KR101528191B1 - Fabrication method of Porous Calcium Phosphate Ceramics Comprising Water Glass - Google Patents

Abstract

The present invention relates to a method for the production of calcium phosphate, comprising: dry mixing a mixture comprising calcium and phosphorus and a pore former; Adding a binder to the mixed dry mixture and kneading the mixture; Aging the kneaded mixture; Charging the aged mixture into an extruder, and then subjecting the mixture to solid-state extrusion by applying pressure; Drying the solid extruded extrudate; Sintering the dried material; The present invention also provides a method for producing a calcium phosphate ceramic porous body comprising the steps of: supporting the sintered sintered body by an etching solution selected from the group consisting of hydrochloric acid, sodium hydroxide, and nitric acid, and etching the sintered body; and coating the etched sintered body with water glass.
Therefore, even if biodegradation occurs during the use of the bone structure, the porous bone substitute having a high porosity and pore size and a three-dimensionally well-connected pore shape can be easily produced while retaining the mechanical strength for a certain period of time. In particular, it is possible to make the skeletal structure of the porous body dense and increase the mechanical strength while increasing the interconnectivity of the porous body pores.

Description

Technical Field [0001] The present invention relates to a method for manufacturing a calcium phosphate ceramic porous body containing a water glass coating layer,

More particularly, the present invention relates to a method for producing a calcium phosphate ceramic porous body containing a water glass coating layer.

Porous bioceramics with a three-dimensionally well-connected pores and excellent biocompatibility are attracting attention as a bone substitute that can promote bone cell proliferation and differentiation. Although it is generally known that autogenous cancellous bone is best used for the treatment of bone defects in orthopedic and oral surgery fields, it is extremely limited because of problems such as limitations of collectable area and volume of autogenous bone and inflammation of the harvested area. In order to solve this problem, it is practiced using a heterogeneous bone substitute manufactured by treating some bones, but it is difficult to mass-produce and has a risk of an immunological problem. In order to solve the problems of autogenous bone and foreign bone substitute, development and clinical application of artificial synthetic bone substitute materials have been attempted.

It is generally known that artificial bone substitutes should have excellent biocompatibility and have a porous structure so that surrounding bone tissue can grow well. That is, the material of the bone substitute is composed of a calcium phosphate-based ceramic mineral such as hydroxyapatite (HAp), calcium triphosphate (β-TCP) and the like, and a porous material having a three-dimensionally connected structure is required. It is also important to match the growth rate of the regenerated bone with the biodegradation rate of the substitute material as well as the properties mentioned above. That is, when the surrounding bone tissue grows, the bone substitute or scaffold should retain the mechanical strength for a certain period of time even if biodegradation occurs. In addition, a method of controlling the porosity and pore size, shape, and connectivity Various attempts have been made.

In order to realize a porous material, a method of forming a porous material such as a templating method, a sponge method, a foaming method, a freeze-drying method, a gel casting method, a rapid prototyping method rapid-prototyping, filter-pressing, extrusion, and the like have been used. In addition, a non-pressurized powder filling molding method in which spray-dried spherical particles are filled in a mold, a binder is infiltrated, molded and fixed and sintered to form a porous article, polymethyl methacrylate (PMMA) a method of forming a template by warm-pressing to form a template, a method of forming a porous body by forming a polymerization reaction by impregnating a sol into the polymer, and a method of making a slurry by using a microwave oven, And a method of producing a porous body by vaporizing it.

Korean Patent Laid-Open Publication No. 2012-0099058 relates to a dynamic bioactive bone graft material having a processed porosity, wherein, in one aspect, a bone graft material having bioactive glass fibers arranged in a porous matrix which can be molded into a desired implantation shape / RTI > The implant may be substantially free of additives and may comprise one or more nanofibers. The porous matrix may comprise a combination of one or more pore sizes, including nanopores, macropores, mesopores, and micropores. In another aspect, there is provided a bone graft material having a matrix comprising a plurality of overlapping and interlocking bioactive glass fibers and having a degree of porosity distributed on the basis of a range of pores provided in the bioactive glass fibers. The distributed porosity may comprise a combination of macropores, mesopores, and micropores, and the matrix may be formed into a desired shape for implantation into a patient.

However, although the conventional template method can easily and inexpensively fabricate nanostructures that are difficult to manufacture, it is difficult to mass-produce a constant structure free from defects in a continuous manufacturing process. The sponge method can also produce a ceramic with a good pore structure, but a process is needed to increase its strength because of its low compressive strength. The freeze-drying method has a problem in that it is difficult to form large pores.

Korean Patent No. 750973 discloses a method of surface treatment of an implant having a stable osseointegration performance over a long period of time, a membrane produced by the surface treatment method, and an implant having the membrane, and Korean Patent No. 675573 Discloses a surface modification method by forming a porous calcium phosphate thin film so as to have a surface having an excellent biocompatibility, cell suitability and bone conduction surface of artificial substitute material for human body implant or medical implant. Waterglass is a well-known material that can be easily adhered to a substrate by an adhesive agent and heating at a relatively low temperature. In addition, silica glass, which is a kind of water glass, releases water-soluble silica in an aqueous solution and has many silanol functional groups on its surface. Silanol groups on the surface are known to act as crystal nuclei of hydroxyapatite in body fluids. The inventors of the present invention have studied a coating method of a calcium phosphate ceramic porous body using such water glass, and analyzed the surface characteristics of the calcium phosphate ceramic porous body produced according to the method of the present invention, while maintaining the biocompatibility, The strength was improved, and the present invention was completed.

Disclosure of the Invention The present invention has been made in order to solve the above-mentioned problems, and it is an object of the present invention to provide a method for producing a porous calcium phosphate- It is an object of the present invention to provide a method of manufacturing a ceramic porous body.

The present invention relates to a method for the production of calcium carbonate, comprising the steps of: dry mixing a mixture comprising calcium and phosphorus and a pore former; Adding a binder to the mixed dry mixture and kneading the mixture; Aging the kneaded mixture; Charging the aged mixture into an extruder, and then subjecting the mixture to solid-state extrusion by applying pressure; Drying the solid extruded extrudate; Sintering the dried material; A method for producing a calcium phosphate ceramic porous body containing a water glass coating layer comprising a step of supporting and etching the sintered sintered body in an etching solution selected from the group consisting of hydrochloric acid, sodium hydroxide and nitric acid, and coating the etched sintered body with water glass .

The mixture containing calcium and phosphorus may also be selected from the group consisting of calcium carbonate, dicalcium phosphate anhydrous, octacalcium phosphate, tetracalcium phosphate, monocalcium phosphate mono Calcium carbonate, monocalcium phosphate monohydrate, dicalcium phosphate dehydrate (DCPD), calcium hydroxide (CaHPO ₄ .2H ₂ O), and calcium hydroxide.

Also, in the dry mixing step, hydroxyapatite (HA) powders may be further mixed.

Further, in the dry mixing step, the Ca / P molar ratio when the calcium phosphate and calcium hydroxide are mixed is 1.5 to 2.

And 50% to 200% by weight of hydroxyapatite powder is added to 100% by weight of the mixture of calcium phosphate and calcium hydroxide.

The pore-forming agent may be any one selected from polyethylene (PE), polypropylene (PP), polyvinyl chloride (PVC), polystyrene (PS), polyvinyl alcohol (PVA), and polymethyl methacrylate . ≪ / RTI >

The binder may be methyl cellulose, starch, or a mixture thereof.

The lubricant may be olive oil polyethylene glycol or a mixture thereof.

The step of drying the solid extruded extrudate further comprises drying the solid extruded extrudate at 40 to 70 DEG C for 18 to 36 hours at a relative humidity of 70% to 30%, drying at 90 to 120 DEG C for 12 to 48 hours Lt; RTI ID = 0.0 > 100% < / RTI > to completely evaporate the water.

The sintering of the dried material may be performed by heating the dried material to 400 ° C at a rate of 0.5 ° C / min, raising the temperature to 700 ° C at a rate of 1 ° C / min, heating the material to 1250 ° C at a rate of 5 ° C / , And maintaining and cooling for 4 to 7 hours.

The etching solution may be any one selected from the group consisting of 0.01 to 1 N hydrochloric acid, 5 to 36 vol.% Hydrochloric acid, 1 to 20 N sodium hydroxide, and 1 to 71 vol.% Nitric acid.

The water glass may be characterized in that the weight ratio of the alkali salt and silica is 1: (2 to 3).

According to the method of manufacturing a calcium phosphate ceramic porous body according to the present invention, it is possible to maintain a mechanical strength for a predetermined period of time even if biodegradation occurs, and to provide a porous bone substitute having a high porosity and pore size and a three- . In particular, it is possible to make the skeletal structure of the porous body dense and increase the mechanical strength while increasing the interconnectivity of the porous body pores.

1 is a SEM image of calcined calcium phosphate, calcium hydroxide and HA according to an embodiment of the present invention,
2 is a SEM image of a PMMA bead as a pore-forming agent according to an embodiment of the present invention,
3 is a SEM image of the microstructure of the sintered calcium phosphate porous body according to the embodiment of the present invention,
4 is a graph showing an XRD pattern of a calcium phosphate ceramic porous body sample according to an embodiment of the present invention,
FIG. 5 is a graph showing a quantitative analysis of the amounts of HA and TCP using a Rietveld analysis method of a crystalline phase of a calcium phosphate ceramic porous body sample according to an embodiment of the present invention,
(B) etching with 0.1N HCl for 4 minutes, (c) etching with 5N NaOH for 4 minutes, and (d) etching with an aqueous solution of 5N NaOH for 4 minutes. 85% H ₃ PO _{4 for} 4 minutes, (e) etching with 36% HCl for 15 seconds, (f) etching with 71% HNO _{3 for} 15 seconds,
7 is a SEM image of a calcium phosphate ceramic porous body according to an embodiment of the present invention after etching with sodium hydroxide,
8 is a SEM image of a ceramic porous body containing a water glass coating layer according to an embodiment of the present invention,
9 is a graph comparing the compressive strengths of the ceramic porous body containing the water glass coating layer before and after coating with water glass according to the embodiment of the present invention.

The present invention relates to a calcium phosphate ceramic which can be used as an osseous body and which is formed by an extrusion method to maintain mechanical strength for a certain period of time even if biodegradation occurs, and has a high porosity and pore size, a porosity having a three- A bone substitute can be easily produced. Particularly, the solid phase reaction of dicalcium phosphate dehydrate (DCPD, CaHPO ₄ .2H ₂ O) and calcium hydroxide (Ca (OH) ₂ ) produces micropores in the skeletal region and the micropores formed by using the pore- A calcium phosphate ceramic porous body having various sizes can be produced.

Also, the porosity and air space interconnectivity of the calcium phosphate ceramic porous body were greatly increased through the etching solution selected from the group consisting of hydrochloric acid, sodium hydroxide and nitric acid.

Further, the calcium phosphate ceramic porous body was coated with water glass to perform water glass coating without blocking the pores of the calcium phosphate ceramic porous body, thereby greatly increasing the compressive strength.

Hereinafter, the present invention will be described in more detail with reference to specific embodiments.

According to an embodiment of the present invention, there is provided a method for producing a calcium-phosphorus-containing composition, comprising: dry-blending a mixture containing calcium and phosphorus and a pore-forming agent; Adding a binder to the mixed dry mixture and kneading the mixture; Aging the kneaded mixture; Charging the aged mixture into an extruder, and then subjecting the mixture to solid-state extrusion by applying pressure; Drying the solid extruded extrudate; Sintering the dried material; And a step of coating and etching the sintered sintered body with an etching solution selected from the group consisting of hydrochloric acid, sodium hydroxide and nitric acid, and coating the sintered body with the water glass to prepare a calcium phosphate ceramic porous body containing a water glass coating layer ≪ / RTI >

The mixture containing calcium and phosphorus may be prepared by mixing calcium carbonate with dicalcium phosphate anhydrous, octacalcium phosphate, tetracalcium phosphate, monocalcium phosphate monohydrate Monocalcium phosphate monohydrate, dicalcium phosphate dehydrate (DCPD, CaHPO ₄ .2H ₂ O), and calcium hydroxide. Preferably, calcium phosphate dicalcium phosphate (DCPD) , CaHPO ₄ .2H ₂ O) and calcium hydroxide are mixed.

In the dry mixing step, a hydroxyapatite (HA) powder may be further mixed.

Wherein the Ca / P molar ratio is 1.5 to 2 when the calcium phosphate and calcium hydroxide are mixed, and 50 to 200% by weight of the hydroxyapatite powder is added to 100 weight% of the calcium phosphate and calcium hydroxide mixture .

In order to adjust the Ca / P molar ratio of the calcium phosphate to calcium hydroxide, the calcium phosphate may be 70 to 80% by weight and the calcium hydroxide may be 20 to 30% by weight based on 100% by weight of the mixture.

HA improves the sintering characteristics and increases the density and strength of HA when the content of HA contained in the final sintered body is adjusted to the ratio of HA and TCP (tricalcium phosphate; Ca ₃ (PO ₄ ) ₂ ). On the other hand, as the amount of HA decreased, the degree of biodegradation of the porous calcium phosphate ceramics increased. However, as the amount of HA increased, the biodegradability for use as a bone substitute decreased.

Therefore, the content of HA in the present invention was adjusted so as to maintain the biodegradability while improving the sintering property.

The pore-forming agent may be polyethylene (PE), polypropylene (PP), polyvinyl chloride (PVC), polystyrene (PS), polyvinyl alcohol (PVA), polymethyl methacrylate But it is preferable to use polymethyl methacrylate (PMMA) beads.

The beads may be conventional beads used for pore formation in the art having a diameter of 10 to 1000 mu m, but preferably polymethyl methacrylate (PMMA) beads having an average of 175 mu m can be used.

The use of the beads makes it possible to produce a porous calcium phosphate ceramic body having large pores.

The binder may be methyl cellulose, starch, or a mixture thereof. Methylcellulose and starch increase the moldability of the dry mix. Further, a lubricant may be further mixed for smooth extrusion in an extruder.

The lubricant may be, but is not limited to, olive oil, polyethylene glycol, or a mixture thereof, wherein the lubricant may be included in an amount of 5 to 20% by weight based on 100% by weight of the dry mixture.

The step of kneading the dry mixture may be carried out until the dry mixture forms a dough-like precursor, which may then be vacuum packed and aged at room temperature for 24 hours.

Then, the aged mixture is charged into an extruder, and pressure is applied to perform solid-state extrusion.

The extruder can be a screw-type extruder, in which the pressure is kept constant within a range of 1 to 10 MPa or 4 to 6 MPa and extrusion is carried out.

If an extrusion process is performed at a uniform pressure using the extruder, a bone substitute having an excellent strength and density can be produced uniformly and repeatedly as compared with a case where an extrusion process is performed with a piston.

The extruded body may be formed into a rod shape using a wire cut, and then the step of drying the extruded body is performed.

The drying step comprises drying the solid extruded extrudate at 40 to 70 DEG C for 18 to 36 hours at a relative humidity of 70 to 30% and drying at 90 to 120 DEG C for 12 to 48 hours to completely evaporate the water Including the process.

When the above process is performed, cracking of the extruded body can be prevented.

The sintering of the dried material is performed by heating the dried material to 400 ° C at a rate of 0.5 ° C / min, raising the temperature to 700 ° C at a rate of 1 ° C / min, heating the material to 1250 ° C at a rate of 5 ° C / To < / RTI > 7 hours and furnace-cooling.

When the above-mentioned process is performed, cracking of the dried material can be prevented, and when the temperature is raised up to 700 ° C in the sintering process, the binder component can be removed due to de-binding process.

And a step of supporting the sintered sintered body by an etching solution selected from the group consisting of hydrochloric acid, sodium hydroxide and nitric acid, followed by etching.

Wherein the sintered body is any one selected from the group consisting of 0.01 to 1 N hydrochloric acid, 5 to 36 vol.% Hydrochloric acid, 1 to 20 N sodium hydroxide and 1 to 71 vol.% Nitric acid. When the sintered body is etched in the above range, And the mechanical strength can be increased. However, when the thickness is out of the above range, the mechanical strength is seriously decreased.

There are various kinds of water glass (liquid silicate), but the weight ratio of alkali salt and silica is 1: 1 - 4, more preferably 1: 2 - 3, but not limited thereto. The pH is preferably about 10 to 11.

The water glass has a viscosity of 1.7 cP to 4.5 cP. The viscosity of the water glass is very important for the uniformity of the coating, economy, and workability. The viscosity of water glass preferred for the present invention is about 35 to 36 seconds at 18 캜 when tested with Ford Cup # 4 desirable. When the viscosity of the water glass is less than the above range, the coating is not easily performed on the calcium phosphate ceramic porous body, and if it is thicker, it is difficult to form a uniform coating film.

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail with reference to the following examples. However, the following examples are intended to illustrate the contents of the present invention, but the scope of the present invention is not limited to the following examples. Embodiments of the present invention are provided to more fully describe the present invention to those skilled in the art.

< Example  1> Preparation of Porous Calcium Phosphate Ceramic Porous Material

The starting material as was used for the calcium phosphate _{(dicalcium phosphate dehydrate, CaHPO 4 ·} 2H 2 O), calcium hydroxide (calcium hydroxide (Ca (OH) 2) , and hydroxyapatite (hydroxyapatite, hereinafter "HA"), pore-forming agent PMMA (poly-methyl methacrylate) beads were used.

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is an SEM image of calcined dicalcium phosphate, calcium hydroxide and HA according to an embodiment of the present invention. Since this calcium phosphate has a relatively large plate shape, it is calcined at 600 ° C and then pulverized.

2 is an SEM image of a PMMA bead as a pore-forming agent according to an embodiment of the present invention. The average diameter of the PMMA beads was 175 mu m.

100 g of calcium phosphate and 30.07 g of calcium hydroxide were dry-mixed to adjust the Ca / P ratio of the calcium phosphate and calcium hydroxide to 1.5.

In the dry mixing step, hydroxyapatite was added to the mixture of calcium phosphate and calcium hydroxide to adjust the ratio of HA / TCP mineral to 0% by weight to 200% by weight of hydroxyapatite powder compared with 100% by weight.

In order to homogeneously mix the dry mixture, ball-milling was performed. In order to prevent contamination during long-time ball milling, the dried mixture was put into a Nalgene bottle, and a zirconium dioxide (ZrO ₂ Ball) was used for ball milling for 4 hours.

The dry mixture was dried using a rotary evaporator and again pulverized using agate mortar. Thereafter, PMMA was added in an amount of 70 vol% and mixed in a mixer.

In order to increase the moldability of the dry mixture, a binder was added and kneaded. A mixture of methylcellulose and starch was used as the binder, and olive oil was added and kneaded as a lubricant for smooth extrusion in an extruder. The mixture was packed in a vacuum packing machine to agitate at room temperature for one day to distribute the lubricant evenly while preventing evaporation of water.

The aged mixture was in the form of a dough and was charged into a screw type extruder of a certain amount of the mixture and subjected to solid-state extrusion by applying pressure thereto. The extrudates were made into rod shapes and were made into blocks using wire cutting.

The solid was extruded at 60 ° C for one day at a relative humidity of 70% to 30%, and dried at 100 ° C for one day to completely evaporate the water. The extrudate was heated to 400 ° C at a rate of 0.5 ° C / min to prevent cracking, and then heated to 700 ° C at a rate of 1 ° C / min. After sintering at a rate of 5 ° C / min to 1250 ° C, And then cooled to complete the sintered body.

< Example  2> Etching through chemical treatment

In order to improve the porosity and interconnectivity of the sintered body, the sintered sintered body is supported on the etching solution selected from the group consisting of hydrochloric acid, sodium hydroxide and nitric acid, and etching is carried out.

First, the surface of the sintered body was polished with a silicon carbide abrasive paper (abbreviation # 2000). In order to etch the sintered body, an etching solution was filled in a centrifuge tube, and the sintered body was put into the chamber, and the etching was performed by controlling the speed and time using a shaking incubator.

The etching solution used was 0.1N HCl, 36% by volume HCl, 5N NaOH, 71% by volume HNO ₃ and 85% by volume H ₃ PO ₄ as a comparative example. HCl, 71 vol% HNO ₃ was 15 seconds, and the remainder was treated for 4 minutes. After etching, the membrane was washed with ethanol and distilled water for 10 minutes in an ultrasonic cleaner to remove the residual chemical solution in the porous body.

< Example  3> Formation of water glass coating layer

To improve the compressive strength of the sintered body with improved porosity and interconnection by chemical etching treatment, a water glass solution was coated. The aqueous solution of water glass was coated using a centrifugal separator using a 15 vol% solution of water glass diluted in water, which was too viscous to be suitable for coating.

The sintered body was immersed in a 15 vol% solution for 10 seconds, and then the centrifugal separator was rotated at 5000 rpm for 1 minute to remove the solution blocking the pores inside the porous body. The sintered body coated with water glass was sufficiently dried in a drying oven at 60 캜, heated to 600 캜 at a rate of 3 캜, held for 2 hours, and then cooled.

< Experimental Example  1> Physical properties of calcium phosphate ceramic porous body

The distribution of crystal phases was confirmed by using an x-ray diffractometer (X'pert MPD-PRO, Panalytical Japan) at 40 kV and 30 mA with copper target and quantified using the X'pert highscore plus program in automatic mode.

Microstructures such as pore size and distribution were observed with an electron microscope (SEM, S-4200, Hitach, Japan). The compressive strength of the sintered body was measured by applying a force in a direction parallel to the extrusion direction and measured at a speed of 0.5 mm per minute using a universal testing machine having a 500 kgf load cell.

The bulk density and the weight of the sintered body were measured to calculate the apparent density. The theoretical density was calculated by calculating the crystal phase fraction using the Rietveld analysis. The compressive strength of the sintered body was measured by applying a force in a direction parallel to the extrusion direction and measured at a speed of 0.5 mm per minute using a universal testing machine having a 500 kgf load cell

Table 1 shows the composition of the dry mix with hydroxyapatite added to control the ratio of HA / TCP mineral.

Composition DCPD (g) Ca (OH) ₂ (g) HA (g) PMMA (g) H ₂ O (ml) MV (g) Starch Oil (ml) H0D100 100 30.07 0

70 vol%



72 vol%



15wt%



5 wt%



10wt%

H50D100 100 30.07 50 H100D100 100 30.07 100 H100D50 100 30.07 200 F100D0 0 0 100

3 is an SEM image of the microstructure of a sintered calcium phosphate porous body according to an embodiment of the present invention. It was found that PMMA beads were homogeneously distributed in the porous bodies of all compositions and homogeneous pores of macro size were produced after sintering. Macro pores were formed only by PMMA in the H100D0 composition sample. However, in the case of the specimens of four different compositions, it was confirmed that micro pores were formed in the strut part in addition to the macro pores. This is thought to be generated by the solid-phase reaction of calcium phosphate (DCPD) and calcium hydroxide (Ca (OH) ₂ ) added to the rest of the composition except for the comparative example H100D0 composition.

Composition Shrinkage (%) Porosity (%) Compressive strength (MPa) Average pore size (탆) H0D100 17.95 ± 1.35 79.52 ± 1.20 6.87 ± 0.31 160.52 + 5.03 H50D100 18.53 + - 1.24 79.04 + - 0.98 7.78 ± 0.29 157.33 + - 3.11 H100D100 19.95 + 1.01 74.64 ± 0.74 8.01 + - 0.87 152.55 + - 4.25 H100D50 24.11 ± 0.98 67.05 ± 1.11 8.62 ± 0.45 147.23 + - 4.11 H100D0 27.18 ± 1.11 62.12 + - 0.88 - 140.87 ± 3.28

Table 2 shows the shrinkage, porosity, compressive strength and average pore size of the sintered calcium phosphate ceramic porous body.

As the amount of HA was increased, the shrinkage and compressive strength increased and the porosity and average pore size decreased. The addition of HA improved the sinterability, but the H100D0 specimen with 100 wt% HA compared to the dry mixture showed cracks inside and showed very low compressive strength.

FIG. 4 is a graph showing an XRD pattern of a calcium phosphate ceramic porous body sample according to an embodiment of the present invention, FIG. 5 is a graph showing the XRD pattern of a calcium phosphate ceramic porous body sample according to an embodiment of the present invention, This graph is a quantitative analysis of the amount of HA and TCP.

The HA / TCP ratio of the sintered body changed linearly with the amount of HA added. Based on the change of the linear ratio, it is expected that the amount of HA of the starting material can be controlled to obtain a porous sintered body having a desired HA / TCP ratio.

The HA phase of the sintered body was increased from about 7.2 wt% (H0D100) to 100 wt% (H100D0) based on 100 wt% of the dry mixture, and the TCP phase was about 92.8 wt% (HOD100) 0% by weight (H100D0). Therefore, H0D100, which has the highest TCP aspect, has the highest biodegradability, and H100D0 is expected to have the lowest biodegradability. In general, the optimal condition of biphasic calcium phosphate (BCP), known as HA: TCP = 6: 4, is the most similar to H100D100, and this composition is expected to have biodegradability suitable for use as a bone substitute .

It was also found that the biodegradability of the porous bone substitute of the present invention can be controlled by controlling the addition amount of HA.

< Experimental Example  2> pore interconnection and Mechanical strength  Improving

6 is an SEM image of the calcium phosphate ceramic porous body according to the embodiment of the present invention after etching. Table 3 shows the characteristics of the calcium phosphate ceramic porous body after the etching treatment.

Etchant Etching condition Weight change (Wt. Change,%) Porosity (%) Compressive strength (MPa) Untreated 71.192 + 0.248 8.881 ± 0737 0.1 N HCl 300 rpm, 4 mins -4.120 + - 2.313 71.152 ± 1.585
(+0.056) 7.644 + 0.026
(-13.929) 36% HCl 300 rpm, 15 sec -23.252 ± 2.848 76.301 + - 1.618
(+7.716) 0.806 ± 0.079
(-71.737) 5 N NaOH 300 rpm, 4 mins 0.000 71.340 + - 2.423
(+0.207) 10.805 ± 0.439
(+13.557) 85% H ₃ PO ₄ 300 rpm, 4 mins + 40.869 + - 3.619 61.110 ± 3.791
(-14.162) 22.154 + 0.336
(+131.607) 71% HNO ₃ 300 rpm, 15 sec -33.582 ± 2.213 78.603 + - 1.288
(+10.417) 0.819 + 0.212
(-90.778)

 After 4 minutes of etching with 0.1N HCl solution, nano-sized micropores were formed in the skeleton, and the weight loss was about 4% and the compressive strength was decreased by about 13%. About 0.05% The porosity was increased. The microstructure of the needle bed was formed by etching with 5N NaOH solution for 4 minutes.

There was no change in the weight before and after etching, but the compressive strength was improved by about 13% and the porosity was increased by about 0.2%.

It was found that the etching of NaOH improved the mechanical strength without changing the weight or the porosity. Etching with 36% HCl and 71% HNO ₃ for 15 seconds resulted in a relatively large weight loss of about 23% and 33%, respectively, and the porosity was greatly increased, but the mechanical strength was significantly reduced. Compressive strengths were reduced by about 70% and 90%, respectively, and the porosity of the pores was increased by about 7% and 10%, respectively. After 4 minutes of etching with 85% H ₃ PO ₄ solution, the weight was increased by about 40% as opposed to other etching solutions. As a result of the observation of the surface, the phenomenon that the pores are clogged was seen because the porous layer reacted with H ₃ PO ₄ to form a coating layer on the surface. As the weight increased, the compressive strength increased by about 132% and the porosity decreased by about 14%.

Therefore, 5N NaOH is suitable for improving the compressive strength without significantly changing other properties, and 0.1N HCl etching is expected to contribute to the formation of micropores. Further 36% HCl and of 71% HNO ₃ If the etching treatment is performed with a lower concentration of the solution, the porosity can be increased without breaking the structure.

In addition, H ₃ PO _{4, which} is a comparative example, is considered to be unsuitable as an etching solution because it causes a decrease in porosity and pore connectivity, while increasing the mechanical strength by blocking the pores and forming a coating layer on the surface.

< Experimental Example  3> Improvement of compressive strength by water glass coating layer

FIG. 8 is a SEM image of a ceramic porous body containing a water glass coating layer according to an embodiment of the present invention, and FIG. 9 is a graph comparing compressive strengths of a ceramic porous body containing a water glass coating layer according to an embodiment of the present invention, .

Table 4 shows the characteristics of a ceramic porous body containing a water glass coating layer.

Etchant Weight change before water glass coating (Wt. Change,%) Weight change after coating with water glass (Wt. Change,%) Porosity (%) Compressive strength (MPa) Untreated + 1.447 + 0.188 68.456 ± 0.670
(-3.843) 14.953 + 0.098
(+68.371) 0.1 N HCl -3.268 + 0.925 + 1.512 + 0.286 71.666 + 1.831
(-0.683) 14.238 + 0.877
(+86.264) 36% HCl -22.481 ± 2.095 + 1.196 + 1.044 75.850 ± 2.115
(-0.591) 0.806 ± 0.234
(+0.248) 5 N NaOH 0.000 + 1.292 + 0.247 71.123 + - 2.562
(-0.304) 16.798 ± 1.214
(+55.465) 85% H ₃ PO ₄ + 39.343 + 4.901 -1.462 + 0.076 57.667 + 8.094
(-5.634) 18.260 ± 0.819
(-17.613) 71% HNO ₃ -33.142 ± 2.973 + 1.847 + 0.150 78.288 ± 1.567
(-0.401) 0.839 + 0.150
(+2.442)

 As a result of SEM observation, it was confirmed that the water glass was coated without blocking the pores of the porous ceramics after coating.

After coating with water glass, only about 1% of the specimens etched with H ₃ PO ₄ weighed and most specimens weighed 1 ~ 2%. Also, the porosity change was not changed as much as about 0.3 ~ 4%, but the compressive strength was greatly increased.

In the case of specimens coated with waterglass directly on the sintered body without etching, the compressive strength was increased by about 68% compared to that before coating. The compressive strength increased by 86% and 55%, respectively, when coated with 0.1N HCl and 5N NaOH.

36% HCl and 71% nitric acid did not show a large increase. The reason for this is that since the strength itself was too low due to excessive etching during the etching process, no strength measurement or increase in strength after coating could be expected.

In the case of H ₃ PO ₄ , the strength was reduced by about 18%. This is probably due to the loss of material (weight loss of 1.5%) due to the reaction between water glass and the coating layer formed after etching.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that such detail is solved by the person skilled in the art without departing from the scope of the invention. will be. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.

Claims (12)

Dry mixing a mixture comprising calcium and phosphorus and a pore-forming agent;
Adding a binder and a lubricant to the mixed dry mixture and kneading the mixture;
Aging the kneaded mixture;
Charging the aged mixture into an extruder, and then subjecting the mixture to solid-state extrusion by applying pressure;
Drying the solid extruded extrudate;
Sintering the dried material;
Supporting and sintering the sintered sintered body on an etching solution selected from the group consisting of hydrochloric acid, sodium hydroxide, and nitric acid; And
And coating the etched sintered body with water glass,
The binder is a mixture of methylcellulose and starch,
Wherein the lubricant is an olive oil. &Lt; RTI ID = 0.0 &gt; 11. &lt; / RTI &gt; The method according to claim 1,
The calcium and phosphorus-
Calcium carbonate, dicalcium phosphate anhydrous, octacalcium phosphate, tetracalcium phosphate, monocalcium phosphate monohydrate, calcium phosphate diphosphate, dicalcium phosphate dehydrate, DCPD, CaHPO ₄ .2H ₂ O), and calcium hydroxide, are mixed together to form a porous calcium phosphate porous body. The method according to claim 1,
Wherein the hydroxyapatite (HA) powder is further mixed in the dry mixing step. [Claim 6] The method according to claim 1, wherein the hydroxyapatite (HA) powder is further mixed with the hydroxyapatite (HA) powder. The method according to claim 1,
In the dry mixing step,
Wherein the Ca / P molar ratio of the mixture containing calcium and phosphorus is from 1.5 to 2. &lt; RTI ID = 0.0 &gt; 11. &lt; / RTI &gt; The method according to claim 1 or 2,
In the dry mixing step,
Mixture containing calcium and phosphorus The hydroxyapatite powder was dissolved in 50 By weight to 200% by weight, based on the total weight of the ceramic porous body. The method according to claim 1,
The pore-
Wherein the waterproof coating layer is any one selected from the group consisting of polyethylene (PE), polypropylene (PP), polyvinyl chloride (PVC), polystyrene (PS), polyvinyl alcohol (PVA), and polymethyl methacrylate &Lt; / RTI &gt; by weight of the calcium phosphate. delete The method according to claim 1,
The step of drying the solid extruded extrudate comprises:
The solid extruded extrudate was dried at 40 to 70 DEG C for 18 to 36 hours at a relative humidity of 70% to 30%
And drying at 90 to 120 ° C for 12 to 48 hours to completely evaporate the water. The method according to claim 1,
The step of sintering the dried material comprises:
The dried material is heated up to 400 ° C at a rate of 0.5 ° C / min, further heated to 700 ° C at a rate of 1 ° C / min, sintered at a rate of 5 ° C / min to 1250 ° C, Wherein the water-repellent coating layer comprises a water-soluble polymer. The method according to claim 1,
The etching solution may contain,
Wherein the calcium carbonate is any one selected from the group consisting of 0.01 to 1 N hydrochloric acid, 5 to 36 vol% hydrochloric acid, 1 to 20 N sodium hydroxide and 1 to 71 vol% nitric acid. The method according to claim 1,
The water-
Wherein the weight ratio of the alkali salt to the silica is 1: (2 to 3). The method according to claim 1,
The water-
And a viscosity of 1.7 cP to 4.5 cP. A method for producing a calcium phosphate ceramic porous body containing a water glass coating layer.

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