JPH0411215B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to an artificial bone material suitable for treatment in dentistry, oral surgery, orthopedic surgery, etc., and more particularly, it relates to artificial bone materials suitable for treatment in dentistry, oral surgery, orthopedic surgery, etc. A granular porous hydroxyapatite sintered body with excellent biocompatibility that can be filled into voids and promote the formation of new bone in the area and integrate with the bone tissue of the living body, and physiological saline. The present invention relates to an artificial bone material composition comprising:

Conventional technology Conventionally, in dental treatment, there has been a problem in which the alveolar bone is resorbed after tooth extraction, making it impossible to secure dentures etc. In addition, in oral surgery and orthopedic treatment, there has been a problem in cases such as traffic accidents, bone tumors, etc. In order to replace the bone lost due to this disease, attempts have been made to transplant bone from other parts of the patient, that is, autologous bone, but since bone tissue other than the damaged area is removed, the patient's There were problems such as the extremely heavy physical and psychological burden and the inability to collect enough autologous bone to fill in extensive bone defects.

Under these circumstances, research on artificial tooth roots and artificial aggregates has been actively conducted in recent years. When implanting these artificial bones into a living body, it is necessary to select materials that are non-toxic, safe, have considerable mechanical strength, and are easy to bond with living tissue. It is said that it is preferable to use a material that naturally disappears in vivo and is replaced by new bone.

In recent years, sintered bodies of calcium phosphate, hydroxyapatite, or calcium phosphate compounds with a special apatite-type crystal structure have been attracting attention as materials that meet these requirements, and research using these materials into artificial bones, artificial joints, artificial tooth roots, etc. is progressing. It is being actively carried out.

By the way, when an artificial bone or tooth root is implanted into the body, in order to make it easier to bond with living tissue, it is necessary to make it porous so that the living tissue can enter the pores and fix it. and to achieve this purpose, e.g. pore size 0.03
It has been proposed to use a porous calcium phosphate sintered body having pores of about 1.2 mm (Japanese Patent Application Laid-Open Nos. 149389-1989 and 7856-1985).

However, this artificial aggregate made of porous calcium phosphate sintered material is hard and brittle.
It has the drawback of not having sufficient mechanical strength, and since the material is dense, it is not necessarily satisfactory in terms of in-vivo absorption and replacement of new bone.

Furthermore, a bone defect filling material has been proposed in which a powder of an apatite-type crystal structure calcium phosphate compound with a crystal grain size of 50 Å to 10 μm is made into a fluid or plastic state by adding physiological saline etc.
−54841). However, since the calcium phosphate compound used in this filling material is in the form of fine powder, when this material is filled into the bone defect and sutured, the fine powder adheres to the surface of the skin wound, making suturing difficult. It has the disadvantage of being.

Problems to be Solved by the Invention The purpose of the present invention is to improve the above-mentioned drawbacks, fill bone defects and voids, promote the formation of new bone in the area, and make the bone itself form bone tissue. The object of the present invention is to provide a composition for an artificial bone material that can be integrated into one body, has excellent biocompatibility, and does not cause any adverse effects during surgery.

Means for Solving the Problem The present inventors have previously determined the pore size suitable for artificial aggregate.
A hydroxyapatite sintered body with continuous pores of 10 to 100 μm was developed (Japanese Patent Application No. 129087/1987), but as a result of further research, it was found that the sintered body had a porosity of 20 to 30% and a grain size of 20 to 30%. Granulate into granules with a diameter of 0.1 to 2.0 mm,
We have found that an artificial bone material made by adding physiological saline to this material can meet the above purpose, and based on this knowledge, we have completed the present invention.

It consists of a granular porous hydroxyapatite sintered body having continuous pores with a pore size of 10 to 100 μm, a porosity of 20 to 30%, and a particle size of 0.1 to 2.0 mm, and physiological saline,
The present invention also provides a composition for an artificial bone material in which the weight ratio of the sintered body to physiological saline is in the range of 2:1 to 1:2.

The granular porous hydroxyapatite sintered body used for the artificial bone material of the present invention has an average particle size of 0.1 to 10μ, for example.
Approximately 25 to 100 parts by weight of a thermally decomposable substance with an average particle size of 10 to 100 μm is added to 100 parts by weight of hydroxyapatite powder of 900 μm, and the mixture is granulated into granules with a particle size of 0.1 to 3.0 mm by a known method. It can be produced by firing at a temperature of ~1400°C. Although the firing can be carried out without applying pressure, it is preferable to carry out the firing by applying a pressure of 300 to 1000 kg/cm ² using a hot press, for example.

The hydroxyapatite used at this time may be apatite synthesized by a dry method or a wet method, or may be a living body apatite recovered from the bones and teeth of various vertebrates. It is desirable to use this raw material, hydroxyapatite, that has been ground into as fine a powder as possible, but due to limitations in equipment such as grinders and classifiers, and handling problems, it is usually used with an average particle size of 0.1 to 10 μm. A range is used.

Next, the thermally decomposable substance is blended in order to form continuous pores with a desired pore size when sintering hydroxyapatite, so the average particle size is 10 to 10.
Must have a diameter of 100 μm. This pyrolyzable material is used per 100 parts by weight of hydroxyapatite powder to obtain a porosity of 20 to 30%.
It is desirable to add it in a proportion of 100 parts by weight. If the porosity is less than 20%, sufficient continuous pores will not be formed, and although it is preferable to use a material with a compressive strength of at least 50 kg/cm ² as an artificial bone, in order to ensure this level of strength, the pores cannot be formed. It is necessary to keep the ratio below 30%. As this thermally decomposable substance, an organic compound such as crystalline cellulose is suitable.

Any means may be used to mix the hydroxyapatite powder and crystalline cellulose as long as they can be mixed uniformly. For example, hydroxyapatite powder and crystalline cellulose may be mixed as is using an appropriate mixer, or hydroxyapatite powder may be formed into granules with a particle size of 20 to 200 μm and then mixed with crystalline cellulose. may be mixed. Furthermore, it is also possible to wet the surface of crystalline cellulose with water or other solvent and apply hydroxyapatite uniformly thereto.

A binder such as polyvinyl alcohol is added to the mixture thus prepared, if necessary, and the mixture is molded into a desired shape and fired at a temperature of 900 to 1400°C. Firing time is usually 0.5 to 3 hours.

In the present invention, the particle size of the granules ranges from 0.1 to 2.0 mm. If the particle size is less than 0.1 mm, when filling and suturing bone defects etc., this particle will adhere to the surface of the skin wound and suturing will be difficult;
If the slurry exceeds this amount, a uniform slurry will not be formed when physiological saline is added to the slurry, making it difficult to handle during surgery.

The composition for artificial bone material of the present invention is in the form of a uniform slurry, which is obtained by adding physiological saline to the thus obtained granular porous hydroxyapatite sintered bodies. The ratio of the hydroxyapatite sintered body to the physiological saline needs to be in the range of 2:1 to 1:2 by weight. If the proportion of sintered hydroxyapatite is too high, it will lack fluidity and cannot be filled smoothly, and if the proportion of physiological saline is too high, the concentration of the sintered body will be insufficient and it will flow out. This will inevitably lead to incomplete filling.

Effects of the invention The artificial bone material of the present invention has a particle size that has continuous pores with a pore size of 10 to 100 μm and a porosity of 20 to 30%.
Because it uses granular porous abatite sintered bodies with a size of 0.1 to 2.0 mm, when it is filled into bone defects or voids, it easily bonds with living tissue, and osteoclasts (50 to 100 μm) do not form in vivo. It has the characteristic that it enters the pores, is rapidly dissolved and absorbed by the action, and is completely replaced by new bone by osteoblasts, and does not adhere to the skin wound surface during suturing. Surgery can be performed easily. Therefore, the artificial bone material of the present invention is suitable for treatments such as dentistry, oral surgery, and orthopedics.

EXAMPLES Next, the present invention will be explained in more detail with reference to Examples.

Example Hydroxyapatite synthesized by a wet method was calcined at 900°C for 1 hour, and then ground to an average particle size of 0.5 μm using a ball mill. Next, 2 parts by weight of polyvinyl alcohol and 50 parts by weight of crystalline cellulose powder with an average particle size of 50 μm were added to 100 parts by weight of this material.
After mixing, this was granulated into granules with a particle size of 0.5 to 3.0 mm, and heated to 1350°C at a heating rate of 100°C/hour.
Sintered at 1350℃ for 1 hour, average pore size 50μm
A granular sintered body of hydroxyapatite with a porosity of 26% and continuous pores was obtained.

100 parts by weight of physiological saline was added to 100 parts by weight of the granular porous hydroxyapatite sintered body thus obtained to form a slurry, thereby obtaining the artificial bone material of the present invention.

Comparative Example A porous hydroxyapatite sintered powder with a particle size of 5 to 10 μm (before granulation in the example) was prepared in the same manner as in the example.
An artificial bone material was obtained by adding 100 parts by weight of physiological saline to 100 parts by weight to form a slurry.

Application Example When a surgery was performed to fill the bone defect in the mandible of a rabbit with the artificial bone material obtained in Example, no adhesion to the skin wound surface was observed and suturing was extremely easy.

When the bone tissue after this surgery was observed under a microscope 12 and 24 weeks later, the following findings were obtained.

After 12 weeks, the new bone tissue formed between the hydroxyapatite granules increases in thickness and density, and a lamellar structure is clearly observed. In addition, osteoclasts appeared in some areas and were found to be resorbing new bone with a lamellar structure formed in contact with hydroxyapatite granules, indicating the progress of active bone remodeling mechanisms. be seen. Furthermore, the proportion occupied by the implanted hydroxyapatite granules is also reduced.

On the other hand, the periosteum of the parent bone is almost normal, and the new bone on the lateral surface of the parent bone shows a lamellar structure, with a single layer of osteoblasts arranged on its edge.

After 24 weeks, the new bone formed between the hydroxyapatite granules becomes thicker and denser.
Hydroxyapatite granules are scattered between the new bones. It can also be seen that the arrangement of the lacunae in the new bone is regular, and the lamellae are arranged in the longitudinal direction of the jawbone. Furthermore, the formation of enlarged Haversian canals and bone marrow is observed, and the hydroxyapatite granules disappear, followed by the formation of mesh-like bone tissue and irregular bone tissue.

Comparative Application Example When the artificial bone material obtained in the comparative example was used to fill a bone defect in the mandible of a rabbit in the same manner as in the application example, the material adhered to the skin wound surface and suturing was difficult. It was hot.

In addition, changes in bone tissue after 12 and 24 weeks were observed using a microscope, and the following findings were obtained.

After 12 weeks, the condition of the parent bone periosteum was the same as in the applied example, and thick lamellar bone was observed on the outside. That is, the new tissue in the intergranular spaces increases in thickness and density, and becomes compact. New bone tissue includes
Many of them are directly bonded to hydroxyapatite granules, but no change in the external shape of the granules is observed.

After 24 weeks, the intergranular spaces were filled with new bone tissue, but fibrous connective tissue was also observed surrounding the hydroxyapatite granules.

Compared to the applied example, there is more fibrous connective tissue, but the activity of bone tissue is low in areas directly connected to hydroxyapatite granules, and the remodeling mechanism progresses slowly.

Claims (1)

[Claims] 1 Consisting of a granular porous hydroxyapatite sintered body having continuous pores with a pore size of 10 to 100 μm, a porosity of 20 to 30%, and a particle size of 0.1 to 2.0 mm, and physiological saline, and A composition for artificial bone material in which the weight ratio of solids to physiological saline is in the range of 2:1 to 1:2.