JP4010774B2 - Calcium phosphate-synthetic resin composite for biomaterial and method for producing the same - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a calcium phosphate-synthetic resin composite having excellent processability, impact resistance and biocompatibility, and a method for producing such a calcium phosphate-synthetic resin composite.
[0002]
[Prior art and problems to be solved by the invention]
Calcium phosphate is excellent in biocompatibility and is used as a biomaterial such as an artificial tooth root and a bone reinforcing material such as dental cement. However, since calcium phosphate is a ceramic, it is inferior in toughness and cannot be used for parts that require impact resistance. For this reason, artificial tooth roots, bone reinforcing materials, and the like are made of non-human harmful metal materials such as titanium and stainless steel. However, since the calcium phosphate compound is far superior from the viewpoint of biocompatibility, it is desired to use a calcium phosphate compound, especially hydroxyapatite.
[0003]
Under the circumstances described above, attempts have been made to combine calcium phosphate compounds with glass materials, metal materials, and synthetic resins, and some of them have already been put into practical use. However, in the case of compounding with a glass material, there is a problem that the glass elutes with time in vivo.
[0004]
Further, a composite material of a calcium phosphate compound and a metal material is generally obtained by embedding calcium phosphate compound particles in a metal frame or sintering a mixture of metal powder and calcium phosphate compound powder. However, in the former case, the calcium phosphate compound may be displaced in vivo. In the latter case, since the calcium phosphate compound powder has a low porosity and a small particle size, the calcium phosphate compound particles exposed on the surface of the composite sintered body are liable to fall off.
[0005]
In addition, attempts have been made to knead calcium phosphate particles in a melted synthetic resin and combine calcium phosphate with a synthetic resin. However, the calcium phosphate particles tend to collapse during kneading, and when the composite is molded. There is a defect that the synthetic resin particles melt and easily cover the surface of the calcium phosphate particles. In addition, there is a problem that burrs are generated during cutting.
[0006]
Accordingly, an object of the present invention is to provide a calcium phosphate-synthetic resin composite having excellent processability, impact resistance and biocompatibility, and a method for producing such a calcium phosphate-synthetic resin composite.
[0007]
[Means for Solving the Problems]
As a result of diligent research in view of the above problems, the present inventors, in a calcium phosphate-synthetic resin composite obtained by pressurizing and heating calcium phosphate particles and synthetic resin particles, joined the synthetic resin particles to each other on the particle surface. The present inventors have found that a calcium phosphate-synthetic resin composite having excellent processability, impact resistance and biocompatibility can be obtained, and arrived at the present invention.
[0008]
That is, the calcium phosphate-synthetic resin composite of the present invention is characterized in that synthetic resin particles are bonded to each other on the particle surface. In the present invention, the synthetic resin particles are joined to each other on the particle surface while maintaining a certain shape without being completely melted. Therefore, in a normal state, the calcium phosphate particles are firmly held by the synthetic resin particles, but at the time of cutting and polishing, the particle interface between the synthetic resin particles and the particle interface between the calcium phosphate particles and the synthetic resin particles are peeled off. It has become. For this reason, there is no problem that the synthetic resin particles melt and cover the surface of the calcium phosphate particles when cutting and polishing, and the processability is extremely excellent.
[0009]
The calcium phosphate particles used in the composite of the present invention are preferably porous particles that are preliminarily sintered at 500 to 1300 ° C. The average particle diameter of the calcium phosphate particles is preferably 0.001 to 10 mm, and the calcium / phosphorus ratio is preferably 1.4 to 2.0 (molar ratio).
[0010]
Furthermore, the synthetic resin particles used in the composite of the present invention are preferably at least partially crosslinked in advance. The synthetic resin particles are preferably made of a water-insoluble acrylic resin or polystyrene resin.
[0011]
In the composite of the present invention, the weight ratio of calcium phosphate particles / synthetic resin particles is preferably 1/9 to 8/2, and the vacuum condition or the condition not containing O ₂ such as inert gas or N ₂ gas. The pressure heat treatment at is more preferable.
[0012]
Further, another method for producing a calcium phosphate-synthetic resin composite according to the present invention includes at least (a) a step of pre-sintering calcium phosphate particles, and (b) a synthetic resin particle so that the calcium phosphate particles are embraced. A step of filling the resin particles and the calcium phosphate particles in a filling mold, and (c) a step of pressurizing and heating the synthetic resin particles and the calcium phosphate particles so that the synthetic resin particles are bonded to each other on the surface. It is characterized by that.
[0013]
At the time of filling, there are gaps between the synthetic resin particles 200 and the synthetic resin particles 200 and between the synthetic resin particles 200 and the calcium phosphate particles 100, as shown in FIG. As shown, the synthetic resin particles 200 are deformed to fill the gaps between the synthetic resin particles 200 and the synthetic resin particles 200 and between the synthetic resin particles 200 and the calcium phosphate particles 100. It becomes the structure which mutually joined on the particle | grain surface.
[0014]
DETAILED DESCRIPTION OF THE INVENTION
The calcium phosphate-synthetic resin composite of the present invention and the production method thereof will be described in detail below.
[0015]
[1] Calcium phosphate particles The calcium phosphate particles used in the present invention have a calcium / phosphorus molar ratio of 1.4 to 2.0, specifically, apatites such as hydroxyapatite and fluorapatite, tricalcium phosphate, and tetracalcium phosphate. Or a mixed powder of two or more of these.
[0016]
The average particle diameter of the calcium phosphate particles is preferably 0.001 to 10 mm, particularly preferably 0.01 to 3.0 mm.
[0017]
The calcium phosphate particles used in the calcium phosphate-synthetic resin composite of the present invention may be porous particles or non-porous particles, but the former is preferred. In the case of porous particles, the porosity is preferably 20 to 70%. The pores may vary in size, but preferably have a diameter of 10 to 2000 μm.
[0018]
Moreover, it is preferable that the calcium phosphate particles used in the present invention are pre-sintered at 500 to 1300 ° C. in advance before the pressure heat treatment. When the pre-sintering temperature is lower than 500 ° C., the calcium phosphate particles tend to collapse during the pressure heat treatment. In addition, porous calcium phosphate particles are not preferable because they are deformed by pressurization and the pores are crushed and the porosity is lost. On the other hand, when the temperature is higher than 1300 ° C., decomposition or deterioration of the calcium phosphate compound occurs. A more preferable pre-sintering temperature is 700 to 1200 ° C.
[0019]
The pre-sintering time (the time for maintaining the pre-sintering temperature) is preferably 1 to 10 hours. If the pre-sintering time is less than 1 hour, the pre-sintering effect cannot be obtained, and even if the treatment is performed for more than 10 hours, the effect is not changed and the cost is increased. A more preferable pre-sintering time is 2 to 5 hours. Moreover, the atmosphere of pre-sintering is not particularly limited, but it is preferably performed in the air for the purpose of preventing decomposition of the calcium phosphate compound.
[0020]
The preliminarily sintered calcium phosphate is adjusted to calcium phosphate particles having an average particle size of 0.001 mm to 10 mm. If the average particle size of the calcium phosphate particles is more than 10 mm, it is not preferable because the calcium phosphate particles easily fall off from the calcium phosphate-synthetic resin composite. On the other hand, if it is less than 0.001 mm, it tends to agglomerate and the dispersibility is deteriorated, and the cost is also increased.
[0021]
[2] Synthetic resin particles The synthetic resin particles used in the calcium phosphate-synthetic resin composite of the present invention are preferably at least partially crosslinked in advance. When the pressure and heat treatment is performed, the synthetic resin particles are deformed to fill the gaps between the particles as shown in FIG. 2, so that the synthetic resin particles are bonded to each other on the particle surface.
[0022]
As the synthetic resin particles used in the present invention, known materials can be used without particular limitation as long as they satisfy the above-mentioned conditions and are not harmful to humans, but water-insoluble acrylic resins, polystyrene resins, etc. are particularly preferable. .
[0023]
The average particle size of the synthetic resin particles is preferably 0.1 to 500 μm, and particularly preferably 1 to 100 μm. Moreover, it is preferable that the average particle diameter of a synthetic resin particle is smaller than the average particle diameter of a calcium phosphate particle.
[0024]
[3] Pressurized heat treatment
(1) Pressure heating apparatus In the present invention, it is preferable to use a pressure heating method for producing a calcium phosphate-synthetic resin composite, specifically, pressure heating in a vacuum or inert N ₂ gas. The method is preferred. The pressurizing heater, vacuum conditions or after He, Ar, in an atmosphere to remove oxygen, such as N _2, calcium phosphate particles and the synthetic resin particles filled between a pair of the type connected to a heat source, under pressure It is a method of heating.
[0025]
An apparatus for performing vacuum (gas replacement) pressure heating will be described with reference to FIGS. The vacuum pressurizing and heating apparatus 1 shown in FIG. 3 is filled in the mold 2 by moving up and down in the mold 2 placed in the vacuum chamber 6 provided with the vacuum pump 7. And punches 4a and 4b for pressing the mixture 3 of calcium phosphate particles and synthetic resin particles, and rams 5a and 5b for driving the punches 4a and 4b. A thermocouple (not shown) for measuring the processing temperature is provided in the mold 2. The gas pump 11 is provided with a gas inlet and a gas cylinder.
[0026]
Each of the rams 5a and 5b is driven by a pressurizing drive mechanism 9 to pressurize the mixture 3 of calcium phosphate particles and synthetic resin particles, and is connected to a power source 8 via a power supply terminal (not shown). , 4b is heated. The control unit 10 is connected to the pressure drive mechanism 9, the power supply 8, the vacuum pump 7, and the thermocouple, and controls the sintering pressure and sintering temperature in the mold 2, the degree of vacuum in the vacuum chamber 6, and the like.
[0027]
As shown in FIG. 4, the mold 2 has an annular integral structure, and has a cavity 2a having a cylindrical, oval or rectangular cross section. Each punch 4a, 4b has a slightly smaller cross-sectional shape that is substantially the same as the cavity 2a so as to move up and down in the cavity 2a of the mold 2. Each punch 4a, 4b is fixed to the ram 5a, 5b.
[0028]
(2) Filling with calcium phosphate particles and synthetic resin particles The calcium phosphate-synthetic resin composite of the present invention is such that the synthetic resin particles are placed on the particle surface so that the synthetic resin particles 200 embrace the calcium phosphate particles 100 as shown in FIG. The structures are joined together. In order to obtain such a calcium phosphate-synthetic resin composite, the synthetic resin particles 200 are filled so as to surround the calcium phosphate particles 100 as shown in FIG. There must be.
[0029]
For this purpose, the weight ratio of calcium phosphate particles / synthetic resin particles is preferably 1/9 to 8/2. When the weight ratio is more than 8/2, the periphery of the calcium phosphate particles is not filled with the synthetic resin particles, and the calcium phosphate particles easily fall off. On the other hand, if it is less than 1/9, the proportion of calcium phosphate is too low, and the biocompatibility is lowered.
[0030]
In the present invention, calcium phosphate particles and synthetic resin particles are mixed in the above ratio and filled into the cavity 2a of the mold 2.
[0031]
(3) Pressurizing and heating treatment By the method as described above, the mixture 3 of calcium phosphate particles and synthetic resin particles is filled into the cavity 2a of the mold 2 and brought into the state as shown in FIG. Seal and deaerate with vacuum pump 7 to maintain a vacuum of about 10 ^-2 Torr. Alternatively, it can be subsequently replaced with an inert gas such as N ₂ gas, He, or Ar, and this treatment can bring about a deoxygenated (low concentration) state, thereby preventing oxidative decomposition of the synthetic resin.
[0032]
The pressure drive mechanism 9 is actuated by the control unit 10 so that at least one of the rams 5a and 5b moves toward each other, and the punches 4a and 4b fixed thereto add a mixture 3 of calcium phosphate particles and synthetic resin particles. Press. The pressure applied by the punches 4a and 4b is preferably 0.5 to 50 MPa, and more preferably 1.0 to 20 MPa. When the applied pressure is less than 0.5 MPa, the bonding between the synthetic resin particles becomes insufficient, and the particles easily fall off from the composite. Moreover, even if it exceeds 50 MPa, the improvement of the shape retention property corresponding to it cannot be obtained, but on the contrary, there arises only a problem that the calcium phosphate particles are collapsed.
[0033]
Next, the punches 4a and 4b are heated from the power source 8. By these actions, the calcium phosphate particles and the synthetic resin particles are heated under pressure. As a result, as shown in FIG. 2, the synthetic resin particles are joined to each other on the particle surface.
[0034]
The mixture 3 of calcium phosphate particles and synthetic resin particles is heated according to a preset temperature raising program. For this purpose, the temperature of the mixture 3 is detected by a thermocouple (not shown) provided in the mold 2 and the output of the thermocouple is input to the control unit 10. The control unit 10 creates a signal for raising the temperature according to the temperature raising program based on the input temperature data, and outputs the signal to the power supply 8. The power supply 8 supplies an appropriate voltage to the rams 5a and 5b in accordance with a command from the control unit 10.
[0035]
The heating temperature is preferably 130 to 300 ° C, more preferably 150 to 250 ° C. If the heating temperature is less than 130 ° C, the adhesion between the synthetic resin particles becomes insufficient, and the particles easily fall off from the composite. If the heating temperature exceeds 300 ° C, the synthetic resin particles melt without maintaining the particle shape. Are undesirable because they may be integrated.
[0036]
The heating time (time for holding at the heating temperature) is preferably 1 to 30 minutes. If the heating time is shorter than 1 minute, the adhesion between the synthetic resin particles is insufficient, and even if the heating time is longer than 30 minutes, the adhesion is not improved, which is not preferable. A more preferable heating time is 3 to 10 minutes.
[0037]
After completion of the pressure heat treatment, the mixture is allowed to cool to room temperature, and the mold is opened to take out the calcium phosphate-synthetic resin composite. In the composite as it is subjected to pressure and heat treatment, if the degree of exposure of calcium phosphate on the surface may be insufficient, the surface may be ground.
[0038]
【Example】
The present invention will be described in more detail with reference to the following examples, but the present invention is not limited thereto.
[0039]
Example 1
1.5g of porous calcium phosphate particles (particle size 0.2-0.3mm, calcium / phosphorus ratio 1.67) pre-sintered at 1200 ° C in an atmospheric furnace, crosslinked acrylic powder (average particle size 90μm, Chemisnow MR-90G, Soken Chemical Co., Ltd. )) 1.5 g was mixed and filled into a filling mold (12 × 22 mm) of a pressure heating apparatus.
[0040]
Next, using a pressure heating apparatus, pressurization of 10 MPa was performed from above and below, and the mixture was heated and held at 200 ° C. for 5 minutes. Thereafter, it was cooled and the pressure was released at room temperature.
[0041]
As a result, a calcium phosphate-synthetic resin composite having a size of 12.0 × 22.0 × 6.9 mm could be molded. The surface of the molded body was shaved by 0.1 mm using a milling cutter, and the surface was observed with an optical microscope and a scanning electron microscope. As a result, calcium phosphate was well exposed on the surface without being covered with an acrylic resin. The three-point bending strength of the calcium phosphate-synthetic resin composite was 24.8 MPa.
[0042]
Example 2
Calcium phosphate particles (average particle size 0.01mm, calcium / phosphorous ratio 1.50) 2.0g pre-sintered at 700 ° C in an atmospheric furnace and crosslinked acrylic powder (average particle size 15μm, Chemisnow MX-1500H, Soken Chemical Co., Ltd.) 1.0 g was mixed and filled into a filling mold (12 × 22 mm) of a pressure heating apparatus.
[0043]
Next, using a pressure heating apparatus, pressurization of 10 MPa was performed from above and below, and the mixture was heated and held at 240 ° C. for 5 minutes. Thereafter, it was cooled and the pressure was released at room temperature.
[0044]
As a result, a calcium phosphate-synthetic resin composite having a size of 12.0 × 22.0 × 5.8 mm could be molded. The surface of the molded body was shaved by 0.1 mm using a milling cutter, and the surface was observed with an optical microscope and a scanning electron microscope. As a result, calcium phosphate was well exposed on the surface without being covered with an acrylic resin. The three-point bending strength of the calcium phosphate-synthetic resin composite was 15.7 MPa.
[0045]
Example 3
0.2 g of porous calcium phosphate particles (particle size 0.2-0.6 mm, calcium / phosphorus ratio 2.0) pre-sintered at 1100 ° C. in an atmospheric furnace, crosslinked acrylic powder (average particle size 1.5 μm, Chemisnow MX-150, Soken Chemical Co., Ltd. )) 1.8 g was mixed and filled into a filling mold (12 × 22 mm) of a pressure heating apparatus.
[0046]
Next, using a pressure heating apparatus, pressurization of 20 MPa was performed from above and below, and the mixture was heated and held at 150 ° C. for 30 minutes. Thereafter, it was cooled and the pressure was released at room temperature.
[0047]
As a result, a calcium phosphate-synthetic resin composite of 12.0 × 22.0 × 6.2 mm could be molded. The surface of the molded body was cut by 0.05 mm using a milling cutter, and the surface was observed with an optical microscope and a scanning electron microscope. As a result, calcium phosphate was satisfactorily exposed on the surface without being covered with an acrylic resin. The three-point bending strength of the calcium phosphate-synthetic resin composite was 16.2 MPa.
[0048]
Example 4
1.5g of porous calcium phosphate particles (particle size 1.0-3.0mm, calcium / phosphorus ratio 1.67) preliminarily sintered at 1000 ° C in an atmospheric furnace, and crosslinked acrylic powder (average particle size 15μm, Chemisnow MX-1500H, Soken Chemical Co., Ltd.) ) 1.5 g was mixed and filled into a filling mold (12 × 22 mm) of a pressure heating apparatus.
[0049]
Next, using a pressure heating apparatus, pressurization of 5 MPa was performed from above and below, and the mixture was heated and held at 240 ° C. for 10 minutes. Thereafter, it was cooled and the pressure was released at room temperature.
[0050]
As a result, a calcium phosphate-synthetic resin composite having a size of 12.0 × 22.0 × 7.1 mm could be formed. The surface of the molded body was shaved by 0.3 mm using a milling cutter, and the surface was observed with an optical microscope and a scanning electron microscope. As a result, calcium phosphate was well exposed on the surface without being covered with an acrylic resin. The three-point bending strength of the calcium phosphate-synthetic resin composite was 21.3 MPa.
[0051]
Example 5
2.4g of porous calcium phosphate particles (particle size 0.2-0.6mm, calcium / phosphorus ratio 1.67) pre-sintered at 1200 ° C in an atmospheric furnace and cross-linked acrylic powder (average particle size 3μm, Chemisnow MX-300, Soken Chemical Co., Ltd.) ) 0.6 g was mixed and filled into a filling mold (12 × 22 mm) of a pressure heating apparatus.
[0052]
Next, using a pressurizing / heating apparatus, pressurization of 1 MPa was performed from the top and bottom, and the mixture was heated and held at 240 ° C. for 20 minutes. Thereafter, it was cooled and the pressure was released at room temperature.
[0053]
Thereby, a 12.0 × 22.0 × 6.0 mm calcium phosphate-synthetic resin composite could be molded. The surface of the molded body was shaved by 0.1 mm using a milling cutter, and the surface was observed with an optical microscope and a scanning electron microscope. As a result, calcium phosphate was well exposed on the surface without being covered with an acrylic resin. The three-point bending strength of the calcium phosphate-synthetic resin composite was 11.2 MPa.
[0054]
Example 6
1.5g of porous calcium phosphate particles (particle size 0.2-0.6mm, calcium / phosphorus ratio 1.67) pre-sintered at 1200 ° C in an atmospheric furnace, and crosslinked acrylic powder (average particle size 3μm, Chemisnow MX-300, Soken Chemical Co., Ltd.) ) 1.5 g was mixed and filled into a filling mold (12 × 22 mm) of a pressure heating apparatus.
[0055]
Next, using a pressure heating apparatus, pressurization of 10 MPa was performed from above and below, and the mixture was heated and held at 240 ° C. for 5 minutes. Thereafter, it was cooled and the pressure was released at room temperature.
[0056]
As a result, a calcium phosphate-synthetic resin composite of 12.0 × 22.0 × 6.7 mm could be molded. The surface of the molded body was shaved by 0.1 mm using a milling cutter, and the surface was observed with an optical microscope and a scanning electron microscope. As a result, calcium phosphate was well exposed on the surface without being covered with an acrylic resin. The three-point bending strength of the calcium phosphate-synthetic resin composite was 38.4 MPa.
[0057]
【The invention's effect】
As described above, in the calcium phosphate-synthetic resin composite of the present invention, since the synthetic resin particles are bonded to each other on the particle surface, the calcium phosphate particles are firmly held by the synthetic resin particles in a normal state. At the time of cutting and polishing, the particle interface between the synthetic resin particles and the particle interface between the calcium phosphate particles and the synthetic resin particles are peeled off. For this reason, there is no problem that the synthetic resin particles melt and cover the surface of the calcium phosphate particles during molding, and the processability is extremely excellent.
[0058]
The calcium phosphate-synthetic resin composite of the present invention having such a structure is suitable for uses such as artificial tooth roots and bone reinforcing materials.
[Brief description of the drawings]
FIG. 1 is an enlarged cross-sectional view showing a state in which a mixture of calcium phosphate particles and synthetic resin particles is filled in a filling mold (before pressure heat treatment).
FIG. 2 is an enlarged sectional view showing a calcium phosphate-synthetic resin composite obtained by pressurizing and heating a mixture of calcium phosphate particles and synthetic resin particles.
FIG. 3 is a schematic view showing the configuration of a vacuum pressurizing and heating apparatus for carrying out the method of the present invention.
4 is an exploded view showing a molding part of the vacuum pressurizing and heating apparatus of FIG. 3. FIG.
5 is a longitudinal sectional view showing a state in which a molding die of the vacuum pressurizing and heating apparatus of FIG. 4 is filled with a mixture of calcium phosphate particles and synthetic resin particles.
[Explanation of symbols]
DESCRIPTION OF SYMBOLS 1 ... Pressure heating apparatus 2 ... Mold
2a ... cavity 3 ... mixture of calcium phosphate particles and synthetic resin particles
4a ... (Top) Punch
4b ... (bottom) punch
5a, 5b ... Ram 6 ... Vacuum chamber 7 ... Vacuum pump 8 ... Power source 9 ... Pressure drive mechanism
10 ... Control unit
11 ... Gas pump

Claims (12)

The calcium phosphate particles and synthetic resin particles pressurized and heat-treated calcium - the synthetic resin composite, the synthetic resin particles to each other, and said calcium phosphate particles and the synthetic resin particles are bonded together at the particle surface, the composite A calcium phosphate-synthetic resin composite for biomaterials, wherein the calcium phosphate is exposed on the surface of the body.  The calcium phosphate-synthetic resin composite according to claim 1, wherein the calcium phosphate particles are pre-sintered.  3. The calcium phosphate-synthetic resin composite according to claim 2, wherein the calcium phosphate particles have a pre-sintering temperature condition of 500 to 1300 ° C. 4.  The calcium phosphate-synthetic resin complex according to any one of claims 1 to 3, wherein the calcium phosphate particles are porous particles.  The calcium phosphate-synthetic resin composite according to any one of claims 1 to 4, wherein the calcium phosphate particles have an average particle size of 0.001 to 10 mm.  The calcium phosphate-synthetic resin complex according to any one of claims 1 to 5, wherein the calcium phosphate particles have a calcium / phosphorus ratio of 1.4 to 2.0 (molar ratio).  The calcium phosphate-synthetic resin composite body according to any one of claims 1 to 6, wherein the synthetic resin particles are previously at least partially crosslinked.  The calcium phosphate-synthetic resin composite body according to any one of claims 1 to 7, wherein the synthetic resin particles are made of a water-insoluble acrylic resin or a polystyrene resin.  The calcium phosphate-synthetic resin composite according to any one of claims 1 to 8, wherein the weight ratio of calcium phosphate particles / synthetic resin particles is 1/9 to 8/2.  The calcium phosphate-synthetic resin composite according to any one of claims 1 to 9, wherein the calcium phosphate-synthetic resin composite is subjected to pressure and heat treatment under vacuum conditions or conditions not containing oxygen. Claims 1 to Ten The calcium phosphate-synthetic resin composite according to any one of the above, wherein the synthetic resin particles are deformed by pressurization and are filled with gaps existing between the particles. Complex. The method for producing a calcium phosphate-synthetic resin composite according to any one of claims 1 to 11 , wherein at least (a) a step of pre-sintering calcium phosphate particles, (b) filling the synthetic resin particles and the calcium phosphate particles Filling the mold, and (c) a method of pressurizing and heating the synthetic resin particles and calcium phosphate particles so that the synthetic resin particles are bonded to each other on the surface.

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