JP2576404B2 - Bone defect, bone void and bone resorbing part manufacturing method - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for fixing a bone defect, a bone cavity, and a bone resorbing portion to a filling site, promoting the formation of new bone at the filling site at an early stage, and integrating it with a bone tissue of a living body. The present invention relates to a method for producing a bone defect, a bone void, and a bone resorbing part filler which can be converted into a bone defect.

[0002]

2. Description of the Related Art Conventionally, in a dental treatment or an orthopedic treatment, another part of a patient himself or herself is used to repair bone lost due to a disease such as periodontal disease, resorption of alveolar bone after tooth extraction, a traffic accident or a bone tumor. Attempts have been made for bone transplantation
In the above-mentioned repair method, since the bone tissue other than the damaged part is excised, the physical and psychological burden on the patient is extremely large, and a sufficient amount of autogenous bone cannot be collected to fill a wide range of bone defects. There is. Therefore, in order to solve the above-mentioned problem, various metal alloys, organic substances, and the like have been proposed as hard tissue substitutes for living organisms. However, when the above-mentioned various metal alloys and organic substances are generally used in a living environment, there is a problem in that they are accompanied by foreign substances such as poor dissolution and toxicity to living bodies.

[0003] Recently, ceramic materials such as alumina, tricalcium phosphate or hydroxyapatite sintered materials or single crystal fillers which have excellent compatibility with living organisms and do not have the above-mentioned disadvantages have attracted attention. . Among them, hydroxyapatite can be expected to generate bone at an early stage after filling, and has the advantage of contacting new bone without passing through connective tissue like alumina, so it is a material with excellent biocompatibility Are known. Fillers using the hydroxyapatite are roughly classified into porous fillers having continuous pores connecting the surface and the inside, and dense fillers having almost no pores inside due to structural characteristics. You.
Even if the porous filler is in a granular form, it is fixed at the filling portion without easily moving after filling, and has excellent early bone formation ability, but applies a load to the filling portion after filling or after suturing. In this case, there is a disadvantage that the porous filler is destroyed and the filled portion is settled, and the strength is weak.

[0004] Furthermore, although the dense filler is excellent in strength, when it is granular, it has a drawback that it moves from the filling point unless it is compacted, and thus has a high biocompatibility. The problem of delayed bone formation arises.

[0005] Further, as a filler that can be fixedly filled at the filling portion, 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 ( JP-A-61-20558) has been proposed. However, even at the present time, even with the filler, fixation to the filling location is not yet sufficient.

[0006] Also, there is known a filler in which the internal structure of hydroxyapatite particles is dense or porous having continuous pores and has a plurality of depressions on the surface. Filler having such a depression on its surface is fixed at the filling site,
It is also excellent in new bone formation ability and the like.

However, when the internal structure is a filler having continuous pores, there is a problem in strength. On the other hand, when the internal structure is dense, the production is performed in two steps of forming a dense portion and forming a concave portion on the surface. And there is a disadvantage that the production is complicated.

[0008]

SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to provide a dent which is excellent in biocompatibility and early bone formation ability, and which is surely fixed to a filling portion without necessarily performing compaction filling or the like. It has on the surface, and the internal structure is formed more densely than the porous granules, the strength in practical use is sufficient, and the ideal bone defect, bone void and no harm at the time of surgery It is an object of the present invention to provide a manufacturing method capable of easily obtaining a bone resorbing part filler.

[0009]

According to the present invention, there is provided a bone defect having a minimum diameter of hydroxyapatite particles of 0.1 to 3.0 mm and a plurality of depressions having a pore diameter of several μm to 500 μm on the surface. A method for producing a filler, a bone void portion and a bone resorbing portion filler, wherein a hydroxyapatite fine powder is made into a slurry, dried immediately after air bubbles are entrapped in the slurry, and then the shortest diameter is 0.1 to 3.0 mm. The present invention provides a method for producing a bone defect portion, a bone void portion, and a filler for a bone resorbing portion, which is characterized in that the material is crushed into granules and then calcined.

Hereinafter, the present invention will be described in more detail. In the production method of the present invention, first, hydroxyapatite fine powder is made into a slurry. The particle size of the hydroxyapatite fine powder is preferably from 0.1 to 90 μm, and the content of the hydroxyapatite fine particles in the slurry is preferably from 60 to 70% by weight.

Next, the slurry is dried immediately after air bubbles are entrapped therein. Entrainment of air bubbles into the slurry can be performed by a method of well stirring the slurry or the like. However, in order to facilitate entrainment of air bubbles in the slurry, preferably 1 part by weight based on 100 parts by weight of the slurry is used.
Up to 10 parts by weight of a flammable organic substance may be added. The combustible organic substance may be any substance that forms a depression after firing, and preferably includes polyvinyl alcohol, ammonium naphthalenesulfonate, ammonium polycarboxylate and the like. The drying temperature is not particularly limited as long as it is a normal drying temperature.
It can be performed at about ° C.

Next, the obtained dried product is pulverized into a granule by a known method to have a shortest diameter of 0.1 to 3.0 mm, and then calcined. Can provide filler particles that are more densely formed than the porous granules obtained in the above. That is, by pulverizing the dried slurry containing a lot of bubbles, cracks can be formed from the bubbles having low strength, and thus a desired depression can be formed in the surface portion. , Ie, particles more densely formed than the porous granules obtained by the impregnation method. The firing temperature is 700 to 120
0 ° C. is preferable, and firing at 1000 to 1200 ° C. is particularly preferable in order to further increase the strength as a filler.

[0013] Furthermore, the surface of the filler has an edge in the uneven portion formed by the depression. If the edge is present in a large amount, it may adversely affect the living tissue around the filling portion. When filling is sometimes performed using an injection tube or the like, the extrusion opening of the injection tube may obstruct the filling operation. Therefore, it is preferable to completely remove or reduce the edge. The removal of the edge can be performed by processing with a pot mill or the like.

A bone defect obtained by the method of the present invention,
Bone void and bone resorption fillers are particles made of hydroxyapatite having an excellent ability to promote bone formation. The fillers are fixed to the fillers on the surface of the particles, and the adhesion and proliferation of new bone cells is achieved. The surface of the particles is provided with a plurality of depressions having a specific shortest diameter for the purpose of improving the particle size.

[0015] The shortest diameter of the produced bone-deficient portion, bone void portion, and bone-resorbing portion filler, ie, the particle composed 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 and bone voids and bone resorbing parts, the gaps formed by the contact of the particles are inappropriately large for penetration of body fluid components. In addition, since the particles are fine, the particles are pushed out of the body from the suture part by the body fluid such as blood after filling or are easily moved to other parts of the body after filling, and it is difficult to fix to the part requiring filling. Becomes On the other hand, if the shortest diameter exceeds 3.0 mm, the amount of filling in the bone defect, the bone void, and the bone resorbing part decreases, and the gap between the particles is too large, so that the gap is filled with bone tissue. It takes a long time to run out, and furthermore, in the field of dentistry, when filling in tooth extraction fossa etc., significant irregularities occur on the mucous membrane surface and there are problems in appearance and function, so it is necessary to be within the above range. is there.

The depression formed on the surface of the particles as the filler is such that when the filler is filled into the bone defect, the bone void, and the bone resorbing part, the adjacent fillers are locked. Fixing, as a whole, the filler is firmly fixed to the desired filling site, and further, the uneven portion formed by the depression is for improving the adhesion and growth 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. When the pore diameter is less than several μm, the adjacent fillers do not lock, the filler is more likely to move from the desired filling point to another site, and if it exceeds 500 μm, the strength is reduced because the strength decreases. Must be within range.
The depth of the depression is preferably in the range of several μm to 50 μm. When the depth of the depression is less than several μm,
In the adjacent filler, the relationship between the irregularities formed by the depressions is not sufficient, and furthermore, the attachment of new bone cells at an early stage cannot be expected. If it exceeds 50 μm, the strength decreases, which is not preferable.

Further, the dents formed on the surface of the particles are preferably provided in an amount of 10 to 100% with respect to the entire surface of the filler, and the specific surface area shape factor φ of the particles is 6.3.
It is preferably in the range of ~ 15. If the specific surface area shape factor φ exceeds 15, the shape of the particles becomes acicular, and the particles may be easily broken into powder due to external force or the like after filling. It is not preferable because it has an undesired effect on the living body such as outflow. On the other hand, if the ratio is less than 6.3, the filling material tends to move from the filling portion to another site after filling, and the generation of adhesion of bone tissue to the filling material surface is undesirably delayed.

[0018]

According to the production method of the present invention, several μm to 5 μm
It is equipped with a plurality of hollows of 00 μm, which can be securely fixed to the desired filling site, and can promote the adhesion and proliferation of new bone cells at an early stage. It is possible to easily obtain a bone defect portion, a bone void portion, and a bone resorbing portion filling material which is more densely formed than the granules and has sufficient strength.

[0019]

EXAMPLES The present invention will be described below in more detail with reference to Examples and Comparative Examples, but the present invention is not limited thereto.

[0020]

Example 1, Comparative Examples 1 and 2 Hydroxyapatite (hereinafter referred to as HAp) synthesized by a wet method was fired at 800 ° C.
And then calcined for 2 hours using a ball mill.
It was pulverized to 0 μm or less to obtain HAp fine particles. The obtained HAp fine particles were mixed with water, and the HAp solid matter concentration was 7%.
A 0% by weight HAp slurry (hereinafter referred to as HAp slurry A) was prepared. At the time of slurrying, in Example 1, 2 parts by weight of the ammonium polycarboxylate was added to 100 parts by weight of the slurry, and the mixture was sufficiently stirred and mixed for more than ten minutes in order to sufficiently involve air bubbles. Next, the obtained HAp slurry is dried at 80 ° C., baked at a calcination temperature of 1200 ° C. for 1 hour, and crushed to form a plurality of depressions on the entire surface of the particles. 0.0 mm particles were sieved.
Finally, edge treatment was performed with a pot mill to obtain a desired filler (Example 1). When the pore size of the depression formed on the obtained filler surface was measured by a scanning electron microscope, it had a pore size of several μm to 100 μm, and the depth was several μm.
m to 50 μm.

FIG. 1 is an enlarged perspective view of the obtained filler particles, and FIG. 1 is a plan view in which the surface of the filler particles is further enlarged.
These are shown in (1a) and (1b). In FIG. 1, reference numeral 1 denotes filler particles obtained in Example 1, and a plurality of depressions 11 having a small pore diameter and depressions 12 having a large pore diameter are formed on the entire surface of the granular filler 1. As shown in (1a) and (1b), the surface of the granular filler 1 had a portion where the small hole diameters 11 were densely packed and a portion where the small hole diameters 11 were densely packed around the large hole diameter 12.

The HAp slurry A was impregnated with a urethane resin having a network structure and dried at 80 ° C.
After firing at 200 ° C. for 1 hour and pulverizing, sieving was performed in the same manner as above to obtain a porous granular filler having a shortest diameter of 0.5 to 1.0 mm (Comparative Example 1). Further, the dried product of HAp was pulverized with an impeller breaker, and then baked at a firing temperature of 12.
Firing at 00 ° C. for 1 hour, then sieving in the same manner as described above, and performing edge treatment in a pot mill to obtain a shortest diameter of 0.5
A dense granular filler of about 1.0 mm was obtained (Comparative Example 2).

[0023]

[Test Example] A bone defect of 4 mm x 4 mm x 3 mm was prepared in the mandible of an adult dog, and the filler obtained in Example 1, Comparative Examples 1 and 2 was applied to the bone defect according to a conventional method. After sterilization, it was filled by press fitting. One week after the operation, palpation and observation were performed, and four weeks after the operation, the adult dog was sacrificed to prepare a specimen, and the state of formation of new bone tissue at the site of the filler was observed. The filling material obtained in Example 1 can be easily filled into the bone defect, and is securely fixed to the bone defect at the time of palpation one week after the operation, and shows the same state as the jaw bone. Was. Further observation of the tissue specimen four weeks later revealed that remarkable new bone tissue was formed around the filler granule adjacent to the bone, and that bone tissue was formed up to the center of the portion filled with the filler. Was.
However, in the porous granular filler obtained in Comparative Example 1, the filler was crushed by press-fitting when filling the bone defect portion, and was difficult to fill. In addition, the filling material that could be barely filled was broken at the time of palpation for one week after the operation or by normal mastication, and was discharged from the filling portion before the preparation of the sample, and the tissue sample was not observed. In the dense filler obtained in Comparative Example 2, the filling operation can be easily performed in the same manner as in Example 1, and the filler can be fixed to the bone defect four weeks after the operation. However, at the time of palpation one week after the operation, the filling material was not securely fixed. To date, no new bone tissue has been formed, and thus each filler particle could not be integrated with the new bone early.

[Brief description of the drawings]

FIG. 1 is an enlarged perspective view of a bone defect, a bone void, and a bone resorbing part filler obtained in Example 1.
a) is a plan view in which a part of the filler surface in FIG. 1 is further enlarged;
(1b) is a plan view further enlarging a portion having a different surface.

[Explanation of symbols]

 1: Filler body, 11: Small hole diameter depression, 12: Large hole diameter depression.

Claims (2)

(57) [Claims] 1. The hydroxyapatite particles have a shortest diameter of 0.1 to 3.0 mm and a pore diameter of several μm on the surface.
A method for producing a bone defect portion having a plurality of depressions of 500 μm, a bone void portion, and a bone resorbing portion filler, wherein a hydroxyapatite fine powder is used as a slurry, and air bubbles are entrapped in the slurry, followed by drying. Next, the shortest diameter is 0.1 to 3.
A method for producing a filler for a bone defect, a bone void, and a bone resorbing part, which is crushed to 0 mm to obtain granules and then fired. 2. The method according to claim 1, wherein the slurry contains a flammable organic substance.