KR101268408B1 - Composition and Manufacturing method for porous calcium phosphate granules by physical foaming - Google Patents

Abstract

The present invention relates to the production of granular bone filler used in the dental and orthopedic field by using a physical foaming method, with a macro-pore structure of 200 ~ 500 ㎛ size, having a micro pore structure of 500 nm ~ 5 ㎛ A method for producing a porous granular bone filler is shown. Conventional dense bone filler has a low specific surface area, the surface of the granule powder is dense, the adhesion of osteoblasts is limited and the absorption occurs only on the surface, so the bone regeneration time is long and the regeneration rate of autologous bone is low. On the other hand, when the porous granular bone filler powder having a macro, micro double pore structure according to the present invention, blood vessels and osteoblasts can grow and move to the inside of the granule powder through macro pores, and the micro pore structure of osteoblasts It provides a surface roughness structure that is very easy to attach, and the inside and outside of the granular powder are absorbed at the same time, resulting in significantly improved bone regeneration and shortened bone fusion period.

Description

Composition and preparation method for porous calcium phosphate powder for physical foaming having a double pore structure {Composition and Manufacturing method for porous calcium phosphate granules by physical foaming}

The present invention relates to a composition for a porous calcium phosphate powder having a macro, micro-pore structure that can be used as a bone marrow restoration and bone filler in the field of dentistry and orthopedics and a method for producing the same.

Currently, in the field of dentistry, granule powder of 500㎛ ~ 2㎜ and orthopedics use 3 ~ 8㎜ size as bone filling material, but it is mostly composed of dense structure without pores or partially closed hole structure. It is possible to attach osteoblasts only to the surface of the granule powder at the time of reclamation, and to combine with autologous bone while absorbing only from the surface, resulting in very limited bone regeneration.

On the other hand, when the calcium phosphate granule powder is prepared in the form of porous granular powder having a macropore structure of 100 to 600㎛ size and a micropore structure of 500nm to 10㎛ size, first, blood vessels grow between the macropores to the inside of the pores. By supplying nutrients to the osteoblasts attached inside, bone formation is achieved by metabolism of osteoblasts in the granule powder, and at the same time, micropores on the surface greatly improve the adhesion of osteoblasts. Simultaneously, bone regeneration can be performed externally, and the bone fusion time with the autologous bone can be very shortened after the procedure, and the autologous bone can be deeply grown to the inside of the pore, so that the regeneration rate of the autologous bone as a whole can be greatly improved.

Such granular powder having macro and micro pore structures is a very useful technique in histological bone regeneration procedures using a mixture of bone marrow or bone marrow stem cells and synthetic bone granule powder of a patient, especially in the orthopedic field.

However, looking at the conventional method for preparing calcium phosphate granule powder, first, preparing a calcium phosphate-based dense block, pulverizing and classifying the same, to prepare a granule powder having a size of 500 μm to 8 mm, or to prepare a calcium phosphate block As in No. 88-000066, a method of forming a waste hole by mixing and molding a polymer binder, starch, wax, and other volatile materials and then volatilizing the volatile material in the heat treatment process is used.

In this case, it is difficult to prepare the granule powder in the form of open pores connected to the pores, and the porosity can be improved as a whole, but bone fusion and osteoblast adhesion with the autologous bone are possible only on the surface, and the internal waste hole is bone fusion with the autologous bone. Since this can not be done at all, since the synthetic material remains as a foreign material after transplantation in vivo, there is a disadvantage in that the autogenous bone occupancy rate is very low with the decrease in bone regeneration efficiency.

In addition, another method of manufacturing the granular powder is to prepare a calcium phosphate block with pores by coating the calcium phosphate paste on a polyurethane sponge and heat-treating it. It is not suitable for use as a granule bone filler.

An object of the present invention for solving the problems as described above, by producing a bone filler powder having a macro, micro-pore structure by the physical foaming method, the bone regeneration at the same time inside and outside the powder is made fast after implantation in vivo Along with the bone fusion effect, the growth and regeneration rate of autologous bone can be significantly improved compared to the conventional dense bone filler.

A feature of the present invention for achieving the above object is to add a polymer resin or a monomer, a surfactant and a blowing agent to the aqueous calcium phosphate slurry to lower the surface tension of the slurry and to rotate the slurry with multiple blades to generate bubbles , As described above, injecting the foamed slurry into a mold and curing the foamed calcium phosphate slurry using the polymerization of the polymer resin or monomer as it is, and sintering the cured porous granules by heat treatment at high temperature. .

The content of the calcium phosphate powder is preferably 10 to 60% by weight based on the total weight of the slurry, the polymer resin or monomer is used to perform an irreversible polymerization process for water.

In addition, the method for curing the foamed calcium phosphate slurry by using one or more polymerization catalysts selected from a polymerization initiator or a sulfate-based and an amine-based one or more selected from azo or peroxide. 0.5 to 5% by weight based on the total weight of the slurry is thermally polymerized at 60 to 100 ° C. for 30 minutes to 4 hours in an inert gas atmosphere such as air to nitrogen or argon, or cured at room temperature.

In addition, in the sintering step, the final porous calcium phosphate granule powder is obtained by heating at a rate of 1 to 5 ° C./min and heat-treating at 1000 to 1350 ° C. for 30 minutes to 4 hours.

In the above surfactant, the surface tension is lowered, and the calcium phosphate slurry foam can be prepared in the process of stirring with an impeller, and when the polymerization initiator or the polymerization catalyst is added thereto and the polymerization is carried out, the pore structure of the calcium phosphate slurry foam is maintained as it is. It may be prepared in the form.

In the polymerization and curing process, the slurry is put into a mold to polymerize and cure, and then, the blocks produced through heat treatment are pulverized and classified to prepare a porous calcium phosphate granule powder having a size of 500 μm to 8 mm. When using a granular plastic mold in which a mold is processed into a spherical shape, a granular powder having a spherical macro and micro-pore structure can be prepared only by separating and heat treating the mold.

According to the present invention as described above, granule powders of various shapes and sizes can be obtained by a simple polymerization process, and macro, micro-connected pore structures can be simultaneously implemented.

Moreover, the foaming method by physical rotary stirring in the foaming method can be easily formed foam, it is very useful because the slurry foam can be cured as it is by polymerization of a polymer resin or monomer.

In addition, compared to the limited bone fusion characteristics of the conventional dense bone filler, the porous bone filler according to the present invention is capable of moving and attaching osteoblasts into the granule powder through the macropores, and also inside the granule powder due to the growth of blood vessels Also, osteoblast proliferation and bone regeneration are possible, and the micropore surface provides easy surface roughness for attachment of osteoblasts, thereby improving the adhesion of osteoblasts, and consequently, bone regeneration is simultaneously performed inside and outside the granule powder. After in vivo transplantation, the bone growth and regeneration rate of the autogenous bones together with the rapid bone fusion effect is significantly improved than the conventional dense bone filler.

1 is a magnified photograph of a porous calcium phosphate granule powder having a macro, micro double pore structure according to the present invention 50 times and 50,000 times with a scanning electron microscope, respectively.
Figure 2 is a photograph of a 30-fold enlarged state before crushing after sintering and firing HA and BCP (60% HA-40% β-TCP) in the form of a block.
Figure 3 is a photograph showing the appearance of granulated powder pulverized by foaming and calcining BCP (60% HA-40% β-TCP), β-TCP, CPP (calcium polyphosphate) in the form of a block.

Hereinafter, an embodiment of the present invention will be described.

Granule powder production method according to the present invention, based on the total weight of the composition, the process of stirring by adding 0.1 to 5% by weight of a dispersant to 20 to 80% by weight of distilled water; Adding and stirring 1 to 15% by weight of a polymer resin or a monomer based on the total weight of the composition as the main binder; Preparing a stable emulsion solution by adding and stirring 0.2-5% by weight of the surfactant based on the total weight of the composition; Adding 1 to 5 wt% of a polyvinyl alcohol or cellulose-based compound as a co-binder based on the total weight of the composition and stirring; Adding and stirring 0.5 to 5 wt% of a blowing agent based on the total weight of the composition; Adding and dispersing 10 wt% to 60 wt% of calcium phosphate powder based on the total weight of the composition; Adding 0.5 to 5% by weight of a polymerization initiator or a polymerization catalyst based on the total weight of the composition; A process of generating calcium phosphate slurry bubbles by stirring at a rotational speed of 10 to 300 rpm with an impeller composed of double to multiple blades; Injecting calcium phosphate slurry into a polyethylene or polypropylene mold, polymerizing and curing; Through the process of heat-treating the cured porous calcium phosphate molded body at 1000 ~ 1350 ℃ to prepare a porous calcium phosphate powder having a macro, micro double pore structure.

The above-mentioned aqueous dispersing agent uses 1 or more types chosen from a polycarboxylic acid ammonium salt, poly ammonium polyacrylate salt, and a polymethylmethacrylate polymer.

In addition, the content of calcium phosphate powder is important to generate bubbles by physical stirring.

When the content of calcium phosphate powder is low, such as 10 to 30% by weight, more preferably 10 to 20% by weight, the viscosity of the slurry is low and fluidity is high, so bubbles are easily generated by the physical stirring process by the impeller. You can. In this case, the porosity is very increased, but there is a disadvantage that the strength is lowered even after molding and heat treatment due to the powder solid content that is too low.

When the powder content is 70 to 80% by weight, the strength is sufficiently high by the high powder solid content, but the waste pores are mainly formed and the porosity is very low.

Therefore, a solid content of a suitable calcium phosphate powder is required, and according to the present invention, the calcium phosphate powder is suitably 30 to 60% by weight, more preferably 40 to 50% by weight.

The calcium phosphate powder is hydroxyapatite, alpha tricalcium phosphate, beta tricalcium phosphate, beta tricalcium phosphate, biphasic calcium phosphate which is a mixture of apatite hydroxide and beta tricalcium phosphate ( biphasic calcium phosphate, calcium metaphosphate, calcium polyphosphate, calcium polyphosphate, tetracalcium phosphate, calcium pyrophosphate, dicalcium phosphate dihydrate, dicalcium phosphate dihydrate Calcium phosphate anhydrous, monocalcium phosphate monohydrate, SiO ₂ -CaO-P ₂ O ₅ based bioglass, SiO ₂ -CaO-P ₂ O ₅ -B ₂ O ₃ based bioglass _{, SiO 2 -CaO-P 2 O} 5 -Na 2 O -based _{bioglass, SiO 2 -CaO-P 2 O} 5 -K 2 O based bio _{Ras, SiO 2 -CaO-P 2 O} 5 -Li 2 O -based _{bioglass, SiO 2 -CaO-P 2 O} 5 -MgO -based bioglass or other SiO ₂ -CaO-P ₂ O ₅ B ₂ based on base compositions One or more selected from among the composite bioglass compositions mixed with one or more selected from O ₃ , Na ₂ O, K ₂ O, Li ₂ O, and MgO is used.

In addition, in order to easily generate bubbles with calcium phosphate slurry, it is necessary to lower the surface tension of the slurry, and suitable surfactants can be used for this purpose, for example, polyoxyethylene nonyl phenyl ether, polyoxyethylene octyl phenyl ether, polyoxyethylene lauryl ether, polyoxyethylene cetyl ether, polyoxyothylene stearyl ether, polyoxyethylene oleic ether, polyoxyethylene branched decyl ether, polyoxyethylene tridecyl ether, polyoxyethylene sorbitan monooleate, polyoxyethylene lauryl amine, polyoxyethylene stearyl amine, polyoxyethylene oleic amine, polyoxyethylene tallow amine, sodium lauryl sulfate, sodium laureth sultate By adding 0.2 to 5% by weight based on the total weight of the slurry or more, it is possible to lower the surface tension and to easily form the slurry bubbles during stirring by the impeller.

In addition, in order to form the foam by physical stirring, and then to cure the calcium phosphate slurry foam as it is, an irreversible polymerization process of the polymer or monomer is required.

This is an aqueous binder of polyvinyl alcohol to cellulose-based binder is hydrolyzed and dissolved in distilled water, and because it undergoes a reversible reaction to water, there is a disadvantage in that it is redissolved again after contact with water after drying, an irreversible polymerization process is required.

For this purpose, epoxyacrylate, epoxymethdiacrylate, diurethane dimethacrylate, aliphatic urethane diacrylate, urethane acrylate, aliphatic urethane methacrylate, aliphatic urethane diacrylate, silicone acrylate, silocone diacrylate, silocone hexaacrylate, polyester acrylate, polyester triacrylate, polyester tetraacrylate, polyester hexaacrylate, polyester At least one selected from urethane acrylate, polyether acrylate, polyether tetraacrylate, polyether urethane acrylate, melamine resin, trichloromelamine, polymelamine-co-formaldehyde, hexakismethoxymethyl melamine, butylated melamine, isobutylated melamine, isobutylated urea melamine, and trinaphthylmethyl melamine.

In addition to the above-described polymer resin, a monomer irreversible polymerization process can be used. As a monomer for this purpose, methyl acrylate, ethyl acrylate, butyl acrylate, isobutyl acrylate, hydroxyehtyl acrylate, methyl methacrylate, ethyl methacrylate, butyl methacrylate, isobutyl methacrylate, allyl methacrylate, ethylene glycol dimethacrylate, hydroxyethyl methacrylate, glycidyl methacrylate, hexandiol diacrylate, hexandiol dimethacrylate, trimethylopropane trimethacrylate, ethyl-3-ethoxy acrylate, triethylene glycol dimethacrylate, hydroxypropyl acrylate, hydroxypropyl methacrylate, hydroxybutyl acrylate, ethoxyethyl acrylate, ethoxyethyl acrylate ethylhexyl acrylate, ethylhexyl methacrylate, lauryl acrylate, lauryl methacrylate, ethylene diacrylate, ethyl-3-amino-3-ethoxy acrylate, tert-butyl acrylate, trimethylsilyl methacrylate, tripropylene glycol diacrylate, hexafluoroisopropyl acrylate, hexafluoroisopropyl methacrylate, phenyl methacry late, tetraethylene glycol diacrylate, polyehtylene glycol phenyl ether acrylate, 2-hydroxy-3-phenoxypropyl acrylate, ethylene glycol dicyclopentenyl ether acrylate, ethylene glycol dicyclopentenyl ether methacrylate, sodium acrylate, sodium methacrylate, tridecyl methacrylate, hexyl acrylate, hexyl methacrylate, isodecyl acrylate , isodecyl methacrylate, cyclohexyl methacrylate, benzyl methacrylate, benzyl 2-ethyl acrylate, ethyl 2-N-propyl acrylate, benzyl 2-N-propyl acrylate, zinc acrylate, butanediol diacrylate, butanediol dimethacrylate, vinyl acrylate, vinyl methacrylate, N- ( Hydroxymethyl) At least one monomer selected from Acrylamide, N, N'-Methylene-bisacrylamide is used.

Polyvinyl alcohol and a cellulose compound may be used as an auxiliary binder of the above-mentioned foaming slurry, and such an auxiliary binder may uniformly coat calcium phosphate powder dispersed with a polymer resin or a monomer under the addition of a surfactant to assist interparticle bonding. have.

The polyvinyl alcohol or cellulose compound is prepared by first dissolving 5 to 10 wt% of polyvinyl alcohol and cellulose compound with respect to the total weight of the distilled water in a separate distilled water, and preparing the solution 1 to 5 wt% based on the total weight of the slurry. Add.

The molecular weight of the polyvinyl alcohol is selected from the range of 1,500 ~ 25,000, the cellulose compound is methyl cellulose, methyl ethyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxy One or more types selected from propylethyl cellulose, carboxycellulose, carboxymethyl cellulose and carboxyethyl cellulose are used.

In addition, the blowing agent is used at least one selected from polyglycol ether (nonionic) surfactants (Tergitol ^® ), polyethylene glycol trimethylnonyl ether (Tergitol ^® TMN), alkylphenylpolyethylene glycol (Tergitol ^® NP), Triton ^® series.

In addition, the method for curing the foam of the calcium phosphate slurry is air to nitrogen, argon by adding 0.1 to 5% by weight of the polymer resin binder selected by using at least one selected from azo-based and peroxide-based polymerization initiators. Thermal polymerization at 60 ~ 100 ℃ 30 minutes to 4 hours in an inert gas atmosphere such as.

As the polymerization catalyst, it is cured at room temperature for 30 minutes to 4 hours using 0.1 to 5% by weight of the weight of the polymer resin binder selected using a sulfate-based and an amine-based.

In this case, at least one selected from ammonium persulfate, ammonium peroxodisulfate, sodium persulfate, sodium peroxodisulfate, potassium persulfate, and potassium peroxodisulfate as the sulfate type, and as the amine type, N, N, N ′, N′-tetramethylethylenediamine, diethylenetriamine , triethylenetetraamine, (2-methylbutyl) amine, bis (2-ethylhexyl) amine, bis (2-methoxyethyl) amine, bis (4-bromophenyl) amine, pentadecafluorotriethylamine, trans-3- (tert-butyldimethylsilyloxy) -N, N- dimethyl-1,3-butadien-1-amine, methoxypolyethylene glycol amine, bis (2-hydroxypropyl) amine, bis (3-aminopropyl) amine, bis (hexamethylene) triamine, bis [3- (trimethoxysilyl) propyl] amine, diethanolamine Use at least one selected from N, N-diethyl (trimethylsilylmethyl) amine, N-allyl-N, N-bis (trimethylsilyl) amine and N-benzyloxycarbonyl- (isopropoxymethyl) amine.

The porous powder compact cured by the above process is heated at a rate of 1 to 5 ° C./min, and heat treated at 1000 to 1350 ° C. for 30 minutes to 4 hours to obtain a final porous calcium phosphate porous powder.

On the other hand, the mold used in the powder manufacturing process may be pulverized after the heat treatment using a block-type mold and sieved to prepare a powder, or by using a granular mold mold can be obtained a granular powder through heat treatment. .

An embodiment of the present invention having the above characteristics will be described in more detail with reference to the accompanying drawings. However, the following examples are merely to illustrate the invention, not limited to the examples specified in the present invention.

<Examples>

20 to 80% by weight, more preferably, 0.1 to 1% by weight of polycarboxylic acid ammonium salt as a dispersant was added to 20 to 50% by weight of distilled water and stirred. A polyvinyl alcohol hydration solution prepared by adding and dissolving 10% by weight of polyvinyl alcohol in a separate distilled water as an auxiliary binder is added in an amount of 3 to 5% by weight based on the total weight of the slurry, or 10% by weight of hydroxypropylmethylcellulose in separate distilled water. The prepared hydroxypropylmethylcellulose hydrated solution prepared by adding and dissolving was added 3 to 5% by weight based on the total weight of the slurry and stirred.

In order to lower the surface tension and make the polymer main binder in a stable emulsion state in water, 0.5 to 2 wt% of polyoxyethylene sorbitan monooleate was added as a surfactant, followed by stirring. Then, urethane acrylate was added as a main binder of the polymer resin 5 to 10 Wt% was added, butyl acrylate was additionally added and stirred in an amount of 3 to 5% by weight as the monomer main binder, and then benzoyl peroxide as a polymerization initiator was added and stirred in an amount of 0.5 to 2% by weight based on the total weight of the slurry. The hydroxyapatite slurry for foaming was prepared by additionally adding hydroxyapatite powder as one of the calcium phosphate powders by 30 to 50% by weight based on the total weight of the slurry and stirring for uniform dispersion.

Slurry bubbles were formed while rotating at a speed of 50-100 rpm with a triple blade.

0.5 to 2% by weight of potassium sulfate and 0.5 to 2% by weight of triethylenetetraamine were added as a polymerization catalyst and stirred slowly.

The hydroxyapatite foam finally prepared by the above method is injected into a mold made of polypropylene with a hemispherical groove of 2 to 8 mm diameter repeatedly processed, and the same mold is covered thereon and left at room temperature for 5 to 15 minutes. It hardened by it.

Spherical foam granules taken out of the mold was heated at a rate of 5 ℃ / min and heat-treated at 1000 ~ 1350 ℃ for 30 minutes to 4 hours to prepare a porous hydroxyapatite granule powder having a macro, micro-pore structure, specific composition Is the same as Examples 1 to 3 of Table 1, Examples 4 to 6 is different from the type of calcium phosphate described above.

Example 1 is too thin so that the skeleton between the macro pores is very thin, Example 3 is too high powder content of the pores are clogged, the powder of Example 2 is shown in Figure 1, Examples 4 to 6 Powder photographs are shown in Figures 2 to 3, Figure 2 is a photograph of an enlarged 30 times before crushing after sintering and firing HA and BCP (60% HA-40% β-TCP) in the form of blocks, Figure 3 Is a photograph showing the granulated powder pulverized by foaming and firing BCP (60% HA-40% β-TCP), β-TCP, and CPP (calcium polyphosphate) in a block form.

In Figure 2 (a) is a photograph of the powder using HA, (b) is a photograph of the powder using BCP, (a) is a photograph of the powder using BCP, (b) is β-TCP, ( c) is a photograph of the powder using CPP.

The pore size of the porous granule powder prepared according to the present invention, the macro pore has a size of 50 ~ 700 ㎛, micro pores of 500nm ~ 10㎛.

Claims (11)

Regarding the total weight of the slurry,
20-50% by weight of distilled water,
0.1-5% by weight of an aqueous dispersant,
0.2-5% by weight of surfactant,
1 to 15% by weight of the main binder polymer resin or monomer,
Polyvinyl alcohol or cellulose-based compound as an auxiliary binder of 1 to 5% by weight,
0.5-5% by weight of blowing agent,
0.5-5% by weight of polymerization initiator or polymerization catalyst,
40 to 50 wt% calcium phosphate powder,
A composition for porous foamed calcium phosphate granular powder for physical foaming having a double pore structure, wherein the granular powder has a macroporous structure connected to each other having a size of 100 to 600 μm and a micro pore structure having a size of 500 nm to 10 μm. The porous phosphoric acid for physical foaming according to claim 1, wherein the dispersant comprises at least one selected from polycarboxylic acid ammonium salts, polyammonium ammonium salts, and polymethyl methacrylate polymers. Calcium granule powder composition. The method of claim 1, wherein the surfactant is polyoxyethylene nonyl phenyl ether, polyoxyethylene octyl phenyl ether, polyoxyethylene lauryl ether, polyoxyethylene cetyl ether, polyoxyothylene stearyl ether, polyoxyethylene oleic ether, polyoxyethylene branched decyl ether, polyoxyethylene tridecyl ether, polyoxyethylene sorbitan monooleate granular powder of porous calcium phosphate for physical foaming having a double pore structure using at least one selected from polyoxyethylene lauryl amine, polyoxyethylene stearyl amine, polyoxyethylene oleic amine, polyoxyethylene tallow amine, sodium lauryl sulfate and sodium laureth sultate Composition. The method of claim 1, wherein the main binder polymer resin, epoxyacrylate, epoxymethdiacrylate, diurethane dimethacrylate, aliphatic urethane diacrylate, urethane acrylate, aliphatic urethane methacrylate, aliphatic urethane diacrylate, silicone acrylate, silocone diacrylate, silocone hexaacrylate, polyester acrylate, polyester triacrylate polyester tetraacrylate, polyester hexaacrylate, polyester urethane acrylate, polyether acrylate, polyether tetraacrylate, polyether urethane acrylate, melamine resin, trichloromelamine, polymelamine-co-formaldehyde, hexakismethoxymethyl melamine, butylated melamine, isobutylated melamine, isobutylated urea melamine, trinaphthylmethyl melamine Composition for porous calcium phosphate granular powder for physical foaming having a double pore structure, characterized in that at least one species is used. According to claim 1, wherein the main binder polymer monomer is methyl acrylate, ethyl acrylate, butyl acrylate, isobutyl acrylate, hydroxyehtyl acrylate, methyl methacrylate, ethyl methacrylate, butyl methacrylate, isobutyl methacrylate, allyl methacrylate, ethylene glycol dimethacrylate, hydroxyethyl methacrylate , glycidyl methacrylate, hexandiol diacrylate, hexandiol dimethacrylate, trimethylopropane trimethacrylate, ethyl-3-ethoxy acrylate, triethylene glycol dimethacrylate, hydroxypropyl acrylate, hydroxypropyl methacrylate, hydroxybutyl acrylate, ethoxyethyl acrylate, ethoxyethyl methacrylate, ethylhexyl acrylate, ethylhexyl methacrylate, lauacrylate , ethylene diacrylate, ethyl-3-amino-3-ethoxy acrylate, tert-butyl acrylate, trimethylsilyl methacrylate, tripropylene glycol diacrylate, hexafluoroisopropyl acrylate, hexafluoroisopropyl methacrylate, phenyl methacrylate, tetraethylene glycol diacrylate, polyehtylene glycol phenyl ether acrylate, 2-hydric oxy-3-phenoxypropyl acrylate, ethylene glycol dicyclopentenyl ether acrylate, ethylene glycol dicyclopentenyl ether methacrylate, sodium acrylate, sodium methacrylate, tridecyl methacrylate, hexyl acrylate, hexyl methacrylate, isodecyl acrylate, isodecyl methacrylate, cyclohexyl methacrylate, benzyl 2-methacrylate, benzyl 2-ethylacrylate Choose from acrylate, ethyl 2-N-propyl acrylate, benzyl 2-N-propyl acrylate, zinc acrylate, butanediol diacrylate, butanediol dimethacrylate, vinyl acrylate, vinyl methacrylate, N- (Hydroxymethyl) Acrylamide, N, N'-Methylene-bisacrylamide Composition for porous calcium phosphate granular powder for physical foaming having a double pore structure, characterized in that it is used one or more. The method of claim 1, wherein the co-binder, polyvinyl alcohol, methyl cellulose, methyl ethyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl ethyl cellulose, A composition for porous calcium phosphate granular powder for physical foaming, characterized in that at least one selected from carboxycellulose, carboxymethyl cellulose and carboxyethyl cellulose is used. According to claim 1, wherein the blowing agent is used at least one selected from polyglycol ether (nonionic) surfactants (Tergitol ^® ), polyethylene glycol trimethylnonyl ether (Tergitol ^® TMN), alkylphenylpolyethylene glycol (Tergitol ^® NP), Triton ^® series Composition for porous foam calcium phosphate granule powder for physical foaming having a double pore structure. The method of claim 1, wherein the polymerization catalyst by the reaction between the sulfate system and the amine system, as the sulfate system, at least one selected from ammonium persulfate, ammonium peroxodisulfate, sodium persulfate, sodium peroxodisulfate, potassium persulfate, potassium peroxodisulfate As an amine type, N, N, N ′, N′-tetramethylethylenediamine, diethylenetriamine, triethylenetetraamine, (2-methylbutyl) amine, bis (2-ethylhexyl) amine, bis (2-methoxyethyl) amine, bis (4 -bromophenyl) amine, pentadecafluorotriethylamine, trans-3- (tert-butyldimethylsilyloxy) -N, N-dimethyl-1,3-butadien-1-amine, methoxypolyethylene glycol amine, bis (2-hydroxypropyl) amine, bis (3-aminopropyl ) amine, bis (hexamethylene) triamine, bis [3- (trimethoxysilyl) propyl] amine, diethanolamine, N, N-diethyl (trimethylsilylmethyl) amine, N-allyl-N, N-bis (trimethylsilyl) amine, N-benzyloxycarbonyl- (isopropoxymethyl) amine is characterized by using at least one selected from Composition for physically foaming porous calcium phosphate granule powder having a double pore structure. The method of claim 1, wherein the calcium phosphate powder is hydroxyapatite, alpha tricalcium phosphate, beta tricalcium phosphate, beta tricalcium phosphate, apatite hydroxide and beta tricalcium phosphate. Biphasic calcium phosphate, calcium metaphosphate, calcium polyphosphate, tetracalcium phosphate, calcium pyrophosphate, and dicalcium phosphate dihydrate dicalcium phosphate dihydrate, dicalcium phosphate anhydrous, monocalcium phosphate monohydrate, SiO ₂ -CaO-P ₂ O ₅ based bioglass, SiO ₂ -CaO-P ₂ O ₅ -B ₂ O ₃ based _{bioglass, SiO 2 -CaO-P 2 O} 5 -Na 2 O -based _{bioglass, SiO 2 -CaO-P 2 O} 5 -K 2 O In the _{bio-glass, SiO 2 -CaO-P 2 O} 5 -Li 2 O -based _{bioglass, SiO 2 -CaO-P 2 O} 5 -MgO -based bioglass or other SiO ₂ -CaO-P ₂ O ₅ based basic composition B ₂ O ₃ , Na ₂ O, K ₂ O, Li ₂ O, having a double pore structure characterized in that at least one selected from a composite bioglass composition mixed with at least one selected from MgO Composition for porous calcium phosphate granule powder for physical foaming. 20-50% by weight of distilled water, 0.1-5% by weight of aqueous dispersant, 0.2-5% by weight of surfactant, 1-15% by weight of main binder polymer resin or monomer, 1-5 A foam was formed by stirring the polyvinyl alcohol or cellulose-based compound, 0.5 to 5% by weight of blowing agent, 0.5 to 5% by weight of polymerization initiator or polymerization catalyst, and 40 to 50% by weight of calcium phosphate powder as impregnated binder by weight. Calcium phosphate slurry producing step,
Injecting the foamed calcium phosphate slurry into the mold as described above, and curing and curing the foamed calcium phosphate slurry using polymerization of the polymer resin or monomer at a temperature of room temperature to 100 ° C,
It comprises a step of sintering the cured porous calcium phosphate molded body by heat treatment at 1000 ~ 1350 ℃,
A method for preparing porous calcium phosphate granule powder for physical foaming having a double pore structure, wherein the granular powder has a macroporous structure of 100 to 600 μm in size and a micro pore structure of 500 nm to 10 μm in size. The method of claim 10, wherein the calcium phosphate slurry is prepared by adding 20 to 50% by weight of distilled water, 0.1 to 5% by weight of an aqueous dispersant and 0.2 to 5% by weight of surfactant based on the total weight of the slurry. and,
1-15% by weight of the main binder polymer resin or monomer is added and stirred to prepare an emulsion solution,
1 to 5% by weight of polyvinyl alcohol or a cellulose compound is additionally added as a co-binder and stirred,
0.5-5% by weight of blowing agent and 0.5-5% by weight of polymerization initiator or polymerization catalyst are further added and stirred,
A method for producing porous calcium phosphate granule powder for physical foaming having a double pore structure, wherein 40 to 50% by weight of calcium phosphate powder is added and stirred to generate bubbles.

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