JPH01131082A - Filler for deficient part and cavity of bone and production thereof - Google Patents

Abstract

PURPOSE:To obtain a filler for filling the deficient part and cavity of bones, effective in promoting the formation of new bones and integrating with the bone tissue of living body, by mixing a dense bioceramic powder with fine bioceramic powder and a binder, compression molding the mixture and baking the product. CONSTITUTION:A densely sintered bioceramic is pulverized and the obtained dense bioceramic powder is mixed with fine bioceramic powder and a binder. The mixture is dried, sieved, compression molded and baked to obtain the objective filler. The bioceramic used as a raw material is tricalcium phosphate, hydroxyapatite, tetracalcium phosphate or a mixture of two or more of the above compounds. The filler is composed of coarse powder of a bioceramic produced by densely sintering a porous sintered material and fine bioceramic powder attached to the coarse powder and has three-dimensionally interconnected pores.

Description

DETAILED DESCRIPTION OF THE INVENTION A. Industrial Field of Application The present invention is intended to fill bone defects and voids caused by, for example, bone tumors in a living body, to promote the formation of new bone there, and to improve the bone tissue of the living body. The present invention relates to a filling material for bone defects and voids that is integrated with the bone, and a method for manufacturing the same.

B Overview of the invention The main component is biocompatible, and osteoblasts can enter the pores.
Using bioceramics, which has the effect of being dissolved and absorbed in the body at the same time as new bone is generated, and quickly replacing autologous bone, it is made of densely sintered coarse powder and fine powder attached to the coarse powder. The filler was obtained as a porous sintered body having three-dimensional continuous pores.

In addition, another invention of the present invention has obtained a manufacturing method for obtaining a filler in the form of a porous sintered body having three-dimensional continuous pores, which is composed of densely sintered coarse powder and fine powder. It is something.

C. Prior Art Conventionally, when prosthesizing a bone defect in a living body, autologous bone has been harvested and transplanted.

However, autologous pre-collection has disadvantages such as an increase in the number of surgeries for storage and transplantation, and greater pain for the patient.

Therefore, alloys and organic substances have been used as hard tissue substitutes for living organisms. However, there were problems such as dissolution in living organisms, toxicity due to deterioration, and foreign body reactions.

Therefore, ceramics are currently used as biomaterials. Bioceramics include alumina, carbon, zirconia, and other bioinert materials that are insoluble and stable in the body, as well as hydroxyavatai) and (Caso (PO4)).
s (OH) 2, hereinafter abbreviated as HAP), tricalcila phosphate A (Ca3 (po,) 2, hereinafter abbreviated as TCP), etc., which are bioactive and biocompatible and cause decomposition, precipitation, and reactions in living organisms. There are some good ones.

However, in the above-mentioned bioceramics, bioinert substances exist as foreign substances in the living body for a long period of time. Furthermore, bioactive ceramics also have different properties such as solubility depending on their components and structures.

FIG. 3 is a diagram showing the solubility of hydroxyavatite and tricalcium phosphate. (Aomizu, Akao.

Ink pad, dental materials, equipment, 3B=67, 1984.1 In the figure, (O) is unprocessed HA, P, (B) is HAP
(△) is a sintered body of HAP, (・) is unprocessed β-TCP, (Im) is a sintered body of β-TCP, (Mu) is a sintered body of β-TCP, (x) is α-TCP, the solvent is 0.9% NaCl, and the temperature is 37±0.5°C.

As shown in the figure, HAP has very low solubility and remains in the body for a long period of time as a filling material for bone defects. β-T
CP has higher solubility than HAP, which is satisfactory to some extent.

Therefore, we decided to use β-tricalcium phosphate, which is absorbed in a shorter period of time than hydroxyapatite and replaced by autologous bone, to provide the best filling material for bone defects and voids. In other words, the best bone defect and void filling material is one that does not cause toxic reactions, integrates with bone in a short period of time, is absorbed by the body, promotes the formation of bone tissue, and finally We decided to obtain a filling material for the bone defects and voids, which would replace all of the bone defects and voids with new bone.

As mentioned above, in order to slightly increase the solubility, β-Tcp was added to
It was used as a porous sintered body.

Generally, porous sintered bodies of three-dimensional network ceramics are produced as follows.

■ Soft urethane foam impregnated with ceramic slurry is dried and then fired.

■Pour a certain amount of H20□ solution into ceramic mud, mix, dry, and then fire.

■By mixing organic beads in ceramic mud, drying, and firing, the organic beads are removed.

Therefore, we made a porous sintered body of β-TCP using method ①.
It was implanted into the mandibular alveolar bone of an adult and histologically observed over a long period of time. Figure 4 is a schematic diagram of an X-ray photograph taken immediately after implantation. In the figure, (1) is the alveolar bone, (2)
) is the gingiva above the alveolar bone (1), and (3) is a porous sintered body of β-TCP embedded in the alveolar bone. FIG. 5 is a schematic diagram of an X-ray photograph of the hexagon after implantation.

The porous sintered body of β-TCP is compatible with bone tissue, and osteoblasts enter the pores of the porous body, and the part where new bone is in direct contact with the surface of β-TCP and the part where the new bone is in direct contact with the surface of β-TCP absorbed,
A portion where bone tissue was formed and entered was observed at a location slightly away from the β-TCP porous sintered body.

However, as shown in Fig. 5, the upper part of the porous sintered body
The blood in the gums had dissolved and the tooth had been gouged out.

That is, the advantage of high solubility of the β-TCP porous sintered body appeared as a disadvantage. This can be considered as follows from the cross-sectional view of the porous sintered body.

FIG. 6 is a schematic cross-sectional view of the porous sintered body.

In the figure, (4) is a sintered body of β-TCP, and (5) is a continuous pore. The β-TCP part (3) in the figure is fired after drying the ceramic slurry, and the porous sintered body part is full of holes, forming continuous pores (5), and has a low density. It has a large surface area and therefore very high solubility.

D Problems to be Solved by the Invention As mentioned above, β
- TCP porous sintered body is good, but - in-shell manufacturing method,
Even if a porous material is made and applied, there is a problem that the amount of dissolution is too large in areas where there is a lot of blood circulation, such as the gums, making it unusable.

The present invention was made to solve this problem, and is a material that can completely replace new bone, and it can dissolve the structure of the bone defect and void filling material even in areas where there is a lot of blood circulation, such as the gums. The aim is to obtain an intact filling material.

Another object of the present invention is to obtain a method for manufacturing a bone defect and void filling material that solves the above-mentioned problems.

Means for Solving Problem E The bone defect and void filling material according to the present invention includes coarse bioceramic powder obtained by densely sintering a porous sintered body;
It is composed of fine bioceramic powder attached to the coarse powder and has three-dimensional continuous pores.

In addition, the method for producing a bone defect and void filling material according to another invention of the present invention includes a pulverization process of densely sintered bioceramics, and a fine powder of the densely sintered bioceramics produced in the pulverization process. Mixing process of bioceramic powder and binder, sieving process after drying, pressure forming process,
and a firing process.

F action In the present invention, the bone defect and void filling material is made of dense bioceramics and fine bioceramics, and has three-dimensional continuous pores, so that all of the material forms new bone in the living body. It is a replacement material and is difficult to dissolve before new bone is formed in areas where there is a lot of blood circulation, such as the gums.

G Example Example 1 FIG. 1 is an enlarged cross-sectional view of a main part showing an example of the present invention. 71 is a fine ceramic particle (diameter 0.3 to 3
．． 0 μm).

Note that the same reference numerals in the figures below indicate the same or corresponding parts.

The operation is shown below. After dropping an aqueous H3P O4 solution in an amount of Ca3(PO4)2 into a suspension of Ca(OH)2 with stirring, reaction and aging were performed for several days.
The resulting precipitate was filtered. Thereafter, it was dried and the powder was calcined at 800°C.

This powder is determined by the X-ray pattern to be β-Ca3 (PO4
12 is the main component (for example, as an impurity, CILI
O(PO4) 6(OH) 2, Ca2P2O□, a
Ca,, (PO4) 2, CagHz (PO4)
Ca-P-0 compounds other than β-Cas (r'o, )2) such as 6.5H20 were Ca-P-0 compounds.

Polyvinyl alcohol (hereinafter abbreviated as PVA) was added as a binder to this calcined material, and the material was pulverized in a ball mill for 7 hours. This was divided into halves, granulated by spraying, and then molded into pellets with a diameter of 60 mm and a thickness of 10 mm. Thereafter, the molded pellets were fired at 900 to 1,400°C, and the fired product was coarsely pulverized using a Raikai machine. This coarsely pulverized powder is passed through a sieve to a diameter of 710 μm or less.
Sorted to 0 μm or more, and for this sorted powder 2,
The calcined material ground in a ball mill is mixed with PVA at a weight ratio of 1 part.
The mixture was mixed together to form a dumpling shape, and then dried at 70°C.

The dried product was lightly crushed with a pestle and then passed through a sieve to form granules with a size of 710 μm or less and 420 μm or more.

The granules were molded using a weak pressure of 0.2 to 300 Kgf/c/ to obtain a porous pellet having a diameter of 8.0 mm and a thickness of 7.0 mm. This pellet is 900 to 1.
It was fired at 300°C. As shown in Figure 1, the cross section of this sintered body is a whole consisting of fine particles with a crystal grain size of 0.3 to 3.0 μm mixed with dense and coarse pieces of sintered body with a diameter of 50 to 500 μm. It is a porous body. This becomes one spherical body with a diameter of φ60 as shown in (8) in Figure 2.
It becomes a sphere of 0 to 1000 μm. These gather together, and between them there is a continuous hole (9) that is much larger than (5) in Figure 1.
is formed.

As a result of implanting this sintered body into the mandibular alveolar bone of an adult and observing it over a long period of time, no large dents due to dissolution were observed even in the areas in contact with the gums.

Example 2 Produced in the same manner as in Example 1, with a coarse powder particle size of 420
It is smaller than μm and larger than 125 μm.

As in Example 1, this sintered body was implanted into the mandibular alveolar bone of an adult and observed over a long period of time. As a result, no large dents due to dissolution were observed even in the areas in contact with the gums.

Example 3 Produced in the same manner as in Example 1, with a coarse powder of 125 μm.
It was made smaller and larger than 37 μm.

The results of the same animal experiments as in Examples 1 and 2 were as good as the results in Example 1.2.

Example 4 Examples 1, 2, 3. The weight ratio of the coarse powder to the powder finely ground using a ball mill was varied.

If the ratio of coarse powder is 5.01.0 or more, it becomes too brittle,
Could not be molded. When the ratio of coarse powder was set to 0.11.0 or less, the amount dissolved was too large.

As a result of animal experiments, sintered bodies with a weight ratio of 5.0 to 0.11.0 were used in Examples 1, 2, and 3. The results were good as well.

Example 5 The β-TCP porous body of Examples 1 to 4 porous body protein (
BMP) was immersed and BMP was attached to the surface of the porous material, and animal experiments were conducted in the same manner as in Examples 1 to 4. As a result, β-T
Bone tissue was formed more quickly than in the case of only the CP porous sintered body, and bone defects were quickly replaced with new bone.

As described above, we used β-TCP porous sintered body to conduct the test on the alveolar bone of an adult mandible. It is also possible to adjust the solubility by changing the shape.

Effects of the Invention The present invention (a porous sintered material having three-dimensional continuous pores, which is composed of a densely sintered bioceramic coarse powder and a fine bioceramic powder attached to the coarse powder) Since it is a body, when used in vivo as a filling material for bone defects and voids, it has biocompatibility, and osteoblasts enter the pores and new bone is generated, and at the same time it is dissolved and absorbed in the body. ,
It is quickly replaced with autologous bone. In addition, because it contains finely sintered bioceramic coarse powder inside, the components are difficult to dissolve even in areas that are in contact with blood flow areas such as muscles, and are filled before new bone grows. This has the effect that the structure of the material is not damaged.

In addition, another invention of B's invention is a process of crushing densely sintered bioceramics, a process of mixing the powder generated in the crushing process with a fine bioceramic powder, and a binder, and sieving after drying. 3, which is composed of a densely sintered bioceramics coarse powder and a fine bioceramics powder.
This has the effect of obtaining a porous sintered body having dimensional continuous pores.

[Brief explanation of the drawing]

Fig. 1 is an enlarged sectional view of the main part showing one embodiment of the present invention, Fig. 2 is an enlarged view of the porous sintered body, and Fig. 3 shows the solubility of hydroxyabacui) and tricalcium phosphate. Figure 4 is a schematic cross-sectional view of an X-ray photograph taken immediately after the entire β-TCP porous body was implanted, and Figure 5 is a photograph taken 6 months after implantation.
6 is a schematic cross-sectional view of a porous sintered body. (5) is a continuous pore, (6) is a dense sintered body of bioceramics, and (7) is a fine particle of ceramics attached to the dense sintered body.

Claims (15)

[Claims] (1) A porous sintered body composed of densely sintered coarse bioceramic powder, fine bioceramic powder attached to the densely sintered coarse bioceramic powder, and A bone defect and void filling material characterized in that the porous sintered body has three-dimensional continuous pores. (2) The bioceramics include tricalcium phosphate,
The bone defect and void filling material according to claim 1, which is made of one or a mixture of two or more of hydroxyapatite and tetracalcium phosphate. (3) The densely sintered bioceramic has a
The bone defect and void filling material according to claims 1 and 2, characterized in that it is sintered at ~1400°C. (4) The bone defect and void filling material according to claim 1 or 3, wherein the densely sintered bioceramic has a theoretical density of 70 to 100%. (5) The bone defect and void filling material according to claim 1, wherein the coarse powder has a diameter of 40 μm to 1000 μm. (6) The fine bioceramic powder has a diameter of 10
The bone defect and void filling material according to claim 1, characterized in that the particle size is .mu.m or less. (7) The bone defect and void filling material according to claim 1, wherein bone morphogenetic protein is adhered and solidified to the continuous pore wall surface of the porous sintered body. (8) Grinding process of densely sintered bioceramics, mixing process of the dense bioceramics powder generated in the grinding process, fine bioceramics powder, and binder, sieving process after drying, processing A method for producing a bone defect and void filling material, comprising a pressure forming step and a firing step. (9) The bioceramics include tricalcium phosphate,
9. The method for producing a bone defect and void filling material according to claim 8, which comprises one or a mixture of two or more of hydroxyapatite and tetracalcium phosphate. (10) The densely sintered bioceramic has a
The method for producing a bone defect and void filling material according to claims 8 and 9, characterized in that the material is sintered at 0 to 1400°C. (11) The method for producing a bone defect and void filling material according to claim 8 or 10, wherein the densely sintered bioceramic has a theoretical density of 70 to 100%. . (12) The method for producing a bone defect and void filling material according to claim 8, wherein the finely sintered bioceramic is crushed to have a diameter of 40 μm to 1000 μm. (13) The fine bioceramic powder has a diameter of 1
Claim 8, characterized in that the diameter is 0 μm or less.
A method for producing a bone defect and void filling material as described in . (14) The method for producing a bone defect and void filling material according to claim 8, wherein the binder is polyvinyl alcohol. (15) In the pressure forming step, the pressure forming pressure is 0.2 to
9. The method for producing a bone defect and void filling material according to claim 8, characterized in that the material is 700 kgf/cm^2.