JPH0583263B2 - - Google Patents

Description

[Detailed description of the invention]

【0001】

TECHNICAL FIELD The present invention relates to a method for manufacturing a bone substitute material used in, for example, oral surgery, orthopedic surgery, etc., to fill in bone defects after surgery for bone tumors, alveolar abscesses, etc.

【0002】

[Prior art and its problems] Conventionally, such bone grafting materials include metals such as cobalt-chromium, titanium, and stainless steel, alumina, zirconia, tricalcium phosphate, hydroxyapatite,
Materials such as ceramics such as calcium phosphate glass, polymeric materials such as silicone resin, and carbon, which are formed into blocks or granules, are used.

[0003] Among these, calcium phosphate materials such as calcium triphosphate, hydroxyapatite, and calcium phosphate glass are materials that have received the most attention in recent years because they have extremely high biocompatibility because they are composed of components similar to bones.

[0004] However, even when using a bone grafting material made of calcium phosphate-based material, since it is originally a foreign substance, the part of the filled bone grafting material close to the living tissue is fused with new bone; Portions away from living tissue are often surrounded by fibrous tissue and softened due to a so-called capsule reaction. As described above, even when a calcium phosphate-based material is used, there is a problem in that tissue incompatibility occurs due to a capsule reaction in areas where healing power is inactive.

[0005] Also, in Japanese Patent Application Laid-open No. 60-21763,
It has continuous pores with a pore size of 10 to 100 μm, and at least
An artificial bone material made of sintered hydroxyapatite with a bending strength of 100 kg/cm ² has been proposed.

[0006] However, in the above artificial bone materials, in order to impart a bending strength of at least 100 Kg/cm ² , it is not possible to increase the porosity, and the number of continuous pores is extremely small, making it difficult to effectively prevent capsule reactions. I couldn't do it.

[0007]

OBJECT OF THE INVENTION The purpose of the present invention is, for example, even in areas where healing power is inactive, away from living tissues.
An object of the present invention is to provide a method for producing a bone grafting material that is fused to new bone and does not cause a capsule reaction.

[0008]

Structure of the Invention The method for producing a bone graft material of the present invention involves mixing and granulating organic combustible particles having an average particle size of 0.01 to 10 μm and calcium phosphate powder having an average particle size of 0.05 to 1 μm; It is characterized by firing something.

[0009] A capsule reaction to a bone grafting material taken into a living body is induced when macrophages attached to the bone grafting material judge this to be a foreign substance. As a result of thorough research into this effect, the present inventors found that if body fluids are circulating in the area to which macrophages have attached, the macrophages will not judge it as a foreign object, and the capsule reaction will not occur. I found out that it can be prevented.

[0010] The present invention focuses on the fact that by forming continuous pores in the bone grafting material, body fluid can flow inside the bone grafting material, preventing a capsule reaction, and promoting fusion with new bone. It was made by In this case, the pore diameter of the continuous pores is important in order not to be judged as a foreign substance by the macrophage, and specifically, the pore diameter needs to be not too large compared to the macrophage.

[0011] For this purpose, the average pore size is 0.01 to 10 μm.
A bone grafting material having continuous pores of In this case, if the average pore diameter is less than 0.01 μm, it will be difficult to manufacture and it will be difficult for body fluids to flow, so that a sufficient effect of preventing capsule reaction will not be obtained. Furthermore, if the average pore size exceeds 10 μm, the pore size is too large compared to the size of the macrophages, and body fluids cannot circulate in the area where the macrophages are attached, making it impossible to obtain a sufficient capsule reaction prevention effect.

[0012] In the present invention, the average particle size of the organic combustible particles is set to 0.01 to 10 μm in order to form continuous pores having the average pore size as described above. Examples of organic combustible particles include synthetic resin beads such as polystyrene, polyvinyl alcohol, and polypropylene;
Finely cut materials such as cellulose and animal fibers are used.

[0013] In addition, in the present invention, the average particle size
Use 0.05-1 μm calcium phosphate powder. As a result, the skeleton made of calcium phosphate powder becomes almost dense, and the pores are made entirely of organic combustible particles. As the calcium phosphate material, various known materials can be used, but hydroxyapatite, calcium triphosphate, etc. are particularly preferred. Calcium phosphate powder as a crude raw material has an average particle size of 1 to 1, for example.
It may be about 10 μm, but it is necessary to grind it with a ball mill or the like to have an average particle size of 0.05 to 1 μm before use.

[0014] When mixing and granulating the above-mentioned calcium phosphate-based material and organic combustible particles, water, polyvinyl alcohol, etc. may be added as a binder if necessary.

[0015] The blending composition of the raw materials is 30 to 70 parts of organic combustible particles per 100 parts by weight of calcium phosphate powder.
Parts by weight are preferred. If the amount of organic combustible particles is less than 30 parts by weight, sufficient porosity cannot be obtained, and if it exceeds 70 parts by weight, the porosity becomes too large and the strength decreases.

[0016] Granulation methods include, for example, mixing calcium phosphate powder and organic combustible particles to form a slurry, drying this into blocks, and then pulverizing it, or granulating it using a pan-type granulator. Methods such as that can be adopted.

[0017] Firing conditions are not particularly limited, but for example, after burning out the organic combustible particles by increasing the temperature from room temperature to about 600°C at around 50°C/Hr,
The temperature is raised at around 100℃/Hr until it reaches 1200℃.
A sintered body can be obtained by holding at a temperature of about 8 hours.

[0018] In a preferred embodiment of the present invention, porous granules having at least one continuous pore within a range of (10 μm) ² on the granule surface are produced. By arranging the continuous pores at a predetermined density in this manner, the probability that the continuous pores will be located at the location where macrophages have adhered is increased, and the capsule reaction can be more effectively prevented.

[0019] Furthermore, in a preferred embodiment of the present invention, the average pore diameter of the continuous pores is 0.01 to 1 μm.
By setting the average pore diameter to 0.01 to 1 μm, macrophages will be able to ride on the pores and adhere to them.
The capsule reaction prevention effect is further enhanced.

[0020] Furthermore, in a preferred embodiment of the present invention, the porosity is 60 to 90%. Porosity is 60%
If it is less than that, it will be difficult to form continuous pores, and body fluids will not be able to circulate sufficiently. On the other hand, when the porosity exceeds 90%, the strength tends to decrease and the material tends to collapse easily.

[0021] In the present invention, the shape of the granules of the bone grafting material is not particularly limited, such as spherical or amorphous. Further, the size of the granules is preferably such that the average diameter is 0.1 to 1 mm in order to facilitate the filling operation. If the average diameter of the granules is less than 0.1 mm, they will be easily washed away by body fluids, and if it exceeds 1 mm, there will be too much space between the granules, making it difficult for them to fuse with new bone.

[0022] When using this bone grafting material, for example, after sterilizing the bone grafting material, it may be mixed with sterilized physiological saline and filled into a bone defect. Thereby, the bone substitute material and the surrounding bone tissue are fused together by the new bone, and the bone defect can be healed.

【0023】

[Example] 600 g of synthetic hydroxyapatite powder (particle size 1 to 10 μm), 400 g of polystyrene beads "Fine Pearl" (trade name, manufactured by Sumitomo Chemical Co., Ltd., average particle size 6 μm), and 2000 ml of distilled water.
was added and mixed and dispersed in a ball mill for 24 hours to obtain a slurry of hydroxyapatite with an average particle size of 0.6 μm. The slurry was placed in a shear dish and dried in a hot air circulation dryer at 100°C for 24 hours to form a dry block.

[0024] This dried block is crushed in a mortar and
It was made into granules of 100 to 1000 μm and fired in an electric furnace.
The firing conditions were to raise the temperature from room temperature to 600°C at a rate of 50°C/Hr, then to 1200°C at a rate of 100°C/Hr, and then to 1200°C.
The temperature was maintained at ℃ for 8 hours, and then the temperature was lowered at a rate of 200℃/hr.

[0025] The thus obtained hydroxyapatite granules were prepared using a stainless steel mesh to have a particle size in the range of 300 to 500 μm.

[0026] This bone grafting material had continuous pores with an average pore diameter of about 4 μm. A 100x electron micrograph of this bone graft material is shown in Fig. 1, a 1000x electron micrograph is shown in Fig. 2, and a 10,000x electron micrograph is shown in Fig. 3.

【0027】

Effects of the Invention As explained above, according to the method of the present invention, the pore diameter and porosity can be easily controlled and the pores are evenly distributed, and the pores are high and can be used as a bone replacement material. Porous granules with sufficient strength are obtained. Further, according to the method of the present invention, calcium phosphate-based particles having continuous pores with an average pore diameter of 0.01 to 10 μm, the pores being uniformly dispersed, and at least one pore existing within a range of (10 μm) ² on the granule surface. Porous granules are obtained.
When such porous granules are used as a bone grafting material, body fluids circulate at the site where macrophages are attached, and macrophages do not detect foreign substances, so they can effectively prevent capsular reactions and interact with new bone. Good fusion can be achieved and healing can be accelerated.

[Brief explanation of the drawing]

FIG. 1 is a 100x electron micrograph showing the particle structure of a bone grafting material obtained in an example of the present invention.

FIG. 2 is an electron micrograph with a magnification of 1000 times showing the particle structure of the bone grafting material obtained in the example of the present invention.

FIG. 3 is an electron micrograph with a magnification of 10,000 times showing the particle structure of the bone grafting material obtained in the example of the present invention.

Claims (1)

[Claims] Claim 1: A bone replacement characterized by mixing and granulating organic combustible particles with an average particle size of 0.01 to 10 μm and calcium phosphate powder with an average particle size of 0.05 to 1 μm, and firing the granulated product. Method of manufacturing wood.