JPH05208044A - Natural hydroxyapatite porous body and its manufacture - Google Patents

Abstract

PURPOSE:To improve the biocompatibility of the natural hydroxyapatite with a living body by controlling the gas hole rate of the natural hydroxyapatite porous body which is obtained by baking the natural bone and the gas hole diameter to each specified range. CONSTITUTION:The natural hydroxyapatite powder which is obtained by mixing the natural bone such the bone of the fish as walleye pollack and the gas hole forming material such as nylon, polyester, and acryl group to from granular bodies and then to mold a green body through the drying process. The obtained green body is degreased at a low temperature of 500 deg.C or so by using a gas furnace or electrical furnace, and then heated at a high temperature of 800-1400 deg.C, and calcined. The gas hole diameter is controlled to 10-100mum according to the dimension of the mixed gas hole forming material. Further, the opened gas hole rate is controlled to 40-80% by properly restricting the baking contraction according to the mixing ratio fo the natural hydroxyapatite and the gas hole forming material or baking temperature. Accordingly, the biocompatibility with living body can be improved.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a natural hydroxyapatite porous body suitable for a biomaterial such as a bone filling material, artificial bone and artificial tooth root, and a method for producing the same.

[0002]

2. Description of the Related Art Hydroxyapatite is a major component of living hard tissues constituting bones and teeth of vertebrates. Therefore, it has been attracting attention as a ceramic material having excellent biocompatibility, and its application to biomaterials such as artificial bones, artificial teeth, artificial tooth roots and bone fillers has been actively promoted. Among them, a hydroxyapatite porous body obtained by finishing it into a porous body has a large contact area between a tissue in the living body and hydroxyapatite, and thus has a high activity in a living body and is considered to be suitable for an artificial bone or the like.
However, these hydroxyapatite porous materials are
Since the open porosity is as low as 30% and the pore diameter is not uniformly controlled, blood vessels do not grow in the pores of the hydroxyapatite porous body when embedded in a living body, and generation of new bone is not promoted. Moreover, since these hydroxyapatites are synthetic, they do not contain trace elements other than calcium and phosphorus contained in hard tissues such as natural bones and teeth. Therefore, nothing is still satisfactory regarding biocompatibility. Further, it is desired to develop a hydroxyapatite porous body having excellent biocompatibility in which new bone and the embedded hydroxyapatite porous body are integrated after being embedded in the living body.

[0003]

DISCLOSURE OF THE INVENTION The inventors of the present invention have conducted extensive studies on the above-mentioned problems of the existing natural hydroxyapatite porous body, and as a result, the pores of the natural hydroxyapatite porous body obtained by firing natural bone. It has been found that the above problems can be solved by controlling the rate and the pore diameter, and the present invention has been completed and the purpose thereof is to provide natural hydroxyapatite having excellent biocompatibility.

[0004]

Means for Solving the Problems The above-mentioned objects are as follows: (1) A natural hydroxyapatite porous body derived from natural bone having open pores having a pore diameter of 10 to 100 μm and an open porosity of 40 to 80%. And (2) 20 to 60% by weight of the pore-forming material,
A method for producing a natural hydroxyapatite porous body, which comprises molding a green body composed of 40 to 80% by weight of natural bone in terms of pure content and firing the green body at 800 to 1400 ° C. Achieved by.

The hydroxyapatite forming the skeleton of the present invention uses natural bone as a starting material. Natural bone-derived hydroxyapatite contains trace elements other than calcium and phosphorus that are not contained in so-called synthetic hydroxyapatite synthesized from calcium and phosphorus salts. It has excellent biocompatibility such as excellent inducibility and little foreign body reaction. Natural bone is subjected to calcination or enzyme treatment once to reduce the residual organic matter as much as possible, and the particle size is 50 μm or less, preferably 10 μm.
It is pulverized to a size of less than or equal to μm, and then molded together with a pore-forming material, and a natural hydroxyapatite porous body is obtained through a firing step.
Examples of the natural bone used in the present invention include livestock bones such as cows, pigs and chickens, walleye pollock, sardines, mackerel, fish bones such as saury, and among them, fish bones in which the growing sea area is clean are preferable, and particularly, Walleye pollack fish bones, which have a stable supply of raw materials with few harmful components, are preferable.

The pore diameter and open porosity of the present invention are essential factors for bone formation ability, that is, for growth of blood vessels and generation of new bone after being implanted in a living body. That is, blood vessels can grow and new bone is generated due to the presence of the continuous vents having the appropriate pore diameter.
The pore diameter of the present invention needs to be controlled to a pore diameter suitable for blood vessel formation. The pore diameter is 10 to 100 μm, preferably 30 to 80 μm. When the pore diameter is less than 10 μm, blood vessel formation is unlikely to occur. On the other hand, when it exceeds 100 μm, there arises a problem that the strength of the natural hydroxyapatite porous body is lowered. The pores of the present invention need to be continuous vents. No blood vessels are created in closed pores. The open porosity of the present invention is 40 to
It is 80%, preferably 50 to 70%. Open porosity 40
% Is less than the effect of blood vessel formation, while 80%
If it exceeds, there arises a problem that the strength becomes low. As mentioned above,
Although the pores of the present invention are continuous pores, the shape can be any shape such as spherical communication, tubular communication, etc., but spherical pores having high strength of the obtained natural hydroxyapatite porous body are preferable. The open porosity needs to be extremely high at 40 to 80%. In order to obtain such a high porosity, a pore forming material is used in the present invention. The pore-forming material is incinerated and removed in the firing process to form pores. The porosity and pore diameter can be strictly controlled by appropriately selecting the size and amount of the pore forming material. Examples of the pore-forming material include organic fibers such as nylon, polyester, acryl, polyethylene, polypropylene, etc., organic resin particles such as acryl, styrene, polyester, polyethylene, phenol, urethane, epoxy, etc. It is not limited to this.

In the natural hydroxyapatite porous material of the present invention, the natural hydroxyapatite powder obtained by treating natural bone and the pore-forming material are mixed in advance to form granules, and the green body is molded by dry pressing. Alternatively, the natural hydroxyapatite powder and the pore-forming material are mixed with water together with an organic binder to form a slurry or clay, which is then molded by extrusion, extrusion, injection molding, semi-dry press molding, etc. to form a green body. .. In particular, when resin particles are used as the pore forming material, a molding method including a pressurizing step is used to form open pores in which the resin particles are in contact with each other. In the present invention, the pore-forming material forming the green body is 20 to 60% by weight, and the natural bone content is 40 to 8 in terms of pure content, excluding the organic matter content and water content that are incinerated at high temperature.
The raw materials are blended so as to be 0% by weight. 2 pore formers
If it is 0% by weight or less, that is, if natural bone exceeds 80% by weight, the porosity of the formed porous body is low and the bone-forming ability is poor. On the other hand, the pore-forming material exceeds 60% by weight, that is, natural bone is 4%.
If it is less than 0% by weight, the workability of the porous body obtained later will be poor.

The obtained green body is first degreased at a low temperature of about 500 ° C. using a gas furnace, an electric furnace or the like, and then 8
It is baked by heating at a high temperature of 00 to 1400 ° C, preferably 1000 to 1300 ° C. If the temperature is lower than 800 ° C., the density of the skeleton of the obtained porous body is poor, and as a result, the strength of the porous body is extremely low and the workability described below is poor. On the other hand, when the temperature exceeds 1400 ° C, natural hydroxyapatite is melted or thermally decomposed. In the present invention, the pore forming material is burnt out in the degreasing step, and the burned part is formed as pores. Therefore, the pore diameter can be appropriately controlled depending on the size of the pore forming material to be mixed. At this time, the resin particles before burning are required to be continuous because they are left as open pores as described above. Further, the open porosity can be appropriately controlled by appropriately limiting the firing shrinkage by the mixing ratio of natural hydroxyapatite and the pore-forming material or the firing temperature. The hydroxyapatite porous material of the present invention is produced by the above-mentioned production method, and its bending strength is preferably 10 kg / cm ² or more, more preferably 20 kg / cm ² or more. If the bending strength is less than 10 kg / cm ^2, it is easily broken when embedded in a living body as a biomaterial. The natural hydroxyapatite porous material of the present invention can be appropriately used according to the shape, form, etc. of the site of use, such as granular or block-like.

[0009]

EFFECTS OF THE INVENTION The natural hydroxyapatite porous body and the method for producing the same according to the present invention can provide a bone filler, an artificial bone, an artificial dental root and the like having excellent biocompatibility.

[Example 1] Alaska pollack was dropped into three pieces, and the obtained middle bones to which fish meat was adhered was added to a natural enzyme disculin-PT aqueous solution having a pH of 0.5 in a weight ratio of 1: 3, and 50 After stirring at 0 ° C. for 2 hours and then boiling for 20 minutes, the bone content was taken out and washed with water. Then, this is immersed in a 1% aqueous hydrogen peroxide solution, boiled for 2 hours, the bone content is taken out and dried, then heated in a gas furnace at a rate of 100 ° C./hr and calcined at 500 ° C. for 1 hour. The residual organic matter was removed. Then, mix with 10 times the amount of water of the middle bone,
Add to ball mill, crush for 2 hours, then filter,
When the drying step was performed, a natural hydroxyapatite powder having a particle size of 2 μm was obtained. The natural hydroxyapatite powder thus obtained was mixed with acrylic resin beads having a diameter of 200 μm at a weight ratio of 60:40, and 1% P was added.
VA solution is added appropriately, and then granulated to a diameter of about 500 μm
After being made into granules, a green body was produced by press molding into a shape of 30 × 40 × 10 mm. Then 200 ° C / h
The temperature was raised at a rate of r, held at 500 ° C. for 2 hours, further raised at the same rate, and fired at 1200 ° C. for 1 hour.

The obtained natural hydroxyapatite porous material was roughly crushed and then sized to obtain granules having a size of 300 to 800 μm, which were embedded in the jaw bone defect portion of a dog, and the biocompatibility thereof was observed 40 days later. For comparison, a commercially available hydroxyapatite alveolar bone filling material was wet pulverized and the particle size was classified to about 3 μm, and a synthetic hydroxyapatite powder was used as a starting material. A hydroxyapatite porous body was prepared and evaluated. The results are shown in Table 1.

Here, the pore diameter and open porosity were determined by the mercury porosimetry method. The biocompatibility and workability were evaluated according to the criteria shown below. The bending strength (σ ₃ ) was 5 × 10 × 60 for the obtained hydroxyapatite porous body.
It was processed into a rectangular strip of mm, and a bending test was performed under the conditions of a span of 40 mm and a crosshead speed of 0.5 mm / min, and the value was calculated according to the following formula. σ ₃ = (3PL) / (2bh ² ) P: load
L: span b: width of test piece h: thickness of test piece

[Biocompatibility] O: Blood vessels are formed in the pores, and new bone is remarkably formed. Δ: Slight blood vessels are generated in the pores, and new bone is recognized. X: No blood vessel is formed, and new bone is slightly formed on the outer periphery of the hydroxyapatite porous body. [Workability] Workability when embedding in a jaw bone defect part ◯: Good Δ: Strength is weak and some granules are broken. X: The strength is weak and the entire granules are broken.

[0014]

[Table 1] From the above results, it can be seen that the hydroxyapatite porous material of the present invention is superior to that obtained from natural bone.

[Example 2] The diameter of the resin beads was variously changed, and the pores thereof were set to the values shown in Table 2, and the firing temperature was set to 1.
A natural hydroxyapatite porous body was prepared and evaluated in the same manner as in Example 1 except that the temperature was 100 ° C. Here, beads having a diameter of 400 μm or more were made of styrene.

[0016]

[Table 2]

From the above results, the pore size of the hydroxyapatite porous material of the present invention is 10 to 100 μm, preferably 3
It can be seen that the thickness is 0 to 80 μm.

[Example 3] Middle bones to which fish meat was adhered were calcined directly at 500 ° C in a gas firing furnace to remove residual organic matter, and then ground with a ball mill to obtain natural hydroxyapatite powder and resin beads. A natural hydroxyapatite porous material was prepared and evaluated in the same manner as in Example 1 except that the mixing ratio was set to the value shown in Table 3.

[0019]

[Table 3]

[Embodiment 4] Beef bones were directly heated in a gas firing furnace to 50
It is calcined at 0 ° C to remove the residual organic matter, and it is 2 with a ball mill.
Grained for 7 hours, then filtered and dried
m natural hydroxyapatite powder was obtained. Natural hydroxyapatite powder thus obtained and a diameter of 30
0 μm expanded polystyrene particles were mixed at a weight ratio of 65:35, 1% PVA solution was appropriately added, and then granulated to give granules having a diameter of 400 to 500 μm, followed by molding according to Example 1, The natural hydroxyapatite porous material obtained by firing at various temperatures for 8 hours was evaluated.

[0021]

[Table 4] The No. 21 sample was significantly melted, and it was found by analysis by X-ray diffraction that hydroxyapatite was significantly decomposed.

[Embodiment 5] In order to obtain the natural hydroxyapatite powder of No. 1 composition shown in Embodiment 1 and tubular communicating holes, nylon beads having a diameter of 70 μm and a length of 10 mm were replaced with water and water-soluble organic material in place of resin beads. Ball mill dispersion was performed with a binder to prepare a fluid slurry. Pour the slurry into a plaster mold and cast it into a mold, 30x
A 40 × 10 mm green body was obtained. When the green body was made into a granular natural hydroxyapatite porous body according to Example 1 and evaluated, the pore size was 63 μm and the open porosity was 65.
%, The biocompatibility was judged to be ◯, the workability was judged to be Δ, and the bending strength was 21 kg / cm ² .

Comparative Example 1 Hydroxyapatite powder of No. 1 composition and resin beads shown in Example 1 were ball mill dispersed together with water and a water-soluble organic binder to prepare a fluid slurry. Pour the slurry into a plaster mold,
Cast molding was performed to obtain a green body of 30 × 40 × 10 mm. The green body was made into a granular natural hydroxyapatite porous body according to Example 1 and evaluated, and the pore size was 4
3 μm, open porosity 25%, biocompatibility ×, workability ◯, bending strength 37 kg / cm ² . Observation of the fine structure with an electron microscope revealed that the pores were spherical but had a closed pore structure.

Claims (2)

[Claims] 1. A natural bone-derived natural hydroxyapatite porous body having open pores having a pore size of 10 to 100 μm and an open porosity of 40 to 80%. 2. A natural hydroxyapatite porous body obtained by molding a green body composed of 20 to 60% by weight of a pore forming material and 40 to 80% by weight of natural bone in terms of pure content, and firing the green body at 800 to 1400 ° C. Production method.