JP2934090B2 - Biological implant material - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a biomaterial (implant material) which can be replaced by bone, and more particularly to an implant material having excellent machinability and biocompatibility.

[0002]

2. Description of the Related Art It is known that a calcium phosphate compound is excellent in biocompatibility, and a sintered body thereof is used as a biomaterial to be substituted for bone and teeth.

In general, a calcium phosphate porous implant material having continuous pores of several tens μm to several hundred μm is used with emphasis on the proliferative properties of a living body, but the strength is extremely low.

Therefore, the present inventors have already disclosed a method for producing a calcium phosphate sintered body having a high biocompatibility and a high strength, as disclosed in Japanese Patent Publication No. 60-25383, in which the atomic ratio of calcium / phosphorus is 1.4-1. 0.75% by weight of phosphoric acid based on the calcium phosphate component after firing, and mixing
By the sintering method, a dense calcium phosphate sintered body having high strength was provided in the normal pressure firing method.

Further, Japanese Patent Publication No. 50744/1985 discloses that a powder mainly composed of a calcium phosphate having a calcium / phosphorus atomic ratio of 1.4 to 1.75 is added in an amount of 0.5 to 15 wt. % Oxide / phosphate frit of alkali metal, zinc and / or alkaline earth metal and sintering, and powder mainly composed of calcium phosphate having a calcium / phosphorus atomic ratio of 1.4 to 1.75 0.5 to 15% by weight, based on the calcined calcium phosphate sintered body, of an oxide-phosphoric acid frit of an alkali metal, zinc and / or alkaline earth metal and Y ₂
A method for sintering containing _{3 to} 23% by weight of O3 is provided. As a result, the range of the transverse rupture force is approximately 13 in the former case.
A new calcium phosphate sintered body having a high strength of 3 to 177 MPa and in the latter case 200 MPa or more was obtained. When these implant materials were implanted into a living body, they were chemically bonded to bone tissue, and showed good results without being easily broken due to high strength.

[0006]

The conventional implant material is manufactured by previously processing the powder in accordance with the shape of the transplanted portion at the time of powder molding, and further performing precision processing after firing.

[0007] However, since the shape of the living tissue on the side to be implanted changes due to the progress of a lesion or the like, the shape of the implant material and the living tissue manufactured in advance before the implant does not match at the time of implanting (at the time of surgery). Problems sometimes occurred. Therefore, development of an implant material that can be easily dimensioned at the time of implant and has excellent biocompatibility has been desired. The aforementioned implant material is dense and has low workability after firing. If the cutting speed is increased by processing using a diamond grindstone, the implant material is broken by chipping, cracking, or the like. In general, porous materials are easy to process after firing, but in particular, calcium phosphate-based porous materials have extremely low strength and are fragile, so that chips and the like often occur during processing and are often damaged.

[0008] The present invention solves the above-mentioned problems, and does not generate chipping, chipping, cracks, or the like during processing, has good workability, has relatively high strength, and is excellent in biocompatibility. The purpose is to provide.

[0009]

According to the present invention, the above object can be achieved by the following.

(1) Consisting essentially of a calcium phosphate compound, the sintered body has an average crystal grain size of 1 μm or less, an average pore size of 1 μm or less, and a porosity of 5 to 55%.
And a bending strength of 40 MPa or more .

(2) The biological implant material according to (1), wherein the calcium phosphate compound has a calcium / phosphorus atomic ratio of 1.4 to 1.75.

(3) The biological implant material according to (1) or (2), wherein the calcium phosphate compound has hydroxyapatite as a main crystal.

(4) The biological implant material according to any one of (1) to (3), wherein the calcium phosphate compound is a complex of hydroxyapatite and tricalcium phosphate.

(5) The above-mentioned (1) to (1), which is prepared from 99.5 to 85% by weight of hydroxyapatite particles having an average particle diameter of 1 μm or less and 0.5 to 15% by weight of a calcium phosphate glass frit. The biological implant material according to any one of 4).

[0015]

Preferred Embodiment A preferred embodiment of the bioimplant material of the present invention consists essentially of a calcium phosphate compound having hydroxyapatite as a main crystal, and the sintered body has an average crystal particle diameter of 1 μm or less and an average air permeability. pore size is at 1μm or less, a porosity of Ri 5-55% der, flexural strength 40MPa
It is characterized by the above.

The calcium phosphate compound referred to in the present invention is preferably hydroxyapatite which is excellent in biocompatibility, particularly preferably a complex of hydroxyapatite and tribasic calcium phosphate. This is because tribasic calcium phosphate elutes in the living body after the implant, and generates pores of a size that allows easy penetration of living tissue.

In the present invention, the term "hydroxyapatite as the main crystal" means that the peak showing hydroxyapatite becomes the maximum when analyzed by X-ray diffraction. The crystal phase composition ratio of hydroxyapatite and tricalcium phosphate can be determined by a known X-ray diffraction method. Specifically, the peak height I of the (2 1 1) plane of hydroxyapatite was measured using CuKα radiation.
_{It can be obtained from HAP} and the peak height I _TCP of the (0 2 10) plane and the (2 17) plane of _tricalcium phosphate by the following equation.

C _TCP = {I _TCP / (I _HAP + I _TCP )} × 100 (%) C _TCP : content of tricalcium phosphate

The preferred content of tribasic calcium phosphate is 10 to 50%.

The calcium phosphate-based glass frit referred to in the present invention includes CaO and P ₂ O ₅ as glass components.
Is contained in an amount of 50% by weight or more. A particularly preferred composition of the glass frit are those described in JP-B-60-50744, P ₂ O ₅ 40~75 mol% and BaO, C
aO-, MgO, containing ZnO, 1 or more alkali metals selected from the group consisting of Na ₂ O and K ₂ O, an oxide 20-55 mole% of zinc and / or alkaline earth metals, and these engagement The amount of the frit is 90 mol% or more of the whole frit, and the remaining components of the frit are B ₂ O ₃ , Fe ₂ O ₃ , Ti
O ₂ , Al ₂ O ₃ , SiO _{2, and the} like are usually mixed in from the frit melting, the raw material itself, other preparation steps, and the like. These impurities may be in a total amount of about 10 mol% or less of the entire frit.

For example, in terms of mol%, P ₂ O ₅ 47%, CaO
H ₃ PO ₄ , CaCO ₃ ,
ZnO is mixed, the mixture is melted in an alumina crucible at 1300 to 1400 ° C., and the melt is quenched in water to form a glass cullet, which is pulverized using a ball mill (for example, alumina). It is preferable to use a glass frit having a specific surface area of about 5 m ² / g.

The method for producing the implant material of the present invention is not particularly limited as long as the above items are satisfied. For example, the implant material is produced by the following method.

As a starting material, a combination of a hydroxyapatite particle having an average particle diameter of 1 μm or less and a calcium phosphate glass frit is preferable, the particle growth during firing is small, and the glass frit has a low viscosity during firing. It is considered that this wets the space between the fine particles and promotes sintering of the neck, so that the target structure can be easily obtained. A metaphosphate such as calcium metaphosphate can be used instead of the glass frit, and produces the same effect, but the effect is low. In addition, a calcium salt such as calcium carbonate is added to a calcium phosphate raw material such as calcium pyrophosphate and monobasic calcium phosphate to prepare a composition similar to that of hydroxyapatite or tribasic calcium phosphate.
Powder obtained by heat treatment (calcination) at 00 to 1400 ° C. can also be used.

Hereinafter, preferred embodiments of the present invention will be described in more detail, including an example of the method for producing a biological implant material of the present invention.

A mixed molded article comprising 99.5 to 85.0% by weight of hydroxyapatite particles having an average particle diameter of 1 μm or less and 0.5 to 15% by weight of a calcium phosphate glass frit was prepared by mixing 9
Bake at 00 to 1300 ° C. Preferably, hydroxyapatite particles having an average particle size of 0.3 to 0.8 μm are 99.0 to 9
3.0% by weight and calcium phosphate glass frit 1
混合 7% by weight of the mixture is shaped and fired at 1000-1200 ° C.

Regarding the mixing ratio of the glass frit,
If the content is less than 0.5% by weight, neck growth between particles is unlikely to occur, and if the firing temperature is increased to promote neck growth, the particles themselves will grow, and the average particle diameter and average pore diameter will increase, and the porosity will increase. And a fired body having low strength and poor machinability can be obtained.

On the other hand, when the content exceeds 15% by weight, the glass frit reacts with hydroxyapatite to form tribasic calcium phosphate. Therefore, a hydroxyapatite containing 0% of hydroxyapatite or a complex of hydroxyapatite and tribasic calcium phosphate cannot be obtained.

The preferred glass frit content is 1 to 7% by weight as described above. If it is less than 1%, a significant effect cannot be obtained as expected, and if it exceeds 7%, the particle size and pore size increase. This is because some of the organizations will be found.

According to the above-mentioned production method, the porosity is not reduced unlike the hot press, and the necking between the particles proceeds favorably. Therefore, the implant material of the present invention can be produced inexpensively and favorably.

The bioimplant material of the present invention is composed of crystal particles (essentially a calcium phosphate compound) having an average crystal particle diameter of 1 μm or less, and further has pores having an average pore diameter of 1 μm or less, so that a relatively high bending strength (40 to 40 μm) is obtained. 7
0 MPa), which is extremely excellent in workability. The average crystal particle diameter and the average pore diameter are measured by observation with a scanning electron microscope (SEM). Specifically, SEM
After photographing the image, the longest diameter and the shortest diameter of each particle or pore are measured, and the square root of the product can be determined as the average particle diameter or the average pore diameter. Further, the average pore diameter can be obtained with higher accuracy by using a mercury intrusion method. An example of the pore diameter distribution curve of the product of the present invention is shown in FIG. 1. According to this, the average pore diameter is at the maximum peak point of about 0.5 μm, and it can be confirmed that there is no pore larger than 1 μm. When the average crystal particle diameter is larger than 1 μm, the average pore diameter tends to increase, and its strength also decreases. However, as its most remarkable effect, its workability, particularly chipping during processing, is liable to occur.

When the average pore diameter is larger than 1 μm, the strength is remarkably reduced. These are improved by lowering the porosity. On the other hand, chipping is liable to occur during processing.

The porosity indicates the total porosity of the open pores and the closed pores, and can be determined from the bulk specific gravity and the true specific gravity using the following equation.

Porosity = {1− (bulk specific gravity / true specific gravity)} ×
100 (%)

The bulk specific gravity can be obtained, for example, from the volume and weight obtained from the external dimensions of the sample. The true specific gravity can be determined by a known method using a specific gravity bottle obtained by crushing a sample. The porosity shows a close relationship with the workability (cutting speed) and the strength. As the porosity increases, the workability improves but the strength decreases. If the porosity is less than 5%, good workability cannot be obtained, and if it exceeds 55%, the flexural strength becomes extremely low (for example, 10 MPa). Porosity is more than 20% 5
0% or less is particularly preferable in terms of balance between strength and workability.

The effect of the present invention can be obtained only when a calcium phosphate compound having a low strength and a fragility is formed into a structure having the above-mentioned average particle diameter, average pore diameter, and porosity. It seems to be due to their synergistic effect.

[0036]

The porous body conventionally used as an implant material has a thickness of several tens μm to several hundred μm in consideration of invasion of living tissue.
The pores serve as defects and have low strength. On the other hand, in the product of the present invention, since the average crystal particle diameter is as fine as 1 μm or less, the neck formed by sintering each particle of the calcium phosphate compound with other particles adjacent to each other is also 1 μm or less, and there are many such necks. Shows relatively high strength.

The workability usually depends mainly on the porosity,
Although it is considered that the larger the porosity, the better the workability is, but the product of the present invention does not have a large neck, and although the porosity is large because it does not show glassy breaking properties such as chipping and cracks, It is considered that excellent workability can be obtained. Further, when a calcium phosphate-based glass frit is added, the glass frit diffuses into the neck portion of the particles during firing, thereby suppressing grain growth and promoting sintering of the neck portion. This further increases the strength and makes it difficult for chipping or the like to occur, so that workability is considered to be increased.

As described above, the implant material of the present invention
Due to the synergistic effect of the average crystal particle diameter, average pore diameter and porosity, it has excellent workability and relatively high strength.

[0039]

The present invention will be described in more detail with reference to the following examples.

Example 1 5% by weight of hydroxyapatite powder having an average particle diameter of 0.6 μm
Of calcium phosphate-based glass frit and 3% by weight of acrylic binder, mixed in acetone, dried, molded at a molding pressure of 800 kg / cm ² , and further subjected to cold isostatic pressure at a molding pressure of 4000 kg / cm ² The molded body was pressed and baked in an electric furnace at a heating rate of 300 ° C./hour and 1100 ° C. for 5 hours. FIG. 2 shows a scanning electron micrograph of a cross section of the fired body. When various characteristics of this fired body were measured, the average crystal particle diameter was 0.7 μm, the average pore diameter was 0.5 μm, and the porosity was 40%.
The crystal phase is composed of hydroxyapatite (about 80%) and β
-Tribasic calcium phosphate (about 20%). Also,
This fired body had a bending strength of 70 MPa. Using a dental rod-shaped diamond grindstone (No. 120) to grind the through-hole by a wet method at a rotation speed of 15000 rpm, it could be cut well without cracks, chipping, chipping or the like. In addition, when implanted in a living body, it exhibited good biocompatibility, and penetration of living bone into the interior of the implant material was observed.

Example 2 A fired body was produced in the same manner as in Example 1 except that cold isostatic pressing was not performed. When various characteristics of this fired body were measured, the average crystal particle diameter was 0.6 μm, the average pore diameter was 0.6 μm, and the porosity was 51%.
The composition of the crystal phase is hydroxyapatite (about 80%) and β-
Tricalcium phosphate (about 20%). Further, this fired body had a bending strength of 45 MPa.

(Comparative Example 1) <Corresponding to Example in Japanese Examined Patent Publication No. 60-50744> A molded article was prepared in the same manner as in Example 2 using a hydroxyapatite powder having an average particle diameter of 1.5 μm. 1300 ° C
For 5 hours. Various properties of this calcined product were measured. The calcined product had an average crystal particle diameter of 3 μm, an average pore diameter of 2 μm, and a porosity of 3%. The crystal phases were composed of hydroxyapatite (about 80%) and β-tertiary calcium phosphate (about 20%).
%)Met. Further, in this fired body, the bending strength is 120.
MPa was indicated. However, when wet grinding was performed with a diamond grindstone in the same manner as in Example 1, machining was difficult, and if forcedly performed, chipping and cracks occurred and were broken.

(Comparative Example 2) A molded article was produced in the same manner as in Example 2 using a hydroxyapatite powder having an average particle diameter of 20 µm, and baked at 1100 ° C for 5 hours. When various characteristics of this fired body were measured, the average crystal particle diameter was 20 μm, the average pore diameter was 12 μm, and the porosity was 40 μm.
%, The crystal phase is composed of hydroxyapatite (about 80%) and β
-Tribasic calcium phosphate (about 20%). Also,
This fired body had a low bending strength of 20 MPa, and when this was wet-ground with a diamond grindstone in the same manner as in Example 1, a chip of 2 to 5 mm was generated.

[0044] (Comparative Example 3) Using the same powder material as Example 1, except pressing the molding pressure 500 kg / cm ² in the same manner as in Example 2 to prepare a molded body, which 2 at 1050 ° C. Time holding calcination was performed. Various properties of this fired body were measured. The average crystal grain diameter was 0.7 μm, the average pore diameter was 0.5 μm, the porosity was 60%, and the crystal phase was composed of hydroxyapatite (about 80%) and β-third. Calcium phosphate (about 20%). Further, in this fired body, the bending strength was 20 MPa or less, and when this was wet-ground with a diamond grindstone in the same manner as in Example 1, chipping (partial detachment of the implant material) occurred.

The bioimplant material according to the present invention has excellent workability and relatively high mechanical strength (flexural strength of 40MP).
a) or more , and is excellent in biocompatibility, so that it can be processed according to the shape of the transplanted portion without causing chipping, cracking, chipping, etc. at the time of implantation (during surgery). In addition, it is possible to remarkably reduce dimensional defects at the time of implant.

[Brief description of the drawings]

FIG. 1 shows a pore size distribution curve of the product of the present invention.

FIG. 2 is a scanning electron micrograph showing a crystal state of a cross section of the product of the present invention in Example 1.

──────────────────────────────────────────────────続 き Continuation of the front page (56) References JP-A-3-191963 (JP, A) JP-A-2-30653 (JP, A) JP-A-63-125259 (JP, A) JP-A-56-125 54841 (JP, A) JP-A-55-140756 (JP, A) (58) Fields investigated (Int. Cl. ⁶ , DB name) A61L 27/00

Claims (5)

(57) [Claims] (1) It is essentially composed of a calcium phosphate compound,
The average pore diameter average crystal grain size of the sintered body is not more 1μm or less is not more 1μm or less, a porosity of Ri 5-55% der, songs
A bioimplant material having a breaking strength of 40 MPa or more . 2. The implant material according to claim 1, wherein the calcium phosphate compound has a calcium / phosphorus atomic ratio of 1.4 to 1.75. 3. The implant material according to claim 1, wherein the calcium phosphate compound has hydroxyapatite as a main crystal. 4. The implant material according to claim 1, wherein said calcium phosphate compound is a complex of hydroxyapatite and tricalcium phosphate. 5. The composition according to claim 1, wherein the composition is prepared from 99.5 to 85% by weight of hydroxyapatite particles having an average particle size of 1 μm or less and 0.5 to 15% by weight of a calcium phosphate glass frit. The biological implant material according to one of the above.