KR20160091034A - Artificial bones containing nano TCP by wet chemical method and preparation method thereof - Google Patents

Abstract

The present invention relates to artificial bones and a method of manufacturing the same. The artificial bones comprise: macro tricalcium phosphate crystals having an average particle size of 1 to 100 m and rectangular plate-like crystals; nano-tricalcium phosphate (TCP) powder having a particle size of 1 to 200 m and lump-like crystals; mesopores having a diameter of 0.2 to 100 m; micropores having a diameter of 0.1 to 150 nm; and macropores having a diameter of 105 to 1,000 m. The mesopores, the micropores, and the macropores are three-dimensionally connected to each other and having an open pore passage formed therebetween. The purpose of the present invention is to provide the method of manufacturing artificial bones which are cost-effective as the method comprises a simple manufacturing procedure, and can easily mass-produce the bones which have enhanced mechanical strength and flexibility.

Description

TECHNICAL FIELD [0001] The present invention relates to a wet nano TCP powder containing artificial bone and a method of manufacturing the same,

TECHNICAL FIELD [0001] The present invention relates to an artificial bone containing tricalcium phosphate (TCP) crystals, which are plate-like rectangular crystals, and a truncated calcium phosphate (TCP) powder, and a method for producing the same. More particularly, An artificial bone capable of being used for various purposes by significantly improving the compressive strength and tensile strength by mixing and processing nano-sized tricalcium phosphate into a macrocturine calcium phosphate having a plate-like rectangular crystal structure produced by a wet process .

Generally, when a bone tissue is damaged due to fracture, trauma, bone tumor, or bone damage, the bone is filled to create a new bone. The most common method for the recovery of bone defects is to implant autogenous bone, allografts, and xenografts. However, bone grafting methods such as autogenous bone graft, allograft bone grafting, and heterogeneous bone grafting have various problems due to biocompatibility depending on the bone defect site and body of a patient.

As described above, a method for preserving a bone defect site without being affected by a bone defect site and physical characteristics of a patient is to manufacture an artificial bone using a powder metallurgy method, which is made by compression and sintering of a metal or ceramics powder, It is implanted in the defect site. At this time, it is important to have a proper pore structure for the bone defect site and to have mechanical properties together.

Conventionally, poly (methyl methacrylate) (PMMA) has been widely used as an artificial bone material because of its strong adhesive strength. However, since it is biodegradable without absorbency and does not achieve chemical bonding with bone, Since the heat generated during the curing reaction of polymethyl methacrylate reaches 80 DEG C and the surrounding tissues are difficult to use in the treatment of the heat-sensitive nervous system, it has excellent affinity with the surrounding tissues, Inorganic materials are being considered as alternatives. Particularly, in order to hydrate the cement, the dissolution of various ionic components is preferentially performed from each reactant, and the dissolved ions react again. In view of this, an inorganic material using calcium phosphate having high solubility is attracting attention

Calcium phosphate-based materials are widely used as a bone substitute material in dental and medical fields. Among them, calcium phosphate-based bone composition is attracting attention due to various advantages such as high biocompatibility, excellent bioactivity, autogenous curing property, low heat generation temperature and excellent moldability, and the artificial bone used for human body is hydrpxyapatite (HA ), Tricalcium phosphate (TCP), tetracalcium phosphate (TTCP), and dicalcium phosphate anhydrous (DCPA).

On the other hand, apatite hydroxide is similar in crystallinity and chemistry to inorganic components constituting actual bones and has a property of binding directly to bones. However, due to low solubility in vivo, bones bonded at the interface can not grow inward, (TCP) binds directly to bones, but it is similar to apatite hydroxide, but dissolves gradually in vivo and eventually disappears, and it is attracting attention as an artificial bone material. However, there is a disadvantage that tricalcium phosphate (TCP)

Korean Patent No. 0807108 discloses a method for producing a bone graft comprising a spherical shape including macro-sized pores using a tricalcium phosphate precursor, a pore precursor, a gelatin solution and a dispersion medium so as to be used as a bone graft material or a bone- Discloses a method for producing spherical granules of porous calcium? -Phosphate, and Korean Patent No. 04460685 discloses a method for producing spherical granules of calcium? -Phosphate, which comprises calcium monophosphate powder or calcium monofluorophosphate containing 10 wt% A method of producing an artificial bone filler by sintering the formed body by forming a compact by press molding is disclosed. However, the above methods have problems in that the size of unit particles is too large, And strength can not be provided.

A first object of the present invention is to provide a method for manufacturing an artificial bone including a simple process, which is cost effective, easy to mass-produce, and improved in mechanical strength and warpage.

The present invention has been made to solve the above-

A macrotricalcium phosphate crystal having an average particle size of 1 to 100 占 퐉 and a crystal form of which is a plate-like rectangular crystal, and a nanotriccium phosphate powder having a particle size of 1 to 200 nm and a crystal form of a mass are mixed and pressed to manufacture a molded article ; And

And firing the formed body. The present invention also provides a method of manufacturing an artificial bone.

According to an embodiment of the present invention, 5 to 15 parts by weight of the nanotriccium phosphate powder may be contained in 10 parts by weight of the macrotriccium phosphate crystal.

According to an embodiment of the present invention, the molded body may further include dry macro-beta-tricalcium phosphate powder having a particle size of 50 to 500 mu m.

According to an embodiment of the present invention, the dry macro-β-tricalcium phosphate powder may be contained in an amount of 50 to 120 parts by weight based on 10 parts by weight of the macrocturine calcium phosphate crystal.

According to an embodiment of the present invention, the macrocturine calcium phosphate crystal may be a plate-shaped rectangular crystal structure having a length-to-width ratio of 1: 1 to 10: 1 and a width to thickness ratio of 1: 0.1 to 1: have.

According to an embodiment of the present invention, the macrocturine calcium phosphate crystal may be a plate-shaped rectangular crystal structure having a length of 1 to 100 탆, a width of 1 to 50 탆, and a thickness of 0.1 to 50 탆.

According to an embodiment of the present invention, the nanotriccium phosphate crystal may be prepared by hydrating a calcium oxide to produce calcium hydroxide; Dissolving the calcium hydroxide in an aqueous solution to prepare calcium ions; And precipitating the aqueous solution in which the calcium ions are dissolved by stirring at 30 to 40 캜 with phosphoric acid at a pH of 4.8-5.5 to prepare a calcium phosphate powder slurry, heating the mixture to 60 to 95 캜 and stirring for 10 to 60 minutes; ≪ / RTI >

According to an embodiment of the present invention, the macrocturine calcium phosphate crystal may be prepared by hydrating a calcium oxide to produce calcium hydroxide; Dissolving the calcium hydroxide in an aqueous solution to prepare calcium ions; And stirring the aqueous solution in which the calcium ions are dissolved with phosphoric acid at a pH of 4.8-5.5 at 60 to 95 ° C to prepare a calcium phosphate powder, and allowing the calcium phosphate powder to stand for 2-300 hours to grow into a plate-like rectangular crystal structure ≪ / RTI >

According to one embodiment of the present invention, the dry macro-β-tricalcium phosphate is prepared by calcining calcium carbonate at 800 to 1,180 ° C. to prepare calcium oxide, then slowly cooling the mixture to 280 to 320 ° C., and then mixing CaHPO ₄ And maintaining the temperature at 400 to 700 ° C for 30 minutes to 3 hours.

According to an embodiment of the present invention, the molded body may further include a bead made of a thermally decomposable resin, wherein the thermally decomposable resin is at least one of polyimide, polyacrylonitrile, polystyrene, polydibenzene, polyvinylpyridine, polypyrrole, A phenol-aldehyde resin, and a urea-aldehyde resin, and may be at least one selected from the group consisting of polythiophene, polyaniline, furfuryl alcohol, polyacrylamide,

The beads made of the thermally decomposable resin may have a particle size of 100 to 1000 mu m.

According to an embodiment of the present invention, the molded body may contain 1 to 50 parts by weight of beads made of a thermally decomposable resin, with respect to 10 parts by weight of the macrotri calcium phosphate crystal.

According to one embodiment of the present invention, the shaped body is formed from anhydrous calcium phosphate (CaHPO ₄ , DCPA), tetra calcium dihydrogenphosphate (Ca ₄ H ₂ P ₆ O ₂₀ , TCHP), hydroxyapatite (HAp) And calcium phosphate dihydrate (CaHPO ₄ 2H ₂ O, DCPD).

According to an embodiment of the present invention, the firing may be performed in a range of 700 to 1180 ° C.

The present invention also relates to a macrocturine calcium phosphate crystal having an average particle size of 1 to 100 占 퐉 and a crystal form of a rectangular plate-like rectangular crystal; A nanotriccium phosphate powder having a particle size of 1 to 200 nm and a crystal form of a mass; A mesopore having a diameter of 0.2-100 탆; Micropores having a diameter of 0.1 to 150 nm and macropores having a diameter of 105 to 1000 탆,

Wherein the mesopores, micropores and macropores are three-dimensionally connected to each other to form open pore channels.

According to one embodiment of the present invention, the artificial bone is contained in 5 to 15 parts by weight of nanotriac calcium phosphate powder per 10 parts by weight of macrocturine calcium phosphate,

A specific surface area of 60-100 m ² / g, and a porosity of 50-70%.

According to an embodiment of the present invention, the artificial bone may further include dry macro-beta-tricalcium phosphate powder having a particle size of 50 to 500 mu m, wherein the dry macro-beta-tricalcium phosphate is macrotriccium phosphate May be contained in an amount of 50 to 120 parts by weight based on 10 parts by weight.

According to an embodiment of the present invention, the artificial bone may be a structure in which at least 80% of the macrocturine calcium phosphate crystals are unilaterally aligned and the nanotriccium phosphate particles are present between the macrotric calcium phosphate crystals.

The artificial bone including nanotriccium phosphate in the macro tricrate calcium phosphate according to the present invention or the artificial bone including macro calcium phosphate, nanotriccium phosphate and dry macro? -Tricalcium phosphate can be used as meso pores, Macro pores are three-dimensionally intertwined with each other to exhibit a porous structure similar to the bone tissue of an organism. More than 80% of the plate-like rectangular macrotriccium phosphate is aligned on one axis, and nanotriccium phosphate particles are present between macrotric calcium phosphate crystals And the tensile strength can be greatly increased as compared with artificial bones made of the conventional dry macro-beta-tricalcium phosphate and nanotriccium phosphate. Therefore, the size of the test piece is large or the tensile strength is required to be high The skeletal bone is applied as cement and artificial bone. And transplantation of the body shows excellent bone regeneration properties in the bone joining procedure.

1 is a schematic diagram of a reaction apparatus for producing TCP according to an embodiment of the present invention.
Fig. 2 is an image of square and circular specimens produced according to Example 1 of the present invention. Fig.
FIG. 3 is an X-ray diffraction (XRD) result of Macrotriccium Phosphate prepared according to the present invention.
4 is an electron micrograph of macrotric calcium phosphate prepared according to the present invention.
FIG. 5 is an electron microscope image showing the crystal growth of macro tricrate calcium phosphate according to the present invention over time. FIG.
Figs. 6 and 7 are electron microscope images of the artificial bone according to the first embodiment of the present invention. Fig.
8 is an electron microscope image of the artificial bone according to the fourth embodiment of the present invention.
9 is an electron micrograph of an artificial bone according to Comparative Example 1 of the present invention.

Hereinafter, the present invention will be described in detail.

The present invention relates to a microtitre calcium phosphate crystal having an average particle size of 1 to 100 占 퐉 and a crystal form of which is a plate-shaped rectangular crystal, and a nanotriccium phosphate powder having a particle size of 1 to 200 nm and a crystal- Producing a shaped body; And firing the molded body. The present invention also provides a method of manufacturing an artificial bone.

According to the present invention, the tricalcium phosphate (hereinafter, referred to as TCP) crystals are produced by a wet process and have a length to width ratio of 1: 1 to 10: 1, and a width to thickness May be a plate-like rectangular crystal structure with a ratio of 1: 0.1 to 1: 1, and the nano-TCP may be in a lump shape.

In the present invention, the average is an average of long axis of macrotric calcium phosphate crystals, which are plate-shaped rectangular crystals, measured by a long axis, and the average particle size differs according to the crystal growth time during the production of the macrocturic calcium phosphate crystal .

According to the prior art, when an artificial bone is produced only with a dry β-TCP of macro-size, it does not provide a sufficient degree of compactness, and its strength characteristics are significantly deteriorated. On the other hand, when artificial bone is manufactured only with nano-sized TCP, since the artificial bone has a high density, the strength of the artificial bone is also increased, but the bending property is greatly reduced,

Accordingly, the inventors of the present invention have found that a β-TCP block that can be applied to a bone cement such as a skull by improving the denseness of an artificial bone by producing an artificial bone including a dry macro β-TCP and a nano- Respectively. However, although the artificial bone including the dry macro-β-TCP and the nano-TCP has improved denseness and warpability of the artificial bone, there is still a problem that the tensile strength is still insufficient for manufacturing a large size specimen including the oral facial bone cement there was.

On the other hand, when an artificial bone is prepared by wet processing with nano-TCP prepared by a wet process, nano-TCP adheres to the surface of the solid crystal structure of macro TCP and solid state interaction Solid state condensation occurs between the nano-TCPs, and a TCP block is formed on the surface of the macro-TCP, with the nano-TCPs attached to the granules. In addition, in the process of manufacturing the molded body, at least 80% of the plate-shaped rectangular macroscopic TCP is uniaxially aligned and arranged in multiple layers as if the bricks are piled up. The nano TCPs are well dispersed in the granular form between the macro TCP layers To form an existing TCP block. Due to such a structure, compressive strength and tensile strength are greatly improved as compared with conventional artificial bones, and it is applicable to a region requiring high tensile strength because of excellent bending property.

In addition, due to the above structure, a difference in compressive strength and tensile strength between the upper and lower surfaces of the specimen may occur.

On the other hand, in general, as the size of the specimen to be manufactured becomes larger, the compressive strength and the tensile strength of the TCP block are lowered. Therefore, according to the method of manufacturing artificial bone of the present invention, since the TCP block according to the conventional method has a limitation on making the size of the specimen large, it can be manufactured by including the macro TCP and the nano TCP, The compressive strength may be 300 to 350 MPa. As described above, if the size of the specimen can be made large, it can be easily industrialized because it can be manufactured using a large artificial bone structure and a three-dimensional printing technique.

According to the present invention, 5 to 15 parts by weight of the nano-TCP powder may be contained relative to 10 parts by weight of the macro-TCP crystal. Preferably, 8 to 12 parts by weight of the nano- . The above range is preferable for producing an artificial bone specimen having excellent tensile strength and compressive strength and excellent bending property.

According to the present invention, the shaped body may further comprise dry macro-beta-tricalcium phosphate powder having a size of 50 to 500 mu m.

The dry macro-β-TCP powder is irregular in crystal form and may be contained in an amount of 50 to 120 parts by weight based on 10 parts by weight of the macro TCP crystal. When the dry macro-β-TCP powder is contained in an amount exceeding the above range, the compressive strength and the tensile strength may be lowered. When the dry macro-β-TCP powder is contained in the above range, the compressive strength and the tensile strength increase are small .

When the dried macro-beta-TCP powder is contained in the molded body, a three-dimensional complex in which macroscopic (plate-like) -nano (dry) -dry macros (irregularly shaped) TCP is mixed is formed and the compressive strength and tensile strength are adjusted to 5 to 50 %, And warpage is increased, which is preferable.

According to the present invention, the macrocturine calcium phosphate crystal may be a plate-like rectangular crystal having a ratio of length to width of 1: 1 to 10: 1 and a ratio of width to thickness of 1: 0.1 to 1: 1, To width-to-width ratio of 1.5: 1 to 7: 1, and the ratio of width to thickness may be 1: 0.4 to 1: 1.

If the elongation ratio is less than 1.5, the macrotric calcium phosphate crystals are unlikely to be uniaxially aligned, so that the tensile strength may be lowered. If the elongation ratio exceeds 7, the ratio is not economically low due to the wet process.

In the present invention, the aspect ratio means a ratio of length to width.

According to the present invention, the macrotric calcium phosphate may be a plate-like rectangular crystal having a length of 1 to 100 탆, a width of 1 to 50 탆, and a thickness of 0.1 to 50 탆. When the length of the macrocturine calcium phosphate is less than 1 탆, the plate-shaped rectangular crystals are difficult to form. When the length exceeds 100 탆, the time required for crystal growth takes a long time, but the increase rate of tensile strength is insufficient .

Meanwhile, the nano-TCP crystal may be prepared by hydrating and reacting calcium oxide to produce calcium hydroxide; Dissolving the calcium hydroxide in an aqueous solution to prepare calcium ions; And precipitating the aqueous solution in which the calcium ions are dissolved by stirring at 30 to 40 캜 with phosphoric acid at a pH of 4.8-5.5 to prepare a calcium phosphate powder slurry, heating the mixture to 60 to 95 캜 and stirring for 10 to 60 minutes; ≪ / RTI >

Specifically, the calcium oxide may be calcined by calcining the calcium carbonate at a high temperature of 800 to 1180 ° C for 1 to 3 hours to obtain calcium oxide, and then hydrating the calcium carbonate by slow cooling to 250 to 350 ° C to produce calcium hydroxide. When the calcium hydroxide is stirred in distilled water for 5 to 7 hours, calcium ions can be produced by dissociation. The aqueous solution in which the calcium ions are dissolved is subjected to a coprecipitation reaction with phosphoric acid at 30 to 40 캜 at a pH of 4.8-5.5 in an atmosphere free of carbon dioxide to prepare a calcium phosphate powder slurry.

It is to carry out the reaction in the carbon dioxide-free atmosphere, Ca ^{2 +,} or Ca compounds it has a nature to easily react with CO ₂ in the environment, the calcium carbonate is disturbance to the β-TCP crystallization generated by the carbon dioxide and the reaction As shown in Fig. Therefore, it is preferable to carry out the reaction in a nitrogen, argon or vacuum environment in which carbon dioxide has been removed, and it is preferable to use ultrapure water or a second or more distilled water from which carbonic acid has been removed.

The optimum range of the phase equilibrium material may vary depending on the pH condition. When the pH is less than 4.2, dicalcium phosphate dihydrate (CaHPO ₄ 2H ₂ O, DCPD) forms the most stable phase, HAp, octacalcium phosphate (OCP), a-tricalcium phosphate (? -TCP) and tetra (? - TCP) are most stable in the pH range of 4.2 to 4.8, A mixed phase of calcium phosphate (TTCP) is formed. Also, when the pH environment is set to 4.8 to 5.5 according to the present invention, a large amount of? -TCP is formed and supersaturated after supersaturation. This pH range can be set by closely controlling the amount of phosphoric acid added, but this can easily be achieved with manual capacity in a massive process.

When the mixture is heated to 60 to 95 ° C and stirred for 10 to 60 minutes, it is preferable since the yield of the solubility, reaction and precipitation is excellent.

The nano-TCP produced by the above reaction may be prepared by further comprising drying in a carbon dioxide-free atmosphere and a temperature of 20 to 125 ° C for 2 to 48 hours, and the temperature range is only an example, and contact with carbon dioxide There is no limit to the atmosphere.

The nano-TCP may be coated with a non-aqueous coating composition selected from the group consisting of a urethane resin, a polyacrylate resin, a paraffin wax, a polyethylene wax, and a fatty acid amide to be used in the artificial bone preparation of the present invention.

When the nano-TCP is coated with the non-aqueous coating to modify the surface to be non-aqueous, the dispersibility of the nano-TCP is improved. Even when mixed with macro TCP, It is possible to disperse the macroscopically uniformly between the macro-TCPs, thereby making artificial bones having uniform strength and warpage. On the other hand, it is preferable that the non-aqueous coating is sintered by a firing reaction.

Meanwhile, the macro TCP crystal is prepared by hydrating a calcium oxide to produce calcium hydroxide; Dissolving the calcium hydroxide in an aqueous solution to prepare calcium ions; And stirring the aqueous solution in which the calcium ions are dissolved with phosphoric acid at a pH of 4.8-5.5 at 60 to 95 ° C to prepare a calcium phosphate powder, and allowing the calcium phosphate powder to stand for 2-300 hours to grow into a plate-like rectangular crystal structure ≪ / RTI >

If the temperature is lower than the above temperature range, the plate-like rectangular crystal structure is hardly formed and crystals having a low tensile strength are produced. If the temperature range is exceeded, the solubility of TCP is high and it is difficult to grow into a macro size.

The dry macro-β-tricalcium phosphate is prepared by calcining calcium carbonate at 1000 to 1800 ° C. to prepare calcium oxide, cooling slowly at 280 to 320 ° C., and then CaHPO ₄ is mixed and pulverized. Min to 3 hours.

According to the present invention, the firing of the artificial bones can be performed at a temperature in the range of 700 to 1180 ° C. If the firing temperature is in excess of the above range, the high-temperature type α-lactic acid having a lower mechanical strength and chemical stability than tricalcium phosphate -TCP, which is undesirable.

When baking at a temperature exceeding the above range, for example, baking at 1500 ° C, alpha-tricalcium phosphate can be produced, and grain growth of the artificial bone can be performed to reduce pores, thereby forming pores smaller than the desired size . If the size of the pores is reduced, the hardness and strength can be improved, but it is not preferable because it is deflected by the impact due to the bending property. In addition, even if the formed body is manufactured in consideration of reduction in pore size, it is difficult to control the degree of reduction of the pore. Therefore, it is preferable to sinter in the recommended range.

According to the present invention, the molded body may be manufactured by further including a bead made of a thermally decomposable resin so that the artificial bone of the present invention has a structure similar to that of a living body bone, so that bone regeneration can be efficiently performed. The beads made of the thermally decomposable resin are preferably decomposed by heat at a temperature lower than the sintering temperature range, and macropores can be generated by the decomposition.

The shape of the beads is not particularly limited as long as it is for forming macropores.

Wherein the thermally decomposable resin is at least one selected from the group consisting of polyimide, polyacrylonitrile, polystyrene, polydibenzene, polyvinylpyridine, polypyrrole, polythiophene, polyaniline, furfuryl alcohol, polyacrylamide, phenol-aldehyde resin and urea-aldehyde resin The beads may have a particle size in the range of 110 to 1000 mu m. If the particle size exceeds the above range, it is not preferable because the size of macropores produced by sintering is too large to produce artificial bones having desired strength and warpage properties.

In addition, the molded body may further include 1 to 50 parts by weight of the beads relative to 10 parts by weight of the macrocturine calcium phosphate crystals,

 If the content of the beads is less than the above range, there is not a large difference between the properties of the artificial bones produced by the production method without adding beads, and when the content of the beads is more than the above range, too much macropores are formed The artificial bone having a remarkably reduced strength characteristic can be produced, which is not preferable. On the other hand, in the above range, the artificial bone having a hierarchical porosity composed of macro-meso-nanopores is formed with a specific surface area of 60-100 m 2 / g and a porosity of 50-70% It can exhibit excellent bone regeneration when it is implanted in the body.

The molded body may be composed of a single component of TCP, but may be made of anhydrous calcium phosphate (CaHPO ₄ , DCPA), tetracalcium dihydrogenphosphate (Ca ₄ H ₂ P ₆ O ₂₀ , TCHP), hydroxyapatite (HAp) Or dicalcium phosphate dihydrate (CaHPO ₄ 2H ₂ O, DCPD). Those skilled in the art, who wish to reproduce or implement the present invention, may selectively include some of the manufacturing methods according to the present invention as necessary to include or exclude these components And the present invention is not limited by the inclusion of such additional ingredients.

The artificial bone produced by the above-mentioned production method is macroscopically β-TCP having an average particle size of 0.5 to 100 μm; Nano-β-TCP having a particle size of 1 to 200 nm; A mesopore having a diameter of 0.2-100 탆; And micropores having a diameter of 0.1-150 nm.

In order to improve the warpage, compressive strength and tensile strength of the artificial bone, dry macro-beta-tricalcium phosphate powder having a particle size of 50 to 500 mu m may be further included. At this time, the dry macro-β-tricalcium phosphate may be contained in an amount of 50 to 120 parts by weight based on 10 parts by weight of the macroctric calcium phosphate.

Further, it is also possible to select from the group consisting of polyimide, polyacrylonitrile, polystyrene, polydibenzene, polyvinylpyridine, polypyrrole, polythiophene, polyaniline, furfuryl alcohol, polyacrylamide, phenol-aldehyde resin and urea-aldehyde resin The present invention can provide an artificial bone having macropores more efficiently so as to have a structure similar to that of a living body bone and to enable efficient bone regeneration have. The macropore may have a diameter of 105-1000 mu m.

The macropores, mesopores, and micropores are three-dimensionally connected to each other to form open pore channels, and exhibit similar porosity to the bone tissue of the organism. In addition, 80% or more of the plate-shaped rectangular macrotriccium phosphate crystals are unilaterally aligned, and nanotrie calcium phosphate particles are well dispersed among the macrotric calcium phosphate, so that the bricks and the bricks are bonded with an adhesive The tensile strength and the compressive strength can be greatly improved. The tensile strength and the compressive strength of the upper and lower surfaces of the artificial bone may differ.

The artificial bone has a compressive strength of 300-350 MPa, a torsional strength of 10-15 kg / f, and a fracture toughness of 2-4 MPa / m ^½ , which is remarkably improved as compared with the artificial bone produced by the conventional method It can be confirmed that the artificial bone is formed.

Hereinafter, the present invention will be described in more detail with reference to preferred embodiments. It will be apparent to those skilled in the art, however, that these examples are provided to further illustrate the present invention, and the scope of the present invention is not limited thereto.

Manufacturing example  1. Macro-sized dry β- TCP  Produce

CaCO ₃ was calcined at 900 ° C for 2 hours in air to obtain a CaO powder. The CaO was slowly cooled, mixed with CaHPO ₄ , and maintained at 600 ° C for 1 hour.

Manufacturing example  2. Nano TCP  Produce

CaCO ₃ was calcined at 1100 ° C for 2 hours to obtain CaO powder. After cooling to 300 ° C, Ca (OH) ₂ was prepared by hydration. The Ca (OH) ₂ was kneaded for 6 hours under distilled water in a carbon dioxide-free atmosphere to prepare an aqueous solution in which Ca ^{2 +} free ions were dissolved. An aqueous solution of phosphoric acid in which a proper amount of PO ₄ ^{3 -} ion corresponding to the TCP composition was dissolved was prepared. A pH meter and a Masterplex pump were used to feed the aqueous solution in which the Ca ^{2 +} free ions dissolved and the aqueous phosphoric acid solution, respectively, to the reactor and stirred at pH 5.0 and 37 ° C to form precipitates. The pH of the reactor was maintained at the same temperature, the reaction temperature was raised to 90 ° C, and the mixture was stirred for 1 hour and dried to prepare nano-TCP having a particle size of 1-200 nm and a particle size of not less than 20 nm.

Manufacturing example  3. Macro TCP  Manufacturing 1.

CaCO ₃ was calcined at 1100 ° C for 2 hours to obtain CaO powder. After cooling to 300 ° C, Ca (OH) ₂ was prepared by hydration. The Ca (OH) ₂ was kneaded for 6 hours under distilled water in a carbon dioxide-free atmosphere to prepare an aqueous solution in which Ca ^{2 +} free ions were dissolved. An aqueous solution of phosphoric acid in which a proper amount of PO ₄ ^{3 -} ion corresponding to the TCP composition was dissolved was prepared. An aqueous solution in which Ca ^{2 +} free ions were dissolved and a phosphoric acid aqueous solution were fed to a reactor at pH 5.0 and 90 ° C using a pH meter and a master flex pump, respectively, and the mixture was allowed to undergo a static growth without stirring to form particles having a size of 1 to 100 μm, Macro TCP having a rectangular crystal structure was prepared.

Manufacturing example  4. Macro TCP  Manufacturing 2.

Macro TCP was prepared by the method of Production Example 3, except that the reaction temperature was changed at 80 캜 instead of 90 캜 in the crystal formation reaction.

Manufacturing example  5. Macros TCP  Manufacturing 3.

Macro TCP was prepared by the method of Production Example 3, except that the reaction temperature was changed at 70 캜 instead of 90 캜 in the crystal formation reaction.

Manufacturing example  6. Macro TCP  Manufacturing 4.

Macro TCP was prepared by the method of Production Example 3, except that the reaction temperature was changed at 55 ° C instead of 90 ° C during the crystal formation reaction.

Manufacturing example  7. Macros TCP  Manufacturing 5.

Macro TCP was prepared by the method of Preparation Example 3, except that the reaction temperature was changed at 37 캜 instead of 90 캜 in the crystal formation reaction. No plate-shaped rectangular crystal structure was formed at 37 占 폚.

Example  One.

3.5 g of the nano-TCP prepared in Preparation Example 2 was added to 3.5 g of the macro-TCP prepared in Preparation Example 3, 2 g of polystyrene beads were added and mixed by a ball mill. The mixture was uniaxially pressed to form a TCP block. The TCP block was firstly fired at 800 DEG C for 3 hours in a quartz tube electric furnace. The first sintered polystyrene beads were sintered to form macropores, and macro-TCP and nano-TCP were entangled to produce mesopores and micropores. After that, a part of the sintered body was cut out and further sintered in a muffle at 1050 ° C for 12 hours to produce an improved artificial bone.

Example  2.

An artificial bone was prepared in the same manner as in Example 1, except that 1.8 g of the nano-TCP prepared in Preparation Example 2 was added to 3.5 g of the macro TCP prepared in Preparation Example 3.

Example  3.

An artificial bone was prepared in the same manner as in Example 1, except that 5.2 g of the nano TCP prepared in Preparation Example 2 was added to 3.5 g of MacroTCP prepared in Preparation Example 3.

Example  4.

35.0 g of the dry macro β-TCP prepared in Preparation Example 1 and 3.5 g of the nano-TCP prepared in Preparation Example 2 were added to 3.5 g of the macro TCP prepared in Preparation Example 3, 2 g of polystyrene beads were added thereto, Lt; / RTI > An artificial bone was prepared in the same manner as in Example 1, except that the mixture was uniaxially pressed to form a TCP block.

Comparative Example  One.

An artificial bone was prepared in the same manner as in Example 1, except that 35.0 g of dry macro-TCP and 3.5 g of nano-TCP were added to make a TCP block.

Comparative Example  2.

An artificial bone was prepared in the same manner as in Example 1, except that 1 g of the nano-TCP prepared in Preparation Example 2 was added to 3.5 g of the macro TCP prepared in Preparation Example 3 to prepare a TCP block.

Comparative Example  3.

An artificial bone was prepared in the same manner as in Example 1, except that 6 g of the nano-TCP prepared in Preparation Example 2 was added to 3.5 g of the macro-TCP prepared in Preparation Example 3 to make a TCP block.

Test Example  One. XRD  analysis

The TCP according to Production Example 1 and Production Example 2 was analyzed by X-ray diffraction (XRD), which is shown in FIG.

Reference Example 1 (blue line) shows XRD results of powders prepared by calcining nano TCP powders synthesized by wet method at 90 ° C according to Production Example 2 at 80 ° C. Referring to FIG. 3, Reference Example 1 calcined at 800 ° C after the synthesis by wet method had similar crystallinity to Production Example 1 (black line) of β-TCP produced by calcination at 900 ° C by a dry method. This means that the TCP powder or crystal synthesized by the wet method has a high reactivity and thus β-TCP of crystal phase which can be treated at a low temperature is obtained.

On the other hand, Reference Example 2 (green line) shows a crystalline state in which the aggregate of nanopowder is nearly amorphous as a result of XRD of the apatite powder synthesized by wet synthesis at 37 ° C. That is, the apatite TCP means a mixed state of the nano HAp and the TCP. Referring to FIG. 3, it can be confirmed that the DCPA phase and the apatite TCP (TCP / HAp) phase are developed together in Production Example 2 (red line). This is because the nano-TCP powder synthesized by wetting absorbs carbon dioxide in the process of measuring XRD and the phase change occurs, and the type and intensity of the XRD phase are gradually changed Respectively. In addition, the peak indicated by the arrow gradually increased in intensity due to the drying of the sample depending on the XRD measurement time and the number of times of measurement.

Specifically, the TCP powder or crystal synthesized by the wet method was found to be changed to a crystal phase pattern (ED electron diffraction pattern) during the measurement by increasing the degree of vacuum by placing it on a grid for TEM measurement and changing the crystal shape to disappear later. That is, the macro and nano TCP crystals prepared by the wet method are defined only at room temperature and atmospheric pressure, and vary greatly depending on the concentration, humidity, temperature, and the like of carbon dioxide in the air. Also, even if the TCP was fabricated by the dry method, the crystal phase began to change due to the instantaneous reaction with water.

Finally, TCP powder used as an artificial bone is a very important procedure parameter to increase the strength according to time with mixing with water and the hardening time it takes. It is stabilized as hard bone component by general hardening, Bone metabolism occurs and the ingredients slowly dissolve into the goal of being converted into the human body. This means that the teeth and bones mimic that the shape and strength of the bones are maintained by the effects of nutrition and exercise such as eating.

The macro-TCP crystals according to the present invention have a large crystal size and a large increase in strength. More than 80% of the macro-TCP crystals are uniaxially aligned and the nano-TCPs are well dispersed between the macro-TCPs, And made artificial bones with good workability.

Test Example  2. Scanning electron microscope image analysis

Macro-TCP according to Production Example 3 of the present invention was photographed using an electron-scanning microscope, which is shown in FIGS. 4 and 5. Macro TCP was found to grow into a plate - shaped rectangular crystal with a larger crystal size with an increase in the settling time.

Next, an artificial bone according to an embodiment of the present invention was photographed by an electron-scanning microscope, which is shown in FIGS. 6 to 8. FIG.

FIG. 6 is an electron microscope image of the artificial bone according to Example 1, and after molding and sintering, it is confirmed that nanotach is well dispersed in macro TCP and sintered to form a dense structure. In addition, referring to FIG. 7, it can be seen that the plate-like macro TCPs are attached to each other like bricks, and the shape of the nano-TCPs adhered therebetween is shown. 8 is a scanning electron microscope of an artificial bone according to Example 4, in which nano TCPs are closely packed between plate-shaped rectangular macroscopic TCPs. These characteristics were confirmed by the strength test that the strength of the artificial bone was greatly improved.

9 is an image of the artificial bone according to Comparative Example 1. It can be seen that the nano-TCP is not well dispersed in comparison with the artificial bone according to Example 1 or 4 and locally exists on the surface of the dry macro β-TCP have.

Test Example  3. Compression strength test

Chow's method (LC Chow, S. Takagi, and E. Perry, Diametral Tensile Strength and Compressive Strength of a Calcium Phosphate Cement: Effect of Applied Pressure, J. Biomed. Material Research, 53 ) 511-517, 2000). Compressive strength test specimens were cut into 10 mm x 5 mm x 70 mm specimens cut with a diamond string to meet the ASTM C39 standard for compressive strength testing. The end of the cylinder sample was sanded with 400 to 600 sandpaper. The overhead speed was 0.5 mm / min. An MTS Synergie 100 machine (MTS System Corp., Eden Prairie, MN) was used, and a wet towel was placed between the compression plate and the sample to prevent specimen slippage. Data was recorded with Testworks 4 software (MTS Corp.).

Test Example  3.1 Compressive strength according to manufacturing temperature

The sintering strength of the artificial bone according to the TCP manufacturing temperature was measured and is shown in Fig. Referring to FIG. 10, the sintering strength was improved as the temperature was increased at the time of TCP production, and the strength was less than 50 at 55 ° C. Therefore, it was confirmed that it is preferable to grow TCP at 70 캜 or higher, preferably 90 캜.

Test Example  3.2. Nano TCP  And macro TCP  Compressive strength according to content

 The compressive strengths according to the contents of macro TCP and nano TCP were measured and are shown in Table 1 below. The content of macro-TCP was 4 g. Referring to the following Table 1, it was confirmed that the compressive strength was not greatly influenced by the content of nano-TPC with respect to macro TCP. On the other hand, the compressive strength of Comparative Example 1 was measured at 106 MPa.

Wet nano-TCP (g) One 2 4 6 8 Compressive strength (MPa) 158 160 162 163 165

Test Example  3.3. The dry macro- TCP  Content and Macro TCP  Content and To the molding pressure  Compressive strength

 The dry macroscopic β-TCP content according to nano-TCP and the compressive strength according to the molding pressure were measured and are shown in FIG. The dry macro-β-TCP was fixed at 20 g and the nano-TCP content was varied. The horizontal axis in Fig. 11 is the content of nano-TCP contained in the specimen.

Referring to Fig. 11, the higher the forming pressure, the better the compressive strength. On the other hand, the content of nano-TCP in the sample was the best in dry macro-β-TCP in the ratio of 10 to 1, and the compressive strength was not greatly improved even if the content of nano-TCP was increased.

Test Example  4. The tensile strength  Test

Test Example  4.1. Top and bottom side The tensile strength

The circular specimens were cut horizontally and vertically, respectively, and the tensile strengths of the upper and lower surfaces were measured, which is shown in Fig. It has been confirmed that the tensile strength of the artificial bone according to the present invention is 20 to 40% higher than that of the side surface.

Test Example 4.2. Tensile strength test

The tensile strengths of artificial bones according to Examples 1 to 4 and Comparative Example 1 were measured and are shown in Table 2 below.

division Example 1 Example 2 Example 3 Example 4 Comparative Example 1 Comparative Example 2 Comparative Example 3 Tensile Strength (MPa) 12.4 8.5 12.6 12.1 5.1 6.7 12.7

As shown in Table 2, the tensile strength was improved as the content of nano-TCP mixed with macro TCP was increased. However, in Comparative Example 2 where the content of nano-TCP was less than 0.5 part by weight with respect to 1 part by weight of macro-TCP, it was confirmed that the content of nano-TCP was too small and the tensile strength was not significantly improved as compared with the conventional artificial bone. In addition, in the case of Comparative Example 3 in which the content of nano-TCP was more than 1.5 parts by weight based on 1 part by weight of macro TCP, it was confirmed that the improvement rate of tensile strength was small, and the bending property was reduced. Therefore, it is preferable that the nano-TCP is contained in a ratio of 0.5 to 1.5 with respect to 1 part by weight of macro-TCP, more preferably, the content of macro-TCP to nano-TCP is in a range of 1: 0.9 to 1.2 .

Claims (19)

A macrotricalcium phosphate crystal having an average particle size of 1 to 100 占 퐉 and a crystal form of a plate-like rectangular crystal, and a nanotriccium phosphate powder having an average particle size of 1 to 200 nm and a crystal form of a mass are mixed and pressed, Producing; And
And firing the formed body. The method according to claim 1,
Wherein the nanotriac calcium phosphate powder is contained in an amount of 5 to 15 parts by weight based on 10 parts by weight of the macro tricrate calcium phosphate crystal. The method according to claim 1,
Wherein the shaped body further comprises dry macro-beta -triccium phosphate powder having a particle size of 50 to 500 mu m. The method of claim 3,
Wherein the dry macro-β-tricalcium phosphate powder is contained in an amount of 50 to 120 parts by weight based on 10 parts by weight of the macrocturine calcium phosphate crystal. The method according to claim 1,
Wherein the macrocturic calcium phosphate crystals are plate-shaped rectangular crystals having a length to width ratio of 1: 1 to 10: 1 and a width to thickness ratio of 1: 0.1 to 1: 1. The method according to claim 1,
Wherein the macrocturic calcium phosphate crystal is a plate-like rectangular crystal having a length of 1 to 100 탆, a width of 1 to 50 탆, and a thickness of 0.1 to 50 탆. The method according to claim 1,
The nanotri calcium phosphate crystal
Hydrating a calcium oxide to produce calcium hydroxide;
Dissolving the calcium hydroxide in an aqueous solution to prepare calcium ions; And
Precipitating the aqueous solution in which the calcium ions are dissolved by stirring with phosphoric acid at 30 to 40 ° C at a pH of 4.8-5.5 to prepare a calcium phosphate powder slurry, then heating to 60 to 95 ° C and stirring for 10 to 60 minutes; The method of manufacturing an artificial bone according to claim 1, The method according to claim 1,
The macrocturic calcium phosphate crystals
Hydrating a calcium oxide to produce calcium hydroxide;
Dissolving the calcium hydroxide in an aqueous solution to prepare calcium ions; And
Stirring the aqueous solution in which the calcium ions are dissolved with phosphoric acid at a pH of 4.8-5.5 at 60 to 95 캜 to prepare a calcium phosphate powder, and allowing the calcium phosphate powder to stand for 2-300 hours to grow into a plate-shaped rectangular crystal The method of manufacturing an artificial bone according to claim 1, The method of claim 3,
Wherein said dry macro-β-tricalcium phosphate is prepared by calcining calcium carbonate to prepare calcium oxide, and then mixing and pulverizing CaHPO ₄ . The method according to claim 1,
Wherein the molded body further comprises a bead made of a thermally decomposable resin. 11. The method of claim 10,
Wherein the thermally decomposable resin is at least one selected from the group consisting of polyimide, polyacrylonitrile, polystyrene, polydibenzene, polyvinylpyridine, polypyrrole, polythiophene, polyaniline, furfuryl alcohol, polyacrylamide, phenol-aldehyde resin and urea-aldehyde resin Wherein the at least one selected from the group consisting of titanium oxide and titanium oxide is at least one selected from the group consisting of titanium oxide and titanium oxide. 11. The method of claim 10,
Wherein the beads have a particle size of 100 to 1000 mu m. 11. The method of claim 10,
Wherein the molded body further comprises 1 to 50 parts by weight of beads made of a thermally decomposable resin with respect to 10 parts by weight of the macrotri calcium phosphate crystal. The method according to claim 1,
The molded body is made of anhydrous calcium phosphate (CaHPO ₄ , DCPA), tetra calcium dihydrogenphosphate (Ca ₄ H ₂ P ₆ O ₂₀ , TCHP), hydroxyapatite (HAp) and dicalcium phosphate dihydrate (CaHPO ₄ 2H ₂ O, DCPD). ≪ Desc / Clms Page number 13 > A macrotricalcium phosphate crystal having an average particle size of 1 to 100 占 퐉 and a crystal form of which is a plate-like rectangular crystal; A nanotriccium phosphate powder having a particle size of 1 to 200 nm and a crystal form of a mass; A mesopore having a diameter of 0.2-100 탆; Micropores having a diameter of 0.1 to 150 nm and macropores having a diameter of 105 to 1000 탆,
Wherein the mesopores, micropores and macropores are three-dimensionally connected to each other to form open pore channels. 16. The method of claim 15,
Wherein the artificial bone is contained in 5 to 15 parts by weight of nanotriac calcium phosphate powder per 10 parts by weight of macrocturine calcium phosphate,
A specific surface area of 60-100 m ² / g, and a porosity of 50-70%. 16. The method of claim 15,
Wherein the artificial bone further comprises dry macro-beta-tricalcium phosphate powder having a particle size of 50 to 500 mu m. 17. The method of claim 16,
Wherein the dry macro-beta-tricalcium phosphate powder is contained in an amount of 50 to 120 parts by weight based on 10 parts by weight of the macro tricrate calcium phosphate. 16. The method of claim 15,
Wherein the artificial bone is a structure in which at least 80% of the macrocturine calcium phosphate crystals are unilamellar and the nanotriccium phosphate particles are present between the macrotric calcium phosphate crystals.

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