JP2000189510A - Bone repair material - Google Patents

Abstract

PROBLEM TO BE SOLVED: To fit a bone repair material to a defective part without worrying about directions and to enable good bone repair by using a porous block material formed by mixing CM chitin and calcium phosphate material granules and specifying the average pore diameter of the surface and the average minor axis and average major axis of the pores in the central part. SOLUTION: The bone repair material is formed of the porous block body formed by mixing CM chitin and the calcium phosphate material granules. The average pore diameter of the surface is specified to 3 to 150 μm and the difference between the average minor axis and average major axis of the pores in the central section is specified to <=20 μm. The ratio of the initial compression strength value in the central part to the initial compression strength value on the surface of the porous block body is specified 80 to 100%. According thereto, orientability is not admitted in the CM chitin fibers in the central molding and the HAP grains are uniformly dispersed and the directivity of the pores is nearly uniform and the molding has specified strength in any directions. Further, the seepage of liquid and the advance of cells take place uniformly from any surfaces. Then, the bone repair may be improved by fitting the bone repair material to the defective part.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a bone repair material which is filled to reconstruct a bone defect lost due to aging, disease, accident or the like.

[0002]

2. Description of the Related Art Granules of calcium phosphate-based materials have been conventionally used as the bone repair material. These granules are filled in the bone defect area in the granular state, and new bone grows rapidly around the granule, and it is expected that this new bone will contain each granule and fill and repair the bone defect area. Was to do.

[0003]

However, the above prior art has the following problems. That is, since it is filled in a granular state, it is extremely difficult to use it except for a bone defect having a pocket shape. In addition, it is difficult to fix to the defect, and it is easy for blood and biological fluids that become wet after filling and suturing to flow out. May excite severe inflammation. Furthermore, even if bone formation progresses, the occupation density of new bone is small due to the presence of a large amount of granules, and it is in a state of structural weakness. In addition, when implant implantation after bone repair is considered, there is a problem that post-processing with a drill or the like is practically impossible due to the presence of hydroxyapatite (hereinafter abbreviated as HAP) and the fragility of bone quality.

[0004]

SUMMARY OF THE INVENTION In order to solve the above-mentioned problems, the present invention comprises a porous block obtained by mixing CM chitin and calcium phosphate-based material granules. The difference between the average minor axis and the average major axis of the holes in the portion is 20 μm or less. Further, it is preferable that the difference in the average pore diameter between the surface and the center of the porous block body thus configured is 20 μm or less.

It is preferable that the porous block body has an initial compressive strength of 0.2 to 8.0 MPa when compressed to a half volume by a one-way press. Further, it is preferable that the difference in the initial strength between the surface and the central portion is within 20%, that is, the ratio of the initial compressive strength value of the central portion to the initial compressive strength value of the surface is 80 to 100%.

[0006] Such a bone repair material of the present invention can be produced by the following procedure.

First, a CM chitin aqueous solution is prepared, and the granules obtained by freezing and pulverizing the same and the separately classified HAP granules are mixed, filled in a mold, and press-molded. Thereafter, the mixture is held at a constant molding pressure, and the CM chitin frozen body granules are welded to each other. Furthermore, it freeze-drys and heat-processes in a vacuum. A low concentration of C
The surface is coated with an aqueous solution of M chitin. Then, freeze-drying and heat treatment in a vacuum are performed again.

[0008] The bone repair material of the present invention can be produced by the above method. In the present invention, after the surface is coated with a particularly low-concentration aqueous solution of CM chitin, freeze-drying and heat treatment in a vacuum are performed again. Is performed.

[0009]

The bone repair material of the present invention has a certain strength in any direction because no orientation is observed in the CM chitin fiber in the molded product. Since there is no orientation, it is possible to fit the defective portion without worrying about the direction when filling the defective portion.

[0010] Further, since the porous body has a substantially uniform pore size, infiltration of body fluids and invasion of cells occur evenly from any surface.

[0011] Further, since the HAP granules are uniformly dispersed, osteoblasts grown on the CM chitin fiber as a scaffold promote bone formation using HAP as a nucleus from any part of the defect. Further, since the CM chitin fiber has no orientation, the molded body can be easily processed with scissors or a scalpel.

Further, according to the bone repair material of the present invention, the additional coating treatment makes it difficult for the HAP to fall out of shape even when trimming with a scalpel or the like.

[0013]

DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, embodiments of the present invention will be described in detail.

The bone repair material of the present invention comprises a porous block obtained by mixing CM chitin and calcium phosphate-based material granules, and has an average pore diameter on the surface of 3 to 150 μm and an average minor diameter of pores at a central portion. Difference in average major axis is 2
0 μm or less. Further, it is preferable that the difference in the average pore diameter between the surface and the center of the porous block body thus configured is 20 μm or less.

The porous block preferably has an initial strength of 0.2 to 8.0 MPa when compressed to a half volume by a one-way press. further,
It is preferable that the difference in the initial strength between the surface and the center is within 20%.

In order to explain the method for producing such a bone repair material of the present invention, first, a CM chitin aqueous solution is prepared at a concentration of 3 to 20% by weight and frozen at -40 ° C or lower. Separately, the HAP granules are classified to 50 to 300 μm. Granules obtained by crushing these frozen products and classified HAP
The granules are mixed at 1/1 to 1/20 = HAP weight / CM chitin weight, the mixture is filled in a mold and pressed. Thereafter, the frozen CM chitin granules are welded to each other by maintaining the molding pressure at a constant molding pressure within 60 minutes. Furthermore, -100 to -20
Lyophilized at 120 ° C. and, for example, 120-160 ° C. × 2 in vacuum
The heat treatment is performed for 4 hours.

With respect to the molded body obtained in this manner, 1 to 5
The surface is coated with a low concentration of wt% CM chitin aqueous solution. Then, freeze-drying is performed again at -100 to -20C, and finally, heat treatment is performed at 120 to 160C for 24 hours in a vacuum.

The reason why it is preferable to set each condition within the above range in the above-mentioned manufacturing method is as follows.

The concentration of CM chitin to be adjusted first is 3 wt%.
When the amount is less than the above, the strength of the molded body is remarkably reduced and handling becomes difficult. On the other hand, when it exceeds 20% by weight, it becomes difficult to form an aqueous solution.

When the lower limit of the classification range of HAP granules is less than 50 μm, cells such as macrophages tend to be swallowed, while when it exceeds 300 μm, the distribution of HAP tends to be uneven.

The HAP weight / CM chitin weight is 1/1.
If it is less than 1, the density of the HAP granules becomes too large and the space for bone formation becomes insufficient. I can't.

When the press forming pressure of the mold is less than 0.1 kgf / mm ² , the strength of the formed body becomes extremely small and handling becomes difficult. On the other hand, when it is more than 8.0 kgf / mm ² , pressure transmission during molding is poor. , Cracks and breakage of the HAP may occur easily.

If the freezing temperature of the molded body is higher than -20 ° C., orientation may occur in the CM chitin fiber, while if it is lower than -100 ° C., cracks may occur due to the difference in thermal expansion.

The concentration of CM chitin for coating is 1 wt.
%, The effect of the coating is unlikely to appear, while 5
Even if it is higher than wt%, the impregnation into the interior is reduced, so that the effect of the coating tends to hardly appear.

When the temperature of the vacuum heat treatment is lower than 120 ° C., the bone is decomposed and absorbed at an early stage before the bone is regenerated, so that there is a possibility that a good bone repair cannot be obtained due to the intervention of soft tissue or the like.

On the other hand, if the temperature is higher than 160 ° C., dissolution is delayed, and decomposition and absorption are too slow, which may hinder bone regeneration.

The reason for limiting the hole diameter of the molded body as described above is as follows.

That is, when the average pore diameter on the surface is less than 3 μm, the penetration of the cells into the inside is delayed, which hinders bone regeneration. The likelihood is high.

Next, if the difference between the average minor axis and the average major axis of the hole at the central portion is larger than 20 μm, the anisotropy of the molded product is too strong, and the shape of the molded product is distorted from the cutting direction when trimming with a scalpel. There is a risk that it will.

The difference in average pore diameter between the surface and the center is 2
If it is larger than 0 μm, the cells may not enter uniformly, and there may be a part where the bone repair is incomplete.

Next, a method of measuring the pore diameter of the molded product will be described.

First, an arbitrary plane in the molded body is photographed with an SEM, and the SEM photograph is automatically obtained by using a commercially available personal computer by software for image correction and diffraction. In addition, the average major axis and average minor axis of the hole at the center are similarly obtained.

The bias (anisotropic) of the directionality of the hole as a characteristic of the molded article can be measured by the following method.

First, an SEM photograph is taken of the XYZ three-axis plane of the molded body as described above. The number Nc of holes per unit length overlapping each of the three axes is calculated, and the average cell diameter 1.5 / Nc is determined. For this average cell diameter, Y
The ratio of the average diameter of the X axis to the axis and the Z axis is determined, and it can be determined that the anisotropy decreases as the ratio approaches 1, and the anisotropy increases as the ratio increases from 1. Incidentally, when the above ratio is 1.2, the rigidity (Young's modulus) in two axial directions
Becomes 2 or more.

[0035]

EXAMPLES Examples of the present invention will be specifically described below along with comparative examples. First, each example product and comparative product were produced by the following method.

Preparation Method (Example Product 1) A 5 wt% CM chitin aqueous solution is prepared , dropped into liquid nitrogen, and the frozen granules in liquid nitrogen are pulverized under cooling to fine powder.

HAP (particle size 63-150 μm)
) Are mixed at a weight ratio of 1/5, and the mixture is filled in a mold and pressed.

Thereafter, molding was carried out while holding at a molding pressure of 4 kg / mm ² , frozen at −78 ° C., freeze-dried, and dried at 160 ° C. ×
A heat treatment is performed for 24 hours.

The obtained compact was impregnated and coated with a 3 wt% CM chitin aqueous solution under reduced pressure, frozen again at -78 ° C., freeze-dried, and subjected to a heat treatment at 140 ° C. × 24 hr to obtain a porous block. .

(Example product 2) A 10 wt% CM chitin aqueous solution is prepared, dropped into liquid nitrogen, and the frozen granules in liquid nitrogen are ground under cooling to fine powder.

HAP (particle size 63-150 μm)
) Are mixed at a weight ratio of 1/5, and the mixture is filled in a mold and pressed.

Thereafter, molding was carried out while holding at a molding pressure of 4 kg / mm ² , frozen at −78 ° C., freeze-dried, and dried at 160 ° C. ×
A heat treatment is performed for 24 hours.

The obtained compact was impregnated and coated with a 1 wt% CM chitin aqueous solution under reduced pressure, frozen again at -78 ° C., freeze-dried, and subjected to a heat treatment at 140 ° C. × 24 hr to obtain a porous block. .

(Example Product 3) A 3 wt% CM chitin aqueous solution is prepared, dropped into liquid nitrogen, and the frozen granules in liquid nitrogen are ground under cooling to fine powder.

HAP (particle size: 63 to 150 μm)
) Are mixed at a weight ratio of 1/5, and the mixture is filled in a mold and pressed.

Thereafter, molding was carried out while holding at a molding pressure of 4 kg / mm ² , frozen at −40 ° C., freeze-dried, and dried at 160 ° C. ×
A heat treatment is performed for 24 hours.

The obtained molded product was impregnated and coated with a 1 wt% CM chitin aqueous solution under reduced pressure, frozen again at -40 ° C., freeze-dried, and subjected to a heat treatment at 140 ° C. × 24 hr to obtain a porous block. .

(Comparative Example Product 1) A 10 wt% CM chitin aqueous solution is prepared, dropped into liquid nitrogen, and the frozen granules in liquid nitrogen are ground under cooling to fine powder.

HAP (particle size 63-150 μm)
) Are mixed at a weight ratio of 1/5, and the mixture is filled in a mold and pressed.

Thereafter, molding was carried out while holding at a molding pressure of 4 kg / mm ² , frozen at −78 ° C., freeze-dried, and dried at 160 ° C. ×
A heat treatment is performed for 24 hours.

The obtained molded body was impregnated and coated with a 5 wt% CM chitin aqueous solution under reduced pressure, frozen again at -78 ° C., freeze-dried, and subjected to a heat treatment at 140 ° C. × 24 hr to obtain a porous block. .

(Comparative Example Product 2) A 1 wt% CM chitin aqueous solution is prepared, dropped into liquid nitrogen, and the frozen granules in liquid nitrogen are ground under cooling to fine powder.

HAP (particle size 63-150 μm)
) Are mixed at a weight ratio of 1/5, and the mixture is filled in a mold and pressed.

Thereafter, molding was carried out while holding at a molding pressure of 4 kg / mm ² , frozen at −20 ° C., freeze-dried, and dried at 160 ° C. ×
Heat treatment was performed for 24 hours to obtain a porous block.

(Comparative Example Product 3) An aqueous solution of 1 wt% CM chitin is prepared and dropped into liquid nitrogen, and the frozen granules in liquid nitrogen are pulverized under cooling to fine powder.

HAP (particle size 63-150 μm)
) Are mixed at a weight ratio of 1/5, and the mixture is filled in a mold and pressed.

Thereafter, molding was carried out while holding at a molding pressure of 4 kg / mm ² , frozen at −78 ° C., freeze-dried, and dried at 160 ° C. ×
A heat treatment is performed for 24 hours.

The obtained compact was impregnated and coated with a 3 wt% CM chitin aqueous solution under reduced pressure, frozen again at -78 ° C., freeze-dried, and subjected to a heat treatment at 140 ° C. × 24 hr to obtain a porous block. .

(Comparative Example Product 4) A 5 wt% CM chitin aqueous solution was prepared, and HAP (particle size: 63 to 150 μm) was mixed with the solution at a weight ratio of 1/5. Flash frozen in nitrogen. Then, it was freeze-dried and subjected to a heat treatment at 160 ° C. for 24 hours to obtain a porous block.

Characteristic evaluation For these examples and comparative examples, the average pore diameter of the surface and the central portion, the difference between the average major axis and the average minor axis of the central hole,
The structural anisotropy, the compressive strength of the molded body (X axis, Y axis,
The Z axis) and the compressive strength of only the central portion (average of the X axis, Y axis, and Z axis) were measured. In addition, the operability during trimming with a scalpel was also evaluated.

Next, the molded products of the product of the example and the product of the comparative example were implanted into a defect of the tibia of a gibbon. Four weeks later, specimens of the implanted part were prepared and subjected to biological evaluation.

Table 1 shows the results of these characteristic evaluations.

[0063]

[Table 1]

As is clear from Table 1, all of the examples had an average surface pore diameter in the range of 5 to 150 μm, the difference between the average major axis and the average minor axis of the central hole was less than 20 μm, and the structure was different. When the anisotropy is less than 1.1 and the difference between the X-axis, Y-axis, and Z-axis of the overall compressive strength of the molded body (initial compressive strength when compressed to 1/2 volume) is 20% or less. there were. Further, the ratio of the initial compressive strength value at the center to the initial compressive strength value on the surface of the porous block was 80 to 100%. These examples have good operability of trimming. In biological evaluation, the absorption of the molded body and the formation of bone around the HAP proceed synchronously, and the formation of new bone It was confirmed that it was functioning effectively as a scaffold.

On the other hand, in Comparative Example 1, the average pore diameter on the surface was as small as 2 μm, the structural anisotropy was as large as 1.5,
The difference between the X-axis, Y-axis, and Z-axis of the compression strength of the molded body (initial compression strength when compressed to 1/2 volume) is larger than 20%,
Further, the ratio of the initial compressive strength value at the center to the initial compressive strength value on the surface of the porous block was out of the range of 80 to 100%. And although the operability of trimming was good,
Poor bioabsorption and insufficient bone formation.

In Comparative Example 2, the average pore diameter on the surface was 150 μm.
It was larger, and it was easy to lose shape during trimming. In Comparative Example 3, the difference between the average pore diameters of the surface and the center was 5%.
0 μm, the structural anisotropy is as large as 1.5, and the difference in compressive strength between the X-axis, Y-axis, and Z-axis of the compact is 20 μm.
%. The ratio of the initial compressive strength value at the center to the initial compressive strength value on the surface of the porous block body is 80%.
１００100%. Furthermore, the strength was small and it was difficult to trim with a scalpel.

In Comparative Example 4, the difference in average pore diameter between the surface and the central portion was 80 μm or more, and the structural anisotropy was 3.
X-axis, Y-axis, Z
The difference in axes was greater than 20%. The ratio of the initial compressive strength value at the center to the initial compressive strength value on the surface of the porous block was out of the range of 80 to 100%. And although the strength was good, it was difficult to trim with a scalpel, and in the biological evaluation, there was a problem that HAP was accumulated.

[0068]

As described above, according to the present invention, the bone repair material of the present invention has no orientation in the CM chitin fibers in the molded product, the HAP granules are uniformly dispersed, and Are almost uniform, and have a constant strength in any direction.
In addition, infiltration of body fluids and entry of cells occur evenly from any surface. Therefore, it is possible to fit the defective part without worrying about the direction when filling the defective part, and it is possible to perform a good bone repair by ideal bone growth.

In addition, according to the present invention, even if trimming is performed with a scalpel or the like, it is difficult for the mold to lose its shape or the HAP to fall off due to the additional coating treatment.

Claims (2)

[Claims] 1. A porous block comprising a mixture of CM chitin and calcium phosphate-based material granules having an average pore diameter of 3 to 150 μm on the surface and a difference between the average minor axis and average major axis of pores at the center of 20 μm. A bone repair material characterized by the following. 2. The ratio of the initial compressive strength value of the central portion to the initial compressive strength value of the surface of the porous block body is 80 to 100.
%. 2. The bone repair material according to claim 1, wherein