JPH0139786B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to a living body hard tissue repair material used for repairing a defect in living body hard tissue such as an alveolar bone or a jawbone or a tooth extraction socket in dental treatment, and the production thereof. It is about law.

Background of the Invention In dental treatment, bone tumors and bone cysts are removed, alveolar bone and jawbone are damaged due to alveolar pyorrhea, and tooth extraction sockets are created by extracting the tooth itself. This often happens. Traditionally, in such cases, the bone defect or tooth extraction socket was left alone and allowed to heal naturally, or the patient's own autologous bone cancellous tissue was harvested and used to repair the bone defect or tooth extraction socket. Various methods have been investigated, such as transplanting allogeneic bone or xenogeneic bone other than autologous bone, and even using artificial biomaterials.
All of these have many problems that are difficult to overcome, and their indications are limited, so they have not yet reached the stage of practical use.

In recent years, synthetic calcium hydroxyapatite (hereinafter referred to as "synthetic hydroxyapatite" throughout this specification) having the formula Cam(PO ₄ ) n(OH) (1.4<m/n<1.7) has been developed. Focusing on its high compatibility with living organisms, research has been conducted to clinically apply it as a material for artificial bones and artificial tooth roots, and many papers have been published (for example, "Ceramics" published by Industrial Technology Center Co., Ltd. "Materials Technology Collection" pp. 1030-1035).

When using synthetic hydroxyapatite as an artificial biomaterial, in addition to the requirements for a general biomaterial, it must also have properties that enable rapid regeneration of bone tissue around it after implantation. In order to rapidly regenerate bone, osteoblasts should be actively differentiated around the implanted biomaterial made of synthetic hydroxyapatite and guided to the biomaterial. It is known that humoral factors secreted from myeloid cells such as monocytes are involved in bone formation.

Prior Art and its Problems According to the literature so far, in conventional research using synthetic hydroxyapatite as a biomaterial,
In order to overcome the body's ability to eliminate foreign substances, synthetic hydroxyapatite particles are sintered at high temperatures to increase the surface area of the particles, thereby allowing osteoblasts to differentiate abundantly and increasing the bone formation rate per unit time. The main focus was on. Many of the biological hard tissue repair materials mainly consist of sintered bodies of synthetic hydroxyapatite particles obtained as described above, which are then molded and fired at a temperature range of 1000 to 1300°C. It was warm.

However, in the repair material obtained in this way, the surface of the synthetic hydroxyapatite particles is made into ceramic by sintering, and therefore, the repair material has no solubility in body fluids, and
The surface area was reduced. Therefore, when this ceramicized synthetic hydroxyapatite sintered body was used as a repair material for biological hard tissue, macrophages could not be induced around it, and osteoblast differentiation was also slow. . Therefore, it takes a long period of several months or more for the bone tissue to regenerate around the area after the treatment, and during this period, the repair material made of the sintered body can prevent bacterial infections and remove foreign substances from the living body. As a result, there were situations in which it was difficult for new bone formation to proceed quickly.

This invention was made in consideration of the interaction between the differentiation mechanism of osteoblasts and the solubility of synthetic hydroxyapatite in body fluids, as described above, and allows for the removal of foreign substances from the surrounding body without causing a foreign body removal action on the living body side. It can quickly form new bone and fuse with living hard tissue, and can be applied to any shape of defect or tooth extraction socket in living hard tissue, and can completely repair them. The object of the present invention is to provide a biological hard tissue repair material that can be easily produced industrially and is satisfactory in terms of cost, and a method for producing the same.

Means for Solving Problems The biological hard tissue repair material according to the present invention has the general formula
Cam( _PO4 )n(OH)(1.4<m/n<
1.7) Cap (PO ₄ ) q (OH) (However, 1.4
<p/q<1.7) A coating layer made of unfired synthetic hydroxyapatite having a composition of <p/q<1.7) is formed.

Furthermore, the method for manufacturing the repair material according to the present invention has the general formula Cam(PO ₄ )n(OH) (where 1.4<m/n<
1.7) A phosphoric acid group is bonded to a fired body of a powder or a molded product formed from a powder of synthetic hydroxyapatite having the following composition, and then the phosphoric acid group is reacted with calcium ions to improve the surface of the fired body. is the general formula Cap(PO ₄ )q(OH) (where 1.4<
The present invention is characterized by forming a coating layer made of unfired synthetic hydroxyapatite having a composition of (p/q<1.7).

In this invention, the synthetic hydroxyapatite for constituting the fired body may be produced by any one of a wet synthesis method, a dry synthesis method, and a hydrothermal synthesis method.

The fired body of the molded product made of synthetic hydroxyapatite is produced by molding powdered synthetic hydroxyapatite into granules, cylinders, prisms, and plates by a conventional method using a compression molding machine or other ordinary molding equipment. It is obtained by molding into a cone or pyramid shape, and then firing at a temperature range of 1000 to 1300°C.

The coating layer of synthetic hydroxyapatite is formed by treating the fired synthetic hydroxyapatite body with a solution of phosphoric acid or its salt, then with a solution of calcium or its salt, and heating the treated product at 100 to 400°C, preferably about 200°C. It is formed by drying at a temperature of °C.
The coating layer thus formed has the general formula Cap(PO ₄ )
It is an uncalcined synthetic hydroxyapatite with the composition q(OH). As seen from X-ray diffraction analysis, this synthetic hydroxyapatite is of poor quality in terms of crystal structure, like the biological hydroxyapatite that constitutes biological hard tissues.

Actions and Effects The biological hard tissue repair material according to the present invention has an inner body composed of a fired body of powdered or molded synthetic hydroxyapatite, and an unfired synthetic hydroxyapatite formed on the surface of the inner body. It has a double structure consisting of a coating layer.

Since the internal fired body is made into ceramic by firing, it exhibits X-ray contrast properties. Therefore, the situation after the treatment can be confirmed with X-rays. Furthermore, by making it into fired ceramic, the mechanical strength of the repair material after filling can be increased.

On the other hand, the synthetic hydroxyapatite that makes up the covering layer is amorphous when viewed from X-ray diffraction analysis, just like the biological hydroxyapatite that makes up the hard tissues of living organisms, so it is difficult to fill bone defects or tooth extraction sockets. Repair materials are
It is slightly soluble in body fluids, and as a result, it can induce macrophages around it, promote differentiation of osteoblasts, and rapidly form new bone. Therefore, the repair material according to the present invention gradually fuses and integrates with the biological hydroxyapatite constituting the hard tissues of the living body, and does not have any effect of eliminating foreign substances on the living body side.

In addition, since the repair material according to the present invention is powder or molded into various shapes such as granules, columns, plates, cones, etc., it can be used for any shape of defective part or tooth extraction socket in biological hard tissue. This can be applied.

Furthermore, since the manufacturing method according to the present invention does not require special equipment or special operations, it is not necessary to spend a lot of money and labor, and it is possible to obtain a cost-effective product.

Examples Examples and usage examples of this invention will be shown to demonstrate the above effects.

Example 1 (Powder) (a) A suspension consisting of 1174 g of calcium hydroxide and 12 parts of distilled water was placed in a 40 stainless steel reaction tank with a stirrer, and approximately 15 parts of water was added. Then, maintain the temperature at 55℃ and add 30% phosphoric acid solution while stirring.
3920 g was added dropwise and stirring continued for a further 2 hours.

The obtained reaction product was dehydrated using a pressure filter, and the dehydrated cake was dried in an oven at a temperature of 190° C. for 2 hours, and then crushed using a pulverizer. Thus the particle size
Powdered synthetic hydroxyapatite 2021 less than 100μm
I got g.

(b) 250 g of this powdered synthetic hydroxyapatite was fired at a temperature of 1250° C. for 2 hours to obtain 243 g of a powdered fired body with a particle size of 100 μm or less.

(c) This powdered fired product was placed in the glass container from step 1, 500 g of 2% phosphoric acid solution was added and the whole was allowed to stand for 1 hour to bond phosphoric acid groups to the surface of the powdered fired product. . Then 1% of calcium hydroxide
A water suspension was added to react the bound phosphate groups with calcium ions. After dehydration, the dehydrated product was dried at 200° C. for 1 hour.

In this way, a coating layer of unfired synthetic hydroxyapatite is formed on the surface of the powder fired body, and the particle size is 100 μm.
The following powdered repair material was obtained.

Example 2 (Molded product) 1500g of the unfired powdered hydroxyapatite obtained in step (a) of Example 1 was taken, and 50g of a 3% aqueous solution of polyvinyl alcohol was added as a binder and mixed. Then, from the obtained mixture, 250 g of granular molded products with a particle size of 0.5 to 1.0 mm were made using a normal compression molding machine.
250 g of cylindrical molding with a diameter of 2 mm and a length of 12 mm, short side 5
250 g of a rectangular plate-shaped molded product with a long side of 15 mm and a thickness of 2 mm and a conical molded product with a bottom diameter of 5 mm and a height of 10 mm were obtained.

These four types of molded products were dried at a temperature of 190°C for 2 hours and then fired at a temperature of 1250°C for 2 hours, resulting in ceramic shaped fired bodies of 240g, 237g, and 242g, respectively.
and 240g were obtained.

The same operation as in step (c) of Example 1 was performed on each of the shaped and fired bodies obtained in this way, and a coating layer of unfired synthetic hydroxyapatite was formed on the surface of each fired body to form granules, cylinders, and plates. Shaped and conical shaped repair materials were obtained.

Analysis Regarding the repair materials according to the present invention obtained in Examples 1 and 2, the internal fired body and the unfired body forming the coating layer were taken and subjected to chemical analysis and X-ray diffraction analysis.

Chemical analysis shows that both have the chemical formula Co ₁₀ (PO ₄ ) ₆
It was confirmed that it is a synthetic apatite with a stoichiometric structure represented by (OH) ₂ .

Further, in X-ray diffraction analysis, the internal fired body showed a typical apatite diffraction pattern, and the coating layer showed an amorphous diffraction pattern in X-ray diffraction analysis.

Usage example 1 5 g of powdered repair material with particle size of 100 μm or less obtained in Example 1 and particle size of 0.5 to 1.0 obtained in Example 2
20 g of granular repair material of mm were mixed. The mixture was sterilized by heating in an oven at 400°C for 6 hours.

The treated product was injected into the jawbone of a Wistar rat weighing 200 g and observed over time.

Three days to one week after the treatment, it was observed that new bone quickly formed around the filled material, and after four weeks, it was observed that the material had completely fused into the jawbone. Ta.

Usage Example 2 10 g of the cylindrical molded repair material obtained in Example 2 and 10 g of the plate-shaped molded repair material were mixed, sterilized in the same manner as in Use Example 1, and the treated material was inserted into the jawbone of a 2-year-old adult dog. were filled and observed over time.

Three days to one week after the treatment, it was observed that new bone quickly formed around the filled material, and after four weeks, it was observed that the material had completely fused into the jawbone. Ta.

Usage Example 3 20g of the conical molded repair material obtained in Example 2 was sterilized in the same manner as in Usage Example 1, and the treated product was filled into the extraction socket of a 2-year-old adult dog's canine tooth, and observed over time. I did it.

One to two weeks after the treatment, it was observed that new bone was rapidly generated around the filled material.
After 15 weeks, it was observed that no changes had occurred in the alveolar bone surrounding the treated tooth extraction socket.
Normally, if the tooth extraction socket is left as is after a tooth extraction, the alveolar bone around the tooth extraction socket will elute into the body fluid and gradually disappear, causing the surrounding healthy bone to atrophy. This will have a negative impact on occlusal recovery.

Claims (1)

[Claims] 1. Firing of a powder or a molded product made from synthetic hydroxyapatite having the general formula Cam(PO ₄ )n(OH) (1.4<m/n<1.7) A coating layer made of unfired synthetic hydroxyapatite having the composition Cap(PO ₄ ) q (OH) (1.4<p/q<1.7) is formed on the surface of the body. Biological hard tissue repair material. 2. A fired body of a powder or a molded product formed from synthetic hydroxyapatite having the general formula Cam( _PO4 )n(OH) (1.4<m/n<1.7),
By bonding phosphoric acid groups and then reacting calcium ions with the phosphoric acid groups, a composition having the general formula Cap(PO ₄ )q(OH) (where 1.4<p/q<1.7) is formed on the surface of the above-mentioned fired body. 1. A method for producing a biological hard tissue repair material, comprising forming a coating layer made of unfired synthetic hydroxyapatite.