JPH0211152A - Artificial bone - Google Patents

Abstract

PURPOSE:To allow the formation of the neonatal bone and the absorption of the artificial bone in a short period of time and to make early treatment of an affected part by combining hydroxyapatite and tricalcium phosphate at the weight ratios of a specific range, thereby extremely uniformly dispersing both. CONSTITUTION:The hydroxyapatite and the tricalcium phosphate are combined in the 5:95-95:5 weight ratio range. The uniformly dispersed ideal artificial bone is obtd. in this way and the formation of the neonatal bone is accelerated by the presence of the hydroxyapatite in the process of forming the neonatal bone at the time of artificial bone implantation. The absorption is accelerated with the tricalcium phosphate present in the bone as the nucleus in the absorption process of the artificial bone.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to an artificial bone as a bioceramic, particularly an artificial bone containing hydroxyapatite and tricalcium phosphate.

[Conventional technology]

Conventionally, it has been known to use various metal alloys, organic substances, etc. as hard tissue substitutes for living organisms.

However, they generally exhibit dissolution deterioration or toxicity to living organisms in the in vivo environment, and have the drawback of being accompanied by foreign body reactions. Therefore, ceramic materials that have excellent compatibility with living organisms and do not have the above-mentioned drawbacks are now being used. Among these ceramic materials, artificial bones made of sintered bodies or single crystals of alumina, carbon, tricalcium phosphate, or hydroxyapatite, which have excellent biocompatibility, are being developed and are attracting attention. In particular, hydroxyapatite is preferable because new bone formation can be expected at an early stage after implantation. Furthermore, unlike alumina, hydroxyapatite does not come into contact with new bone through connective tissue, and has excellent affinity.

On the other hand, there is also a method of using these materials in the form of a porous body as a filler for bone defects and voids.

Insufficient strength.

For example, in Japanese Patent Application Laid-Open No. 60-21763.

As an artificial bone material, a porous hydroxyapatite sintered body having continuous pores with a pore size of 10 to 100 μm and which is rapidly dissolved and absorbed to replace new bone, and a hydroxyapatite powder containing a thermally decomposable substance, for example.

A method for manufacturing the sintered body, which is manufactured by adding crystalline cellulose, is disclosed.

As mentioned above, hydroxyapatite is extremely excellent as an artificial bone material and has remarkable biocompatibility. However, since the solubility product in water is small at around 10-59,
Practically speaking, it is hardly absorbed in the living body. In other words, histologically, it exists for a long period of time as an inorganic foreign substance in living organisms.

In addition, the aforementioned tricalcium phosphate is a material that is easily absorbed in living organisms, but it has a strong foreign body reaction when implanted into living organisms.
The disadvantage is that the amount of new bone formation is low.

[Problem to be solved by the invention]

Therefore, an object of the present invention is to provide an ideal artificial bone that has excellent affinity and remarkable osteogenic ability, and at the same time is uniformly dispersed and is practically absorbed in the living body.

Another object of the present invention is to provide an artificial bone that causes less foreign body reaction and integrates with surrounding bone tissue, particularly in a short period of time, without the need for connective tissue.

Yet another object of the present invention is to provide an artificial bone that can particularly quickly repair and restore the structure and function of a bone tissue defect site.

[Means to solve the problem]

According to the present invention, there is provided a uniformly dispersed artificial bone characterized in that the weight ratio of hydroxyapatite to tricalcium phosphate is in the range of 5=95 to 95:5.

The present invention will be explained in more detail below.

In the present invention, we focused on the ability of hydroxyapatite to promote bone formation, in that when hydroxyapatite is filled into bone defects and bone voids, new bone is generated in the area at an early stage. By using tricalcium in combination, we succeeded in producing a new artificial bone that compensates for the drawbacks of both hydroxyapatite and tricalcium phosphate.

In the present invention, the weight ratio of hydroxyapatite and tricalcium phosphate should be in the range of 5:95 to 95:5. By arbitrarily selecting the weight ratio of hydroxyapatite and tricalcium phosphate within the above range, it is possible to control the degree of new bone formation and resorption of the artificial bone during implantation into a living body. An ideal artificial bone, when implanted into a bone defect or void, should promote the repair of the bone defect or void as quickly as possible, and should not be a tissue that is natural to the living body. Preferably, it is absorbed by the living body. If the amount of hydroxyapatite is less than 5% by weight, it is not preferable because the desired osteogenic ability cannot be obtained. On the other hand, if the amount of hydroxyapatite is more than 95% by weight, absorption into the living body will be poor.

In the present invention, it is essential that hydroxyapatite and tricalcium phosphate be uniformly dispersed. Unless uniform dispersion is achieved, the ability of hydroxyapatite to promote bone formation and the absorbability of tricalcium phosphate into the living body cannot be sufficiently developed. However, uniform dispersion cannot be achieved simply by mixing hydroxyapatite and tricalcium phosphate.

In the present invention, we understood and developed the bone metabolism mechanism when implanting an artificial bone, and found that hydroxyl By having both apatite and tricalcium phosphate present, we were able to obtain practically sufficient bone formation promoting ability and absorbability.As for the conduit unit, for example, published by Art Supply Shoten and edited by Eiaki Takahashi "Overview of Bone Histological Dynamics" in "Bone Shape Pre-Measurement Handbook", pages 3 to 17, and "Bone Science", published by Ishiyaku Publishing, written by Tatsuo Suda, "Bone Science", pages 65 to 75. ``Tissue Development and Growth''.

In the present invention, the area of the pipe conduit unit is 0.5 to 1.0 m
The reason why the presence of both hydroxyapatite and tricalcium phosphate materials in the area of 200 m2 provides practically sufficient bone formation promoting ability and absorbability is that bone remodeling is performed on a bone unit (cortical bone part). ) and the value of the canal unit, but this is because the canal part (cancellous bone part) is particularly easy to absorb and its area is easy to measure.In other words, in the process of new bone formation when implanting an artificial bone, hydroxyl The presence of apatite promotes the formation of new bone, and in the resorption process of artificial bone, absorption is promoted using the existing tricalcium phosphate as a core. It is highly preferred that both materials are present.In the present invention, the size of the conduit unit may include voids such as micropores.

In the present invention, the primary particles forming the artificial bone are uniformly dispersed from the molding stage to 10 μm or less, particularly 5 μm.
It is preferable to set the particle size to the following, because it is necessary to prevent abnormal particle growth due to agglomerated particles during sintering.

In order to further promote absorption of the artificial bone of the present invention into a living body, microcracks or micropores may be added to the artificial bone.

In the present invention, in order to achieve the above-mentioned uniform dispersion, it is preferable to synthesize and mold primary particles as fine as possible by a wet synthesis method. In wet synthesis, the synthesis temperature has a large effect on the particle size of the primary particles, and the lower the temperature, the finer the primary particles can be synthesized. The temperature range that can be preferably used for wet synthesis in the present invention is about 0°C to
In the range of 80°C, more preferably from 0°C to 50°C
is within the range of If the synthesis temperature exceeds 80°C, the particle size of the primary particles produced becomes large, and if it is lower than 0°C, stirring becomes impossible due to freezing, which is not desirable. Although the particle size of the dried primary particles synthesized by the wet synthesis method is extremely fine, they aggregate during the drying and calcination stages, so it is preferable to crush them after calcination. However, in the artificial bone of the present invention, as long as the particle size of the primary particles is 10 μm or less, particularly 5 μm or less, the presence of aggregate particles is acceptable. It is a non-stoichiometric hydroxyapatite with a ratio of calcium to phosphorus different from the theoretical value of 1.67, and when calcined, a mixed system of hydroxyapatite and tricalcium phosphate in a uniformly dispersed state is obtained. This is because even if this mixed system is baked after molding, the dispersion state is maintained well.

In the present invention, in addition to the wet synthesis method described above, hydroxyapatite and tricalcium phosphate, which have been separately synthesized in advance by a known wet synthesis method, dry synthesis method, or hydrothermal synthesis method, may be used by mixing and dispersing them. You can also do it.

The artificial bone material of the present invention can be preferably used in the form of either granules or porous materials.

〔Example〕

The present invention will be explained in more detail below using Examples.

Lf2LL While maintaining the temperature at 5°C and stirring calcium hydroxide suspension 2Q with a concentration of 0.5 mol/Q, add a phosphoric acid aqueous solution with a concentration of 30% by weight to Ca by varying the amount added. /P molar ratio is 1.66.1.64.1.6 respectively
Hydroxyapatite was synthesized so that the ratios were 0.1.57, 1.54 and 1.51, and a suspension was obtained. This suspension was centrifuged and then dried at 105°C for a day and a night.

The obtained dried product was calcined at 800"C for 3 hours and finely pulverized, and then 60 g of a 5% aqueous solution of polyvinyl alcohol with a degree of polymerization of 1700 was added, mixed, dried, and molded to remove the binder. When observed with a transmission electron microscope, the particles were found to be extremely fine.

When the particle size of the secondary particles was measured, it was approximately 0.03 in dry matter.
μm, the calcined product was about 0.1 μm, and the average particle size (agglomerated particle size) of the pulverized product after fine pulverization was about 1.5 μm. Next, a sintered body was manufactured by firing at a temperature of 1100°C. The sintered bodies were identified and quantified by X-ray diffraction, and as a result, they were all hydroxyapatite and tricalcium phosphate. The amount of tricalcium phosphate corresponding to the above Ca/P molar ratio is 7.18.40.58.7 respectively
6 and 94% by weight. When the sintered body was made into a thin section and the dispersion state was observed using a polarizing microscope, it was found that hydroxyapatite and triphosphate were observed in the area corresponding to the pipe unit (0.5 to 1.0 mm2) in all of the above compositions. The presence of calcium was confirmed.

Further, when these thin pieces were etched with an aqueous hydrochloric acid solution and the particle diameter was measured using a scanning electron microscope, no particles larger than 2 μm were observed.

Disappointing and using the dried products of each Ca/P molar ratio produced in Example 1, the polyurethane foam was molded into a porous shape by replicating its shape, and fired at a temperature of 1100°C to form a porous material with a size of 7X7X9ia. A porous body was manufactured. The porous body had an average pore diameter of 280 μm and a porosity of 85%.

A hole was made in the medial condyle of the dog's tibia, and eight types of manufactured porous bodies were implanted. In June, 1 year, and 2 years after the surgery, the implanted part was removed, cut in the long axis direction of the tibia, and polished to approximately 100 μm.
A thin section of m was prepared. These thin sections were subjected to contact microradiography using a soft X-ray device, and the area ratio of the porous body and new bone was further measured using an image analysis device. The results are shown in Tables 1 and 2 below. The same procedure was carried out for the case where the tricalcium phosphate was 100% by weight and the case where the hydroxyapatite was 100% by weight. The results are also shown in Tables 1 and 2.

As is clear from the results shown in Tables 1 and 2, the area ratio of the embedded porous material tends to decrease as the embedding period progresses and as the tricalcium phosphate content increases. It can be determined that it is easily absorbed by the living body. In particular, when tricalcium phosphate was 100% by weight, the amount present after two years was very small and easily absorbed, but new bone formation was low over the entire period.

In addition, when hydroxyapatite is 100% by weight,
Bone formation was good, but the remaining amount of the porous material two years later was almost the same as before implantation, indicating that it was not absorbed.

Furthermore, after the above measurements, these thin sections were polished to 20 μm and subjected to histological observation. the result.

When tricalcium phosphate was 100% by weight, the appearance of foreign body giant cells was particularly large and was observed over a long period of time. In the resorption window, osteoclasts release 1, which is considered to be the primary particle of the porous material.
It was observed that particles of around μm were eroded, and the shorter the implantation period, the more remarkable the erodibility was.

11 Commercially available hydroxyapatite powder (average particle size 5 μm)
60 parts by weight of tricalcium phosphate powder and 40 parts by weight of tricalcium phosphate powder were mixed in a pot mill, calcined at 800°C for 3 hours, finely pulverized, and mixed with polyvinyl alcohol 5 having a degree of polymerization of 1700.
% aqueous solution was added, mixed and dried, and then molded. After removing the binder, it was fired at a temperature of 1100°C to obtain a sintered body.

When the sintered body was made into a thin section and the dispersion state was observed using a polarizing microscope, it was found that the area corresponding to the pipe unit (0.5 to 1.0 mm
”), the proportion free of hydroxyapatite and tricalcium phosphate particles was approximately 30%. Also, when the particle size was measured in the same manner as in Example 1, it was approximately 5%.
Many of the particles were larger than μm, and many particles with a maximum size of 10 μm were also observed.

A test was carried out in the same manner as in Example 2 using the same formulation as in Example 3. The results are shown in Tables 1 and 2 below.

Table 1 Area ratio of porous body (hereinafter referred to as blank space) [Effects of the invention] According to the present invention, hydroxyapatite and tricalcium phosphate are extremely uniformly dispersed and embedded into bone defects and voids in living organisms. In some cases, new bone formation and artificial bone resorption can be observed in a short period of time, and early healing of the affected area can be achieved.

patent issuer

Claims (1)

[Claims] A uniformly dispersed artificial bone characterized in that the weight ratio of hydroxyapatite to tricalcium phosphate is in the range of 5:95 to 95:5.