Synthesis and preparation method of alpha tricalcium phosphate

Abstract

The invention relates to the technical field of preparation of alpha-tricalcium phosphate, and discloses a synthetic preparation method of alpha-tricalcium phosphate, which comprises the following steps: S1, first neutralization reaction: firstly weighing 20-30g of phosphoric acid, putting into a beaker, adding deionized water after the phosphoric acid is completely placed, and stirring for 30-60 minutes; putting the beaker on a constant-temperature heating magnetic stirrer for stirring after the addition is finished, so as to obtain a mixed solution of phosphoric acid and water; meanwhile, a first part of calcium carbonate is uniformly added in the stirring process, magnetic stirring is continued after adding is completed, and a first reaction solution is obtained after stirring is completed; through an innovative process of adding a calcium source step by step for three times, the pH value of a reaction system is adjusted step by step, smooth transition from acidity to alkalescence is realized, the molar ratio of calcium to phosphorus is accurately controlled to be maintained in a target range, the problem of local excessive or insufficient calcium is avoided from the source, and the final product is only alpha-tricalcium phosphate and is free of other crystal phase impurity phases; the requirement of the medical bone repair material on the crystal phase purity is met.

Description

Technical Field

[0001] This invention relates to the field of α-tricalcium phosphate preparation technology, specifically to a method for synthesizing and preparing alpha-tricalcium phosphate. Background Technology

[0002] Tricalcium phosphate (α-TCP) is a key material in the field of biomedical inorganic non-metallic materials. Due to its excellent biocompatibility, biodegradability, and osteoconductivity, it is widely used in bone repair applications such as bone cement matrices, artificial bone scaffolds, and dental prostheses. Its core characteristic is its high-temperature stable crystalline phase. The purity and particle size distribution of the product directly determine the degradation rate of downstream bone repair materials and their integration with new human bone. Therefore, precise control of the calcium-phosphorus raw material ratio and thermal processing technology is necessary during preparation to ensure that the material performance meets standards.

[0003] In the existing technology system, the preparation of α-tricalcium phosphate generally uses phosphoric acid, calcium carbonate, and calcium hydroxide as basic raw materials, following the common technical path of calcium-phosphorus raw material mixing reaction - precursor treatment - high temperature sintering. In the industry, the molar ratio of calcium-phosphorus raw materials is usually adjusted to approach the target stoichiometry. High temperature sintering (which needs to reach above the α phase transformation temperature) is used to promote the transformation of the low-temperature phase into the α phase, and the crystal form is fixed by cooling process. At the same time, in order to meet the downstream processing requirements, the particle size of the product needs to be controlled in the micron range to ensure the reactivity of subsequent bone repair materials.

[0004] However, most existing technologies use a one-time mixing of calcium and phosphorus sources to adjust the ratio, which can easily lead to uneven local raw material concentrations causing the calcium-to-phosphorus ratio to deviate from the target value, resulting in the formation of impurities such as β-tricalcium phosphate and hydroxyapatite. These impurities can disrupt the original degradation characteristics of the material, causing a mismatch between material degradation and new bone formation during bone repair. Furthermore, it is difficult to control the impurity content at low levels, failing to meet the stringent requirements for high purity of α-tricalcium phosphate in medical settings, thus limiting its application in high-end bone repair. Summary of the Invention

[0005] To address the shortcomings of existing technologies, this invention provides a method for synthesizing and preparing alpha tricalcium phosphate, which solves the problems of multiple impurity phases, uneven particle size, and difficulty in ensuring safety of α-TCP.

[0006] To achieve the above objectives, the present invention provides the following technical solution: a method for synthesizing and preparing alpha tricalcium phosphate, comprising the following steps: S1. First neutralization reaction: First, weigh 20-30g of phosphoric acid and place it in a beaker. After the phosphoric acid is added, add deionized water. After the addition is complete, place the beaker on a constant temperature magnetic stirrer and stir to obtain a mixed solution of phosphoric acid and water. At the same time, add the first portion of calcium carbonate evenly during the stirring process. After the addition is complete, continue to stir magnetically. After stirring is complete, the first reaction solution is obtained. S2, Second neutralization reaction: Weigh calcium hydroxide into a second beaker, add deionized water to form a Ca(OH)2 suspension; then use a separatory funnel to dropwise add the first reaction solution obtained in S1 into the Ca(OH)2 suspension. During the dropwise addition, the mixture is continuously stirred by a magnetic stirrer heated to a constant temperature. After titration and stirring are completed, the second reaction solution is obtained. S3, Third Calcification Reaction: Weigh out the second part of calcium carbonate and add it evenly to the second reaction solution obtained in S2. After the addition is complete, stir continuously for at least 12 hours using a magnetic stirrer heated at a constant temperature. After stirring is complete, the third reaction solution is obtained. S4. Solid-liquid separation: Let the third reaction liquid obtained in S3 stand, and after standing, centrifuge it. After centrifugation, collect the solid product obtained by centrifugation. S5. Ball milling: Place the solid product obtained in S4 into the fixed container of the ball mill, set the parameters according to the ball mill operation specifications, and start the ball mill. After the ball milling is completed, the ball milled product is obtained. S6. Secondary centrifugation and drying: The ball milling product obtained in S5 is centrifuged again. After centrifugation, the solid obtained from the second centrifugation is collected. The solid obtained from the second centrifugation is placed in a vacuum drying device and then vacuum dried. After drying, the dried precursor is obtained. S7. High-temperature sintering and rapid cooling: The dried precursor obtained in S6 is ground and placed in a high-temperature furnace. It is sintered at a preset temperature for a preset time. After sintering, the sintered product is immediately subjected to rapid cooling treatment. After rapid cooling, α-tricalcium phosphate primary product is obtained. S8. Refining: Grind the primary product of α-tricalcium phosphate obtained in S7, and after grinding, sieve it through a sieve with a preset mesh size to obtain high-purity α-tricalcium phosphate.

[0007] Preferably, in step S1, the mass of phosphoric acid is 29.98 g, the volume of added deionized water is 1000 mL, the mass of the first calcium carbonate is 13.13 g, and the duration of continuous magnetic stirring is 90 min.

[0008] Preferably, in step S2, the mass of calcium hydroxide is 10.13 g, and the volume of deionized water added is 1000 mL; the total duration of titration and stirring is 4 h; the diameter of the separatory funnel is 5-8 mm, and the outlet is checked for blockage every 10-15 minutes during the titration process. If it is blocked, it is cleaned and the titration continues.

[0009] Preferably, in step S3, the mass of the second portion of calcium carbonate is 13.13g; the temperature of the constant temperature heating magnetic stirrer is set to 30-35℃, the stirring rate is 300-350r / min, and the continuous stirring time is 12-15h.

[0010] Preferably, in step S4, the settling time is 4-5 hours; the centrifugation parameters are 3000 r / min and 15 min.

[0011] Preferably, in step S5, the grinding medium in the fixed container of the ball mill is ZrO2 ceramic balls, and the mass ratio of ZrO2 ceramic balls to the solid product obtained in step S4 is 8-10:1; the operating parameters of the ball mill are: start the first control key, adjust the second control key to 12 and press it again to display 120, and execute the start command; the ball milling time is 2 hours.

[0012] Preferably, in step S6, the operation steps of the vacuum drying equipment are as follows: turn on the main switch, open the valve on the right side of the balance port to draw a vacuum, and turn off the vacuum when the vacuum gauge reading is -13kPa; set the temperature on both sides of the equipment to 80℃; the drying time is 24h; and the parameters of the secondary centrifugation are 3000r / min and 15min.

[0013] Preferably, in step S7, the sintering temperature of the high-temperature furnace is 1400℃ and the sintering time is 5.5h; the rapid cooling treatment involves immersing the sintered product along with the vessel in deionized water at 20-25℃, with a cooling rate ≥500℃ / min; in step S8, the preset mesh size sieve is 500 mesh with an aperture of 0.0308mm, and a vibrating sieve is used to assist in sieving with a vibration frequency of 50-60Hz.

[0014] A high-purity α-tricalcium phosphate prepared by the above-described preparation method has XRD patterns showing sharp double peaks corresponding to the (2 2 10) and (0 0 12) crystal planes at 2θ of 30.7° and 31.5°. All diffraction peaks match the α-TCP standard card PDF#09-0348 and are free of impurity peaks. The SEM morphology of the high-purity α-tricalcium phosphate is an irregular polygonal plate-like or tabular crystal.

[0015] Preferably, the high-purity tricalcium α-phosphate particles have an irregular polygonal plate-like or plate-like crystal morphology, and the particle size is mainly distributed in the range of 1-3 micrometers.

[0016] This invention provides a method for synthesizing and preparing alpha-tricalcium phosphate. It has the following beneficial effects: 1. This invention employs an innovative process of adding calcium source in three steps to gradually adjust the pH value of the reaction system, smoothly transitioning from acidic to weakly alkaline, and precisely controlling the calcium-phosphorus molar ratio to maintain it within the target range. This avoids the problem of local calcium excess or deficiency from the source, ensuring that the final product is only α-tricalcium phosphate, without other crystalline impurities, thus meeting the requirements for crystalline purity of medical bone repair materials.

[0017] 2. This invention, by clearly defining the medium and rate parameters of the quenching process, rapidly crosses the temperature range for the transformation of α-tricalcium phosphate to other crystalline phases, effectively suppressing crystal transformation and ensuring the stability of the α phase; at the same time, it optimizes the ball milling and sieving processes to directly prepare particles suitable for downstream bone repair material processing requirements, eliminating the need for additional grinding steps, avoiding the risk of particle agglomeration, simplifying the process flow, and reducing production costs.

[0018] 3. This invention uses grinding media of a specific material to avoid the introduction of impurities by traditional metal grinding media; a centrifugation treatment step is added after ball milling to remove ultrafine impurity particles generated during the grinding process, ensuring that the product is free from additional impurity contamination, meets the strict standards for biosafety of medical implant materials, and can be safely applied in bone repair scenarios. Attached Figure Description

[0019] Figure 1 This is the XRD pattern of α-tricalcium phosphate of the present invention; Figure 2 This is a SEM image of the α-tricalcium phosphate of the present invention. Detailed Implementation

[0020] The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention. Example

[0021] Please see the appendix Figure 1-2 This invention provides a method for synthesizing and preparing alpha tricalcium phosphate, comprising: (a) Preparation of raw materials and equipment Raw materials: Phosphoric acid (H3PO4, analytical grade, mass fraction 85%), calcium carbonate (CaCO3, analytical grade, particle size 500 mesh), calcium hydroxide (Ca(OH)2, analytical grade), deionized water (conductivity ≤10μS / cm); Equipment: constant temperature heating magnetic stirrer (temperature control accuracy ±1℃), separating funnel (with constant pressure valve), high-speed centrifuge (maximum speed 12000r / min), planetary ball mill (equipped with ZrO2 ceramic balls), vacuum drying oven (vacuum range -0.1~0MPa), box-type high-temperature furnace (maximum temperature 1400℃, adjustable heating rate), vibrating screen (equipped with 500 mesh screen), X-ray diffractometer, field emission scanning electron microscope, inductively coupled plasma mass spectrometer.

[0022] (II) Specific Operating Procedures S1: The first neutralization reaction includes the following sub-steps: S1.1 Weigh 29.98g of phosphoric acid and slowly pour it into a 500mL beaker; S1.2 Add 1000mL of deionized water and stir until homogeneous (allow to cool naturally to room temperature). S1.3 Place the beaker on a constant temperature heating magnetic stirrer and set the stirring speed to 300 r / min; S1.4. Slowly add 13.13g of calcium carbonate (first portion) and stir continuously for 90min until no bubbles are generated and the solution is clear, to obtain the first reaction solution (the main component is calcium dihydrogen phosphate).

[0023] S2: The second neutralization reaction includes the following sub-steps: S2.1 Weigh 10.13g of calcium hydroxide, add 1000mL of deionized water, and stir to form a uniform suspension; S2.2 Place the suspension on a magnetic stirrer and set the stirring speed to 350 r / min; S2.3 Transfer the first reaction solution to the separatory funnel and add it to the suspension at a dropping rate of about 1 drop / second. S2.4 After the addition is complete, continue stirring until the total time is 4 hours. Monitor the pH in real time to ensure it is stable at 6.5~7.0, and obtain the second reaction solution (the main component is amorphous calcium phosphate).

[0024] S3: The third calcification reaction, including the following sub-steps: S3.1 Add 13.13g of calcium carbonate (second part) to the second reaction solution. S3.2 Adjust the temperature to 32℃, stir at 320r / min, and continue stirring for 14h to obtain the third reaction solution (the main component of which is tricalcium phosphate precursor). S4: Solid-liquid separation, including the following sub-steps: S4.1. Let the third reaction solution stand for 5 hours and pour off the supernatant. S4.2 Transfer the remaining turbid liquid to a centrifuge tube, centrifuge at 3000 r / min for 15 min, and collect the white solid at the bottom of the tube (crude precursor).

[0025] S5: Ball milling process, including the following sub-steps: S5.1 Transfer the solid product to a ZrO2 ceramic jar and add ZrO2 ceramic balls (mass ratio 8:1). S5.2 Set the ball mill speed to 120 r / min, ball mill for 2 hours, and collect fine white powder.

[0026] S6: Secondary centrifugation and drying, including the following sub-steps: S6.1. Add deionized water to the ball-milled product to form a suspension, and centrifuge twice at 3000 r / min for 15 min. S6.2. Collect the solid and transfer it to a vacuum drying oven. Set the vacuum level to -13 kPa and the temperature to 80°C. Dry for 24 hours to obtain the dried precursor.

[0027] S7: High-temperature sintering and rapid cooling, including the following sub-steps: S7.1 After grinding the dried precursor, transfer it to an alumina crucible and place it in a high-temperature furnace; S7.2, Increase the temperature to 1400℃ at a rate of 5℃ / min, and sinter at that temperature for 5.5 hours; S7.3. Immediately after sintering, immerse the crucible in 25°C deionized water for rapid cooling to obtain the primary product of α-tricalcium phosphate.

[0028] S8: Refining, including the following sub-steps: S8.1. Grind the initial product and pass it through a 500-mesh vibrating screen (frequency 55Hz, sieving for 10 minutes). S8.2 Collect the powder that passes through the sieve, which is high-purity α-tricalcium phosphate.

[0029] (III) Product performance testing and results (1) Phase analysis (XRD) Sample preparation: Take a small amount of product and compress it into a tablet (10 mm in diameter and 1 mm in thickness). Detection conditions: Scanning range 2θ = 10°~60°, scanning rate 5° / min; Results: The XRD pattern showed sharp double peaks at 2θ = 30.7° and 31.5°, corresponding to the (2 2 10) and (00 12) crystal planes of α-TCP, which perfectly matched the standard card PDF#09-0348, with no impurity peaks (e.g., Figure 1 As shown in the figure, it is proven to be a pure α-TCP phase.

[0030] (2) Morphology and particle size analysis (SEM) Sample preparation: The powder was fixed with conductive adhesive, sputtered with gold, and then placed in a scanning electron microscope; Observation conditions: accelerating voltage 15kV, amplification factor 5000x; Results: The product consisted of irregular polygonal plate-like crystals with clear particle boundaries, no agglomeration, and a particle size distribution in the range of 1–3 μm (e.g., ...). Figure 2 As shown in the figure, it meets the optimal particle size requirements for bone cement application.

[0031] (3) Detection of heavy metal content (ICP-MS) Detection method: Weigh 0.1g of powder, digest with nitric acid (1:1), and make up to 100mL before detection.

[0032] Therefore, the conclusion is that the product has excellent biosafety and meets the requirements for medical implant materials.

[0033] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A method for synthesizing and preparing alpha-tricalcium phosphate, characterized in that, Includes the following steps: S1. First neutralization reaction: First, weigh 20-30g of phosphoric acid and place it in a beaker. After the phosphoric acid is added, add deionized water. After the addition is complete, place the beaker on a constant temperature magnetic stirrer and stir to obtain a mixed solution of phosphoric acid and water. At the same time, add the first portion of calcium carbonate evenly during the stirring process. After the addition is complete, continue to stir magnetically. After stirring is complete, the first reaction solution is obtained. S2, Second neutralization reaction: Weigh calcium hydroxide into a second beaker, add deionized water to form a Ca(OH)2 suspension; then use a separatory funnel to dropwise add the first reaction solution obtained in S1 into the Ca(OH)2 suspension. During the dropwise addition, the mixture is continuously stirred by a magnetic stirrer heated to a constant temperature. After titration and stirring are completed, the second reaction solution is obtained. S3, Third Calcification Reaction: Weigh out the second part of calcium carbonate and add it evenly to the second reaction solution obtained in S2. After the addition is complete, stir continuously for at least 12 hours using a magnetic stirrer heated at a constant temperature. After stirring is complete, the third reaction solution is obtained. S4. Solid-liquid separation: Let the third reaction liquid obtained in S3 stand, and after standing, centrifuge it. After centrifugation, collect the solid product obtained by centrifugation. S5. Ball milling: Place the solid product obtained in S4 into the fixed container of the ball mill, set the parameters according to the ball mill operation specifications, and start the ball mill. After the ball milling is completed, the ball milled product is obtained. S6. Secondary centrifugation and drying: The ball milling product obtained in S5 is centrifuged again. After centrifugation, the solid obtained from the second centrifugation is collected. The solid obtained from the second centrifugation is placed in a vacuum drying device and then vacuum dried. After drying, the dried precursor is obtained. S7. High-temperature sintering and rapid cooling: The dried precursor obtained in S6 is ground and placed in a high-temperature furnace. It is sintered at a preset temperature for a preset time. After sintering, the sintered product is immediately subjected to rapid cooling treatment. After rapid cooling, α-tricalcium phosphate primary product is obtained. S8. Refining: Grind the primary product of α-tricalcium phosphate obtained in S7. After grinding, sieve it through a sieve with a preset mesh size to obtain high-purity α-tricalcium phosphate.

2. The method for synthesizing and preparing alpha-tricalcium phosphate according to claim 1, characterized in that, In step S1, the mass of phosphoric acid is 29.98 g, and the volume of deionized water added is 1000 mL; the mass of the first calcium carbonate is 13.13 g; and the duration of continuous magnetic stirring is 90 min.

3. The method for synthesizing and preparing alpha-tricalcium phosphate according to claim 1, characterized in that, In step S2, the mass of calcium hydroxide is 10.13 g, and the volume of deionized water added is 1000 mL; the total time for titration and stirring is 4 h; the diameter of the separatory funnel is 5-8 mm, and the outlet is checked for blockage every 10-15 minutes during the titration process. If it is blocked, it is cleaned and the titration continues.

4. The method for synthesizing and preparing alpha-tricalcium phosphate according to claim 1, characterized in that, In step S3, the mass of the second portion of calcium carbonate is 13.13g; the temperature of the constant temperature heating magnetic stirrer is set to 30-35℃, and the stirring rate is 300-350r / min; the continuous stirring time is 12-15h.

5. The method for synthesizing and preparing alpha-tricalcium phosphate according to claim 1, characterized in that, In step S4, the settling time is 4-5 hours; the centrifugation parameters are 2800-3200 r / min and 15 min.

6. The method for synthesizing and preparing alpha-tricalcium phosphate according to claim 1, characterized in that, In step S5, the grinding medium in the fixed container of the ball mill is ZrO2 ceramic balls, and the mass ratio of ZrO2 ceramic balls to the solid product obtained in step S4 is 8-10:

1. The operating parameters of the ball mill are: start the first control key, adjust the second control key to 12 and press it again to display 120, and execute the start command. The ball milling time is 1-3 hours.

7. The method for synthesizing and preparing alpha-tricalcium phosphate according to claim 1, characterized in that, In S6, the operation steps of the vacuum drying equipment are as follows: turn on the main switch, open the valve on the right side of the balance port to draw a vacuum, and turn off the vacuum when the vacuum gauge reading is -13kPa. Set the temperature on both sides of the equipment to 80℃. The drying time is 20-30h. The parameters of the secondary centrifugation are 2800-3200r / min and 15min.

8. The method for synthesizing and preparing alpha tricalcium phosphate according to claim 1, characterized in that, In step S7, the sintering temperature of the high-temperature furnace is 1200-1500℃, and the sintering time is 5-6h; the rapid cooling treatment involves immersing the sintered product along with the vessel into deionized water at 20-25℃, with a cooling rate ≥500℃ / min; in step S8, the preset mesh size sieve is 300-600 mesh with an aperture of 0.0308mm, and a vibrating sieve is used to assist in sieving with a vibration frequency of 50-60Hz.

9. A high-purity α-tricalcium phosphate prepared by the preparation method according to any one of claims 1-8, characterized in that, The XRD pattern of the high-purity α-tricalcium phosphate shows sharp double peaks at 2θ of 30.7° and 31.5°, corresponding to the 2 2 10 and 0 0 12 crystal planes. All diffraction peaks match the α-TCP standard card PDF#09-0348 and there are no impurity peaks. The SEM morphology of the high-purity α-tricalcium phosphate is an irregular polygonal plate-like or tabular crystal.

10. The high-purity α-tricalcium phosphate according to claim 9, characterized in that, The high-purity tricalcium α-phosphate particles have an irregular polygonal plate-like or plate-like crystal morphology, and the particle size is mainly distributed in the range of 1-3 micrometers.

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