Porous calcium phosphate material as well as preparation method and application thereof

Abstract

The invention discloses a porous calcium phosphate material and a preparation method and application thereof, and the preparation method comprises the following steps: mixing ceramic powder, a pore-forming agent and a binder to obtain a mixture; carrying out compression molding on the mixture to obtain a green body; the green body is dried for 3-5 h at the temperature of 50-70 DEG C, and part of the pore-forming agent is removed; calcining and cooling the dried green body to obtain a porous calcium phosphate material; the ceramic powder is selected from one or more of tricalcium phosphate, hydroxyapatite, bioglass, calcium silicate, calcium carbonate, aluminum oxide, titanium dioxide, silicon oxide, silicon carbide and silicon nitride, and in the ceramic powder, the weight percentage of tricalcium phosphate is 50-100%. According to the method for preparing the porous calcium phosphate material, the technological process is simplified, the porosity of the prepared porous calcium phosphate material reaches 65% or above, the hole diameter of a macro hole is 100-800 microns, and the hole diameter of a micropore is 1t; the material can be used as a biological scaffold for tissue-engineered bones, and can also be used as a filling material for bones of non-load-bearing parts.

Description

Technical Field

[0001] The invention belongs to the technical field of biomaterials, and in particular relates to porous calcium phosphate materials, preparation methods and applications thereof. Background Art

[0002] Bone grafting is a procedure performed to replace bone or enhance bone healing in surgeries such as orthopedic reconstruction and spinal fusion. In this type of surgery, it is common to harvest a certain amount of bone from the patient's pelvis for autologous transplantation. However, when the patient's bone quantity or quality is not sufficient to assist in this type of surgery alone, other bone grafting options must be considered, such as choosing artificial bone materials for surgery.

[0003] Calcium phosphate materials are similar to inorganic components of bone matrix, have natural affinity with bone tissue, and have good biocompatibility. Artificial bones prepared with calcium phosphate materials as the base material are increasingly widely used. Common calcium phosphate artificial bones have a porous shape, which can provide a good environment for bone cell growth and proliferation, but the disadvantage is that the higher the porosity, the more difficult it is to ensure strength, which limits its application in load-bearing parts.

[0004] The information disclosed in this background technology section is only intended to enhance the understanding of the overall background of the invention and should not be regarded as an acknowledgment or any form of suggestion that the information constitutes the prior art already known to a person skilled in the art. Summary of the invention

[0005] The purpose of the present invention is to provide a porous calcium phosphate material, a preparation method and application thereof. The porous calcium phosphate material has a high porosity and excellent mechanical strength, and can be used as a tissue engineering bone biological scaffold or as a filling material for bones in non-load-bearing parts.

[0006] In order to achieve the above object, a technical solution provided by a specific embodiment of the present invention is as follows:

[0007] A method for preparing a porous calcium phosphate material comprises the following steps:

[0008] Mixing ceramic powder, pore former and binder to obtain a mixture;

[0009] Pressing the mixture into a shape to obtain a green body;

[0010] Dry the green body at 50-70°C for 3-5h to remove part of the pore-forming agent;

[0011] calcining the dried green body and cooling it to obtain a porous calcium phosphate material;

[0012] The ceramic powder is selected from one or more of tricalcium phosphate, hydroxyapatite, bioglass, calcium silicate, calcium carbonate, aluminum oxide, titanium dioxide, silicon oxide, silicon carbide and silicon nitride, and the weight percentage of tricalcium phosphate in the ceramic powder is 50-100%;

[0013] The pore former is selected from one or more of stearic acid, cetyl alcohol, myristyl alcohol, stearyl alcohol, cetostearyl alcohol, and glyceryl mono- and distearate;

[0014] The binder is selected from one or more of polyvinyl alcohol, gelatin, collagen, hyaluronic acid, chitosan, alginate, alginate, polyoxyethylene polyoxypropylene vinyl ether block copolymer and polyglycolic acid.

[0015] In one or more embodiments of the present invention, the weight ratio of the ceramic powder to the pore former is (1-2):1; and / or the weight ratio of the ceramic powder to the binder is (6-4):1.

[0016] In one or more embodiments of the present invention, the particle size of the ceramic powder is 50 nm to 100 μm.

[0017] In one or more embodiments of the present invention, the binder is a polyvinyl alcohol solution with a concentration of 2 to 8 wt%.

[0018] In one or more embodiments of the present invention, the calcination temperature is 1100-1200° C., and the calcination time is 3-5 hours.

[0019] In one or more embodiments of the present invention, during calcination, the temperature is raised from room temperature to the calcination temperature at a heating rate of 3-5° C. / min.

[0020] Another specific embodiment of the present invention provides a technical solution as follows:

[0021] The porous calcium phosphate material is prepared by the above-mentioned method for preparing the porous calcium phosphate material.

[0022] In one or more embodiments of the present invention, the macropore size of the porous calcium phosphate material is 100-800 μm; and / or,

[0023] The micropore diameter of the porous calcium phosphate material is less than 10 μm.

[0024] In one or more embodiments of the present invention, the porosity of the porous calcium phosphate material is ≥ 65%.

[0025] Another specific embodiment of the present invention provides a technical solution as follows:

[0026] The porous calcium phosphate material is applied to bone repair by combining the porous calcium phosphate material with a polypeptide. The porous calcium phosphate material is prepared by the above-mentioned method for preparing the porous calcium phosphate material.

[0027] Compared with the prior art, the porous calcium phosphate material prepared by the present invention has a porosity of more than 65%, the macropore diameter can be controlled at 100-800 μm, the micropore diameter can be controlled at <10 μm, and has excellent mechanical strength. When used in combination with a polypeptide, it can be used as a tissue engineering bone bioscaffold and can also be used as a filling material for non-load-bearing bones.

[0028] In terms of the use of raw materials in the preparation, fewer types of raw materials are used than in the prior art, the process is simpler, and compared with other collagen carriers, the use of the porous calcium phosphate material of the present invention to load polypeptides has no animal-derived risk and no disease transmission risk.

[0029] After the porous calcium phosphate material of the present invention is implanted in a patient's body and degraded, the degradation products, calcium ions and phosphate ions, are elements absorbed by bone cells, are beneficial to bone growth, and have high bone inductivity. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments recorded in the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0031] Figure 1 This is a schematic diagram of the appearance of the porous calcium phosphate material in Example 1 of the present invention;

[0032] Figure 2 This is a scanning electron microscope image of the macropores of the porous calcium phosphate material in Example 1 of the present invention;

[0033] Figure 3 This is a scanning electron microscope image of the micropores of the porous calcium phosphate material in Example 1 of the present invention;

[0034] Figure 4 This is a schematic diagram of the appearance of the porous calcium phosphate material in Comparative Example 1 of the present invention;

[0035] Figure 5 This is a schematic diagram of the appearance of the porous calcium phosphate material in Comparative Example 2 of the present invention;

[0036] Figure 6 This is a schematic diagram of the appearance of the porous calcium phosphate material in Comparative Example 3 of the present invention;

[0037] Figure 7 It is a mechanical curve diagram of 10 samples of the porous calcium phosphate material in Example 1 of the present invention in the ball indentation strength test. DETAILED DESCRIPTION

[0038] In order to enable those skilled in the art to better understand the technical solutions in the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work should fall within the scope of protection of the present invention.

[0039] In bone transplantation, in addition to autologous transplantation, allogeneic bone transplantation can be selected, that is, the bones of deceased family members or other successfully matched donors are used and implanted after processing. However, the sources of such implants are limited, difficult to obtain, and expensive. The implant part will remain in the patient's body for many years, and there is a chance of immune rejection and disease transmission. In addition, xenogeneic transplantation can also be selected, that is, bones or tissues from animal sources, such as pigs and cows, are used and implanted after processing. Such implant parts will remain in the patient's body for many years and have a high risk of spreading diseases. In addition, artificially produced materials are easy to obtain, and good biocompatibility, osteoconductivity, osteoinductivity, and degradation ability can be achieved through design, but such simple compounds do not contain proteins that stimulate the patient's body cells to form bones, and their ability to repair large-area defects by themselves is limited.

[0040] Therefore, by adding growth factors that promote bone formation by body cells to synthetic materials, it is possible to induce undifferentiated mesenchymal stem cells to differentiate and proliferate into chondrocytes and osteoblasts, promote the differentiation and maturation of osteoblasts, participate in the positive growth and development of bones and cartilage and their reconstruction process, and thus accelerate the repair of bone defects.

[0041] The present invention selects to use a polypeptide and a porous calcium phosphate material in combination, and utilizes the polypeptide to improve the osteoinductivity and osteogenic effect. At the same time, in order to improve the porosity and strength of calcium phosphate artificial bones, a porous calcium phosphate material with high porosity and high strength is prepared by a specific preparation method, which can promote tissue fluid infiltration and cell growth.

[0042] A specific embodiment of the present invention provides a method for preparing a porous calcium phosphate material, comprising steps 1-4.

[0043] Step 1, mixing ceramic powder, pore former and binder to obtain a mixture.

[0044] Specifically, the ceramic powder is selected from one or more of tricalcium phosphate, hydroxyapatite, bioglass, calcium silicate, calcium carbonate, aluminum oxide, titanium dioxide, silicon oxide, silicon carbide and silicon nitride, and the weight percentage of tricalcium phosphate in the ceramic powder is 50-100%. The pore former is selected from one or more of stearic acid, cetyl alcohol, myristyl alcohol, octadecyl alcohol, cetostearyl alcohol, mono- and di-stearic acid glyceryl esters; the binder is selected from one or more of polyvinyl alcohol, gelatin, collagen, hyaluronic acid, chitosan, alginates, alginate, polyoxyethylene polyoxypropylene vinyl ether block copolymers and polyglycolic acid.

[0045] The weight ratio of ceramic powder to stearic acid is (1-2):1; the weight ratio of ceramic powder to binder is (6-4):1; preferably, the binder is a polyvinyl alcohol solution with a concentration of 2-8wt%, and the polyvinyl alcohol solution is prepared by heating and stirring polyvinyl alcohol and purified water, the heating temperature is 50-90°C, and the stirring speed is 200-400r / min. By controlling the proportion of the pore-forming agent, the porous calcium phosphate material forms a porous structure, and at the same time, the proportion of the binder is controlled so that the ceramic powder can be formed and maintain a certain strength. The particle size of the ceramic powder is 50nm-100μm, wherein the tricalcium phosphate is β-tricalcium phosphate powder with a particle size of 1-50μm.

[0046] Furthermore, the temperature is controlled below 30°C during mixing, and mixing can be carried out at room temperature of 25°C. After the raw materials are mixed, the mixing condition is observed while stirring. The mixing is completed when the powder is completely adhered to the surface of the pore-forming agent, there is no pore-forming agent without adhered powder, and there is no loose powder pile that has not been mixed with the binder.

[0047] Step 2, pressing the mixture into a shape to obtain a green body.

[0048] Specifically, according to the actual size requirements, pour the mixture into a mold of appropriate size, apply pressure manually, and additionally beat to compact any loose parts that may exist, and observe that there is no loose powder.

[0049] Step 3, drying the green body at 60-70° C. for 3-5 hours.

[0050] Specifically, in this step, the moisture and part of the pore former in the green body are removed by drying. If the pore former is completely removed in this step, it is easy to cause the green body to become loose and collapse. If calcination is performed directly without drying, during the sintering process, as the temperature rises, the melted pore former will melt part of the green body, which is prone to cracking, bulging in the middle or melting and collapse. By limiting the drying temperature and drying time, during the drying process, part of the pore former in the green body will melt and run out of the green body, and the partially melted pore former will not cause the green body to collapse. At the same time, it can also ensure that the green body can form a porous structure after subsequent calcination, and has a certain strength. During the specific drying, the green body can be placed on a dust-free cloth, and the dust-free cloth absorbs the moisture and pore former running out of the green body.

[0051] Step 4, calcining the dried green body and cooling it to obtain a porous calcium phosphate material.

[0052] Specifically, the calcination temperature is 1100-1200°C, the heating rate is 3-5°C / min, and the time is 3-5h. By controlling the calcination temperature and time, the pore-forming agent is burned and decomposed, and a porous structure is formed in the green body. The appropriate heating rate helps the powders to combine, thereby ensuring the strength of the finished product.

[0053] Another specific embodiment of the present invention provides a porous calcium phosphate material, which is prepared by the above-mentioned method for preparing the porous calcium phosphate material.

[0054] Specifically, the macropore size of the porous calcium phosphate material is 100-800 μm, the micropore size of the porous calcium phosphate material is <10 μm, and the porosity is ≥65%. Appropriate pore size and porosity are conducive to tissue fluid infiltration and cell growth, and can improve the biocompatibility and bone inductivity of the porous calcium phosphate material.

[0055] Another specific embodiment of the present invention provides an application of a porous calcium phosphate material, wherein the porous calcium phosphate material and a polypeptide are combined and applied to bone repair, and the porous calcium phosphate material is prepared by the above-mentioned method for preparing the porous calcium phosphate material.

[0056] The present invention is further described in detail below in conjunction with specific embodiments.

[0057] Example 1

[0058] The porous calcium phosphate material is specifically prepared as follows:

[0059] Take 60 g of β-tricalcium phosphate, 30 g of stearic acid and 15 g of 8 wt % polyvinyl alcohol solution, mix them evenly to obtain a mixture;

[0060] 3.5 g of the mixture was poured into a mold with a groove size of 5 mm × 10 mm, and manually pressed and hammered to compact the loose parts and form a green body;

[0061] The green body was placed in a drying oven at 60°C for 3 h and then cooled to room temperature;

[0062] The dried green body is placed in a box-type resistance furnace, heated to 1100°C at a heating rate of 3°C / min, calcined for 3 hours, and cooled to room temperature to obtain a porous calcium phosphate material.

[0063] The resulting porous calcium phosphate material is Figure 1 As shown in Figure 2, the structure is intact and the size at the time of molding is maintained. The macropore scanning electron microscope image of the porous calcium phosphate material is shown in Figure 2. Figure 2 As shown by Figure 2 It can be seen that the macropore diameter is about 450μm, and the macropore is spherical as a whole. The micropore scanning electron microscope image is as follows Figure 3 As shown by Figure 3 It can be seen that the pore size is about 5 μm, and the micropores are mainly distributed in the solid part of the porous calcium phosphate material.

[0064] Example 2

[0065] The porous calcium phosphate material is specifically prepared as follows:

[0066] Take 60 g of β-tricalcium phosphate, 60 g of stearic acid and 10 g of a 5 wt% polyvinyl alcohol solution, mix them evenly to obtain a mixture;

[0067] 3.5 g of the mixture was poured into a mold with a groove size of 5 mm × 10 mm, and manually pressed and hammered to compact the loose parts and form a green body;

[0068] The green body was placed in a drying oven at 60°C for 3 h and then cooled to room temperature;

[0069] The dried green body is placed in a box-type resistance furnace, heated to 1100°C at a heating rate of 3°C / min, calcined for 3 hours, and cooled to room temperature to obtain a porous calcium phosphate material.

[0070] Example 3

[0071] The porous calcium phosphate material is specifically prepared as follows:

[0072] Take 60 g of β-tricalcium phosphate, 30 g of stearic acid and 15 g of 8 wt % polyvinyl alcohol solution, mix them evenly to obtain a mixture;

[0073] 3.5 g of the mixture was poured into a mold with a groove size of 5 mm × 10 mm, and manually pressed and hammered to compact the loose parts and form a green body;

[0074] The green body was placed in a drying oven at 67°C for 3 h and then cooled to room temperature;

[0075] The dried green body is placed in a box-type resistance furnace, heated to 1100°C at a heating rate of 3°C / min, calcined for 3 hours, and cooled to room temperature to obtain a porous calcium phosphate material.

[0076] Example 4

[0077] The porous calcium phosphate material is specifically prepared as follows:

[0078] Take 60 g of β-tricalcium phosphate, 30 g of stearic acid and 15 g of 8 wt % polyvinyl alcohol solution, mix them evenly to obtain a mixture;

[0079] 3.5 g of the mixture was poured into a mold with a groove size of 5 mm × 10 mm, and manually pressed and hammered to compact the loose parts and form a green body;

[0080] The green body was placed in a drying oven at 70°C for 3 h and then cooled to room temperature;

[0081] The dried green body is placed in a box-type resistance furnace, heated to 1100°C at a heating rate of 3°C / min, calcined for 3 hours, and cooled to room temperature to obtain a porous calcium phosphate material.

[0082] Example 5

[0083] The porous calcium phosphate material is specifically prepared as follows:

[0084] Take 60 g of β-tricalcium phosphate, 30 g of stearic acid and 15 g of 8 wt % polyvinyl alcohol solution, mix them evenly to obtain a mixture;

[0085] 3.5 g of the mixture was poured into a mold with a groove size of 5 mm × 10 mm, and manually pressed and hammered to compact the loose parts and form a green body;

[0086] The green body was placed in a drying oven at 60°C for 3 h and then cooled to room temperature;

[0087] The dried green body is placed in a box-type resistance furnace, heated to 1160° C. at a heating rate of 3° C. / min, calcined for 3 h, and cooled to room temperature to obtain a porous calcium phosphate material.

[0088] Example 6

[0089] The porous calcium phosphate material is specifically prepared as follows:

[0090] Take 60 g of β-tricalcium phosphate, 30 g of stearic acid and 15 g of 8 wt % polyvinyl alcohol solution, mix them evenly to obtain a mixture;

[0091] 3.5 g of the mixture was poured into a mold with a groove size of 5 mm × 10 mm, and manually pressed and hammered to compact the loose parts and form a green body;

[0092] The green body was placed in a drying oven at 60°C for 3 h and then cooled to room temperature;

[0093] The dried green body is placed in a box-type resistance furnace, heated to 1200°C at a heating rate of 3°C / min, calcined for 3 hours, and cooled to room temperature to obtain a porous calcium phosphate material.

[0094] Example 7

[0095] The porous calcium phosphate material is specifically prepared as follows:

[0096] Take 60 g of β-tricalcium phosphate, 30 g of stearic acid and 15 g of 8 wt % polyvinyl alcohol solution, mix them evenly to obtain a mixture;

[0097] 3.5 g of the mixture was poured into a mold with a groove size of 5 mm × 10 mm, and manually pressed and hammered to compact the loose parts and form a green body;

[0098] The green body was placed in a drying oven at 60°C for 3 h and then cooled to room temperature;

[0099] The dried green body is placed in a box-type resistance furnace, heated to 1100°C at a heating rate of 4°C / min, calcined for 3 hours, and cooled to room temperature to obtain a porous calcium phosphate material.

[0100] Example 8

[0101] The porous calcium phosphate material is specifically prepared as follows:

[0102] Take 60 g of β-tricalcium phosphate, 30 g of stearic acid and 15 g of 8 wt % polyvinyl alcohol solution, mix them evenly to obtain a mixture;

[0103] 3.5 g of the mixture was poured into a mold with a groove size of 5 mm × 10 mm, and manually pressed and hammered to compact the loose parts and form a green body;

[0104] The green body was placed in a drying oven at 60°C for 3 h and then cooled to room temperature;

[0105] The dried green body is placed in a box-type resistance furnace, heated to 1100°C at a heating rate of 5°C / min, calcined for 3 hours, and cooled to room temperature to obtain a porous calcium phosphate material.

[0106] Example 9

[0107] The porous calcium phosphate material is specifically prepared as follows:

[0108] Take 60 g of β-tricalcium phosphate, 30 g of stearic acid and 15 g of 8 wt % polyvinyl alcohol solution, mix them evenly to obtain a mixture;

[0109] 3.5 g of the mixture was poured into a mold with a groove size of 5 mm × 10 mm, and manually pressed and hammered to compact the loose parts and form a green body;

[0110] The green body was placed in a drying oven at 60°C for 3 h and then cooled to room temperature;

[0111] The dried green body is placed in a box-type resistance furnace, heated to 1100°C at a heating rate of 7°C / min, calcined for 3 hours, and cooled to room temperature to obtain a porous calcium phosphate material.

[0112] Example 10

[0113] The porous calcium phosphate material is specifically prepared as follows:

[0114] 30 g of β-tricalcium phosphate, 10 g of hydroxyapatite, 10 g of calcium carbonate, 10 g of silicon oxide, 30 g of cetyl alcohol and 15 g of a polyvinyl alcohol solution with a mass concentration of 8 wt% are mixed uniformly to obtain a mixture; the particle size of hydroxyapatite is 1 to 100 μm, the particle size of calcium carbonate is 1 to 20 μm, and the particle size of silicon oxide is 50 nm to 1 μm;

[0115] 3.5 g of the mixture was poured into a mold with a groove size of 5 mm × 10 mm, and manually pressed and hammered to compact the loose parts and form a green body;

[0116] The green body was placed in a drying oven at 60°C for 3 h and then cooled to room temperature;

[0117] The dried green body is placed in a box-type resistance furnace, heated to 1100°C at a heating rate of 3°C / min, calcined for 3 hours, and cooled to room temperature to obtain a porous calcium phosphate material.

[0118] Embodiment 11

[0119] The porous calcium phosphate material is specifically prepared as follows:

[0120] 48 g of β-tricalcium phosphate, 5 g of hydroxyapatite, 4 g of silicon carbide, 3 g of calcium silicate, 30 g of stearic acid and 15 g of a polyvinyl alcohol solution with a mass concentration of 8 wt % are mixed uniformly to obtain a mixture; the particle size of hydroxyapatite is 1 to 100 μm, the particle size of silicon carbide is 50 nm to 1 μm, and the particle size of calcium silicate is 1 to 20 μm;

[0121] 3.5 g of the mixture was poured into a mold with a groove size of 5 mm × 10 mm, and manually pressed and hammered to compact the loose parts and form a green body;

[0122] The green body was placed in a drying oven at 60°C for 3 h and then cooled to room temperature;

[0123] The dried green body is placed in a box-type resistance furnace, heated to 1100°C at a heating rate of 3°C / min, calcined for 3 hours, and cooled to room temperature to obtain a porous calcium phosphate material.

[0124] Comparative Example 1

[0125] The porous calcium phosphate material is specifically prepared as follows:

[0126] Take 60 g of β-tricalcium phosphate, 30 g of stearic acid and 15 g of 8 wt % polyvinyl alcohol solution, mix them evenly to obtain a mixture;

[0127] 3.5 g of the mixture was poured into a mold with a groove size of 5 mm × 10 mm, and manually pressed and hammered to compact the loose parts and form a green body;

[0128] The green body was placed in a drying oven at 80°C for 3 h and then cooled to room temperature;

[0129] The dried green body is placed in a box-type resistance furnace, heated to 1100°C at a heating rate of 3°C / min, calcined for 3 hours, and cooled to room temperature to obtain a porous calcium phosphate material.

[0130] During the preparation process, local collapse of the green body was observed during calcination, e.g. Figure 4 shown.

[0131] Comparative Example 2

[0132] The porous calcium phosphate material is specifically prepared as follows:

[0133] Take 60 g of β-tricalcium phosphate, 30 g of stearic acid and 15 g of 8 wt % polyvinyl alcohol solution, mix them evenly to obtain a mixture;

[0134] 3.5 g of the mixture was poured into a mold with a groove size of 5 mm × 10 mm, and manually pressed and hammered to compact the loose parts and form a green body;

[0135] The green body was placed in a drying oven at 40°C for 3 h and then cooled to room temperature;

[0136] The dried green body is placed in a box-type resistance furnace, heated to 1100°C at a heating rate of 3°C / min, calcined for 3 hours, and cooled to room temperature to obtain a porous calcium phosphate material.

[0137] During the preparation process, when calcining, it is observed that the green body is boiling before calcining, and the green body is melting, such as Figure 5 shown.

[0138] Comparative Example 3

[0139] The porous calcium phosphate material is specifically prepared as follows:

[0140] Take 60 g of β-tricalcium phosphate, 30 g of stearic acid and 15 g of 8 wt % polyvinyl alcohol solution, mix them evenly to obtain a mixture;

[0141] 3.5 g of the mixture was poured into a mold with a groove size of 5 mm × 10 mm, and manually pressed and hammered to compact the loose parts and form a green body;

[0142] The green body is placed in a box-type resistance furnace, heated to 1100°C at a heating rate of 3°C / min, calcined for 3 hours, and cooled to room temperature to obtain a porous calcium phosphate material.

[0143] During the preparation process, the green body was observed to collapse during calcination and could not maintain the shape at the time of molding, such as Figure 6 shown.

[0144] Comparative Example 4

[0145] The porous calcium phosphate material is specifically prepared as follows:

[0146] Take 60 g of β-tricalcium phosphate, 30 g of stearic acid and 15 g of 8 wt % polyvinyl alcohol solution, mix them evenly to obtain a mixture;

[0147] 3.5 g of the mixture was poured into a mold with a groove size of 5 mm × 10 mm, and manually pressed and hammered to compact the loose parts and form a green body;

[0148] The green body was placed in a drying oven at 60°C for 1 h and then cooled to room temperature;

[0149] The dried green body is placed in a box-type resistance furnace, heated to 1100°C at a heating rate of 3°C / min, calcined for 3 hours, and cooled to room temperature to obtain a porous calcium phosphate material.

[0150] During the preparation process, it was observed that the green body collapsed during calcination and could not maintain the shape at the time of molding.

[0151] The performance of the porous calcium phosphate material was tested:

[0152] (1) Dissolving the polypeptide in clinical water for injection to prepare a polypeptide solution with a concentration of 1 to 10 mg / mL, dripping the solution onto the porous calcium phosphate material until the porous calcium phosphate material no longer absorbs the solution, and calculating the absorption rate of the porous calcium phosphate material to the solution based on the mass of the solution before and after dripping;

[0153] (2) A ball indentation strength test was carried out in accordance with YY / T 1558.3-2017. Ten samples were taken from each embodiment and comparative example. Based on the mechanical curves of the ten samples, the maximum force value of each curve was taken and the average value was calculated.

[0154] Table 1 Performance test results

[0155]

[0156]

[0157] In combination with the embodiments, comparative examples 1 and 2, it can be seen that drying the green body at 60-70°C is helpful to obtain a porous calcium phosphate material with a size that meets the requirements and a complete structure, and the porous calcium phosphate material has a high porosity and excellent mechanical strength. When used in combination with a polypeptide, it can effectively absorb the polypeptide solution, thereby helping to induce bone growth after implantation in the patient. When the drying temperature is higher than the limited range of the present invention, too much stearic acid is removed during the drying process, resulting in the inability to effectively combine the powders, so that the green body collapses during calcination, and the structural integrity and mechanical strength cannot be ensured; and when the drying temperature is too low, the moisture in the green body cannot be effectively removed, and the amount of stearic acid removed is too little, so that the green body melts during calcination, and a porous calcium phosphate material that meets the requirements cannot be obtained.

[0158] Combining Example 1 and Comparative Example 3, it can be seen that when the green body is directly calcined without drying, the green body melts during calcination because the stearic acid is not removed, and the size during molding cannot be maintained.

[0159] In combination with Example 1 and Examples 7-9, the heating rate during calcination will affect the performance of the finished product. An appropriate heating rate helps the powders to effectively combine, thereby helping to obtain a porous calcium phosphate material with a complete structure and excellent mechanical strength, while also ensuring that the porous calcium phosphate material has a high porosity.

[0160] Combining Example 1 and Comparative Example 4, it can be seen that the drying time is too short, the moisture in the green body is not effectively removed, and too little stearic acid is removed, so that the green body melts during calcination, and a porous calcium phosphate material that meets the requirements cannot be obtained.

[0161] In combination with Example 1, Example 10 and Example 11, the use of β-tricalcium phosphate and other powders can ensure that the porous calcium phosphate material has a higher porosity, and the mechanical strength of the porous calcium phosphate material is further improved, but the parts other than β-tricalcium phosphate cannot be completely degraded.

[0162] It will be apparent to those skilled in the art that the invention is not limited to the details of the exemplary embodiments described above and that the invention can be implemented in other specific forms without departing from the spirit or essential features of the invention. Therefore, the embodiments should be considered exemplary and non-limiting in all respects, and the scope of the invention is defined by the appended claims rather than the foregoing description, and it is intended that all variations falling within the meaning and scope of the equivalent elements of the claims be included in the invention. Any reference numeral in a claim should not be considered as limiting the claim to which it relates.

[0163] In addition, it should be understood that although the present specification is described according to implementation modes, not every implementation mode contains only one independent technical solution. This description of the specification is only for the sake of clarity. Those skilled in the art should regard the specification as a whole. The technical solutions in each embodiment may also be appropriately combined to form other implementation modes that can be understood by those skilled in the art.

Claims

1. A method for preparing a porous calcium phosphate material, characterized in that: The following steps are involved: Mixing ceramic powder, pore former and binder to obtain a mixture; Pressing the mixture into a shape to obtain a green body; Dry the green body at 50-70°C for 3-5h to remove part of the pore-forming agent; calcining the dried green body and cooling it to obtain a porous calcium phosphate material; The ceramic powder is selected from one or more of tricalcium phosphate, hydroxyapatite, bioglass, calcium silicate, calcium carbonate, aluminum oxide, titanium dioxide, silicon oxide, silicon carbide and silicon nitride, and the weight percentage of tricalcium phosphate in the ceramic powder is 50-100%; The pore former is selected from one or more of stearic acid, cetyl alcohol, myristyl alcohol, stearyl alcohol, cetostearyl alcohol, and glyceryl mono- and distearate; The binder is selected from one or more of polyvinyl alcohol, gelatin, collagen, hyaluronic acid, chitosan, alginate, alginate, polyoxyethylene polyoxypropylene vinyl ether block copolymer and polyglycolic acid.

2. The method for preparing the porous calcium phosphate material according to claim 1, characterized in that: The weight ratio of the ceramic powder to the pore-forming agent is (1-2):1; and / or, The weight ratio of the ceramic powder to the binder is (6-4):

1.

3. The method for preparing the porous calcium phosphate material according to claim 1, characterized in that: The particle size of the ceramic powder is 50nm-100μm.

4. The method for preparing the porous calcium phosphate material according to claim 1, characterized in that: The binder is a polyvinyl alcohol solution with a concentration of 2-8 wt%.

5. The method for preparing the porous calcium phosphate material according to claim 1, characterized in that: The calcination temperature is 1100-1200°C and the time is 3-5h.

6. The method for preparing the porous calcium phosphate material according to claim 1, characterized in that: During calcination, the temperature is raised from room temperature to the calcination temperature at a heating rate of 3 to 5°C / min.

7. A porous calcium phosphate material, characterized in that: The porous calcium phosphate material is prepared by the preparation method of any one of claims 1 to 6.

8. The porous calcium phosphate material according to claim 7, characterized in that: The macropore diameter of the porous calcium phosphate material is 100 to 800 μm; and / or, The micropore diameter of the porous calcium phosphate material is less than 10 μm.

9. The porous calcium phosphate material according to claim 7, characterized in that: The porosity of the porous calcium phosphate material is ≥65%.

10. An application of a porous calcium phosphate material, characterized in that: The porous calcium phosphate material and the polypeptide are combined and applied to bone repair. The porous calcium phosphate material is prepared by the method for preparing the porous calcium phosphate material according to any one of claims 1 to 6.

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