TWI804100B - A method for producing porous composite material - Google Patents

Abstract

A method for producing a porous HAP/β-TCP composite material, at least comprising steps of providing a dry powder mixture, providing a granulated mixture, and processing an annealing schedule. The dry powder mixture includes 40wt%~55wt% of hydroxyapatite (HA), 25wt%~40wt% of beta tricalcium phosphate (β-TCP) and 10wt%~20wt% of polyethylene with 250µm~600µm microns in size. The granulated mixture is prepared by mixing the dry powder mixture and a sugar solution, and then subsequent be treat base on the annealing schedule. The annealing schedule includes inputting a temperature form 80℃~100℃ into 400℃~500℃ with a heating rate of 20℃~30℃/hour, then exposure at the temperature.

Description

Manufacturing method of porous composite material

The invention relates to a manufacturing method of a porous composite material, which can be used as a filler of bone tissue.

In medicine, a common application of porous ceramic materials is in the form of porous ceramic particle matrices for reconstructing bone tissue in surgery, traumatology and dentistry. The biological behavior of ceramic materials based on hydroxyapatite (HAP) and β-tricalcium phosphate (β-TCP) is influenced by various factors (e.g., chemical and phase composition, microstructure, pore size, and distribution) .

The bioactive material with HAP and β-TCP has a chemical composition similar to that of bone tissue. Due to the bioresistance of HAP and the bioresorbability of β-TCP, the composite material HAP/β-TCP has advantages, and the biodegradation of β-TCP can also promote the formation of bone tissue. To use the above-mentioned composite material as a filler for bone voids, it must have macropores of 100-1000 μm and micropores of 1-20 μm at the same time.

Existing studies (Upgrading Calcium Phosphate Scaffolds for Tissue Engineering Application, Key Engineering Materials, Vol.377, pp.19-42, 2008) pointed out that the structure of this implanted filler is similar to the bone structure, providing the best postoperative bone recovery. quick. to make bones For tissue growth in implant fillers, the required minimum opening size should be 100-135 μm. In addition, the more openings, the more effective the growth and fixation process of bone tissue will be (Hydroxyapatite and Hydroxyapatite-Based Ceramics, Inorganic Materials, Vol.38, No.10, pp.973-984, 2002). There are micropores commensurate with the size of plasma proteins in the material, which will increase the adsorption of proteins and make osteoblasts proliferate and promote the process of biological integration. Therefore, for practical applications, ceramics with a bimodal pore size distribution are desired.

Calcium phosphate materials with a porous structure of macropores can be produced by combustion additives, polymer sponge replication (through impregnation of organic sponges followed by annealing), and slurry foaming methods, but the existing granulation methods It is not allowed to produce particles with both macropores and micropores.

High microporosity can be achieved using liquid porogens, which can be liquid hydrocarbons or water. The microporosity of the particles can be determined by the amount and composition of the liquid in the interstices between the calcium phosphate crystallites. In addition, the mode of subsequent heat treatment of the particles (temperature and duration) determines the rate at which vapors and gases leave the particles when heated. speed.

U.S. Patent Publication No. US 20030193106 discloses a method for obtaining porous materials, which is to add magnesium-containing materials to the mixture of HAP/β-TCP, form the above-mentioned powder materials on the surface of the polyurethane sponge frame, and then anneal at a high temperature at 1000-1200 ° C Burn to remove the sponge frame. By replicating the pore structure of the polymer matrix, the resulting ceramic material has macropores with sizes ranging from 200 to 600 μm.

US Patent Publication No. US 5171720A discloses a method for manufacturing a porous ceramic sintered body, which has macropores of 20-2000 μm and three-dimensional interconnected micropores formed by the gaps between sub-particles. The spherical particles of hydroxyapatite with an average particle size of 10 μm and an average particle size of 1 μm are mixed, and the above materials are mixed with methylcellulose solution to form a gel. After the gel is dried, it is annealed at 1200 ° C for 4 hours.

Russian Patent Publication No. RU2395476C1 discloses a method for manufacturing porous hydroxyapatite particles, which is to calcinate hydroxyapatite powder obtained from natural biological bone materials at a temperature of 950-1000 ° C, and crush the calcined material to obtain a powder of no more than 35 μm particles. Next, prepare a plastic block of 1 part by weight of paraffin and 3 parts by weight of hydroxyapatite powder, extrude the block, and then heat-treat at 750-800°C to remove the paraffin and make granules. The final product is a particle of 0.8mm to 2mm, containing interconnected pores of 100 to 350μm at a content of 50~70vol%.

Russian Patent Publication No. RU2303580C2 discloses a method for preparing porous hydroxyapatite ceramics. The material contains micropores smaller than 10 μm and interconnected pores larger than 100 μm at a content of 41 to 70 vol%. The manufacturing method includes forming the composition of hydroxyapatite powder and gelatin into spherical particles with a diameter of 400-600 μm , and pressing it into a blank with an open intergranular porosity of 30-54vol.% ( raw blanks), the blanks are heat-treated at a temperature of 900 to 1250°C, while the gelatin and sintered hydroxyapatite powder particles are burned off.

Russian Patent Publication No. RU2555348C discloses a method for producing ceramic particles through a calcium carbonate-hydroxyapatite system. The powder of calcium carbonate and hydroxyapatite is suspended through the principle of immiscibility and polyacrylamide solution in vegetable oil. The particles obtained by the technique of dispersion of suspension in medium, then, the particles are dried and sintered at 620~700°C. The obtained porous ceramic particles have a size of 100 to 2000 μm , an open porosity of 40 to 80%, and a pore diameter of 20 to 400 μm .

The invention provides a manufacturing method of a porous composite material, at least including the following steps: providing a dry powder mixture, providing a granulation mixture, and performing an annealing step on the granule mixture.

The dry powder mixture comprises 40wt% to 55wt% of hydroxyapatite (HAP), 25wt% to 40wt% of β-tricalcium phosphate (β-TCP) and 10wt% to 20wt% of polyethylene (PE) particles, The particle size of the polyethylene particles is between 250 μm and 600 μm.

The granulation mixture is to mix the dry powder mixture with an aqueous sugar solution, the concentration of the aqueous sugar solution is to contain 30g to 60g of monosaccharide or disaccharide per 100ml of water, and the aqueous sugar solution is based on the total weight (100wt%) of the dry powder mixture Add 8ml to 20ml and perform wet granulation to form a granule mixture.

The annealing step of the particle mixture is to carry out the following control procedures in sequence: program one, increase the temperature to 80°C to 100°C, and then maintain the temperature; program two, increase the temperature to 400°C to 400°C at a heating rate of 20°C to 30°C per hour 600°C, then hold the temperature; step 3, increase the temperature to 900°C to 1500°C within 8 hours to 20 hours, then hold the temperature; step 4, lower the temperature from the temperature of step 3 to obtain an annealed product.

Additionally, disaccharides include sucrose, lactose or maltose.

In addition, in program one, the temperature is increased to 80°C to 100°C within 10 minutes to 30 minutes, and then the temperature is maintained for 1 hour to 5 hours.

Wherein in procedure two, after raising the temperature to 400° C. to 600° C., then maintaining the temperature for 1 hour to 5 hours.

Wherein in procedure three, after raising the temperature to 900° C. to 1500° C., then maintaining the temperature for 3 hours to 10 hours.

In procedure four, the temperature in procedure three is lowered to 300° C. to 500° C. within 20 hours, and then cooled to room temperature.

The dry powder mixture is first mixed with HA and β-tricalcium phosphate to form a premix, and then the premix is mixed with polyethylene.

In this embodiment, a method for manufacturing a porous composite material is provided. The porous composite material is a particle containing hydroxyl apatite (HAP) and β-tricalcium phosphate (β-TCP), which can be used as a bone material , the above-mentioned porous composite material contains 50-70 vol.% of particles with a particle diameter of 100-500 μm.

The manufacturing method comprises the steps of: providing a dry powder mixture, comprising 45wt% to 55wt% of HAP, 25wt% to 40wt% of β-TCP and 10wt% to 20wt% of polyethylene (PE) particles, the particle size of the polyethylene particles Between 250 μm and 600 μm; provide a granulation mixture, mix the dry powder mixture with an aqueous sugar solution, the concentration of the aqueous sugar solution is 30 g to 60 g of monosaccharide or disaccharide per 100 g of water, and the aqueous sugar solution is based on the dry powder Add 8ml to 20ml based on the total weight of the mixture (100wt%), and carry out wet granulation to form a particle mixture; and carry out an annealing step to the particle mixture, and the annealing step is to carry out the following control procedures in sequence: Program 1, increase the temperature to 80°C to 100°C, and then maintain the temperature; Program 2, increase the temperature to 400°C to 600°C at a rate of 20°C to 30°C per hour, and then maintain the temperature; Program 3, in 8 hours Increase the temperature to 900° C. to 1500° C. within 20 hours, and then maintain the temperature; Step 4, drop the temperature from the temperature of Step 3 to 300° C. to 500° C. to obtain an annealed product.

The resulting clumps of annealed product can then be separated and sieved to obtain particles of a predetermined size.

In the aforementioned manufacturing method, the combination of disaccharide and granular PE in the sugar solution is used as a porogen, and the sugar solution is used as an adhesive to ensure high microporosity. PE can produce macropores up to 350 microns. The size and quantity can be adjusted through the size and content of PE, so composite material particles with macropores and micropores can be obtained.

In addition, the dry powder mixture is first mixed with HAP and β-TCP to form a pre-mixture, and then the pre-mixture is mixed with PE granules. The HAP content in the dry powder mixture is about 45wt%, 47wt%, 49wt%, 51wt%, 53wt% or 55wt%, and the β-TCP content is about 25wt%, 27wt%, 29wt%, 32wt%, 35wt%, 38wt% Or 40wt%, PE particle content is 10wt%, 12wt%, 14wt%, 16wt%, 18wt% or 20wt%. In addition, the particle size of the PE particles can be about 250 μm, 300 μm, 350 μm, 400 μm, 450 μm, 500 μm, 550 μm or 600 μm, and the particle size of the PE particles can also be a mixture of at least two of the above particle sizes.

The above-mentioned aqueous sugar solution can contain 30g, 35g, 40g, 45g, 50g, 55g, or 60g of monosaccharide or disaccharide in every 100ml of water, the monosaccharide can be glucose, fructose and galactose, and the disaccharide can be sucrose, lactose or maltose. When preparing the granulation mixture, the amount of sugar water added is approximately Based on the total weight (100wt%) of the dry powder mixture, 8ml, 9ml, 10ml, 13ml, 15ml, 18ml or 20ml of sugar aqueous solution is added.

In one specific embodiment, the granulation mixture only contains HAP, β-TCP, PE granules, and aqueous sugar solution.

In one of the specific implementations, the dry powder mixture has HAP 51wt%, β-TCP 34wt%, 400mn ~ 600mn PE 15wt%, the granulation mixture is based on the total weight of the dry powder mixture (100%), and the concentration About 10ml of sugar water is 45g/100g water.

The function of the annealing step is to sinter the HAP and β-TCP inside the particle mixture, and decompose the PE particles, so that the annealed product has a pore size of a predetermined size. For example, interconnect holes having an average size of 150 μm, 200 μm, 250 μm, 300 μm, 350 μm, 400 μm, 450 μm, or 500 μm are formed.

In procedure one of the annealing step, the temperature may be increased to 80° C. to 100° C. within 10 minutes to 30 minutes, and then maintained at the temperature for 1 hour to 5 hours. The time interval set for raising the temperature may be 12 minutes, 14 minutes, 16 minutes, 18 minutes or 20 minutes, and the raised temperature may be 80°C, 85°C, 90°C, 95°C or 100°C. The time interval for maintaining temperature can be 1 hour, 2 hours, 3 hours, 4 hours or 5 hours.

In program 2 of the annealing step, the temperature set in program 1 is increased to 400° C. to 600° C., and then the temperature is maintained for 1 hour to 5 hours. The temperature increased in procedure two can be 400°C, 450°C, 500°C, 550°C or 600°C, and the time interval for holding the temperature can be 1 hour, 2 hours, 3 hours, 4 hours or 5 hours.

In procedure three of the annealing step, the temperature maintained in procedure two is increased to 900° C. to 1500° C., and then the temperature is maintained for 3 hours to 10 hours. The temperature increased in program three can be 900°C, 1000°C, 1100°C, 1200°C, 1300°C, 1400°C or 1500°C, set for The time interval for increasing the temperature can be 8 hours, 12 hours, 14 hours, 16 hours or 20 hours, and the time interval for maintaining the temperature can be 3 hours, 4 hours, 5 hours, 7 hours, 9 hours or 10 hours.

In procedure four of the annealing step, the temperature maintained in procedure three is lowered to 300° C. to 500° C. within 8 hours to 20 hours, and then the annealed product is naturally cooled to room temperature. In the first stage of program four, the temperature can be lowered to 300 ° C, 350 ° C, 400 ° C, 450 ° C or 500 ° C, and the time interval for cooling can be 8 hours, 12 hours, 14 hours, 16 hours or 20 hours, then, Allow the product to cool naturally to room temperature.

In the above-mentioned implementation, the reason for choosing PE particles as the porogen is that PE has the characteristics of not absorbing water, which can reduce the variable factor in the reaction process, and the decomposition temperature of PE particles is 380 degrees, which can be used during annealing. Make the holes more stable, so larger perforations can be formed in the annealed product.

Specific implementations are provided below to better understand the connotation of the present invention.

Experimental example 1. Preparation of HAP/β-TCP complex

120g of HAP and 80g of β-TCP were weighed and poured into a tank, pre-mixed for 10-15 seconds, poured into a laboratory knife mill and ground for 3 seconds. Pour the ground powder into a 2-liter jar, put 35 grams of 400μm~600μm PE particles as a porogen, and then mix it with a laboratory mixer for 5 minutes. Pour the resulting dry powder mixture into a stainless steel bowl and continue stirring.

Next, add 50ml of sugar water (concentration: 45g/100g distilled water) into the dry powder mixture in two equal parts, and wait for the appearance of round aggregates in the stainless steel bowl to judge that the powder material has reached the required consistency. Granulated on a granulator.

The granules obtained by the granulator were evenly distributed on the _Al2O3 ceramic plate of the high-temperature furnace, _and the annealing step was performed according to the following temperature control program: (1) increased to 85 °C within 15 minutes; (2) exposed at 85 °C 3 hours; (3) increase the temperature to 500°C at a heating rate of 26°C/hour; (4) expose at 500°C for 2 hours; (5) increase the temperature to 1100°C within 12 hours; (6) in Expose at 1100°C for 5 hours; (7) Drop from 1100°C to 400°C within 14 hours; (8) Cut off the power of the furnace and let it cool naturally to room temperature.

After annealing, pour the annealed product into 1~2 plastic tanks, fix it on the platform of a rotary shaker, and process it at a speed of 100rpm for 2 minutes to separate the particle clusters into individual particles.

The particles are then screened for size within 2-3 minutes using sieves with mesh sizes of 0.5mm, 1.0mm and 2.0mm and laboratory sieving equipment. The porosity of the product was 70%, and at 50 vol.% of the resulting particles, there were interconnected pores with an average size of 300 µm.

Comparative example 1

Similar to Experimental Example 1, but the step (3) of the temperature control program was changed to a heating rate of 50° C./hour, and finally the obtained particles disintegrated.

Comparative example 2

Similar to Experimental Example 1, but using granular PE with a size smaller than 200 μm as porogen, there are almost no macropores (>100 μm) in the resulting particles.

Claims (9)

A method for manufacturing a porous composite material, comprising: providing a dry powder mixture comprising 40wt% to 55wt% of hydroxyapatite (HAP), 25wt% to 40wt% of β-tricalcium phosphate (β-TCP) And 10wt% to 20wt% polyethylene (PE) particles, the particle size of the polyethylene particles is between 400 μm to 600 μm; a granulation mixture is provided, the dry powder mixture is mixed with an aqueous sugar solution, and the concentration of the aqueous sugar solution is 100ml of water contains 30g to 60g of monosaccharide or disaccharide, the sugar aqueous solution is based on the total weight of the dry powder mixture, adding 8ml to 20ml, and performing wet granulation to form a granular mixture; An annealing step, the annealing step is to carry out the following control procedures in sequence: program one, increase the temperature to 80°C to 100°C, and keep the temperature; program two, increase the temperature to 400°C at a heating rate of 20°C to 30°C per hour °C to 600 °C, then hold the temperature; program three, increase the temperature to 900 °C to 1500 °C within 8 hours to 20 hours, and then hold the temperature; program four, lower the temperature from the temperature of the program three to obtain an annealed product. The production method according to claim 1, wherein the disaccharide comprises sucrose, lactose or maltose. The manufacturing method as described in Claim 1, wherein in the first procedure, the temperature is raised to 80° C. to 100° C. within 10 minutes to 30 minutes, and then the temperature is maintained for 1 hour to 5 hours. The manufacturing method according to claim 1, wherein in the second procedure, after raising the temperature to 400° C. to 600° C., the temperature is maintained for 1 hour to 5 hours. The manufacturing method as described in Claim 1, wherein in the third procedure, after raising the temperature to 900° C. to 1500° C., the temperature is maintained for 3 hours to 10 hours. The manufacturing method according to claim 1, wherein in the fourth step, the temperature of the third step is lowered to 300° C. to 500° C. within 8 to 20 hours, and then cooled to room temperature. The manufacturing method as claimed in item 1, wherein the dry powder mixture comprises 49wt% to 53wt% of hydroxyapatite (HAP), 30wt% to 35wt% of β-tricalcium phosphate (β-TCP) and 13wt% % to 16wt% of polyethylene (PE) particles with a particle size of 300 μm to 600 μm. The manufacturing method according to claim 1, wherein 9ml to 12ml of the sugar aqueous solution is added to the granulation mixture based on the total weight of the dry powder mixture. The manufacturing method according to claim 1, wherein the dry powder mixture is first mixed with the HA and the β-tricalcium phosphate to form a pre-mixture, and then the pre-mixture is mixed with the polyethylene.