JPS62224356A - Living body hard tissue prosthetic material and its production - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

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 the law.

BACKGROUND OF THE INVENTION In dental treatment, removal of bone tumors and bone cysts, as well as defects in the alveolar bone and jawbone due to alveolar pyorrhea, etc.
Often, an extraction socket is created by extracting the tooth itself. Traditionally, in such cases,
Either the bone defect or tooth extraction socket is left alone and allowed to heal naturally, the cancellous tissue of the patient's own autologous bone is harvested and used to repair the bone defect or tooth extraction socket, or allogeneic bone other than autologous or xenogeneic bone is used. Various methods of bone grafting and even the use of artificial biomaterials have been investigated, but these all have many problems that are difficult to overcome and have limited indications. However, it has not yet reached the practical stage.

In recent years, synthetic calcium hydroxyapatite (hereinafter referred to as "synthetic hydroxyapatite" throughout this specification) has the formula Cam (PO4)n (OH) (1.4<m/n<1.7). Focusing on its high compatibility with living organisms, research has been conducted on the clinical application of this material as a material for artificial bones or artificial tooth roots, and many papers have been published. Published "Ceramics Materials Technology Collection" 1030-103
(page 5).

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, it is sufficient to actively differentiate osteoblasts around the imbued biomaterial made of synthetic hydroxyapatite and guide them to the biomaterial. One type of factor is humoral factors secreted from myeloid cells such as monocytes.
It is known that these are jointly involved in bone formation.

Prior art and its problemsAccording to previous literature, in conventional research using synthetic hydroxyapatite as a biomaterial, synthetic hydroxyapatite particles were sintered at high temperatures in order to overcome the biological body's ability to eliminate foreign substances. The main focus has been on increasing the bone formation rate per unit time by increasing the surface area of the particles, thereby enriching the differentiation of osteoblasts. Many of the biological hard tissue repair materials mainly contain sintered bodies of synthetic hydroxyapatite particles obtained as described above, which are then molded for 10 minutes.
It was obtained by firing at a temperature range of 00 to 1300°C.

However, in the repair material obtained in this way, the surface of the synthetic hydroxyapatite particles is made into a ceramic by sintering, so the repair material has no solubility in body fluids and has a reduced surface area. was. Therefore, when the ceramized 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, after the procedure, a long period of several months or more is required for the bone tissue to regenerate around the area, and during this period, the repair material made of the sintered body can become infected with bacteria and eliminate foreign substances from the living body. In some cases, it was difficult for the generation of new bone to progress rapidly due to the effects of the drug.

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 integrate it with living hard tissue, and it can also be applied to any shape of defect in living hard tissue or tooth height, and can completely repair them. Moreover, it is an object of the present invention 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 manufacturing the same.

Means for Solving the Problems The biological hard tissue repair material according to the present invention has the general formula 〇am(
PO4)n (OH) (1°4<m/n<1.
C.
ap (PO4)Q (OH) (However, 1.4<
A coating layer made of unfired synthetic hydroxyapatite having a composition of I)/(1<1°7) is formed.

Furthermore, the method for manufacturing the repair material according to the present invention is based on the general formula 〇am
(PO4)n (OH) (However, 1゜4<m/
n < 1.7), to the fired body of a powder or a molded product formed from the powder,
By bonding phosphoric acid groups and then reacting calcium ions with the phosphoric acid groups, the general formula 〇at)(
PO4)Q(OH) (1.4<I)/Q<1
．． The present invention is characterized in that a coating layer made of unfired synthetic hydroxyapatite having a composition of 7> is formed.

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

The fired body of the molded product made of synthetic hydroxyapatite is produced by converting powdered synthetic hydroxyapatite into granules, cylinders or prisms, plates, or cones by a conventional method using a compression molding machine or other ordinary molding equipment. It is formed into a shape such as a pyramid or a pyramid, and then 100%
It was obtained by firing at a temperature range of 0 to 1300°C.

The coating layer of synthetic hydroxyapatite is obtained by treating the fired synthetic hydroxyapatite body with a solution of phosphoric acid or its salt, and then treating it with a solution of calcium or its salt, so that the treated product has a
It is formed by drying at a temperature of 400°C, preferably about 200°C. The coating layer thus formed is an unfired synthetic hydroxyapatite having a structure of the general formula Cap (PO4)Q (OH).

As seen from X-ray diffraction analysis, this synthetic hydroxyapatite is similar to biological hydroxyapatite that constitutes biological hard tissue.
It has an amorphous crystal structure.

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.

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

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. The repair material 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 121 g of distilled water was placed in a 401 stainless steel reaction tank equipped with a stirrer, and approximately 15 g of water was added. Then set the temperature to 5
While maintaining the temperature at 5°C, 30% phosphoric acid solution 392 (EJ) was added dropwise while stirring, and stirring was continued for an additional 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. In this way, powdered synthetic hydroxyapatite 20120 with a particle size of 100 μm or less was obtained.

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) Place this powdered fired body in a glass container of 11,
% phosphoric acid solution was added at a time of 500 g and the whole was allowed to stand for 1 hour to bond phosphoric acid groups to the surface of the powdered fired product. Then, a 1% aqueous suspension of calcium hydroxide was added to dissolve the bound phosphorus F.
11 was reacted with calcium ions. After the dehydration treatment, the dehydrated product was dried at 200° C. for 1 hour.

In this way, a coating layer of unfired synthetic hydroxyapatite was formed on the surface of the powder fired body to obtain a powdered repair material with a particle size of 100 μm or less.

Example 2 (Molded product) 1500 (J) of unfired powdered hydroxyapatite obtained in step a) of Example 1 was taken, and 50O of a 3% aqueous solution of polyvinyl alcohol was added as a binder. mix,
The resulting mixture was molded using a conventional compression molding machine to obtain particles with a particle size of 0.
250g of 5-1.0ml1 granular molding, diameter 2m
m Cylindrical molding 2500 with a length of 12 mm, short side 5+++
250 g of rectangular plate-shaped molded product with n+ long side 15 mm and thickness 2 mm
And bottom diameter 5mm height 10111! 1 of conical moldings were obtained in each case.

These four types of molded products were dried at a temperature of 190° C. for 2 hours and fired at a temperature of 127° C. for 2 hours to obtain 24001237 (J), 242 g and 240 g of ceramicized molded and fired bodies, respectively.

Example 1 for each shaped and fired body thus obtained
The same operation as in step C) was performed to form a coating layer of unfired synthetic hydroxyapatite on the surface of each fired body to obtain granular, cylindrical, plate-like, and conical shaped repair materials.

Regarding the repair materials according to the present invention obtained in Analysis 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.

In chemical analysis, both have the chemical formula CO1o (P O4)a
It was confirmed that it is a synthetic apatite having 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.

Use Example 1 5 g of the powdered repair material with a particle size of 100 μm or less obtained in Example 1 and 5 g of a particle size of 0°5 to 1.0 μm obtained in Example 2. Qmm granular repair material 20 () was mixed. The mixture was heated in an oven at 400° C. for 6 hours and sterilized.

The treated product was filled 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.

Use Example 2 The cylindrical molded repair material 109 obtained in Example 2 and the plate-shaped molded repair material 100 were mixed, sterilized in the same manner as in Use Example 1, and the treated material was prepared into a 2-year-old adult jawbone. The cells were filled with water and observed over time.

3 days to 1 after treatment! After 4 weeks, it was observed that new bone was rapidly generated around the filled material, and after 4 weeks, it was observed that the material was completely fused and integrated with the jawbone.

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

One to two weeks after the treatment, it was observed that new bone was rapidly generated around the filled material, and after 151A, no changes had occurred in the alveolar bone around the treated tooth extraction socket. It was acknowledged that there was no. 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 body fluids and gradually disappear, causing the surrounding healthy bone to atrophy. This will have a negative impact on occlusal recovery.

that's all Patent applicant: Taihei Kagaku Sangyo Co., Ltd. procedural amendment type 4°3・] April 2nd, 1986

Claims (2)

[Claims] (1) General formula Cam(PO_4)n(OH) (however,
1.4<m/n<1.7) Cap(PO_4)q(OH) (However, 1 .4<p/q<1.7) A biological hard tissue repair material comprising a coating layer made of unfired synthetic hydroxyapatite having the following composition. (2) General formula Cam(PO_4)n(OH) (however,
1.4<m/n<1.7) A phosphoric acid group is bonded to a powder or a molded product formed from the powder made of synthetic hydroxyapatite having the following composition, and then calcium ions are attached to the phosphoric acid group. is reacted, and the general formula Cap(PO_4)q(
OH) (where 1.4<p/q<1.7) A method for producing a biological hard tissue repair material, comprising forming a coating layer made of unfired synthetic hydroxyapatite having the following composition.