edge of the particles is a cubic shape, occasionally found in the sample and corresponding to Na₄Zr₂Si₃O₁₂, about 1.5 µm. glass phase is bioactive.

The thickness of the resulting coating was 0.15-0.2 µm. The coating is dense, uniform and covers the entire surface. The compressive strength of the sample is (650 ± 15) MPa.

As can be seen from the above examples, bioactive glass-ceramic materials obtained by the claimed method meet the requirements for implants and can be recommended as materials for the treatment of bone defects. The tensile strength of the resulting bioceramics is several times higher than the values of the prototype, which allows you to expand the range of its possible use.

Claims (2)

1. A method for producing bioactive ceramics based on zirconium dioxide by heat treatment of a mixture containing zirconium and glass components, characterized in that the mixture uses a solution in organic solvents containing sodium oleate, tetraethoxysilane, calcium oleate, tributyl phosphate and zirconyl oleate, from the original the mixtures are preliminarily distilled off solvents, then the precursor is subjected to pyrolysis at 1300°C for 30 minutes, the resulting product is cooled to room temperature, crushed, pressed, calcined in a muffle furnace to a temperature of 1300°C and cooled in two stages: first, in a separate annealing chamber at at a temperature of 550°C with exposure for an hour, and then when cooled to room temperature in the switched off annealing chamber. 2. The method according to p. 1, characterized in that the composition of bioactive ceramics obtained from the initial mixture has the following ratio of components, wt. %: 60-90 ZrO ₂ and 40-10 "Bioglass 45S5".