KR100750190B1 - Effective bone filler and manufacturing methods thereof - Google Patents

Abstract

The present invention relates to a bone filler used to repair bone tissue in which defects have occurred due to a fracture, and more particularly, to a bone filler and a method for producing the same, which improve bone fusion by adjusting particle size and density. The present invention consists of at least a first type and a second type of calcium phosphate compound particles having different relative densities, wherein the first type particles have a relative density of 90% or more, and the particles of the second type of aggregate are The relative density is less than about 70%, the particles provide a powdery bone filler, characterized in that the average particle diameter is about 100 ~ 400 ㎛. The bone filler of the present invention is designed to exert selective dissolution characteristics determined by the density difference to secure the bone conduction path after the procedure and exhibit effective bone repair properties.

Calcium phosphate compounds, bone repair, bone conduction, porous granules, dense granules, bone filler

Description

Bone filler effective for bone repair and its manufacturing method {EFFECTIVE BONE FILLER AND MANUFACTURING METHODS THEREOF}

1 is a view schematically illustrating a process of repairing a bone by a mixture composed of particles having two different densities according to the present invention.

2 is a diagram schematically illustrating the precipitation behavior according to the dispersion state of the suspension.

3 is a graph showing the viscosity change of the suspension with the addition amount of the dispersant.

Figure 4 is a graph showing the viscosity change of the solution with pH when 0.5 ml of the dispersant is added.

5 is a procedural diagram illustrating each step of the method for producing granular powder according to an embodiment of the present invention.

Figure 6 is a procedure showing the steps of producing a granular powder according to another embodiment of the present invention.

7A and 7B are micrographs of the state before and after sintering of the low density powder prepared by the spray drying method, respectively, and FIG. 7C is an enlarged photograph of the particles of FIG. 7B at high magnification.

8 is an electron microscope photograph of a state after sintering of a high density powder prepared by a spray drying method.

9A is an electron micrograph of a high density granular powder spray-dried and fluidized bed drying, and FIG. 9B is an electron micrograph taken at a higher magnification.

FIG. 10 is an electron micrograph of the powder after crushing, crushing once, crushing five times and screening.

11A to 11C are optical micrographs showing the progress of bone tissue after 8 weeks in the case where the damaged bone is not filled with nothing, when the cerahene is filled and when the powdery bone filler of the present invention is filled.

12A to 12B are views conceptually illustrating a method of manufacturing a block bone filler in the present invention.

FIG. 13 is an electron micrograph photographing a cross-sectional microstructure of a block-shaped bone filler dried and sintered by injecting a β-TCP suspension in which a dispersant is added to the low-density powdery β-TCP bone filler.

The present invention relates to a bone filler used to repair bones in which defects have occurred due to damage such as fractures, and more particularly, to bone fillers and methods for producing the same, which improve bone repairability by controlling particle size and density. It is about.

Bone fillers can be divided into powder-type powders that are largely sprayed on the damaged areas to fill the damaged areas, and block-shaped fillers that are molded and / or sintered according to the defect shape of the damaged areas and implanted in the damaged areas. In the specification, the term 'bone filler' is used to refer to only the former powdery bone filler or both, and when referring to the latter case only, the term 'block bone filler' is used.

Bioactive materials used as bone filler also include resin-based materials such as polymethyl methacrylate (PMMA), but they are insoluble in the body and do not form chemical bonds with bones. Due to the difficulty in use, inorganic bioactive materials are replacing them.

Inorganic bioactive materials are mainly calcium phosphate compounds such as hydroxyapatite (HA), Ca ₄ P ₂ O ₉ (tetracalcium phosphate; TTCP) and CaHPO ₄ 2H ₂ O (dicalcium phosphate, DCPD), α-Ca ₃ PO ₄ (tricalcium phosphate) (α-TCP), β-Ca ₃ PO ₄ (β-TCP), Ca ₂ P ₂ O ₇ (calcium pyrophosphate, CPP), etc. are used, and gypsum (CaSO ₄ · 1 / 2H ₂ O) as the main raw material may be used.

Until now, the research on bone filler has been mainly studied on the block bone filler. Block-type bone filler has a three-dimensional network of internal pores to provide bone conduction pathways. Such a three-dimensional network structure is prepared by using a foamed resin such as a sponge as a matrix, impregnating or coating a slurry of a calcium phosphate compound therein, and then removing the resin as a mother by a method such as heating. In the prepared bone filler, the pore distribution inside the bone filler is entirely dependent on the pore distribution of the foamed resin used. For example, Korean Patent Publication No. 2002-14034 discloses a method for preparing bone filler by coating a calcium phosphate compound slurry on a porous polymer filter having three-dimensional network pores and then burning off the polymer. According to this method, the open pores inside the porous polymer filter are converted to the pores of the bone filler.

The pores of the bone filler during living transplantation act as a blood supply and bone conduction pathway to grow natural bone, and the bone filler itself gradually dissolves and disappears in vivo. At this time, it is known that the pore transverse diameter is about 100 μm or more, more preferably 150 μm or more for effective bone conduction.

As such, the bone filler must be formed with large diameter open pores. However, the above-described conventional pore forming method can be applied to the block bone filler, but it is difficult to apply to the powder bone filler. This is because it is impossible to form open pores having a diameter of 100 μm or more that is artificially uniform and distributed inside the amorphous powder in the above-described manner.

The present invention is to solve the above problems, an object of the present invention is to provide a powder-like filler that can provide a spongy bone structure required for bone repair after the procedure to the bone or tooth defects.

Furthermore, another object of the present invention is to provide a block-type filler which can be manufactured using the above-described powder-type filler.

It is also an object of the present invention to provide a manufacturing method suitable for the production of the above-described powder filler and block filler.

In the present invention, "spherical" is divided according to the shape of individual particles, and the total of particles is referred to as "powder". On the other hand, "powder-type filler" means the filler corresponding to the block-type filler, it is defined as a filler of powder or granular powder consisting of individual particles.

In order to achieve the above technical problem, the present invention, in the block-shaped bone filler, is divided into a porous region and a dense region having a different density inside, at least one of the porous region or the dense region is three-dimensionally connected sponges It has a structure, the porous region provides a block-type bone filler, characterized in that the relative density is 70% or less, the dense region is 90% or more relative density.

In another aspect, the present invention is spray drying the suspension containing the calcium phosphate-based compound to form a spherical powder having an average particle diameter of less than 100 ㎛, fluidized bed while injecting the suspension containing the spray-dried spherical powder and calcium phosphate-based compound It provides a method for producing a calcium phosphate-based bone filler comprising the step of drying and granulating to form granular powder and sintering the granular powder. In the process of the invention, the suspension may further comprise a dispersant.

In another aspect, the present invention is the step of filling a calcium phosphate-based granular powder having an average particle diameter of 100 ~ 400㎛ in a mold designed to a predetermined shape, injecting a suspension of calcium phosphate-based compound into the filled mold, the suspension is injected It provides a method for producing a calcium phosphate-based block-shaped bone filler comprising the step of drying the mold to produce a molded body and the step of sintering the molded body. In the process of the invention said suspension may comprise a dispersant.

Hereinafter, the present invention will be described in detail with reference to the accompanying drawings.

The bone filler of the present invention is a mixture of two types of particles. One is a particle having a dense microstructure having a relative density of 90% or more, and the other is a porous particle having a relative density of 70% or less. The porous particles contain fine pores of several micrometers therein.

C. T. A. Klein et al., J. Biomed. Mater. Res. In a paper entitled "Biodegradation behavior of various calcium phosphate materials in bone tissue" presented at 17: 769, a porous bone filler with internal pores was found to be a dense bone by implanting the block-shaped bone filler into the femur of the rabbit. It has been reported to have a higher biosoluble than the filler.

According to this aspect, two types of particles having different densities in the bone filler of the present invention each have different biodissolution rates. In the present invention, the porous particles in the granular powder in the bone filler are dissolved at the beginning of the procedure to provide a conductive path for bone conduction. This conductive path is not provided by the micropores inside the porous particles, but by the voids generated when the porous particles are dissolved into a living body. The dense particles provide the spongy bone structure necessary for bone growth as a result of the dissolution of the porous particles to assist in the bone repair process.

1 is a view schematically illustrating a process of repairing a bone by a mixture composed of two different densities of particles (D, P) according to the present invention. Referring to FIG. 1, when the dense particles D and the porous particles P are arranged inside the damaged bone (a), the porous particles P are selectively dissolved by contact with blood (b). The space (B) in which the porous particles (P) are dissolved serves as a path for bone conduction, and the dense particles (D) provide a scaffold for bone conduction like the spongy bone structure, thereby helping to rebuild bone tissue. (c).

According to the mixing ratio of the dense particles (D) and the porous particles (P) constituting the filler in the reference drawings and the relative relationship of each particle, the arrangement relationship shown in a plane may not be as shown, and even if there is no separate description, It is apparent that one of ordinary skill in the art can easily design the mixing ratio of the bone filler such that the desired alignment relationship is obtained through simple mathematical calculations considering particle size and relative density.

Various studies have been presented on the size of three-dimensional pores required for bone conduction to be repaired in a block bone filler. For example, Klawiter et al., Published in the 1971 Biomedical Material Symposium (Biomed. Mater. Symp., Vol 2, pp 161), showed that the minimum diameter of pores required for bone conduction was 100 μm and the optimal diameter was 150. On the other hand, Fleetley, in a 1983 paper published in the Journal of Orthopedic Surgery (Clin. Orthop., Vol 179, pp 246), suggested that the optimal diameter of pores for bone conduction is 500 µm. Chang also published a 2000 paper published in Biomaterials (vol 21, pp 1291), modeling cylindrical pores of various diameters. It was found that it is 300 ㎛. In addition, Gautier published a 1998 paper published in the Journal of the Korean Society of Dynamics (Vol 19, pp133), suggesting that the minimum diameter of pores for bone conduction is 300 µm and the optimal diameter is 560 µm. As such, the optimum diameter of the pores required for bone conduction has been suggested to vary from about 150 to about 560 μm. However, considering the most recent publication of Chang and the results observed in the cylindrical model pores, the optimum diameter is Judging to 300 μm would be desirable.

From this point of view, in the present invention, the larger the particle diameter of the dense particles (D) is, the more preferable, and it is preferable to have an average particle diameter of at least 200 μm. In addition, in order to provide a bone conduction path having a particle diameter of 100 μm or more, the porous particles (P) preferably have an average particle diameter of 100 μm or more. As described above, the dense particles and the porous particles of the present invention have an average particle diameter of 100 µm or more required, and are composed of agglomerates of a plurality of fine powders as will be described later. The total of mold particles is called "granular powder".

As described above, the powdered bone filler of the present invention is composed of high density granular particles and low density granular particles. In the present invention, the density of the individual granular particles constituting the bone filler is made through the density control of the aggregates described below.

A. Principle of Density Control of Aggregates

The density of the aggregates produced from the suspension is determined during the sedimentation process, in particular by the physical / chemical properties acting between the particles of the powder in the suspension. For example, when the repulsive force is applied between the powder particles, a dense aggregate is produced during the water removal process, and high density is ensured even after sintering. On the other hand, when the attractive force acts between the particles of the powder, the density of the aggregate decreases, and a porous and low density aggregate is obtained even after sintering.

2 is a diagram schematically showing the precipitation behavior according to the dispersion state of the suspension. First, (a) of FIG. 2 shows a process in which the suspension is precipitated in a well dispersed state with dispersion stability. The particles dispersed over time are suspended for a long time and gradually precipitated from the bottom to form a precipitate. do. According to such precipitation behavior, a compact molded body can be obtained.

FIG. 2 (b) is a diagram illustrating the precipitation behavior of the suspension in a state in which dispersion stability is low due to insufficient repulsive force between particles. Particles in this state are likely to readily agglomerate upon impact due to Brownian motion. Aggregated particles do not have the time required for dense precipitation, and eventually the aggregated aggregates show a low density.

Methods of estimating the force acting between the particles in the suspension include measuring the zeta potential and measuring the viscosity of the suspension. Even if the suspension contains the same volume fraction of powder, the viscosity of the suspension will be different if the forces acting between the particles of the powder are different. For example, the viscosity of the suspension decreases when there is repulsion between particles. Thus, by observing the viscosity of the prepared suspension, the density thereof can be expected when preparing aggregates with the same suspension.

On the other hand, the force acting between the particles of the powder in the suspension is greatly influenced by the state of charge of the particle surface and the surface adsorbent material. Polymeric materials, such as dispersants, are easily adsorbed to the particles in the suspension and exert a repulsive force by the motion of the polymer can be effective in reducing the viscosity and achieving a dense aggregation state.

Through the following experiments, the effect of the addition of the dispersant on the viscosity of the suspension and the density before and after sintering of the precipitate is examined in detail.

A-1. Experiment of correlation between viscosity of dispersant and suspension

10 g of β-TCP powder was dispersed in 10 ml of distilled water using Darvan C as a dispersant, and the viscosity of the suspension was measured. The amount of dispersant added was varied to observe the change in viscosity with the amount of dispersant. 3 is a graph showing the viscosity change of the suspension with the addition amount of the dispersant. Referring to FIG. 3, when about 0.02 ml of the dispersant is added, the viscosity is about 12 cP, and as the amount of the dispersant is increased, the viscosity decreases to about 7 to 8 cP, and when the dispersant reaches 0.07 ml or more, the viscosity is again. It can be seen that the increase. The graph shown indicates that dispersants should be added in the appropriate range to obtain a low viscosity suspension. In addition, it can be seen from the graph shown that the dispersant introduced in excess of the required amount may cause interference between the dispersants and increase the viscosity.

In addition, according to the experiments of the inventors, the viscosity of the suspension also changes depending on the pH of the solution. Figure 4 is a graph showing the viscosity change of the solution with pH when 0.5 ml of the dispersant is added. As shown, the viscosity of the suspension shows a minimum viscosity in a narrow pH range. Thus, it can be seen that the pH of the suspension may also be an important variable in order to obtain dense granular particles.

A-2. Observation of Sintering Characteristics of Precipitates

Table 1 below shows the dry relative density and the relative density after sintering when the obtained precipitate was dried and sintered according to the concentration of solids in the suspension and the addition of dispersant.

When no dispersant was added, the maximum value of the solid fraction of the suspension was up to 30%. The dry precipitate had a density of 44% when the solid fraction of the suspension was 20% and about 71% after sintering. When the solid fraction was 30%, the dry density of the precipitate increased to about 49%, but after sintering, it showed a relative density of 71%.

If 0.05 ml of dispersant is added, the maximum solid fraction of the suspension increases to 50%. The dry relative density and sintered relative density of the precipitates were 59% and 93%, respectively, when the solid content was 20%, and the dry and sintered relative densities of the molded body were 61% and 91%, respectively, when the solid content was 40%. .

When 0.075 ml and 0.2 ml of the dispersant were added, a slight decrease in the dry relative density and the sintered relative density was observed as compared with the case where 0.05 ml of the dispersant was added.

Darvan C (ml / 10g) Solid content concentration (%) Drying Relative Density (%) Sintered Relative Density (%) 0 20 44 71 30 49 71 0.05 20 59 93 40 61 91 0.075 20 63 90 40 56 91 0.2 20 58 90 40 56 90

From the above test results, it can be seen that the appropriate amount of dispersant added in the suspension decreases the viscosity of the precipitate and increases the relative density of the precipitate. In addition, it can be seen that the dry relative density and the sintered relative density of the precipitate have a very strong correlation.

B. Method of Making Coarse Granular Particles

Conventional calcium phosphate-based spherical powder bone filler is produced by spray drying. A suspension containing a calcium phosphate compound is sprayed to form droplets, and the formed droplets have a spherical shape by surface tension, and the sprayed droplets are dried by a method such as hot air drying to form spherical particles. At this time, the larger the size of the droplets, the longer it takes to dry, but the droplets that are not sufficiently dried are entangled on the spray dryer wall and cannot maintain the spherical particle shape. Therefore, it is difficult to produce spherical calcium phosphate particles of 100 µm or more intended by the present invention by the conventional method.

The present inventors present a new method for producing calcium phosphate-based particles which maintain spherical shape despite particle size of 100 μm or more. 5 is a flowchart illustrating a method of manufacturing coarse calcium phosphate-based bone filler according to an embodiment of the present invention.

Referring to FIG. 5, a spherical powder having a particle size of 100 μm or less is prepared from a calcium phosphate suspension by a conventional spray drying method (S110). This process can be carried out by conventional spray drying methods.

Subsequently, the spray dried spherical powder is dried in a fluidized bed (S120). In this step, the spray-dried flocculated powder is introduced into the fluidized bed drying furnace as seeds for grain growth. In addition, the same suspension as the suspension used in the above spray drying step is introduced into the fluidized bed drying furnace to induce grain growth of the seed.

Once the desired size, eg average particle diameter 200-400 μm, is obtained through fluid bed drying, granulated powders of granular particles are prepared by sintering the obtained particles at an appropriate temperature, for example 1100 ° C. for β-TCP. (S130).

On the other hand, it is also possible to produce the granular powder by a method different from that described in connection with FIG. 6 is a procedural diagram illustrating a step of preparing granular powder by introducing a grinding process.

Referring to Figure 6, after the suspension is precipitated (S210), the precipitate is dried (S220). The suspension here is suitably selected depending on the density of the granular powder to be finally obtained. Drying of the precipitate can be carried out in a conventional electric furnace, for example at a temperature of 80 ℃.

Subsequently, the dried precipitate is calcined (S230). Plastic sintering is carried out below the sintering temperature of the calcium phosphate compound. The sintering temperature should be appropriately selected in consideration of the grinding characteristics in the grinding step described later. For β-TCP, the appropriate sintering temperature is about 1000 ° C.

Next, the pre-sintered precipitate is crushed for a suitable time by a crusher such as a pin crusher (pin crusher) (S240), and the particles of the desired size is selected (S250). The grinding step and the sorting step may be performed in a batch by a pin crusher employing a screen. Since the grinding time affects the size and shape of the particles, an appropriate grinding time should be selected according to the desired particle shape and particle size.

Next, granulated particles are manufactured by sintering the selected particles (S260).

C. Powder Preparation

C-1. Preparation Example of Low Density Powder

10 g of β-TCP powder was dissolved in distilled water to prepare a suspension without addition of a dispersant. To the prepared suspension was added polyvinyl alcohol (PVA) at a mass ratio of 5% relative to β-TCP as a binder. The prepared suspension was put into a disk spray dryer to prepare a dry powder. At this time, the disk rotation speed of the spray dryer was maintained at 7000 rpm, the powder was dried by injecting hot air at 95 ℃ into the spray dryer.

The particles obtained were then sintered at a temperature of about 1180 ° C. to produce particles of low density.

7A and 7B are micrographs photographing the particles before and after sintering, respectively. It can be seen from the photographs shown that particles having an average particle diameter of 100 μm or less are obtained by spray drying. The density of the particles before and after sintering was 44% and 70%, respectively. FIG. 7C is an enlarged photo of FIG. 7B showing that micropores are formed in the particles.

C-2. Production Example of High Density Powder

10 g of β-TCP was dispersed in distilled water and Durbanse added 0.05 ml and 0.5 g of PVA to prepare a suspension. At this time, the pH of the suspension was maintained at 8. The powder was prepared by spray drying and sintering the suspension prepared under the same conditions as the low density powder manufacturing method described above.

8 is an electron microscope photograph of the powder after sintering. It can be seen from the picture shown that a powder consisting of spherical particles of about 100 μm or less is obtained, and from the high magnification picture at the bottom of the picture, the particles are composed of fine grains of about 1 to 3 μm and are in a very dense state. From the photograph, the relative density of the particles is judged to be 90% or more.

To obtain coarser granular particles, a fluid bed drying process was introduced using spray dried particles as seeds. A suspension of the same composition as the suspension used for spray drying was introduced into a fluid bed drying furnace to induce particle growth of the spray dried particles.

Figure 9a is an electron micrograph of the particles after the fluidized bed drying, Figure 9b is an electron micrograph taken at a higher magnification. It can be seen that the particle size as a whole compared to Figure 8, the average particle diameter is 200 ㎛ or more. The enlarged photograph of FIG. 9B shows that the particles obtained by fluidized bed drying are composed of very dense fine grains as well as the particles upon spray drying. The relative density of the particles is judged to be 90% or more.

C-3. Other Preparation of High Density Granular Powder

The same suspension as in Example C-2 was precipitated to prepare a precipitate. The precipitate was dried at a temperature of 80 ° C. and then calcined at a temperature of 1000 ° C. Subsequently, the sintered precipitate was crushed and then ground and screened with a pin crusher. In order to grasp the pulverization characteristics according to the pulverization time, a sample pulverized once and five times was prepared.

Fig. 10 (a) is an electron micrograph of a crushed state, (b) is an electron micrograph of the powder that has been pulverized once, (c) is an electron micrograph of the powder which has been pulverized five times. As the number of grinding increases, it can be seen that the particle shape changes from an angular shape to a round shape. 10 (d) is a view showing the shape of the powder obtained after screening after crushing five times. It can be seen that the powder obtained after the screen is composed of spherical particles having an average particle diameter of 200 μm or more.

D. Experimental Example of Transplantation of Powdery Bone Filler

Animal tests were performed using the mixture of granular particles obtained in C-1 and C-2 described above as bone filler. Animal testing was performed on rabbits, and for comparison with the present invention, when the damaged bone was filled with nothing, cerasob, a commercial powdered bone filler made from TCP of Curasan, was filled. Was used as a control. In each case, the bone tissue repair was observed after 8 weeks of sacrifice. 11A to 11C are micrographs of bone tissues observed when bones are filled with nothing, respectively, when Cerajan is filled and when the mixture of the present invention is filled, and the findings are as follows.

Most of the defects were filled with connective tissue when the damaged bone was filled with nothing. New bone was observed only at both ends of the defect, but no anatomical or functional aggregate was formed.

In the case of filling cerasin, it could be observed that new bone starting at both ends of the defect was formed in connection with the implant. In addition, island-like new bones were formed adjacent to the lower periosteum. The graft was not absorbed as a whole, but the appearance of the new bone formed around the graft was somewhat irregular, which may be due to a small amount of absorption from the surface or to the surface structure of the ceracle itself. In addition, the connective tissue was filled between the new bone around the graft and the new bone formed around the implant, which prevented the formation of functional aggregates.

In the case of the bone filler of the present invention, the absorption findings of some low-density granules were observed, and new bone was formed therein. In addition, new bones formed at both ends of the defect were well bonded without boundary separation, and island-like new bone formed adjacent to the inner periosteum was also observed, and new bone formation was active around high density granular particles with weak absorption. Could be observed. In the case of high-density granular particles, the surface absorption is more advanced than that of cerahem and it is well connected with surrounding new bone without any connective tissue.

E. Block-type Bone Fillers and Preparation Examples thereof

Preparation examples and experimental examples of the bone filler of the present invention described above is based on a powdery bone filler. However, the technical idea of the present invention may be applied to a block type bone filler.

12A to 12B are views conceptually illustrating a method of manufacturing a block bone filler in the present invention. Referring first to FIG. 12A, a powdered bone filler prepared by the embodiment of the present invention described above is filled in a mold. The bone filler may be any one of a high density bone filler or a low density bone filler. Subsequently, a calcium phosphate suspension is injected into the mold (FIG. 12B). The suspension is a suspension having a high density in the subsequent precipitation, drying and sintering steps when the filled powder bone filler is a low density bone filler, i. Suspensions are used. In contrast, when the filled powder bone filler is a high density bone filler, a suspension without dispersant may be injected.

When the injection of the suspension is completed, the molded body is demolded by drying for a period of time. The demolded shaped body is sintered at an appropriate sintering temperature. The sintering process can be carried out in the same manner as the method for producing the powdered bone filler described above.

Figure 13 is a photograph of the fine structure of the dried and sintered block-shaped bone filler by injecting the β-TCP suspension with a dispersant added to the low density powder type β-TCP bone filler. As shown, the blocky bone filler has a structure in which the porous region defined by the powdered bone filler and the dense region defined by the injected suspension coexist. Therefore, like the powdered bone filler described above, it is possible to exhibit efficient bone conduction characteristics by dissolution rate difference.

The embodiments of the present invention described above are merely illustrative of the embodiments of the present invention. Those skilled in the art to which the present invention pertains can make various modifications and modifications to the above-described embodiments, the modifications and modifications to the extent that does not depart from the scope of the technical spirit of the present invention the scope of the present invention Will belong to.

The bone filler of the present invention is designed to exert selective dissolution characteristics determined by the density difference to secure a bone conduction path after the procedure, thereby exhibiting effective bone repair properties. In particular, it is suitable to be used as a repair agent in bone defects caused by various bone diseases.

In addition, the present invention provides a reliable method for imparting the density difference of the individual particles constituting the bone filler, and enables the production of coarse spherical particles of 100 μm or more. Accordingly, by providing a significant difference in the density between the particles to maximize the selective dissolution properties, it is possible to improve the bone repair rate through a wide conductive path provided by the coarse particles.

Claims (6)

delete delete Preparing a suspension by dispersing the calcium phosphate compound and the dispersing agent in distilled water; Spray drying the suspension to form a spherical powder having an average particle diameter of 100 μm or less; Injecting the spray-dried spherical powder into a fluidized bed drier, and fluidized-bed drying while injecting a suspension containing the calcium phosphate compound to form granular powder; And Sintering the granular powder, A method for producing a calcium phosphate-based bone filler, which comprises calcium phosphate-based particles having an average particle diameter of 100 to 400 µm. delete delete delete

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