JPH03280958A - Calcium phosphate compound molded object and its manufacture - Google Patents

Abstract

PURPOSE:To further promote growth of a newborn bone by enveloping an osteoblast infiltration hole of specific opening bore to form a specific surface area and preparing a molded object with a calcium phosphate compound having hole porosity within a specific range in the substrate part. CONSTITUTION:After a primary grain of 30 to 200mum mean grain size is pelletized from calcium phosphate compound powder of 5mum grain size or less and a binder fluid, a secondary grain is pelletized from this primary grain, the binder fluid and the calcium phosphate compound powder. Next, this secondary grain, left as it is or after baked, is molded by applying a binder, and then a molded object, left as it is or after baked, is impregnated with calcium phosphate compound-containing slurry and baked. The obtained molded object has a surface area of 10 times or more the molded object surface area by enveloping an osteoblast infiltration hole having a 30 to 500mum opening bore.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to a calcium phosphate compound molded article having properties suitable as a material for filling bone defects or voids, and a method for producing the same.

[Conventional technology] When bone damage occurs due to an accident, illness, tooth extraction, etc.
Filling of bone defects or voids is required.

Various metals such as stainless steel such as 5US316, Ti and Ti alloys, Vitalium, and plastics, as well as organic materials, are used as hard tissue substitutes for living organisms, but these do not have good affinity for living organisms and are not compatible with bones. There were also cases where there was no binding property at all, and there were also cases where the dissolved material was toxic due to dissolution or deterioration during use.

Therefore, there is a need for materials that are not only harmless to living tissues but also have excellent affinity and binding properties.
Ceramic materials are attracting attention as materials that satisfy these requirements. Among them, calcium phosphate ceramics are
It has the same components as bone and shows high affinity with bone.
Moreover, it has been attracting attention because it forms a chemical bond with bones.

Calcium phosphate ceramics include apatites, especially hydroxyapatite [Ca6(PO4)10(O
H)2] and β-TCP [β-Ca s(P 04
)2] has received particular attention in recent years. However, in actual clinical applications, the initial osteogenicity of these drugs is not necessarily good, and in some cases, tissue cells surround their surfaces, inhibiting their bonding with bone, and this drawback can be improved. There is a need.

One solution to this problem is to encourage the invasion of osteoblasts,
A molded article having continuous pores with a pore diameter of 10 to 30 μm has been proposed in order to increase the bonding strength. For example, JP-A-60-
No. 21763 and JP-A No. 62-158175 disclose a method of mixing organic matter into hydroxyapatite (hereinafter referred to as HAP) raw material powder and burning off the organic matter during firing to form a porous body, or JP-A No. 62-1.2680. The publication discloses a method in which a molded body is once pulverized to produce granules with a high surface roughness, and the granules are remixed and fired to form a porous body.

However, in the former method, in which HAPi powder and organic matter are simply mixed and fired, if the mixing is not done sufficiently, the pore distribution will be uneven, and the pores will not be continuous, making it difficult to achieve the desired goal of osteoblast invasion. There are drawbacks such as "unevenness" resulting in dead flowers and failure to obtain the expected mechanical strength. In addition, the latter method, in which a rough surface is formed by pulverization and then mixed and fired to form a porous body, not only complicates the manufacturing process but also makes it difficult to control the particle size distribution during pulverization, making it difficult to control the porosity. There have been problems such as difficulty in cleaning the rice, the tendency to cause variations in pore distribution, and the fact that the crushed grains have sharp corners, making it difficult for living cells to attach to the rice.

[Problems to be Solved by the Invention] Therefore, the present inventors have developed a calcium phosphate compound molded body that has good osteoblast penetration and can be quickly replaced with new bone through dissolution and absorption. The calcium phosphate compound molded body, for which the application has been filed (Japanese Patent Application No. 63-263279), has a surface area that is more than 10 times the surface area of the molded body by encapsulating osteoblast penetration holes with an opening diameter of 30 to 500 μm. It is characterized in that the porosity of the pores in the matrix excluding the osteoblast infiltration pores is 30% or less, and by providing continuous open pores on the surface of the molded body and increasing the surface area, bone By promoting the invasion of blast cells and exerting the effect of continuous elution of Ca, Ca can be supplied throughout the growth period of new bone, improving the osteoinductive function and further promoting the growth of new bone. It has become possible.

The reason why the substantial surface area of the molded body in the prior invention is set to be 10 times or more of the theoretical surface area is that if it is less than 10 times, the invasion of osteoblasts and the elution rate of Ca will be low and the osteoinductivity will be poor. In order to increase the theoretical surface area of the molded body by 10 times or more, the opening diameter of the osteoblast cell penetration hole is set to 30 to 500 μm.

However, creating osteoblast entry holes as described above has the disadvantage of reducing the strength, so in order to prevent the strength from decreasing, the porosity of the pores in the matrix excluding the osteoblast entry holes was reduced to 30%. It was determined as follows.

Further, the molded body of the above-mentioned prior invention can be obtained from calcium phosphate compound powder with a particle size of 5 μm or less and a binder liquid with an average particle size of 30 μm.
~200 μm primary particles are granulated, then the primary particles,
After granulating secondary particles from a binder liquid that is the same as or different from the binder liquid and a calcium phosphate compound powder that is the same or different from the calcium phosphate compound, the secondary particles are granulated as they are or after being fired, and then Alternatively, it can be obtained by adding different binder liquids, molding and firing.

However, it has been found that even with the calcium phosphate compound molded article according to the prior invention, a part of the molded article tends to fall off when it is implanted into a bone defect, and it is difficult to further improve the strength of the molded article. technology is required.

[Means for Solving the Problems] The present invention has been made focusing on the above circumstances, and includes the following three points:
It has a surface area that is 10 times or more than the surface area of the molded product by including osteoblast penetration holes having a diameter between 0 and 500 μm, and the porosity of the pores in the matrix excluding the osteoblast penetration holes is 30%. The gist of the following calcium phosphate compound molded article is that fine particles of a calcium phosphate compound that is the same as or different from the calcium phosphate are infiltrated into the pores of the substrate.

In addition, in producing the above calcium phosphate compound, primary particles with an average particle size of 30 to 200 μm are granulated from a calcium phosphate compound powder with a particle size of 5 μm or less and a binder solution, and then the primary particles are made in the same manner as the binder solution. Or, after granulating secondary particles from a different binder liquid and a calcium phosphate compound powder that is the same as or different from the above-mentioned calcium phosphate compound, the secondary particles are granulated as they are or after being fired, and then a binder liquid that is the same as or different from the above-mentioned binder liquid is granulated. A method may be used in which the resulting molded body is either used as it is or after being fired, impregnated with a slurry containing a calcium phosphate compound that is the same as or different from the calcium phosphate compound, and then fired.

[Function] The calcium phosphate compound molded body according to the present invention is obtained by impregnating the molded body with a slurry containing apatite fine particles of 1 μm or less, preferably 0.5 μm or less, for the purpose of strengthening the bond between the particles of the fired body. The strength of the molded product can be improved because it is obtained by deeply impregnating the slurry into the molded product through the open pores of the molded product according to the capillary principle, followed by drying and firing.

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

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

In addition, as an inorganic binder, slurry of calcium phosphate,
For example, a suspension of HAP or a suspension of β-TCP can be used. Furthermore, calcium phosphate sol, which is a reaction product of calcium alkoxide and phosphorus oxygen acid alkyl ester in a non-aqueous solvent, can also be used as an inorganic binder (it also contains an organic component, but the organic component is removed when dry or Since it volatilizes in the early stage of firing, it can be classified as an inorganic binder). Preferred examples of the calcium phosphate sol include HAP sol and β-TCP sol. Then, during drying and firing, volatile components and thermally decomposed components in the binder component are removed, and these portions become osteoblast entry holes and pores in the matrix portion.

Further, as the calcium phosphate slurry used in the present invention, those mentioned above as the inorganic binder can be used.

Further, the present invention is not limited by the firing temperature, but if the firing temperature exceeds 1300°C, apatite will convert to αTCP, which is highly soluble and harmful, so it is preferable that the firing temperature is 1300°C or lower. .

Furthermore, if you want to increase the density of the matrix part of the molded body, the molded body before firing can be heated to 90°C under HIP (hydrostatic high pressure pressing method) conditions.
Heat treatment may be performed at 00°C or higher. Furthermore, by curing the surface of the molded product in a steam atmosphere, the distortion of the HAP can be eliminated.

[Example] Experimental Example 1 500 g of HAP powder with a particle size of 5 μm or less was charged into a pan-type transfer granulator with a diameter of 360 mm, and 480 ml of 5% polyvinyl alcohol (PVA) liquid was sprayed for 20 minutes at a pressure of 1 kg/cm2 or less. While spraying with a particle size of 50-1
Granulated to a size of 00 μm, then 903 H
AP powder was added to adjust the humidity to obtain primary particles. Furthermore, this one
Add 300ml of 10% PVA solution to the next particle under the same conditions as above.
120 g of HAP powder was gradually added while spraying for 0 minutes to granulate secondary particles. 10% PV in the secondary particles
A test piece of Comparative Example 1 was prepared by adding Liquid A 51 to form a molded body, and firing the molded body at 1250°C.

The above molded body before firing and the molded body of Comparative Example 1 had an average particle size of 0.
．． The molded bodies obtained by impregnating a suspension containing 0.5% of 5 μm HAP and then firing at 1250° C. were used as test pieces of Inventive Example 1 and Inventive Example 2, respectively. Theoretical surface area, actual surface area, osteoblast penetration pore diameter (average), and strength by 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 made from calcium phosphate compound powder with a particle size of 5 μm or less and a binder liquid with an average particle size of 3 μm.
Primary particles with a size of 0 to 200 μm are granulated, and then 2
After granulating the secondary particles, the above-mentioned binder liquid was added to the secondary particles, which was then molded and fired. When animal tests were conducted using the above-mentioned test pieces, all cases showed very good bone formation within 2 weeks. From the fact that it showed induction ability, it can be seen that the above-mentioned test piece had good osteoblast invasiveness and that new bone was formed quickly due to appropriate elution of Ca.

Experimental Example 2 Secondary particles granulated in the same manner as Experimental Example 1 were dried for 12
Calcined at 00℃, particle size 600-1000μm (average 70μm)
Porous granules with a diameter of 0 μm) were obtained.

A test piece of Comparative Example 2 was prepared by adding 10 ml of 10% PVA liquid to the granules to form a molded body, and firing the molded body at 1250°C.

The above molded body before firing and the molded body of Comparative Example 2 had an average particle size of 0.
．． The molded bodies obtained by impregnating a slurry containing 5% of 5 μm HAP and then firing at 1250° C. were used as test pieces of Inventive Example 3 and Inventive Example 4, respectively.

Next, using the molded body of Comparative Example 2, the process of impregnating it with a slurry containing 5% HAP with an average particle size of 0.5 μm and drying it was repeated five times, and then firing it at 1250°C. was used as the test piece of Example 5 of the present invention.

Theoretical surface area, actual surface area, osteoblast penetration pore diameter (average), and strength by destructive test were measured for the above four types of test pieces. The results are also listed in Table 1.

In addition, when animal tests were conducted using the above test pieces, all showed very good bone flexion conductivity within 2 weeks.

Experimental example 3 Calcium ethoxide 260g, triethyl phosphite 20
0 g was dissolved in a mixed solution of 1.3 f of ethylene glycol and 21 g of ethyl alcohol, and then 10 ml of pure water was carefully added to obtain an apatite sol.

On the other hand, HAP powder 5 is placed in a pan transfer granulator with a diameter of 360 ma+.
Apatite sol 5 obtained as described above by charging 00g of
00ml for 20 minutes at a spray pressure of 1 kg/c
After spraying at a volume of less than m2, the particles were granulated to a particle size of 50 to 100 μm, and then 90 g of HAP powder was added thereto to control the humidity to obtain primary particles. Furthermore, 120 g of HAP powder was gradually added to the primary particles while spraying 300 ml of the apatite sol for 20 minutes under the same conditions as above to granulate secondary particles. The secondary particles were dried and then fired at 1200°C to obtain porous granules with a particle size of 600 to 1000 μm (average 700 μm). 5 ml of the apatite sol was added to the granules, molded, and fired at 1250° C. The molded product obtained was used as a test piece of Comparative Example 3.

Next, 5 ml of the apatite sol was added to the molded body obtained in Comparative Example 3.
A molded body obtained by impregnating the sample with the following and firing at 1250°C was used as a test piece of Example 6 of the present invention.

The theoretical surface area, actual surface area, osteoblast penetration pore diameter (average), and strength by destructive test were measured for the above two types of test pieces. The results are also listed in the 's1 table.

In addition, when an animal test was conducted using the above test piece, All showed very good osteoinductive ability within 2 weeks.

Fruit surface The calcium phosphate compound molded product according to the present invention is obtained by impregnating a slurry containing a calcium phosphate compound and then firing it, so it can be seen that the strength is improved compared to the comparative example. Furthermore, it can be seen that Example 6 of the present invention, in which the above 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, osteoblasts have good invasiveness, new bone is formed quickly due to appropriate elution of Ca, and it can be used as a filling material for bone defects. A calcium phosphate compound molded article having excellent mechanical strength and a method for producing the same can now be provided.

Claims (2)

[Claims] (1) It has a surface area that is more than 10 times the surface area of the molded product by including osteoblast entry holes with an opening diameter of 30 to 500 μm, and the porosity of the pores in the matrix excluding the osteoblast entry holes. 30% or less, the calcium phosphate compound molded product being characterized in that fine particles of a calcium phosphate compound that is the same as or different from the calcium phosphate are infiltrated into the pores in the substrate portion. (2) A method for producing a calcium phosphate compound molded article according to claim (1), wherein the calcium phosphate compound powder having a particle size of 5 μm or less and a binder liquid are used to produce an average particle size of 30 to 2 μm.
After granulating primary particles of 00 μm, and then granulating secondary particles from the primary particles, a binder liquid that is the same as or different from the binder liquid, and a calcium phosphate compound powder that is the same or different from the calcium phosphate compound, The secondary particles are molded as they are or after being fired, a binder liquid the same as or different from the binder liquid is added thereto, and the obtained molded body is molded as is or after being fired, a calcium phosphate compound which is the same as or different from the calcium phosphate compound is added. 1. A method for producing a calcium phosphate compound molded article, which comprises impregnating a slurry containing the compound and firing the resulting product.