JPH0534021B2 - - Google Patents

Description

[Detailed Description of the Invention] <Industrial Application Field> The present invention is a biomedical ceramic material,
Bone defects and bone voids that are fixed at filling points in bone defects, bone voids, and bone resorption areas, and that can promote the early formation of new bone at the filling points and integrate with the bone tissue of the living body. and bone resorption part filling materials.

<Conventional technology> In conventional dental treatment or orthopedic treatment, patients' other parts of themselves are used to repair bone lost due to diseases such as periodontal disease, alveolar bone resorption after tooth extraction, traffic accidents, or bone tumors. Attempts have been made to perform bone grafting, etc., but these repair methods place an extremely heavy physical and psychological burden on the patient as bone tissue other than the damaged area is excised, and it is difficult to fill in a wide range of bone defects. There is a problem that a sufficient amount of autologous bone cannot be collected.

In order to solve the above-mentioned problems, various metal alloys, organic substances, and the like have been proposed as hard tissue substitutes for living bodies. However, when the various metal alloys and organic substances mentioned above are generally used in a biological environment, there is a problem in that they are accompanied by foreign body reactions such as poor solubility and toxicity to living organisms.

Recently, ceramic materials such as fillers made of sintered bodies or single crystals of alumina, tricalcium phosphate, or hydroxyapatite, which have excellent compatibility with living organisms and do not have the above-mentioned drawbacks, have attracted attention. Among them, hydroxyapatite can be expected to generate new bone quickly after filling, and unlike alumina, it has the advantage of coming into contact with new bone without going through connective tissue, so it has been used as a material with particularly excellent biocompatibility. Are known. Due to its structural characteristics, the filler using hydroxyapatite is a porous filler having continuous pores connecting the surface and the inside;
It is broadly classified into dense filling material with almost no pores inside. Even though the porous filling material is in the form of granules, it is fixed at the filling site without easily moving after filling, and has excellent early bone formation ability;
If a load is applied to the filling area after filling or suturing, the porous filling material is destroyed and the filling area sinks, resulting in weak strength.

In addition, although dense filling materials have excellent strength, they have the disadvantage that if they are in granular form, they will move from the filling site unless compacted. The problem arises that the formation is delayed.

Furthermore, as a filler that can be fixed and filled at a filling location, a dense filler having a shortest diameter of 0.1 to 3.0 mm and a specific surface area shape factor φ of 6.3 to 15 (Japanese Patent Application Laid-Open No. 61-20558 ) has been proposed. However, even with this filling material, the current situation is that it is still not sufficiently fixed to the filling location.

<Problems to be Solved by the Invention> Therefore, an object of the present invention is to provide a material that has excellent biocompatibility and early bone formation ability, and that can be reliably fixed at the filling site without necessarily performing compaction filling, etc. The object of the present invention is to provide an ideal filling material for bone defects, bone cavities, and bone resorption sites that has sufficient strength for practical use and does not cause any adverse effects during surgery.

<Means for Solving the Problems> According to the present invention, the particles are made of hydroxyapatite, the shortest diameter of the particles is 0.1 to 3.0 mm, and the surface has a plurality of depressions with pore diameters of several μm to 500 μm. A filling material for a bone defect, a bone cavity, and a bone resorption region is provided, which is characterized by comprising the following.

The present invention will be explained in more detail below.

The filling material for bone defects, bone cavities, and bone resorption areas of the present invention is particles made of hydroxyapatite that has an excellent ability to promote bone formation, and the filling material is fixed to the filling site on the surface of the particles, In addition, the particle is characterized in that the surface thereof is provided with a plurality of depressions having a specific shortest diameter in order to improve the adhesion and proliferation of new bone cells.

The shortest diameter of the filler for bone defects, bone cavities, and bone resorption sites of the present invention, that is, particles made of hydroxyapatite, is in the range of 0.1 to 3.0 mm. If the shortest diameter of the particles is less than 0.1 mm, when filling bone defects, bone cavities, and bone resorption areas, the gaps created when the particles come into contact with each other may be inappropriate for the infiltration of body fluid components. Due to the large size and fineness of the particles, after filling, the particles may be pushed out of the body through the sutures by body fluids such as blood, or may easily move to other parts of the body, leading to the possibility that they may not reach the area that requires filling. Fixation becomes difficult. On the other hand, if the shortest diameter exceeds 3.0 mm, the amount of filling in bone defects, bone voids, and bone resorption areas will be small, and the gaps between the particles will be too large, causing the bone tissue to fill in the gaps. Furthermore, in the dental field, when filling tooth extraction sockets etc., significant unevenness occurs on the mucosal surface, causing problems in terms of appearance and function, so it is set within the above range. There is a need.

In the present invention, the depressions formed on the surface of the filler particles are designed to lock adjacent fillers together when the filler is filled into bone defects, bone voids, and bone resorption areas. fixed, as a whole;
The filling material is firmly fixed to the desired filling location, and the uneven portion formed by the depression is for improving the attachment and proliferation of new bone cells,
The pore diameter of the depression needs to be in the range of several μm to 500 μm, and in order to further increase the strength as a filler, the pore diameter is preferably in the range of several μm to 100 μm. If the pore diameter is less than several μm, adjacent fillers will not lock together and the filler will easily move from the desired filling location to another location, and if it exceeds 500 μm, the strength will decrease. Must be within the range. Further, the depth of the depression is preferably in the range of several μm to 50 μm. If the depth of the depression is less than several μm, the unevenness formed by the depression will not have sufficient interaction with the adjacent filling material, and furthermore, the attachment of new bone cells at an early stage cannot be expected. Exceeding this is not preferable because the strength decreases.

Furthermore, it is preferable that the depressions formed on the surface of the particles be 10 to 100% of the entire surface of the filler, and the specific surface area shape coefficient φ of the particles is
A range of 6.3 to 15 is preferred. If the specific surface area shape factor φ exceeds 15, the shape of the particles becomes acicular, and the particles may easily break and become powdered due to external force after filling, and furthermore, the powdered pieces may be transferred to other parts of the body. This is not desirable because it may cause unfavorable effects on living organisms, such as leakage. On the other hand, if it is less than 6.3, the filling material tends to move from the filling site to other parts after filling, and the formation of adhesion of bone tissue to the surface of the filling material is delayed, which is not preferable.

In order to prepare the filling material for bone defects, bone cavities, and bone resorption areas of the present invention, for example, the particle size is 0.1 to 90μ.
The fine hydroxyapatite powder of m is made into a slurry of 60 to 70% by weight, and the resulting slurry is thoroughly stirred to entrain many air bubbles in the slurry, and then immediately dried. At this time, preferably 1 to 10 parts by weight of a combustible organic substance may be added to 100 parts by weight of the slurry in order to make the slurry more likely to incorporate air bubbles. The obtained dried product is made into granules of 0.1 to 3.0 mm by a known method, and then calcined and processed to remove the edges present in the protruding parts of the obtained particle surface using a pot mill or the like to form the desired surface. It is possible to obtain particles that have depressions and whose interior is more densely structured than porous granules obtained by the impregnation method. That is, by pulverizing a dried slurry containing many bubbles, the bubbles can be broken starting from the weaker-strength portions, thereby forming desired depressions in the surface portion. The combustible organic substance may be any substance that forms a depression after firing, and preferable examples include polyvinyl alcohol, ammonium naphthalene sulfonate, ammonium polycarboxylate salt, and the like. Further, the firing temperature is preferably 700 to 1200°C, and particularly preferably 1000 to 1200°C in order to further increase the strength as a filler. Furthermore, the surface of the filler is
It is preferable to completely remove or reduce the edges present in the uneven portion formed by the depression. If these edges are present in large quantities, they may have an unfavorable effect on the living tissue around the filling point, and if a syringe is used for filling, the ejection opening of the syringe may become clogged, interfering with the filling operation. This is not desirable.

<Effects of the Invention> The filling material for bone defects, bone cavities, and bone resorption areas of the present invention has a plurality of depressions of several μm to 500 μm on the surface, so it can be securely fixed at the desired filling location. Moreover, it is possible to promote the attachment and proliferation of new bone cells at an early stage. Furthermore, in addition to the above-mentioned surface structure, the internal structure of the filling material is dense, so it has sufficient strength and can be used in bone defects and bones in periodontal surgery, orthopedics, etc., which are susceptible to external forces. It is extremely useful as a filling material for cavities and bone resorption areas.

<Examples> The present invention will be explained in detail below using Examples and Comparative Examples, but the present invention is not limited thereto.

Example 1, Comparative Examples 1 and 2 Hydroxyapatite synthesized by wet method (hereinafter referred to as
HAp) was calcined at a firing temperature of 800° C. for 2 hours, and then ground to an average particle size of 90 μm or less using a ball mill to obtain fine HAp particles. The obtained HAp fine particles were mixed with water to prepare an HAp slurry (hereinafter referred to as HAp slurry A) having a solid concentration of HAp of 70% by weight. In Example 1, 2 parts by weight of polycarboxylic acid ammonium salt was added to 100 parts by weight of the slurry, and the mixture was thoroughly stirred and mixed for more than 10 minutes to thoroughly incorporate air bubbles. Then, after drying the obtained HAp slurry at 80 °C,
The particles are fired for 1 hour at a temperature of 1200°C and then crushed to form multiple depressions on the entire surface of the particles, and then the shortest diameter is
Particles of 0.5-1.0 mm were sieved. Finally, edge treatment was performed in a pot mill to obtain a desired filler (Example 1). When the pore diameter of the depression formed on the surface of the obtained filler was measured using a scanning electron microscope, the pore diameter was several μm to 100 μm, and the depth was several μm to 50 μm.

An enlarged perspective view of the obtained filler particles is shown in Fig. 1, and a further enlarged plan view of the surface of the filler particles is shown in Fig. 1.
Shown in Figures a and 1b. In the figure, reference numeral 1 denotes the filler particles obtained in Example 1, and a plurality of depressions 11 with small pore diameters and depressions 12 with large pore diameters are formed on the entire surface of the granular filler 1. As shown in Figures 1a and 1b, on the surface of the particle filler 1, there were areas where small pores 11 were concentrated and areas where small pores 11 were concentrated around large pores 12.

In addition, after impregnating the HAp slurry A into a network-structured urethane resin and drying it at 80°C, the firing temperature was
After baking at 1200° C. for 1 hour and pulverizing, the mixture was sieved in the same manner as described above to obtain a porous granular filler having a shortest diameter of 0.5 to 1.0 mm (Comparative Example 1).

Furthermore, after pulverizing the dried HAp with an impeller breaker, it was fired at a firing temperature of 1200°C for 1 hour, then sieved in the same manner as above, and edge treated with a pot mill to produce powder with a shortest diameter of 0.5 to 1.0 mm. A dense granular filler was obtained (Comparative Example 2).

Test Example A bone defect of 4 mm x 4 mm x 3 mm was created in the mandible of an adult dog, and the filling materials obtained in Example 1, Comparative Examples 1 and 2 were filled into the bone defect using the usual method. After sterilization, it was filled by press fitting. One week after the surgery, the dogs were observed by palpation, and four weeks after the surgery, the adult dogs were sacrificed to prepare specimens, and the state of formation of new bone tissue at the filling material site was observed. The filling material obtained in Example 1 could be easily filled into the bone defect, and when palpated one week after the surgery, it was already securely fixed to the bone defect and exhibited a condition similar to that of the jawbone. Ta. In addition, observation of the tissue specimen after 4 weeks showed that new bone tissue was noticeably formed in the area surrounding the filler granules adjacent to the bone, and bone tissue formation was also observed up to the center of the area filled with the filler. Ta. However, comparative example 1
In the porous granular filler obtained in the above, the filler broke during press-fitting when filling the bone defect, making it difficult to fill the bone defect. In addition, the filling material that could barely be filled was destroyed during palpation or normal chewing one week after the surgery, and was ejected from the filled site before specimen preparation, making it impossible to observe the tissue specimen. . Furthermore, with the dense filling material obtained in Comparative Example 2, the filling operation could be easily performed in the same manner as in Example 1, and the filling material could be fixed in the bone defect 4 weeks after the surgery. However, during palpation one week after surgery, the filling material was not securely fixed, so when observing the state of formation of new bone tissue during tissue specimen observation, it was difficult to place the filling material in the center of the site. No new bone tissue had been formed until then, and therefore each filler particle could not be integrated with the new bone at an early stage.

[Brief explanation of drawings]

FIG. 1 is an enlarged perspective view of the bone defect, bone void, and bone resorption region filling material obtained in Example 1, and FIG. The figure, and FIG. 1b in the figure, are plan views in which different parts of the surface are further enlarged. 1... Filler main body, 11... Recess with small pore diameter, 12... Recess with large pore diameter.

Claims (1)

[Claims] 1. Bone defects and bone cavities, which are particles made of hydroxyapatite, the shortest diameter of which is 0.1 to 3.0 mm, and whose surface is provided with a plurality of depressions with pore diameters of μm to 500 μm. and bone resorption filler.