JP2892092B2 - Calcium phosphate compound molded article and method for producing the same - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to a calcium phosphate compound molded product having a suitable performance as a material for filling a bone defect or a void, and a method for producing the same.

[Related Art] When bone damage occurs due to an accident, disease, tooth extraction, or the like, it is necessary to fill a bone defect or a void.

Various metals and organic substances such as stainless steel such as SUS316, Ti and Ti alloys, vitalium, and plastic are used as hard tissue substitutes for living organisms. In some cases, the dissolved substance had no binding property and the dissolved substance was not toxic during use.

Therefore, needless to say, materials that are harmless to living tissues and have excellent affinity and binding properties have been required, and ceramic materials have been attracting attention as satisfying these requirements. Among them, calcium phosphate-based ceramics have been attracting attention because they have the same components as bone, exhibit high affinity with bone, and form a chemical bond with bone.

As calcium phosphate-based ceramics, apatites, especially hydroxyapatite [Ca ₆ (PO ₄ ) ₁₀ (OH) ₂ ]
And β-TCP [β-Ca ₃ (PO ₄ ) ₂ ] have been particularly noted in recent years. However, they do not always have good initial osteogenic properties in practical clinical applications, and in some cases there are situations where tissue cells surround these surfaces and inhibit their association with bone, and it is necessary to remedy this drawback. There is.

As one of the solutions to this point, a molded article provided with continuous pores having a pore diameter of 10 to 30 μm has been proposed in order to promote the invasion of osteoblasts and increase the bonding strength. For example, JP-A-60-21
No. 763 and Japanese Patent Application Laid-Open No. Sho 62-158175 disclose a method in which an organic substance is mixed with hydroxyapatite (hereinafter referred to as HAP) raw material powder, and the organic substance is burned off during firing to form a porous body. Discloses a method in which a compact is once pulverized to produce a granular material having a high surface roughness, which is remixed and fired to form a porous material.

However, in the former method of simply mixing the HAP raw material powder and an organic substance and firing the mixture, if the mixing is not performed sufficiently, the pore distribution tends to be less than continuous pores. There are drawbacks such as the occurrence of "unevenness" resulting in dead holes and the inability to obtain the expected mechanical strength. The latter method of forming a rough surface by pulverization and then mixing and firing to form a porous body not only complicates the manufacturing process but also controls the porosity due to the difficulty in controlling the particle size distribution during pulverization. However, there are problems such as difficulties in carrying out, variation in the pore distribution, and difficulty in attaching living cells due to sharp corners of the crushed particles.

[Problems to be Solved by the Invention] Therefore, the present inventors have developed a calcium phosphate compound molded body having good penetration of osteoblasts and prompt replacement with new bone by lysis and absorption. The application has been filed (Japanese Patent Application No. 63-263279). The calcium phosphate compound molded body has a surface area of 10 times or more the surface area of the molded body by including an osteoblast intrusion hole having an opening diameter of 30 to 500 μm, and a substrate excluding the osteoblast intrusion hole. The porosity of the pores in the part is not more than 30%, and by providing continuous open pores on the surface of the molded article to increase the surface area,
By exerting the action and effect of continuous elution of Ca, Ca can be supplied throughout the growth period of the new bone, and the osteoinductive function is improved, thereby enabling the growth of the new bone to be further promoted.

In the invention of the prior application, the substantial surface area of the molded body was set to 10 times or more of the theoretical surface area, because if it is less than 10 times, the osteoblast invasion and Ca elution rate are small, and the osteoinductivity is not good. In order to make the theoretical surface area of the molded body 10 times or more, the opening diameter of the osteoblast cell intrusion hole is set to 30 to 500 μm.

However, there is an inconvenience that the strength is reduced when the osteoblast invasion hole is provided as described above. Therefore, in order to prevent the strength from decreasing, the porosity of the stoma in the matrix portion excluding the osteoblast intrusion hole is set to 30% or less. I decided.

Further, the molded article of the invention of the prior application is prepared from a calcium phosphate compound powder having a particle diameter of 5 μm or less and a binder liquid to have an average particle diameter of 30 μm.
After granulating primary particles of about 200 μm, and then granulating secondary particles from the primary particles, a binder liquid the same or different from the binder liquid, and a calcium phosphate compound powder same or different from the calcium phosphate compound The secondary particles can be obtained as they are or after calcination, by adding a binder liquid which is the same as or different from the above-mentioned binder liquid, molding and firing.

However, it has been found that even when the calcium phosphate compound molded article according to the above-mentioned prior invention is embedded in a bone defect part, it is found that a part of the molded article is likely to fall off, further improving the strength of the molded article. Technology is needed.

[Means for Solving the Problems] The present invention has been made by focusing on the above circumstances,
By including an osteoblast intrusion hole having an opening diameter of 30 to 500 μm, the surface area of the molded body is at least 10 times the surface area of the molded body, and the porosity of the stoma in the matrix portion excluding the osteoblast intrusion hole is 30%. The following calcium phosphate compound molded body is characterized in that fine particles of the same or different calcium phosphate compound as the calcium phosphate are caused to penetrate into pores in the substrate portion.

In producing the above calcium phosphate compound, primary particles having an average particle size of 30 to 200 μm are granulated from a calcium phosphate compound powder having a particle size of 5 μm or less and a binder solution, and then the same as the primary particles and the binder solution. Or, after granulating secondary particles from a different binder liquid and the same or different calcium phosphate compound powder as the calcium phosphate compound, the secondary particles are directly or calcined, and then the same or different binder liquid as the binder liquid is used. Then, a method may be used in which the obtained molded body is directly or calcined, and then impregnated with a slurry containing the same or different calcium phosphate compound as the calcium phosphate compound and calcined.

[Operation] The calcium phosphate compound molded article according to the present invention is obtained by impregnating a molded article with a slurry containing fine particles of apatite of 1 μm or less, preferably 0.5 μm or less, for the purpose of strengthening the bonding between the particles of the fired body. According to the control described above, the slurry is impregnated deeply through the open pores of the molded body and then dried and fired, whereby the strength of the molded body can be improved.

In addition, the strength of the molded body can be further increased by repeating the steps of impregnating the slurry and drying and firing.

As the binder according to the present invention, a polyvinyl alcohol solution, a hydroxypropyl cellulose solution, and other commonly used organic binders can be used.

As the inorganic binder, a slurry of calcium phosphate, for example, a suspension of HAP or a suspension of β-TCP can be used. Further, a calcium phosphate sol or the like, which is a reaction product of a calcium alkoxide and an alkyl ester of phosphorus oxyacid in a non-aqueous solvent, can also be used as an inorganic binder (an organic component is also contained. Since it evaporates early in the firing, it can be included in the category of inorganic binders). Preferred examples of the calcium phosphate sol include HAP sol and β-TCP sol. At the time of drying and baking, the volatile component and the thermal decomposition component in the binder component are removed, and this portion becomes the osteoblast cell entry hole and the pore of the matrix portion.

As the calcium phosphate-based slurry used in the present invention, those mentioned above as the organic binder can be used.

Further, the present invention is not limited by the firing temperature, but when the firing temperature exceeds 1300 ° C., since the apatite is transferred to αTCP which is highly soluble and harmful, the firing temperature is 130.
The temperature is preferably set to 0 ° C. or lower.

If it is desired to further increase the density of the substrate part of the molded body, the molded body before firing should be 900 ppm under HIP (Hydrostatic High Pressure Pressing).
Heat treatment may be performed at a temperature of not less than ℃. Also, if the surface of the molded body is cured in a steam atmosphere, the distortion of HAP can be eliminated.

[Example] Experimental Example 1 HAP having a particle size of 5 μm or less was placed in a pan-type rolling granulator having a diameter of 360 mm.
Charge 500g of powder, 5% polyvinyl alcohol (PVA)
While spraying 480 ml of the liquid at a spray pressure of 1 kg / cm ² or less for 20 minutes, the particles were granulated to a particle size of 50 to 100 μm, and 90 g of HAP powder was added thereto to adjust the humidity to obtain primary particles.
Further, 300 ml of 10% PVA solution is added to the primary particles under the same conditions as above.
While spraying for 20 minutes, 120 g of HAP powder was gradually added to granulate secondary particles. A molded article was obtained by adding 5 ml of a 10% PVA solution to the secondary particles, and the molded article was fired at 1250 ° C. to obtain a test piece of Comparative Example 1.

The average particle size was added to the above-mentioned molded body before firing and the molded body of Comparative Example 1.
After impregnation with a suspension containing 0.5% of HAP 0.5%, 125
The molded bodies obtained by firing at 0 ° C. were used as test pieces of Inventive Example 1 and Inventive Example 2, respectively. The theoretical surface area, actual surface area, osteoblast invasion pore size (average), and strength by a destructive test were measured for the above three types of test pieces. The results are shown in Table 1.

The above three types of test pieces were all prepared from a calcium phosphate compound powder having a particle size of 5 μm or less and a binder solution to obtain an average particle size.
30-200 μm primary particles are granulated, then the primary particles,
After granulating the secondary particles from the binder liquid and the calcium phosphate compound powder, the above-mentioned binder liquid was added to the secondary particles, and the mixture was molded and baked. All showed very good osteoinductive ability in 2 weeks, indicating that the test piece had good osteoblast invasiveness and new bone was formed promptly by appropriate Ca elution. .

Experimental Example 2 Secondary particles granulated in the same manner as in Experimental Example 1 were dried and dried.
It was calcined at 00 ° C to obtain porous granules having a particle size of 600 to 1000 µm (average 700 µm). A 10% PVA solution (10 ml) was added to the granules to form a molded body. The molded body was fired at 125 ° C. to obtain a test piece of Comparative Example 2.

The average particle size was added to the above-mentioned molded body before firing and the molded body of Comparative Example 2.
After impregnating a slurry containing 5% of 0.5 μm HAP,
The molded bodies obtained by firing at 1250 ° C. were used as test pieces of Inventive Example 3 and Inventive Example 4, respectively.

Next, using the molded product of Comparative Example 2, H
After repeating the process of impregnating and drying the slurry containing 5% of AP five times, the molded product obtained by firing at 1250 ° C. was used as a test piece of Example 5 of the present invention.

The theoretical surface area, actual surface area, osteoblast invasion pore size (average), and strength by a destructive test were measured for the above four types of test pieces. The results are shown in Table 1.

In addition, when an animal test was performed using the above-mentioned test piece, all showed very good osteoinductive ability in 2 weeks.

Experimental Example 3 Calcium ethoxide 260 g, triethyl phosphite 200 g
With ethylene glycol 1.3 and ethyl alcohol 2
Was dissolved in the above mixture, and 10 ml of pure water was carefully added to obtain an apatite sol.

On the other hand, 500 g of HAP powder was charged into a 360 mm diameter pan tumbling granulator, and 500 ml of the apatite sol obtained as described above was sprayed at a spray pressure of 1 kg / cm ² or less for 20 minutes to give a particle size of 5.
The mixture was granulated to have a particle size of 0 to 100 μm, and 90 g of HAP powder was added thereto to adjust the humidity to obtain primary particles. Further, 300 ml of the apatite sol was added to the primary particles under the same conditions as above.
While spraying for 120 minutes, 120 g of HAP powder was gradually added to granulate secondary particles. The secondary particles are dried and fired at 1200 ° C.
Porous granules of 600 to 1000 μm (average 700 μm) were obtained.
The granules were molded by adding 5 ml of the apatite sol,
The molded body obtained by firing at 0 ° C. was used as a test piece of Comparative Example 3.

Next, 5 ml of the apatite sol was added to the molded article obtained in Comparative Example 3.
And fired at 1250 ° C. to obtain a molded article of Example 6 of the present invention.

The theoretical surface area, actual surface area, osteoblast invasion pore size (average), and strength by a destructive test were measured for the above two types of test pieces. The results are shown in Table 1.

In addition, when an animal test was performed using the above-mentioned test piece, all showed very good osteoinductive ability in 2 weeks.

Since the calcium phosphate compound molded article according to the present invention is obtained by impregnating the slurry containing the calcium phosphate compound and then firing, the strength is improved as compared with the comparative example. In addition, it can be seen that Example 6 of the present invention, in which the above-described slurry impregnation and drying steps were repeated five times, had particularly high strength.

[Effects of the Invention] Since the present invention is configured as described above, the penetration of osteoblasts is good, the formation of new bone is performed promptly by the appropriate Ca elution, and the bone-filled composite material As a result, a calcium phosphate compound molded article having excellent mechanical strength and a method for producing the same can be provided.

Claims (2)

(57) [Claims] The present invention has an osteoblast infiltration hole having an opening diameter of 30 to 500 μm, and has a surface area of at least 10 times the surface area of the molded body, and a pore in a matrix portion excluding the osteoblast intrusion hole. What is claimed is: 1. A calcium phosphate compound molded article having a porosity of 30% or less, characterized in that fine particles of the same or different calcium phosphate compound are penetrated into the pores of said substrate portion. body. 2. A method for producing a calcium phosphate compound molded article according to claim 1, wherein the calcium phosphate compound powder having a particle diameter of 5 μm or less and a binder liquid have an average particle diameter of 30 μm.
After granulating primary particles of about 200 μm, and then granulating secondary particles from the primary particles, a binder liquid identical to or different from the binder liquid, and a calcium phosphate compound powder identical to or different from the calcium phosphate compound After the secondary particles are directly or calcined, the same or different binder liquid as the binder liquid is added and molded, and the obtained molded body is directly or calcined, and the same or different phosphoric acid as the calcium phosphate compound is used. A method for producing a calcium phosphate compound molded body, comprising impregnating and firing a slurry containing a calcium compound.