JPH0534020B2 - - Google Patents

Description

[Detailed description of the invention]

<Industrial Application Field> The present invention relates to a calcium phosphate porous bone substitute material that promotes the formation of new bone, has excellent biocompatibility, and has high strength. <Prior art> Various porous materials having a three-dimensional network structure for filling bone defects and bone cavities to form new bone have been developed.
Japanese Patent Application No. 166843 provides a bone defect and bone cavity filling material having a three-dimensional network structure and having a hole channel having uneven portions in which new bone is likely to be generated. Also known are foaming porous bone grafting materials in which a foaming agent such as hydrogen peroxide is added to a calcium phosphate raw material slurry to foam the material. However, although the bone defect and bone cavity filling materials have uniform pore diameters, they do not have sufficient strength, and in the foamed porous bone filling materials, the pores are discontinuous and the pores are oriented in different directions. It has the disadvantage that it is difficult for osteoblasts to invade due to its nature. <Problems to be Solved by the Invention> Therefore, an object of the present invention is to provide a high-strength calcium phosphate porous bone grafting material that has excellent biocompatibility and can promote the formation of new bone. <Means for Solving the Problems> According to the present invention, a calcium phosphate porous body having a three-dimensional network structure having a continuous pore channel through which osteoblasts can penetrate to the center of the porous body, A calcium phosphate porous bone grafting material having pores with a pore diameter of 0.5 μm or less in the skeleton, and the porosity of the pores being 5 to 50% of the total pores in the pore channel and pores. is provided. The present invention will be explained in more detail below. The calcium phosphate porous bone graft material of the present invention is characterized in that pores having a pore diameter of 0.5 μm or less and having a continuous pore channel and a specific porosity are formed in the porous skeleton. In the present invention, the calcium phosphate compound forming the porous body includes CaHPO ₄ .2H ₂ O, CaHPO ₄ , Ca ₃ (PO ₄ ) ₂ , Ca ₅ (PO ₄ ) ₃ OH, Ca ₄ O
( _PO4 ) ₂ , _{CaP4O11 ,} Ca( _PO3 ) _{2 , Ca2P2O7} , _Ca
Examples include (H ₂ PO ₄ ) ₂ ·H ₂ O, which can be used alone or as a mixture of two or more. Among these compounds, tricalcium phosphate [Ca ₃ (PO ₄ ) ₂ ], hydroxyapatite [Ca ₅
(PO ₄ ) ₃ OH], tetracalcium phosphate [Ca ₄ O
(PO ₄ ) ₂ ] can be said to be a preferable compound because new bone formation is particularly rapid. Among these, the most preferred compound is hydroxyapatite, which produces new bone particularly quickly, and among these, hydroxyapatite obtained by heat treatment at 500° C. or higher, particularly preferably 700 to 1250° C., is particularly preferred because it produces new bone quickly. The upper limit temperature of the heat treatment is not particularly limited, but since hydroxyapatite starts to decompose, it should be lower than the decomposition temperature. Further, the calcium phosphate compound that can be used in the present invention may be artificially synthesized by a known production method, or it may be a natural compound obtained from bones or the like. In the present invention, the calcium phosphate compound described above is used as a porous body, and pores with a pore diameter of 0.5 μm or less are provided in the porous body skeleton. Here, the relationship between the pore channels and the pores will be explained with reference to a partially enlarged sectional view of the calcium phosphate porous bone grafting material of the present invention shown in FIG. In FIG. 1, 1 indicates a porous body skeleton which is a sintered body of a calcium phosphate compound, and 2 indicates a pore channel communicating within the porous body. The porous skeleton 1 is provided with pores 3 with a pore diameter of 0.5 μm or less, and osteoblasts that invade the pore channel 2 also invade the pores 3, resulting in unprecedented biocompatibility. And rapid new bone formation can be expected. Although the enlarged cross-sectional view of a part of the calcium phosphate porous bone graft material shown in FIG. 1 is shown in a plan view for the sake of explanation, it is actually a porous body having a three-dimensional network structure. The pore diameter of the pore is
If it exceeds 0.5 μm, it is not preferable because the proliferation of cells decreases. Furthermore, the porosity of the pores is
5 to 5 for the entire pore channel and pores
It is in the range of 50%. If the porosity of the pores is less than 5%, the initial adhesion of cells will be poor, and
If it exceeds 50%, the strength of the porous body decreases, causing problems in practicality, so it is necessary to keep it within the above range. Further, the total porosity of the pore channels and pores is preferably 40 to 97%. The pore channel is not particularly limited as long as it communicates so that osteoblasts can penetrate into the center of the porous body, but it is preferable that the pore diameter be adjusted to allow smoother penetration of osteoblasts. It is desirable that the thickness is 50 μm or more. Since the calcium phosphate porous bone graft material of the present invention has the above-mentioned communicating pore channels and has specific pores, it has substantially uniform strength from the three-dimensional direction, and preferably from the three-dimensional direction. It is desirable that the porous bone grafting material has a strength of 50 kg/cm ² or more. To prepare the calcium phosphate porous bone grafting material of the present invention, for example, the calcium phosphate compound is made into a slurry, and a combustible organic substance such as polyvinyl alcohol, methyl cellulose, starch, or sucrose and calcium phosphate fine powder are added to the slurry. After mixing, a foaming agent such as hydrogen peroxide, urea, dry ice, or ammonium nitrate is added to produce a foamed calcium phosphate slurry. Next, the foamed calcium phosphate slurry is injected into or impregnated into a porous organic resin such as urethane foam having a three-dimensional network structure with continuous pore channels, and then dried to remove the porous organic resin. It can be obtained by a method such as heating. In the method, the average particle size of the foamed calcium phosphate slurry is preferably
The particle size of the calcium phosphate fine powder is preferably 0.1 to 30 μm. In addition, the blending ratio of calcium phosphate fine powder and combustible organic matter added to the slurry is 0.1 to 50% by weight, respectively, based on the entire foamed calcium phosphate slurry.
The foaming agent is preferably added in an amount of 1.0 to 20% by weight. At this time, the entire foamed calcium phosphate slurry is adjusted to 100% by weight. Furthermore, although the drying and heating described above differ depending on the type of each component, it is preferable to carry out the drying at 30 to 110°C for 12 to 160 hours;
It is desirable to carry out at 500-1250°C. At this time, drying and heating can also be carried out in several parts.
In the method, by performing a heating step,
The porous organic resin is burnt out and the pore channels become continuous pores, and the pores generated by the foaming agent during heating are confined within the slurry.
Uniform pores can be formed in the porous framework. <Effects of the Invention> The calcium phosphate porous bone grafting material of the present invention has a continuous pore channel through which osteoblasts can penetrate into the center of the porous body and specific pores in the porous skeleton. It has excellent biocompatibility,
New bone can be formed quickly. Furthermore, since the mechanical strength in three-dimensional directions is almost uniformly excellent, it is expected that it will be used in place of conventional porous bone graft materials in the future. <Examples> The present invention will be described in more detail below with reference to Examples and Comparative Examples, but the present invention is not limited thereto. Example 1 150 g of hydroxyapatite fine powder with a particle size of 1 to 20 μm and polyvinyl alcohol powder were added to 450 g of hydroxyapatite slurry with an average particle size of 2 μm.
After adding and mixing 20 g, 24 c.c. of 30% by weight hydrogen peroxide solution was added to prepare a foamed calcium phosphate slurry. The resulting slurry was then poured into a urethane foam, foamed and dried in a dryer at 110°C for 24 hours. Next, the obtained dried product is heated to
Transferred to an electric furnace (manufactured in
The temperature was then raised at a rate of 2°C/min from 500 to 900°C. After that, after holding at 900℃ for 3 hours,
The temperature was lowered to room temperature at a rate of °C/min to obtain a porous bone graft material. The porosity of pores with a pore diameter of 0.5 μm or less existing in the porous skeleton of the porous bone graft material obtained was measured using a porosimeter (manufactured by Shimadzu Corporation) and found to be 34.4%. In addition, all pores (average diameter 100 μm
The porosity of the continuous pore channels and pores was 55%. Furthermore, the obtained porous bone graft material was cut into a size of 10 x 10 x 10 mm, and the compressive strength was measured when force was applied from three directions: the upper part, the lower part, and the lateral part.The upper part was 162.2 Kg/cm ² and the lower part was 170.0. Kg/ ^cm2 ,
The side weight was 157.7Kg/ ^cm2 . Example 2 Pores with a pore diameter of 0.5 μm account for 5% of the total pores, 35
A porous bone graft material was produced in the same manner as in Example 1, except that the porous bone filling material was adjusted to 50%. Next, each of the porous bone graft materials obtained was crushed into pieces of 0.5 to 10 mm.
After filling a 1.4φcm x 2.3Lcm column (manufactured by Pharmacia Co., Ltd.), 3T3-E1 cells were added to the column.
10 ⁶ /cc was flowed for 3 c.c., and the residual rate of cells in the solution that passed through was measured. The results are shown in Table 1. Comparative example 1 Pores with a pore diameter of 0.5 μm account for 1% of the total pores, 70
Porous bone filling materials were manufactured in the same manner as in Example 2, except that the porous bone filling materials were prepared to have a % of %. The results are shown in Table 1.

[Table] From Table 1, it was found that cell adhesion was good when the porosity of pores with a pore diameter of 0.5 μm was in the range of 5 to 50% of the total pores. Example 3 The porous bone graft material produced in Example 1 was prepared in a 5×5×
It was cut into 5 mm pieces and implanted into the tibia of a beagle dog. 4
After a week, the porous bone graft material was removed and cut.
Observation of the amount of new bone on the cut surface revealed that new bone was well formed.

[Brief explanation of the drawing]

FIG. 1 is a partially enlarged sectional view of the calcium phosphate porous bone prosthesis material of the present invention. 1... Porous body skeleton, 2... Void channel, 3
……pore.

Claims (1)

[Claims] 1. A calcium phosphate porous body with a three-dimensional network structure having a continuous pore channel through which osteoblasts can penetrate to the center of the porous body, the porous body skeleton having pores with a pore diameter of 0.5 μm or less, The pores have a porosity of 5 to 50% of the total pores of the pore channel and pores.