JPH06296676A - Bioimplant material and its production - Google Patents

Abstract

PURPOSE:To enhance initial bone propagatability by using particles of specific grain sizes which consist of calcium phosphate-based ceramics and have fine pores as the bioimplant material to be adequately used as an artificial bone packing part material. CONSTITUTION:This bioimplant material is formed out of a material which consists of the calcium phosphate-based ceramic, has groups of connected particles having 20 to 800mum sizes, has the fine pores existing within the respective particles and has three-dimensionally communicated pores of 2 to be 200mum made to exist among the particles. The internal pores are formed as <=2mum pores connected to each other. The calcium phosphate-base ceramic contg. hydroxyl apatite and calcium tertiary phoshate as the main crystal phase is used. Such bioimplant material is produced by granulating the raw material powder of the fine calcium phosphate-based raw material to a granular form and molding the granules unde 1 to 100kg/cm<2> pressure, then firing the molding at 700 to 1400 deg.C.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a bioimplant material and a method for producing the same. This bioimplant material can be suitably used as an artificial bone filling member in the medical fields such as orthopedics, plastic surgery, brain surgery, oral surgery, and dentistry.

[0002]

2. Description of the Related Art Calcium phosphate compounds are known to have excellent biocompatibility, and their sintered bodies are known to be materials that are chemically bound to bone or replaced with bone. As a method for producing a calcium phosphate calcined product having high biocompatibility and high strength, the inventors of the present invention have disclosed in JP-B-60-50744 that a calcium phosphate having a calcium / phosphorus atomic ratio of 1.4 to 1.75 is mainly used. It was proposed that the powder to be added contains 0.5 to 15% by weight of an alkaline earth metal oxide-phosphate frit based on the calcined body of calcium phosphate after calcining, and the mixture was molded into a predetermined shape and calcined. By this method, a bioimplant material having excellent biocompatibility and high mechanical strength was obtained. When these implant materials were transplanted into a living body, they chemically bonded to bone tissue, and because of their high strength, they were not easily broken and showed good results.

[0003]

However, even with these materials, it takes about one month to bond with new bone, and further improvement in biocompatibility, particularly improvement in bone growth in the early stage after surgery is desired. It was Although a porous material may be required for the implant material, the conventional porous material has a low strength and is easily damaged during operation, and the operability is poor, so that the machinability after firing is extremely poor. Further, in the case of impregnating a porous body with a drug and filling it in the living body, an implant material that stably supports a large amount of the drug and slowly releases it has been desired.

The object of the present invention is to provide a bioimplant material which is excellent in biocompatibility, particularly bone growth in the initial stage, is suitable for stable drug loading, and has relatively high mechanical strength, and a method for producing the same. Especially.

[0005]

Means for Solving the Problem The means is that the bioimplant material is provided with a group of linked particles of calcium phosphate-based ceramics having a size of 20 to 800 μm,
It is characterized in that pores are present inside each particle and pores of 2 to 200 μm which are three-dimensionally communicated between the particles are present.

The means for producing the fine powder of calcium phosphate-based raw material having an average particle diameter of 5 μm or less is 20 to 8
Granulated into granules of 00μm, ^of 1~100Kg / cm2
It is characterized in that it is formed by pressure and then fired at 700 ° C to 1400 ° C.

[0007]

The function of the present invention is roughly as follows, although it may be inferred. The excellent biocompatibility of the implant material of the present invention is formed by connecting particles having pores.
Due to heavy pore structure (bimodal pore distribution). In particular, when the crystal structure is a composite structure composed of hydroxyapatite (hereinafter, also referred to as “HAP”) and tricalcium phosphate (hereinafter, also referred to as “TCP”), a synergistic effect with the double pore structure is obtained. Be expected.

That is, taking the composite crystal structure of HAP and TCP as an example, the pores of 2 to 200 μm between the particles facilitate the invasion of body fluid and promote the growth of new bone. Further, the fine continuous pores in the particles facilitate the elution of TCP, which is a constituent phase other than HAP, to form new pores,
Induce living bone. Thus, excellent biocompatibility is exhibited.

The good mechanical strength of the present implant material is due to the tissue in which the substantially spherical particles form a neck and are connected. The implant material is also suitable as a carrier for impregnating the drug, which is based on the pore size distribution, and the pores between the approximately spherical particles facilitate the free diffusion and penetration of the drug-impregnated solution, and Numerous fine pores inside become sites for drug loading, allowing impregnation of a large amount of drug. On the other hand, when the drug is released, the release from the inside of the approximately spherical particles to the inside of the particles passes through the fine pores in the particles, so that the drug is released relatively slowly over a long period of time, and even once inside the implant material. The drug released between the particles is rapidly supplied to the outside of the implant material by free diffusion due to the relatively large interparticle pores.

In the method for producing the present implant material, the calcium phosphate raw material powder is not particularly limited as long as it is a raw material containing at least one of phosphorus and calcium such as hydroxyapatite and tricalcium phosphate. However, the total amount of calcium / phosphorus (Ca / Ca)
The P) atomic ratio is preferably 1.4 to 1.75 in terms of biocompatibility. For example, HAP only (plain) or HA
A mixed powder of P powder and a small amount of calcium carbonate or a mixed powder of calcium hydroxide powder and TCP powder is used.

Particularly preferred is a mixture of HAP powder and calcium phosphate-based glass frit (powder).
This mixed powder chemically reacts by the firing process and the frit changes to become a mixed crystal phase of HAP and TCP or a TCP phase. The great advantage of this mixed powder is that
A liquid phase is generated during firing to significantly promote the bonding (neck formation) between the fine HAP powders and between the molded substantially spherical particles. And, the growth of this neck is a very important factor for achieving both high porosity and mechanical strength.

The target implant material can be obtained with other raw material powders, but in any case, the growth of the neck of the fired body is insufficient, the strength is low, and particles may fall off. This HA
Only in the case of the mixture of P powder and calcium phosphate type glass frit (powder), even though it has a high porosity of 50 to 70% by volume, the particles do not fall off even if rubbed with hands, and the particles are crushed by fingers or the like. It did not show quite high strength. Wet processing using a diamond grindstone did not break easily, and good cutting was possible.

The average particle size of these starting materials is important,
If the particle size is larger than 5 μm, the neck between the fine powder particles in the particle is hard to progress, and the substantially spherical neck between particles does not grow. Therefore, particles may fall off the fired body,
The fired product tends to have low strength. Therefore, it is necessary that the average particle size is 5 μm or less, preferably 3 μm.
m or less. Incidentally, when the particle size of the starting material becomes small,
The size of the micropores formed in the particles of implant material is reduced.

From these raw materials, once the particle size is 20-800.
Granulate into substantially spherical secondary particles of μm. As this granulation method, spray drying using a spray dryer is preferable.
Specifically, a viscosity of 5 is obtained by adding an organic binder such as polyethylene oxide (PEO) or an emulsion type acrylic binder, a dispersant, and water to a mixture of raw material powders.
Adjust to ~ 30cp slurry and spray dryer to 2
Granulate into substantially spherical secondary particles of 0 to 800 μm.

The diameter of the secondary particles is selected according to the structure of the intended implant material, and the operating conditions of the spray dryer (concentration of powder, rotation speed of spindle, drying temperature).
Can be controlled by. When the diameter of the secondary particles is large, the pore diameter between particles formed in the implant material also becomes large. Depending on the conditions of the spray dryer, several μ may be present in the secondary particles.
Although there may be a cavity having a size of m to several tens of μm or more, it can be used as it is.

[0016] The granulated substantially spherical secondary particles (hereinafter,
Also referred to simply as “spherical particles”. ) Is 1 to 100 kg / c
Molding is performed by a pressure molding method such as a die press, a rubber press, and an underwater press with a molding pressure of m ² . When a mixture of HAP powder and calcium phosphate-based frit is used as a raw material, a preferable molding pressure is 10 to 60 Kg / cm ² . These compacts have a porosity of about 60-75%.

In the case of producing ordinary dense ceramics, the molding pressure is 500 to 800 Kg in a die press.
/ Cm ² , 1000 to 2000 kg / in a hydrostatic press
In contrast to cm ² , the molding pressure in the production method of the present invention is extremely low. That is, in the present invention,
When the granulated spherical particles are molded under such a low pressure, the granulated spherical particles do not crush and the spherical particles come into uniform contact with each other. As a result, an implant material having a bimodal pore size distribution can be manufactured.

Therefore, if the molding pressure exceeds 100 kg / cm ² , the granulated spherical particles are crushed and the desired bimodal pore size distribution cannot be obtained. On the other hand, the molding pressure is 1 kg
If it is less than / cm ² , the granulated particles are not sufficiently contacted with each other to obtain a homogeneous molded product, and the growth of the neck is insufficient even after firing. Therefore, the strength of the fired body is low and it cannot withstand cutting.

In order to increase the pores between the spherical particles, organic combustible particles having a size substantially equal to that of the spherical particles may be mixed and molded. In addition, when the spherical particles are subjected to dry molding by a centrifugal force with a centrifugal separator, the granulated particles are uniformly subjected to molding pressure, which is preferable for obtaining a homogeneous molded body.
This is because there is no inconvenience that the pressure becomes uneven between the peripheral portion and the central portion as in the die molding.

These compacts are fired at a temperature of 700 ° C. to 140 ° C.
The above-mentioned implant material is obtained by firing at 0 ° C. Especially when HAP powder and calcium phosphate-based frit are used, firing at 1000 to 1300 ° C. is preferable. When the firing temperature is lower than 700 ° C., neck growth between particles is difficult to proceed, and the implant material in which particles are connected cannot be obtained. If it is higher than 1400 ° C, the densification will proceed and the porous body will not have a good pore distribution.

The porosity varies depending on the firing temperature and is 70
By firing at 0 to 1100 ° C., densification does not proceed, pores are maintained, and necks between fine particles and secondary particle spheres grow. As a result, in firing at 1100 ° C., a structure in which secondary particles form a neck and are connected to each other is formed, and pores of 2 to 200 μm that are three-dimensionally connected are formed in the gaps between the secondary particles and the secondary particles. Further, continuous pores of 2 μm or less are formed in the secondary particles due to neck growth between the raw material fine particles, and a bioimplant material having a double pore structure can be obtained.

As already mentioned, the frit becomes a liquid phase and HA
The P fine particles and the secondary particles react with each other to form a mixed crystal phase of HAP and TCP. At temperatures above 1100 ° C, the amount and size of fine pores in the secondary particles gradually decrease, but the pores between the granulated secondary particles do not decrease, and an implant material with improved strength can be obtained. Therefore, the firing temperature can be selected from the balance between the amount of pores and the mechanical strength depending on the actual use.

[0023]

【Example】

- 95 wt% HAP powder of Example 1 The average particle diameter of 0.6μm and calcium phosphate glass frit (CaO-P ₂ O ₅ 90%
5% by weight or more) to prepare a water-based slurry in which a polyethylene oxide-based binder is added to the mixed powder.
Almost spherical particles having an average particle diameter of about 80 μm were granulated with a spray dryer.

The granulated particles were filled in a press mold and molded into a cylindrical sample having a diameter of 10 mm at each molding pressure of 0.5 to 500 Kg / cm ² . The obtained molded body was fired in an electric furnace at a temperature rising rate of 300 ° C./hour for 2 hours at each temperature to obtain Sample No. 1-14 were produced. Table 1 shows manufacturing conditions and characteristics of these samples.

[0025]

[Table 1] As seen in Table 1, sample No. Since 1 to 14 belong to the scope of the present invention, they have a high porosity of 25 to 73%, and the particles do not easily fall off even if they are rubbed with a finger or the like, and are not damaged by ordinary handling. there were. Then, when the crystal phase on the surface was identified by X-ray diffraction, HAP-TCP containing all TCP phases (30%)
Was a composite crystal phase of. Therefore, it has been clarified that the structure having the same quality as those of these samples is an implant material having high strength and excellent biocompatibility.

Next, a typical structure (Sample N) is shown in FIGS.
o.5 and sample No. 12) scanning electron microscope (hereinafter,
Abbreviated as "SEM". ) An observation photograph is shown. 1 (Sample No. 5) and FIG. 2 (Sample No. 12), the sample belonging to the present invention has a structure in which secondary particles of the calcium phosphate ceramics of about 80 μm are connected to each other, and in the gap between the secondary particles. It was found to have pores of about 10 to several tens of μm that are three-dimensionally connected. Moreover, each secondary particle was composed of finely linked primary particles, and open pores of at least 1 μm or less were observed. That is,
It was confirmed that the entire sample had a bimodal pore distribution structure. In No. 12, densification in the particles is progressing.

Sample No. 5 and sample N are shown in FIGS.
o. 12 shows the pore size distributions by the mercury porosimetry. According to this, a bimodal pore distribution of large pores of several μm to 100 (device limit) μm and fine pores of 2 μm or less was observed. This means that S shown in FIGS.
It basically agrees with the observation result of EM. However, in the pore size distribution determined by the mercury porosimetry, the pore size is markedly underestimated because, in principle, the porosity is controlled by the pressure equilibrium with the narrowest pore size of the continuous pores (ink bottom effect). Therefore, it is impossible to quantify the actual distribution by the mercury injection method, and it is considered that the SEM observation result is more reliable.

Examples 2-3-HAP powder 9 having an average particle diameter of 0.6 μm as a raw material powder
A sample of Example 2 was manufactured in the same manner as in Example 1 except that a mixed powder of 9% by weight and 1% by weight of calcium carbonate was used.
The characteristics of the sample No. It is shown in Table 2 as 15 to 20.

Example except that 85% by weight of HAP powder having an average particle size of 0.6 μm and 15% by weight of calcium phosphate glass frit (90% by mole or more of CaO-P ₂ O ₅ ) were used as the raw material powder. The sample of Example 3 was manufactured in the same manner as in Example 1. The characteristics of the sample No.
It shows in Table 2 as 21-26.

[0030]

[Table 2] Although the sample of Example 2 was obtained as a porous body having a bimodal pore size distribution in which secondary particles of substantially spherical shape were connected, as shown in Table 2, as compared with that of Example 1, it was lighter with fingers. Even if rubbed, the particles were likely to come off, and the mechanical strength was also slightly low.

In the same manner as in Example 1, the sample of Example 3 yielded a porous body having a good bimodal pore size distribution in which substantially spherical secondary particles were connected, and the particles did not fall off even when lightly rubbed with a finger. It did not happen and had high mechanical strength. The difference from Example 1 was that the constituent crystal phase was TCP.

Comparative Examples 1 to 5 Using the same raw material powder as in Example 1 or Example 3, a sample of Comparative Example 1 was manufactured at a molding pressure of 0.5 Kg / cm ² . The characteristics of the sample No. It shows in Table 3 as 27-30. Using the same raw material powder as in Example 1, molding pressure 5
The sample of Comparative Example 2 was manufactured at 00 Kg / cm ² . The characteristics of the sample No. Table 3 as 31, 32
Shown in.

HA having an average particle diameter of 7 μm was used as the raw material powder.
A sample of Comparative Example 3 was manufactured in the same manner as in Example 1 using a mixed powder of 95% by weight of P powder and 5% by weight of calcium phosphate-based glass frit. The characteristics of the sample No. It is shown in Table 3 as 33 and 34.

A sample of Comparative Example 4 was produced in the same manner as in Example 1, except that the same raw material powder as in Example 1 was used and the average particle size of the granulated particles was about 10 μm. The characteristics of the sample No. It shows in Table 3 as 35 and 36. A sample of Comparative Example 5 was manufactured in the same manner as in Example 1 except that the firing temperature was 500 ° C. The characteristics of the sample No.
It is shown in Table 3 as 37 and 38.

[0035]

[Table 3] As can be seen from Table 3, the sample of Comparative Example 1 was not a fired body with particles falling off, low strength, and handling. This is because it is difficult to uniformly contact and fill the granulated particles,
It is considered that this is due to the formation of large cavities in the molded body.

In the sample of Comparative Example 2, the granulated particles were crushed at the time of molding to form a high-density molded body, and a porous body having a single pore size when fired at 1100 ° C. and a dense high-strength implant material having no pores when fired at 1300 ° C. Became. In each of the samples of Comparative Example 3, the strength of the fired body was low, the particles easily dropped when rubbed with a finger, and the shape was not retained even by light handling. It is considered that this is because the growth of the neck between the raw material powders and between the spherical particles hardly progressed.

The sample of Comparative Example 4 was an implant material having a single pore diameter with few large pores formed in the fired body. In the sample of Comparative Example 5, the growth of the neck of the fired body did not occur, and the particles fell off and were easily broken.

-Comparative Example 6-A sample was manufactured in the same manner as in Example 1, except that the firing temperature was 1500 ° C. As a result, the densification proceeded regardless of the molding pressure, and the closed pores remained without the pores connected in three dimensions.

[0039]

The present invention is useful as a bioimplant material having high mechanical strength, good biocompatibility, and excellent drug loading.

[Brief description of drawings]

1 is a sample No. 1 of Example 1. FIG. 5 shows a particle structure of No. 5, (A) is a scanning electron micrograph at a magnification of 200, and (B) is a scanning electron micrograph at a magnification of 2000.

2 is a sample No. 1 of Example 1. FIG. 12 shows a particle structure of No. 12, (A) is a magnification of 200, and (B) is a magnification of 2000.
2 is a scanning electron micrograph of FIG.

3 is a sample No. 1 of Example 1. FIG. 5 is a graph showing the results of measuring the pore size distribution of No. 5 by the mercury penetration method.

4 is a sample No. 1 of Example 1. FIG. It is a graph which shows the result of having measured the pore diameter distribution of 12 by the mercury intrusion method.

Claims (5)

[Claims] 1. A group of connected particles, each having a size of 20 to 800 μm, made of calcium phosphate ceramics,
A bioimplant material having pores inside each particle and pores of 2 to 200 μm which are three-dimensionally communicated between the particles. 2. The bioimplant material according to claim 1, wherein the internal pores are continuous pores of 2 μm or less. 3. The bioimplant material according to claim 1, wherein the calcium phosphate ceramics contains hydroxyapatite and tricalcium phosphate as main crystal phases. 4. A fine calcium phosphate-based raw material powder having an average particle diameter of 5 μm or less is granulated into granules having a particle diameter of 20 to 800 μm, molded at a pressure of 1 to 100 Kg / cm ² , and then at 700 ° C. to 1400 ° C. A method for producing a bioimplant material, which comprises firing. 5. The method for producing a bioimplant material according to claim 4, wherein the calcium phosphate-based raw material powder is a mixture of hydroxyapatite powder and calcium phosphate-based frit, and the molding pressure is 10 to 60 Kg / cm ² .