JPH09234243A - Composite higher strength implant material and its production method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an ideal biological material which has higher mechanical strength than a bone, has rigidity and toughness, is difficult to suffer initial breakage, has higher connection ability, bone conductivity, and bone induction ability with a biological bone and has higher decomposition and absorption ability with in vivo because of use of bioceramics, and the biological material keep its strength until hard tissues are cured, then gradually is decomposed and absorbed. SOLUTION: This composite material is made in such a manner that bioceramics particles with diameter of 0.2 to 50μm are distributed in a crystalline thermoplastic polymer material with in vivo decomposition and absorptivity by 10 to 60% by weight. In a higher strength implant material of press-oriented forming body in which polymer crystals are press-oriented and its crystallization rate is 10 to 70%, crystals are oriented in parallel to multiple reference axes. A composite material in which bioceramics particles are distributed in a crystalline thermoplastic polymer materials with in vivo decomposition and absorptivity is created in advance, are melted and formed to make a pre forming body, and the pre-forming body is cold-pressed, filled, and oriented to produce an oriented forming body.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to an extremely strong composite of a novel particle of bioactive bioceramic and a biodegradable and absorbable crystalline thermoplastic polymer and a matrix polymer reinforced composite material. A high implant material and a manufacturing method thereof. More specifically,
INDUSTRIAL APPLICABILITY The present invention is biodegradable and absorbable, is replaceable with a living body, and at the same time has a bioactive novel and useful artificial bone, artificial joint, artificial tooth root, which has a bond with a living body and an inducibility of tissues. The present invention relates to a more ideal biomaterial useful for applications such as bone filler, bone cement, and bone prosthesis.

[0002]

2. Description of the Related Art It is safe without toxicity, stays in the body for a while, and its function is mechanically and physiologically maintained until healing.
It is made of a material that achieves its purpose and then gradually decomposes and disintegrates, is absorbed by the living body, and is excreted outside the body through the metabolic circuit of the living body. An implant that replaces the living body and reconstructs the original state of the living body is one of the ideal biomaterials.

In recent years, artificial bones, artificial joints, artificial tooth roots, bone filling materials, bone prosthesis materials for the purpose of substituting living bones and cartilage which are hard tissues have been used for the purpose of fixing fractures of cartilage or hard bones at various sites. Bone cements are made from various metals, ceramics and polymers. Among them, the metal bone-bonding material has a mechanical strength and elastic modulus much higher than that of the living bone, and therefore, there is a problem that the strength of the surrounding bone is lowered due to stress protection after the treatment. Further, although the ceramic bone cement is excellent in hardness and rigidity, it has a fatal defect that it is easily broken because it is brittle. Also, since polymers are usually less strong than bone, efforts are being made to increase strength. On the other hand, bioactive bioceramics, which can be directly bonded to bone, are often used by directly implanting or contacting the human body for the purpose of recovering or enhancing biological function.

In addition, it is strongly bonded directly to the living body, and
Bioceramics, which are gradually replaced by living organisms, have unknown potential, so further research is ongoing. However, although bioceramics generally have high rigidity and hardness, they have a brittle property that they are easily chipped or cracked by an impact force, which is a momentary force, as compared with metals, so their use as implants is limited. However, development of a material having toughness without brittleness is desired.

On the other hand, polymers used for implanting around hard tissues of living bodies are currently silicone resins used for replacing cartilage, curable acrylic resins as dental cement, ligaments. Some examples are known, such as braids of polyester or polypropylene fibers for use. However, ultra-high molecular weight polyethylene, which is inert and has high strength, which is used as a substitute for hard tissue in the living body,
Polypropylene, polytetrafluoroethylene, etc.
That alone is not sufficiently strong to replace living bone. Therefore, if these are used alone as a screw, a pin, or a plate for the purpose of joining substitute bones or bones, they are easily broken, cracked, or twisted and damaged.

Therefore, an attempt has been made to make an implant having high strength by using a composite technique of plastics. For example, carbon fiber reinforced plastic is one example. When it is embedded in a living body for a long period of time, peeling occurs between the fiber and matrix plastic, or the peeled carbon fiber breaks to leave the living body. It is not practical because it causes irritation and inflammation. In recent years, polyorthoester (butylene terephthalate-polyethylene glycol copolymer), which is said to bind to bone, has begun to attract attention, but the strength of this polymer itself is lower than that of living bone, and after binding to bone, There remains a problem of whether or not the physical behavior of the living body can be synchronized with the living bone. Unlike the above polymers that are non-absorbable in vivo, biodegradable and absorbable polylactic acid, polyglycolic acid, lactic acid-glycolic acid copolymer, and polydioxanone have been used as absorbable sutures for quite some time. It is clinically used. If each polymer used in this suture can be used as a bone-bonding material, it is not necessary to perform re-operation after healing, and the excellent property that biological tissue is reconstructed after the polymer is absorbed and disappears. There has been a long-standing idea that a bone cement material having Under such circumstances, researches using the above biodegradable and absorbable polymer as an osteosynthesis material have been actively conducted.

[0007] For example, a self-reinforcing bone-bonding device in which fibers of polyglycolic acid are fused has been proposed (US Pat. No. 4,968,317) and used clinically.
It has been pointed out that the decomposition is rapid, and that peeling between fused fibers and the disintegrated fibrous strips rarely stimulate the surrounding living body to cause inflammation. Further, JP-A-59-97654 discloses a method for synthesizing polylactic acid and a lactic acid-glyco-glycolic acid copolymer which can be used as a biodegradable and absorbable bone-joining device. It is the polymerization product itself that is mentioned as the bone-bonding material, nothing is said about the molding process of this material, and no attempt is made to increase its strength to the level of human bone.

Therefore, in order to increase the strength, a biodegradable and absorbable polymer material such as polylactic acid containing a small amount of hydroxyapatite (hereinafter simply referred to as HA) is molded and then heated in the longitudinal direction. For producing an osteosynthesis pin that has been stretched and oriented in the direction (Japanese Patent Laid-Open No. 63-68155), high molecular weight polylactic acid having a viscosity average molecular weight of 200,000 or more after melt-molding, and lactic acid-glyco-acrylic acid copolymer A bone-bonding material (Japanese Patent Laid-Open No. 198553/1989) obtained by stretching the molded body of No. 1 was proposed. In the bone cement or pin obtained by these manufacturing methods, the crystal axis (molecular axis) of the polymer material is essentially uniaxially oriented in the major axis direction, so that bending strength and tensile strength in the major axis direction are improved. To do. In particular, in the case of the latter, in the case of a bone cement having a viscosity average molecular weight of 200,000 or more after melt molding, it is practical because it has high strength even at a low stretch ratio that does not cause fibrillation.

However, in the bone cement essentially obtained by stretching only in the long axis direction, the molecules (crystals) are basically oriented only in the long axis direction which is the molecular chain axis (crystal axis). So
The anisotropy of the orientation with respect to the lateral direction, which is the direction perpendicular to the major axis direction, is large, and the strength in the lateral direction becomes relatively weak.
Further, according to the above-mentioned JP-A-63-68155, H
A mixture containing 5% by weight of A was stretched to 162 M.
Although the maximum bending strength of Pa is obtained, when the HA content of 20% by weight is included, the bending strength is a value when the bending strength is unstretched.
It will be lowered to 74 MPa, which is slightly higher than MPa.

However, this maximum strength value also does not sufficiently exceed that of cortical bone, and voids generated by stretching become a porous heterogeneous body in which a large number of voids are present at the interface between the filler and the matrix polymer. However, it cannot be used at all for implants that require high strength such as bone substitutes and bone cements. The publication also describes a method for producing a plate obtained by press-molding a biodegradable and absorbable polymer material powder such as polylactic acid containing a small amount of HA. The mixture of lactic acid was simply melt-pressed, and no concept aimed at increasing the strength in consideration of orientation is found.

[0011]

SUMMARY OF THE INVENTION It is an object of the present invention to provide a high-strength implant material that can solve these problems all at once and a method for producing the same.

[0012]

Means for Solving the Problems As a result of various studies on the above problems, the present inventors have found that bioceramic powder having a size of particles or aggregates of particles of 0.2 to 50 μm can be decomposed and absorbed in vivo. Due to particle and matrix polymer reinforcement, which is a dense, oriented molded body in which crystalline, thermoplastic polymer (hereinafter simply referred to as polymer) is substantially uniformly dispersed, and the crystals of the polymer are oriented by pressure. It was found that the above problems can be solved by forming a new composite material and using it as an implant material, and completed the present invention.

That is, the present invention is as follows: [1] Implant Material A biodegradable and absorbable crystalline thermoplastic polymer matrix having a size of particles or aggregates of particles of 0.1.
A composite material comprising a molded body in which 10 to 60% by weight of a bioceramic powder having a particle size of 2 to 50 μm is substantially uniformly dispersed, and the crystals of the matrix polymer are oriented by pressure, and the crystallinity thereof is Provided is a high-strength implant material, which is a particle and matrix polymer reinforced composite material, which comprises a pressure-oriented molded body having a content of 10 to 70%.
It is also characterized in that the crystals of the molded body are oriented essentially parallel to a plurality of reference axes. In addition, bioceramics powders are surface bioactive sintered hydroxyapatite, bioglass or crystallized glass biomedical glass, bioabsorbable unsintered hydroxyapatite, dicalcium phosphate, tricalcium phosphate, tetracalcium. It is also characterized in that any one of phosphate and octacalcium phosphate is used alone or as a mixture of two or more kinds. Also,

The biodegradable and absorbable crystalline thermoplastic polymer is either polylactic acid or lactic acid-glycolic acid copolymer, and its initial viscosity average molecular weight is from 10 to 10.
It is also characterized by the fact that it is 600,000. It is also characterized in that the thermoplastic polymer is polylactic acid and the bioceramic powder is unfired hydroxyapatite. It is also characterized in that the above-mentioned molded body is an oriented molded body obtained by pressure orientation by compression molding or forging molding. In addition, the molded body has a bending strength of 150 to 320 MPa,
It is also characterized in that the bending elastic modulus is 6 to 15 GPa. It is also characterized in that the above-mentioned oriented molded body is subjected to cutting processing and the like, and the bioceramic powder is exposed on the surface thereof. Also,

[11] Method for producing implant material (1) A crystalline thermoplastic polymer that is biodegradable and absorbable in advance and a bioceramic powder are prepared in a substantially uniform mixture, and then the mixture is prepared. A method for producing a high-strength implant material by pressure orientation, in which a preform is melt-molded to form a preform, and the preform is cold-press-filled into a cavity of a closed mold and plastically deformed to form an oriented compact. I will provide a. Further, (2) it is characterized in that the above-mentioned pressure orientation is carried out by cold press-filling into a cavity of a closed mold having a cross-sectional area smaller than that of the preform. In addition, (3) the crystallinity of the polymer of the pressure orientation molded body is 10 to 7
It is also characterized in that the preform is press-fitted and filled into the cavity of the closed mold so as to be 0%. Also,

(4) The mixture of the polymer and the bioceramics powder mixes and disperses the bioceramics powder in a solvent solution of the polymer substantially uniformly, and precipitates it with a non-solvent for the polymer. It is also characterized in that it is created by doing so. (5) The biodegradable and absorbable crystalline thermoplastic polymer is polylactic acid or lactic acid-glycolic acid copolymer having an initial viscosity average molecular weight of 150,000 to 700,000, and the viscosity average after melt molding is It is also characterized in that the molecular weight is 100,000 to 600,000. Further, (6) it is also characterized in that the preform is press-fitted into the cavity of the mold having a cross-sectional area of ⅔ to ⅕ of the cross-section of the preform. Further, (7) it is also characterized in that the plastic deformation temperature of the preform is a temperature at which the crystallization can occur between the glass transition temperature and the melting temperature of the polymer. It is also characterized in that (8) the pressure orientation is a compression orientation or a forging orientation. Further, (9) the present invention is also characterized in that the pressure oriented molded body is further cut.

Hereinafter, the present invention will be described in detail, but before that, it will be clarified from the viewpoint of a composite material that the present invention is a composite material by a new reinforcing method. <Characteristics of the composite material of the present invention> 1) When a large amount of minute materials are dispersed in the material for the purpose of improving the characteristics of the material, the former is referred to as a base material (matrix) and the latter is referred to as a dispersion material. A composite material is created by mixing these two kinds of substances in a macro phase, not in a microscopic mixture at a molecular level, and with excellent properties not found in a single substance.

As described above, the method of forming a material having superior properties (higher strength) by compounding different kinds of materials depends on the form of the dispersion material (reinforcement material) to be put in the matrix.
It can be classified as follows. Dispersion-strengthened compos
ite materials, Particle-reinforced composite
materials), Fiber-reinforced composite mat
erials).

The implant material of the present invention belongs to the composite material of The polymer as the matrix is polylactic acid or its copolymer, which is a thermoplastic and crystalline biodegradable and absorbable polymer, and the dispersant is the above-mentioned bioceramics in the form of fine particles.

2) By the way, conventionally, from the standpoint of material engineering, implants, which are composite materials made from the combination of, have been regarded as promising, and many such studies have been tried for a while. However, the method in which short fibers of bioceramics are filled as a dispersant and strengthened, for example, does not give good results because the fiber pieces stimulate the living body and cause inflammation. In addition, the above-mentioned self-reinforced method in which fibers of polylactic acid or polyglycolic acid having the same morphology as the fiber-reinforced ones were surface-fused was also considered, but the fusion interface between the fibrils was not microscopically Since it is homogeneous and peels easily between fibers, there is a drawback that the decomposed fragments rarely cause irritation to the living body. Since biomaterials must be safe and biocompatible without being toxic (due to harmfulness) to living organisms, they are disqualified from this point.

3) Now, even for the filler-filled composite material, if the bioceramic powder and the matrix polymer are simply mixed according to a conventional method, a composite material having a high strength as high as the object of the present invention is obtained. Is not an easy thing to get. In general, the properties of a filler-filled composite material include the morphology of the filler [shape (powder, spherical, plate-like, etc.), particle size, surface area], and functionality (in this case, binding to bone, bone). Inducibility, hard tissue induction capacity such as osteoconductivity, and bioavailability), and the nature of the polymer. The mechanical properties of the matrix polymer
And the content of fillers, morphology, orientation, interfacial force and other factors. Since many of these factors are intricately intertwined with each other, it is necessary to understand the effect of one factor on the overall properties in order to develop the desired structural and functional properties.

4) This point will be described in some detail.
In the composite material in which the filler is filled, the properties in which remarkable effects are exhibited are elastic modulus, tensile strength, elongation property, toughness, hardness and the like. In the case of the filler-filled composite material in the case of the present invention, particles having extremely small L / D (length / particle diameter) of bioceramics are selected, so that elasticity of the composite material reflecting high rigidity of bioceramics is selected. The modulus can be increased more effectively than the strength of the matrix polymer itself by increasing the filler loading. However, as the filling amount increases, the tensile strength, elongation, toughness, etc. tend to decrease. Therefore, the issue is how to increase the elastic modulus and to make other properties more than the strength of the original matrix polymer.

That is, it can be said that the compounding is a technique for synergistically drawing out the excellent properties of the dispersant and the matrix and for offsetting the defects. The elastic modulus is a value in a region where the degree of deformation is small, whereas mechanical properties such as tensile strength, bending strength, torsional strength, elongation and toughness are expressed in a region where the degree of deformation is relatively large. Therefore, basically, the elastic modulus is little affected by the interfacial adhesive force between the particles and the matrix, and the latter physical properties are greatly affected. Therefore, it will be noticed that if the interfacial adhesion is increased, the latter physical properties of goodness can be obtained.

5) A positive method for increasing the interfacial adhesion is
This is to bond the polymer as the matrix and the bioceramics as the dispersant with a coupling agent.
As the coupling agent, several ones represented by silicone type and titanium type are used in composite materials for industrial purposes. Therefore, these may be used.

However, at present, it cannot be said that the safety of this kind of compound to the living body has been deeply studied. Although these coupling agents are used for non-absorbable dental bone cement, which is a highly-filled material, there is no known case where it is actually applied to biodegradable and absorbable biomedical materials. Presently unknown, its use in the present invention should be avoided. That is, the method of chemically bonding the matrix polymer and the bioceramics particles to increase the interfacial force is a non-absorbable method for hard tissue implants that are decomposed and absorbed in the living body to replace the tissue as in the present invention. Unlike in the case of implants, the coupling agent is gradually exposed during the degradation process, so it is better not to use it at this time because the safety issue is still unsolved. In addition, the surface activity of bioceramics is impaired, which is not desirable.

6) By the way, a thermoplastic crystalline polymer
It is known that, in a system in which fine particles of the same concentration are mixed with each other, generally, when the degree of dispersion of fine particles is improved, impact strength, tensile strength, and elongation at break are relatively improved. Similarly, the size of the fine particles has a great influence on the physical properties of the composite material, and generally, the impact strength, the tensile strength, the compressive strength, the elastic modulus and the like relatively increase as the size decreases at the same concentration. The reason is that when the size is reduced, the surface area is relatively increased, so that the surface energy is relatively increased, and when the contact area with the polymer is also increased, it effectively functions as a nucleating agent for crystallization of the polymer. Yes, and as a result, the physical bond between the dispersant and the matrix is strengthened. In consideration of the above facts, it is only necessary to mix the smallest possible ceramic fine powder within a certain concentration range and in a state of good dispersion.

7) However, as in the present invention, bioceramics are mixed with a thermoplastic crystalline biodegradable and absorbable polymer to give extremely high strength equal to or higher than that of cortical bone, and When a composite material having a complicated function that enables early healing and replacement of living bone by induction and conduction is sought, these problems cannot be easily solved by only simple mixing as described above.

8) Specific measures for solving the problems of the present invention will be described below. As the particle size of the fine inorganic powders decreases, so does the surface area of the particles, and the particles easily secondary agglomerate, even by the generation of small surface charges, much larger than the size of a single particle. It usually forms an agglomerate. Therefore, it is technically not easy to obtain a uniform dispersion system in which aggregates of large fine particles do not exist in a particle-reinforced composite material having a relatively high filler concentration. The ease with which secondary aggregates are formed depends on the chemical structure of the fine particles, but the fine particles of bioceramics used in the present invention form aggregates relatively easily in a well-dried state. It is common to see that particles with an average particle size of a few μm have a size of 100 μm or more and aggregate.

9) By the way, it is known that the strength when not accompanied by a large deformation such as Notch Charpy impact does not depend on the size of the aggregate, but depends on the maximum diameter of individual particles. In addition, the composite material is a matrix polymer when it is subjected to bending, pulling, twisting, or other forces that cause large deformation and eventually fracture.
It is usually destroyed at the point of smaller deformation than when it is deformed and destroyed. These phenomena are caused by the fact that relatively large particles and agglomerates different from the polymer existing in the matrix behave differently from the matrix due to the deformation. That is, since the interface between the matrix and the particles is a discontinuous portion in which the external deformation energy that has propagated in the matrix cannot be transferred as it is, the interface between the two causes a fracture.

10) However, when the particles are finely and uniformly dispersed, the barrier for energy propagation is small, unlike the case where large particles or agglomerates are present, so the deformation energy resists. The matrix polymer of the composite material ruptures at a deformation amount closer to the time when the polymer deforms and ruptures by itself, since less is propagated throughout the system. In other words, a filler-filled composite material in a poorly dispersed state in which large particles are present (even if they are uniformly dispersed) or small particles form a large aggregate is large. It can be said that the strength at the time of breaking by deformation is smaller than the strength at the time of breaking only the matrix polymer containing no dispersed particles.

11) Therefore, it is possible to form a uniform dispersion system that is composed only of particles having a small particle size that does not significantly affect the amount of deformation and strength at the time of deformation fracture and does not form a large aggregate. , Is absolutely necessary when seeking high mechanical strength. That is, the fine particles of the bioceramics of the present invention have an appropriate temperature [hydroxyapatite (HA)].
Is 600 to 1250 ° C., apatite wollastonite glass ceramics (AW) is 1500 ° C., tricalcium phosphate (TCP) is 1150 ° C., 1400
C.], and then mechanically crushed into pieces, about 0.2 to 50 .mu.m, more preferably 1 to 10 several .mu.m.
It is necessary to use a system in which the particle size is selected and the agglomerate is uniformly dispersed so that the size of the aggregate is 50 μm or less.

Of course, in the case of non-calcined wet HA (wet HA), it is not necessary to calcine and pulverize, and the crystal particles in this range obtained by precipitation during synthesis can be used as they are. The size of this particle is not only necessary for satisfying the above-mentioned physical strength, but also has an important relationship with the reactivity exhibited by the surrounding osteoblasts, as will be described later. Systems satisfying such conditions have improved impact strength, surface hardness, elastic modulus, etc., which are strengths when subjected to small deformation, and bending and tensile strength, which are strengths when subjected to large deformation. The strength of torsion, etc. maintains the matrix polymer itself, and is a composite material with increased rigidity.

12) Here, one effective method for mixing bioceramics, such as HA, which relatively easily agglomerates, into the matrix without secondary agglomeration is to use bioceramics in a polymer dissolved in a solvent. Is added and well dispersed, and this dispersion is precipitated with a non-solvent. Bioceramics / polymer weight ratio is 10%
It is possible to mix from the following low ratios to high ratios exceeding 60%.

When the amount of bioceramics added is less than 10%, the volume ratio of bioceramics is small, and therefore the properties of direct binding to bone, bone conduction, and osteoinduction, which are expected of bioceramics, are difficult to develop, and the bioceramics cannot be expressed. Replacement with bone is also slow. On the other hand, if it exceeds 60%, the fluidity at the time of thermoforming of the mixed system becomes insufficient, so that molding becomes difficult. And
Since the amount of the polymer in the molded product is insufficient and the binder effect is not exerted, the filler and the polymer are easily separated from each other, so that the strength becomes brittle. Therefore, the preferable mixing ratio is 20 to 50.
%, But most preferably 30-40% by weight. Within this range, the desirable properties of both the dispersant and the polymer matrix as a composite material are remarkably exhibited in terms of both structure and function.

The conditions, objects and methods for obtaining a uniform dispersion have been described above from the viewpoint of obtaining a mixed system of bioceramics and polymer. 13) However, even if the composite material of polymer and filler uniformly dispersed in this way is processed by a normal thermoforming method, the strength of the high-strength plastic is exceeded, and the strength of cortical bone (bending strength of 150 to A biomaterial exceeding 200 MPa) cannot be obtained. In general, a polymer containing a large amount of filler has poor flowability and is difficult to thermoform. In addition, thermoforming is more difficult when a titanium-based coupling agent, which is extremely effective in improving fluidity, cannot be used, as in the present invention, in consideration of safety to living bodies.

When this composite of a polymer having poor fluidity and ceramic powder is kneaded and thermoformed by extrusion molding which is a molding method in which a shearing force is applied during melting, the polymer itself deforms and flows with its original flow characteristics. However, since the filled inorganic filler does not have the property of plasticizing and flowing due to heat, a boundary is generated at the interface between the polymer and the filler particles during movement due to flow deformation, and a void (void) intervenes, A molded product having a coarse density is formed. The strength of the porous molding containing a lot of voids is low. Therefore, in order to prevent the formation of voids, a pressure type molding method such as injection molding or press molding is generally used for molding such a polymer filled with a large amount of filler.

14) However, in such a usual molding method, the polylactic acid or its copolymer of the present invention is easily thermally deteriorated by shearing force or is significantly hydrolyzed by a small amount of contained water. Since it deteriorates, a high-strength molded product cannot be obtained at all. Nevertheless, if the heating conditions, drying conditions, and molding conditions of press molding are strictly adjusted, it may be possible to mold a plate with some deterioration of the polymer, but the polymer itself has a higher molecular structure and higher order. Since it is not reinforced at the structural level, it still does not have the strength to surpass cortical bone.

15) Stretching is one method for increasing the strength of a polymer which is crystalline and thermoplastic such as poly (L-lactic acid) and its copolymer. This is to pull both ends of a rod, which is a primary molded product, or the other end having one end fixed, outward from the molded product at a certain specific temperature (temperature Tm at which the polymer melts and flows). Is a plastic working for obtaining a secondary molded product having higher strength by uniaxially stretching in the long axis direction to orient the molecular chains and the crystal phase generated at that time in the tensile direction (MD).

Although the object and method are different from those of the present invention,
A method of mixing a small amount of HA of 5% and uniaxially stretching the primary molded body in the long axis direction is disclosed in the above-mentioned Japanese Patent Publication No. 3-63901. However, when the filler-filled polymer is stretched in this manner, the polymer is filled with the polymer as described above.
The polymer itself moves in the machine direction with the plastic deformation of the polymer, but the filler particles themselves do not move in perfect synchronization with the plastic deformation of the polymer. It is unavoidable that a demarcation occurs and a void occurs there. In particular, in the above-mentioned free width uniaxial stretching, which is a method in which an external force is not applied from the direction perpendicular to the stretching direction in the stretching process, the force acting by the stretching causes the material to be diluted per unit volume. Then, when the draw ratio becomes higher, the polymer changes from the microfibrils to the fibrillated state, but in this state, a micro discontinuous space is generated between the fibrils, so that the density of the material further decreases.

16) From this fact, the stretch-molded product of the composite material in which the filler is dispersed in a large amount has a larger number of voids as the filler filling amount increases, and the deformation amount due to the stretching increases. The larger (the larger the draw ratio), the larger the voids. Furthermore, the particle size of the filler is not adjusted, the dispersion is poor, and the number and size of voids are even more uneven in a system containing large agglomerates. In fact, since such a voided composite material is easily cut during stretching, the intended stretched product cannot be obtained. Thus, a stretched composite material containing voids does not provide the high-strength molding required by the present invention.

17) Therefore, the present inventor has earnestly studied and achieved the object by the following molding method. The billet of the polymer containing a large amount of bioceramics uniformly dispersed as described above is melt-molded by a method such as extrusion or compression molding under the condition that thermal deterioration is suppressed as much as possible, and the billet is further added with a polymer. It is a method of forming an oriented compact by compression molding or forging for the purpose of pressure orientation.

According to this method, the external force at the time of orientation molding acts in the inward direction toward the material body, which is opposite to the stretching,
The material becomes dense. As a result, the interface between the particles and the matrix changes to a more intimate state, and even the air-containing microvoids that existed at the interface during the mixing process are extinguished, so that high density is obtained. In other words, the two are even more integrated. In addition, the matrix polymer and the crystal phase are oriented in the matrix polymer, so that the obtained composite material exhibits significantly high strength. In this case, the orientation of the crystal obtained by press-filling the billet, which is the primary molded product, into the cavity of the mold having a cross-sectional area smaller than the cross-sectional area of the billet over a part or the whole is Since a force is applied by "sliding" from the plane, it is possible that the morphology has a strong tendency to have a plane orientation parallel to a certain reference axis, unlike uniaxial orientation by simply stretching in the long axis direction. .

Therefore, the characteristics that the anisotropy due to the orientation is small and it is strong against the deformation such as the twist are exhibited. However,
The degree of orientation is essentially controlled to such an extent that the molecular chain lamella is oriented, and is not so high that voids are generated due to the microfibrils and fibril structures observed when the draw ratio is high. 18) The strengthening method of the composite material of the present invention has been described above, but comparing this with that of the conventional composite material, FIG.
As shown in, the difference in morphology is clear. That is,
The conventional particle-reinforced type (a) and fiber-reinforced type (b) express the physical strength of the filled particles and the fibers themselves in the system by increasing the filling rate as much as possible, and at the same time, the matrix polymer. It is a method aimed at essentially increasing the strength depending on the chemical and physical bond strength with.

In the fiber reinforced type (b), the entanglement of fibers with each other actually works effectively for improving the strength. In this case, if a matrix polymer having a relatively high strength is used, such a high strength can be obtained. 19) However, there is no example of the present invention in which the matrix of this system is strengthened by performing secondary processing for crystal (molecular chain) orientation. The present invention is particle-reinforced
In addition to the strengthening method of (a), by aligning the matrix polymer under pressure as described above, the crystal (molecular chain) is oriented, and by making the interface between the particles and the matrix polymer more closely, more precise It is a strengthening method of (c) that strengthens by creating a system [particle strengthening + matrix strengthening type]. That is, the present invention relates to a novel method of physically strengthening a matrix polymer by cold secondary molding which has not been conventionally performed, and a composite system obtained thereby, and a difference from the conventional method is clear. .

(A) High Strength Implant Material The implant material of the present invention has a size of particles or aggregates of particles of 0.2 to 50 μm in a crystalline thermoplastic polymer which is basically biodegradable and absorbable. Is a composite material in which 10 to 60% by weight of the bioceramic powder is substantially uniformly dispersed, and the crystals of the polymer are oriented by pressure, and the crystallinity is 10 to 70%. It is characterized in that it is a certain pressure oriented molded body. Here, the "molded body obtained by compression molding or forging molding in which a closed molding die is pressed and filled and oriented is simply referred to as a" pressurized molded body ".

The contents will be described in detail below. (a) Bioceramics As the bioceramics used in the present invention, for example, sintered hydroxyapatite, bioglass-based or crystallized glass-based biomedical glass, unbaked hydroxyapatite, dicalcium phosphate, tricalcium phosphate, tetracalcium phosphate, Any one of octacalcium phosphate, calcite, diopside, etc., or a mixture of two or more thereof can be mentioned. The bioceramics are generally classified into 1) surface bioactive ceramics and 2) bioabsorbable ceramics.

1) Surface bioactive bioceramics Fired hydroxyapatite (HA), bioglass biograss, ceravitar, crystallized glass AW glassceramics and crystallized glass bioverit 1, implant-1, β-crystallized glass, diopside and the like. 2) Bioabsorbable bioceramics Unbaked HA (unbaked HA), dicalcium phosphate
Α-tricalcium phosphate (α-TCP),
β-tricalcium phosphate (β-TCP), tetracalcium phosphate (TeCP), octacalcium phosphate (OCP), dicalcium phosphate
To hydrate octacalcium phosphate (D
CPD / OCP), dicalcium phosphate / anhydride / tetracalcium phosphate (DCPA)
・ TeCP), calcite, etc.

The above-mentioned bioceramics have different degrees of bioactivity and cause a difference in the speed and morphology of new bone formation. Therefore, they are used alone or in combination of two or more so as to have the required bioactivity. . Among them, unbaked HA is very similar to HA in the living body, unlike unbaked HA, completely absorbed and disappeared in the living body, and has high activity.
It is one of the most effective bioabsorbable active powders for the system of the present invention because it is safe and has a track record of actual use.

(B) Particle Size of Bioceramic Powder The term “bioceramic powder” as used herein generally refers to primary particles of bioceramics or secondary particles that are aggregates (aggregates) of the same. 1) The particle size of the bioceramic powder is 0.2 to 50 μm in order to obtain a high-strength composite material based on the above reason.
Preferably, those having a particle size of primary particles or secondary aggregates (aggregation) lumps of 1 to 10 μm are used. The above-mentioned particle size is preferable also from the viewpoint of uniformly dispersing with the crystalline thermoplastic polymer which is biodegradable and absorbable.

Particle size of bioceramic powder is 50 μm
In the case of an upper limit close to, it is desirable that the size is an aggregate size when primary particles of about 10 μm are secondary aggregated.
When the independent primary particles have a size close to 50 μm,
This is not desirable because the composite material breaks (breaks) during yielding. The pressure-oriented molded product is finally finished into an implant material having various fine shapes by a method such as cutting. If the particle size is large, a fine and delicate shape will be chipped or cracked at the interface of the powder, making it difficult to process.
Therefore, it can be said that the particle size of 50 μm is the upper limit that determines the fineness of the shape of the implant material.

2) Further, the lower limit particle size of 0.2 μm corresponds to, for example, the size of primary particles of unbaked HA. Normal,
The fine particles aggregate to form secondary aggregated particles of several μm to several dozen μm. When a system in which bioceramic particles or agglomerates having an apparent average particle size within such a range are uniformly dispersed in a polymer matrix, high strength is obtained, and its absorption promptly leads to living bone. Both properties of the implant being replaced are satisfied at the same time. Then, an implant composite material having a fine shape is obtained.

3) When such an implant material containing bioceramics is embedded in a living body, the bioceramics powder which appears on the surface directly passes through the surrounding living bone and fibrous connective tissue. Alternatively, since it is indirectly bound via HA deposited on the surface, an initial fixation between the two can be obtained early. This property is preferable for implant materials such as pins and screws for the purpose of joining and fixing fractures. Further, the present invention can also be applied to plates, bone substitutes of different shapes, and bone cements, which could not be used due to insufficient strength in the past, because of their bondability to bone.

4) The implant material used as a bone fracture fixation material in bone maintains the strength required for fixation for at least 2 to 4 months required for bone union, and then from the surface in contact with body fluid. It takes a process in which hydrolysis gradually progresses and deteriorates. During this process, the bioceramic powder contained inside is gradually exposed to body fluid. After that, body fluid further penetrates into the interior of the implant along the interface between the bioceramic powder and the polymer. As a result, the hydrolysis of the polymer and the absorption of the decomposed substance into the living body become faster than in the case of the system containing no bioceramics alone. In addition, in this process, the exposed bioceramic powder promotes the invasion of new bone and sometimes becomes a nucleus of bone formation to form a trabecular bone. Then, in some cases, it is absorbed by osteoclasts or discharged from bone holes. In this way, biological bone can effectively enter and replace the lost bone hole of the implant material.

5) The process and morphology in which bone holes are replaced by living bone by the implant material of the present invention vary considerably depending on the type of bioceramics contained therein and the shape, size or content of the granules. The implant material of the present invention has a small amount of polymer as compared with the implant material made of a single polymer, and thus the implant material of the present invention has a small amount of polymer. It is possible to avoid the risk of an inflammatory reaction due to the foreign body reaction caused by the frequent occurrence. It is unbaked H
It is particularly effective in the case of fully absorbable bioactive particles such as A. Further, the speed of bone hole repair can also be adjusted arbitrarily by selecting the type, size, and amount of bioceramics.

(C) Composition of Polymer The polymer is not particularly limited as long as it is a crystalline thermoplastic polymer which is biodegradable and absorbable, but among them, biosafety and biocompatibility are confirmed, and it is already in practical use. Polylactic acid and various polylactic acid copolymers (for example, lactic acid-glycolic acid copolymer) are preferably used. The polylactic acid is preferably a homopolymer of L-lactic acid or D-lactic acid, and the lactic acid-glycolic acid copolymer has a molar ratio of 99: 1 to 75:25 and is a glycol. It is preferable because it has better hydrolysis resistance than an acid homopolymer.

In addition, amorphous D, L-polylactic acid or its lactic acid-glycolic acid copolymer, lactic acid-caprolactone copolymer, or biodegradable and absorbable biocompatibility compatible with the homopolymer or copolymer. A small amount of the above polymer may be mixed in order to facilitate plastic deformation or to impart toughness to the orientation-molded body obtained by pressure orientation. Of course, considering the reaction with the living body or the decomposition rate,
A polymer with a small amount of unreacted monomers and catalyst residues removed and purified is good.

(D) Molecular weight of raw material polymer and preform 1) The above-mentioned polymer is required to have physical properties such as strength of at least a certain value or more as a bone-bonding material. Since it is inevitably lowered at the stage of melt molding into the body, the polymer is polylactic acid or lactic acid-
In the case of a glycolic acid copolymer, it is important to use one having an initial viscosity average molecular weight of 150,000 to 700,000, preferably 250,000 to 550,000. When a polymer having a molecular weight in this range is used, it can be melt-molded under heating to finally obtain a preform having a viscosity average molecular weight of 100,000 to 600,000.

2) The polymer can be made into a composite material for high-strength implant materials by subsequent plastic deformation in the cold for orientation of molecular chains (crystals) by pressure orientation. If the conditions are properly set and manipulated during the plastic deformation process, the decrease in molecular weight can be suppressed as much as possible. The range of the viscosity average molecular weight of the polymer constituting the implant material containing the bioceramics is
There is a difference from the range in the case of implants obtained by molding only the same in the same manner. This is because a large amount of bioceramic powder is included, and therefore the apparent melt viscosity and the degree of deterioration during the process are different.

When the polymer according to the present invention has a molecular weight within this range, and a molded body in which molecular chains (crystals) are oriented by a pressure operation is actually used in vivo, for example, as an osteosynthetic material. , Maintaining the same or higher strength as living bone for at least 2 to 4 months, which is the average period required for bone fusion,
After that, the debris produced by the decomposition of the bone cement material gradually decomposes at a rate at which it does not show an inflammatory reaction due to a strong foreign body reaction with surrounding tissue cells. During this process, the bioactive properties of the bioceramics are developed so that an initial bond with the bone is obtained and then the replacement with the bone proceeds moderately.

3) The initial viscosity average molecular weight of the polymer is 15
If it is less than 10,000, the melt viscosity is low, so that there is an advantage that molding is easy, but high initial strength cannot be obtained. In addition, since the strength of the body is rapidly reduced, the strength maintenance period is shorter than the period required for bone fusion. After the implantation in the living body, 1.
Since a large amount of low-molecular weight debris may be generated in a short period of time within 5 to 2 years, there is a risk of inflammation due to the foreign body reaction. The initial viscosity average molecular weight of the polymer is 70
If the temperature is too high, the polymer will not flow easily when heated, and high temperatures and high pressures will be required when making a preform by melt molding, which will be caused by high shear stress and friction during processing. Due to heat, it causes a large decrease in molecular weight,
The final molecular weight of the implant material is 7
The strength is lower than that when the value of less than 100,000 is used, and the strength is smaller than the expected value.

With a polymer having a low initial viscosity average molecular weight of 150,000 to 200,000, a relatively large amount of 30 to 60% by weight of bioceramic powder can be filled, but if the molecular weight becomes lower after melt molding. Since it is easy to break (yield fracture) when yielding due to an external force such as bending deformation, it is preferable to keep the filling amount to a low filling amount of 10 to 30% by weight, and the deformation degree R described later to be kept relatively small. good. On the other hand, it is relatively difficult to melt-mold a polymer having a high viscosity-average molecular weight of 550,000 to 700,000. Therefore, it is much more difficult to melt-mold a polymer having a large amount of 40 to 60% by weight of bioceramic powder. is there. Therefore, the amount of bioceramic powder should be 20% by weight or less, and the degree of deformation R should be kept small.

In short, the initial viscosity average molecular weight is 200,000 to
If it is about 550,000, the filling amount and deformation degree R in a relatively wide range
Can be selected. In addition, the strength maintenance period in vivo is appropriate, and the rate of decomposition / absorption is also moderate. 4) When the filling amount of the filler is large, the fluidity of the mixture is poor, so in order to reduce the melt viscosity and facilitate the molding,
A low molecular weight polymer having a viscosity average molecular weight of 100,000 or less, or 10,000 or less may be added as a lubricant in a small amount so as not to affect the physical properties of the final implant. If the amount of residual monomer in the polymer used is large, it will lead to a decrease in the molecular weight in the process of processing, and the degradation in vivo will be faster.
It is desirable to control the amount to about 0.5% by weight or less.

When the filler is highly loaded at 40% by weight or more, it is made of a soft bioabsorbable polymer or polylactic acid D-isomer and L-isomer optical isomers for the purpose of increasing the interfacial bond strength between them. The complex may be surface-treated as a filler before use. Subsequent manipulation of the molecular (crystal) orientation by press-fitting into the mold gives a high-strength pressure-oriented compact, ie a material for implants, without substantially reducing the molecular weight. Then, high strength screw-shaped, pin-shaped, rod-shaped, disk-shaped, button-shaped, by secondary processing such as cutting, milling, punching, and punching.
A bone-bonding material having a tubular shape or other desired shape is manufactured.

(E) Crystallinity The pressure-oriented oriented body of the present invention has a range of crystallinity in consideration of the balance between two requirements of having high mechanical strength and having a moderate hydrolysis rate. Should be selected to be 10 to 70%, preferably 20 to 50%. When the crystallinity exceeds 70%, the apparent rigidity is high, but it lacks toughness and becomes brittle, and easily breaks when stress is applied in the body. Further, the decomposition is slower than necessary, and it takes a long time to be absorbed and eliminated in the body, which is not desirable.

On the contrary, when the crystallinity is as low as less than 10%, the improvement in strength due to the crystal orientation cannot be expected. Considering the mechanical strength, the speed of disappearance due to decomposition and absorption, and the low irritation to the living body, the appropriate crystallinity is 10 to 70%, preferably 20 to 50%. 10
Even with a low crystallinity of 20%, the effect of the filler improves the strength as compared with the case of no filling. Also, 50 to 7
Even with a high crystallinity of 0%, it is unlikely that fine crystals will be generated in the process of plastic deformation due to pressure and adversely affect decomposition and absorption in vivo.

(F) Density Since the implant material of the present invention is a three-dimensionally pressure-oriented molded body, it has a higher density than a conventional stretch-oriented molded body. It depends on the degree of deformation,
A mixture of bioceramics in the 20% range is 1.4-
1.5g / cm ³ , 1.5% for 30% mixed
1.6g / cm ³ , mixed with 40% is 1.6 ~
1.7 g / cm ³ , 1.7% for those mixed in the 50% range
It becomes 1.8 g / cm ³ . This high density is also an index showing the denseness of the material and is one of the important factors that support high strength.

(G) Crystal Morphology Since the implant material of the present invention is produced by pressure orientation, the crystals (molecular chains) of the molded body are oriented essentially parallel to a plurality of reference axes. In general, as the number of reference axes increases, the strength anisotropy of the molded body decreases, so that the material is less likely to be broken by a relatively weak force from a certain direction, such as a directional material. The proof of the fact that the crystals of the molded body in the implant material of the present invention are oriented essentially parallel to a plurality of reference axes will be explained with reference to FIGS. That is, FIG.
(B) is a vertical cross-sectional view and a plan view showing a state of crystals when a round rod is pressure-oriented by a compression orientation method as a typical example of pressure orientation.

As shown in FIGS. 1 (a) and 1 (b), the crystal morphology of the pressure-oriented compact is basically the axis L (simply referred to as the central axis) which is the mechanical core of the compact. That is, from the upper side to the lower side in FIG. 1 (a) along a number of reference axes N that are obliquely inclined from the outer peripheral surface toward the axis L of the center where the mechanical points on which external forces are concentrated during molding Oriented continuously and in parallel. In other words, a large number of reference axes N having a radial oblique orientation around the central axis L continuously form a substantially conical shape in the circumferential direction as shown in FIG. 1B, which is shown in FIG. As described above, they are continuously oriented in the vertical direction and are oriented parallel to the reference axis N to form a continuous phase of a substantially conical surface. That is, it can be regarded as an oriented structure in which the conical crystal planes are continuous in the vertical direction of the central axis L, and the crystal planes extending from the outer circumference to the center are oriented in the central axis direction.

Such a crystal state is achieved by the billet 1 being greatly sheared by friction during compression molding and being crystallized at the same time as being oriented obliquely from the outer peripheral surface toward the central axis L. In FIGS. 1 (a) and 1 (b), a cylinder such as a round rod has been described, but a pressure-oriented molded body such as a flat plate instead of a cylinder is as shown in FIGS. 2 (a) and 2 (b). In addition, the axis that becomes a mechanical core by receiving a large shearing force from both side surfaces does not become the center line, and the surface M including this axis and parallel to both opposite side surfaces of the plate and equidistant (middle). To form.

Therefore, the crystals of the plate-shaped pressure-oriented compact are:
An oblique reference axis N extending from the opposite side surfaces of the plate toward the surface M
Oriented parallel to. Further, since the axis L or the surface M including the axis L, which is the mechanical core of the molded body, is a point where the force from the outside is concentrated, by adjusting the force from the surroundings or both side surfaces during the pressure orientation, The point where the force from the outside is concentrated deviates from the center or the center, and the crystal is in the state of the crystal oriented toward the off-axis L or the plane M deviated to the left or right from the center.

(B) Manufacture of Implant Material The manufacture of the implant material of the present invention is basically carried out by (a) substantially uniform biodegradable and absorbable crystalline thermoplastic polymer and bioceramic powder. (B) Then, the mixture is melt-molded to form a preform (for example, a billet), and (c) the preform is narrowed in a molding die whose lower end is essentially closed. Molds that are either press-filled (in the case of compression orientation) into the cavity of a closed mold with space or whose cross-sectional thickness or width is either partially or wholly smaller than that of the preform. In the narrow space of the mold, or by press-fitting the mold space (in the case of forging orientation) into the mold cavity that is smaller than the space that houses the preform,
It is characterized in that the preformed body is formed into a pressure oriented formed body while being plastically deformed in the cold.

(A) Preparation of Mixture of Polymer and Bioceramic Powder 1) In order to mix and disperse the bioceramic powder, which is relatively easily aggregated, in the matrix polymer, for example, dichloromethane or chloroform may be used. It is desirable to employ a method in which a bioceramic powder is added to a matrix polymer dissolved in a solvent such as the above and dispersed well, and this dispersion is precipitated by adding a nonsolvent such as ethanol or methanol to form a mixture. In this case, the dissolved concentration of the polymer and the ratio of the solvent to the non-solvent may be adjusted depending on the kind of the polymer and the degree of polymerization.

2) The mixing ratio of bioceramic powder / matrix polymer is 10% to 60% by weight, preferably 20 to 50% by weight, and more preferably 30 to 40% by weight. When the mixing ratio is less than 10% by weight, the volume ratio occupied by the bioceramic powder is small, so that the properties of direct binding to bone, osteoconduction, and osteoinduction, which are expected of the bioceramic powder, are difficult to be expressed, and the bioceramic powder is not easily combined with the living bone. The substitution of is much slower, much like the polymer alone.

On the other hand, if it exceeds 60% by weight, the fluidity at the time of thermoforming of the mixed system becomes insufficient, making the molding difficult, and the amount of the polymer in the molded product becomes insufficient, so that the binder effect is not exerted. Therefore, the filler and the polymer are easily separated from each other, so that the strength becomes brittle. Further, since the bioceramic powder is exposed from the surface of the bone cement quickly during the decomposition process in the living body, there is a possibility that the harmfulness to the living body may be manifested. When the mixing ratio is within this range, desirable properties of both the bioceramic powder and the polymer matrix can be remarkably exhibited in both structure and function of the composite material.

(B) Melt molding 1) Although the composite material of the present invention belongs to the particle reinforced composite material,
A polymer system containing a large amount of bioceramic powder, such as the implant material of the present invention, generally has poor fluidity, and thus is difficult to thermoform. Furthermore, the implant must be considered for safety in the living body, and it is more difficult to perform molding under the present circumstances where the titanium-based coupling agent, which is extremely effective in improving fluidity, cannot be used.

When this composite material having poor fluidity is kneaded and thermoformed by general extrusion molding in which shearing force is applied during melting, the polymer itself deforms and flows with the original fluidity characteristics, but the filled bioceramic powder Since the body does not have the property of plasticizing and flowing by heat, a boundary is generated at the interface between the polymer and the bioceramics particles during movement due to flow deformation accompanying molding, and voids intervene, resulting in a molded body with coarse density. However, it is inevitable that the strength of the molded body tends to be low.

2) A ram (plunger) method is used for primary molding (melt molding to form a preform) of a polymer system containing a large amount of filler such as bioceramic powder as in the present invention. Although the melt extrusion method of is advantageous,
It is also possible to use a pressure-type molding method such as special injection molding or compression molding in consideration of the above problems so that voids are hard to be formed. In short, the melt molding for obtaining the billet may be carried out under the temperature condition of the melting point of the polymer or higher, but if the temperature is too high, the molecular weight is remarkably decreased, so devise it to prevent thermal deterioration at a temperature slightly higher than the melting point. It is desirable to perform melt molding so that voids do not exist.

For example, when the polylactic acid having an initial viscosity average molecular weight of about 150,000 to 700,000 is used as a polymer, its melting point or more and 200 ° C. or less, preferably about 190.
By selecting the temperature condition of ° C and sufficiently dehydrating and drying the polymer in advance, the viscosity average molecular weight after the melt molding can be maintained at 100,000 to 600,000. Similarly, in terms of pressure conditions, in order to prevent the molecular weight from decreasing due to heat generation due to friction, the minimum pressure capable of melt molding, for example, 300 kg / cm ² or less, preferably 150 to 250 k.
It is desirable to adopt g / cm ² . However, this varies considerably depending on the composition and size (thickness, diameter, length) of the preform (billet), so it may be changed depending on the situation.

3) It is desirable that the billet be melt-molded so as to have a cross-sectional shape similar to the cross-sectional shape of the cavity of the mold for pressure orientation molding, and if the cavity has a circular cross-sectional shape, it is larger. The billet is melt-molded so as to form a cylindrical body having a circular cross-sectional shape. In this way, if the cross-sectional shape of the billet is similar to the cross-sectional shape of the cavity, the billet can be plastically deformed while being uniformly compressed from the surroundings and press-filled into the cavity.
It is possible to obtain a homogeneous pressure-oriented molded body.

4) At that time, it is desirable that the billet is melt-molded so that the cross-sectional area thereof is 1.5 to 5.0 of the cross-sectional area of the cavity. After passing through the secondary process by pressure orientation in this way, a desired shape is cut out by tertiary processing such as cutting. 5) In some cases (especially in the case of a complicated cross-sectional shape), the billet that is the preformed body has a desired shape suitable for the next step, that is, secondary molding by pressure orientation, for example, forging orientation or compression orientation. It may be cut out.

(C) Pressure molding into a closed mold (i) A billet, which is a primary molded product, is subjected to pressure molding in a closed mold for secondary molding to obtain a molded product oriented in multiple axes. That is, for example, the ram extrusion method and the compression molding method are basically used to form the billet with a cross-sectional area of 2
Closed mold having a cross-sectional area of / 3 to 1/5 (however, 2 /
3 to 1/5 having a single value over the entire mold, or partially having a cross-sectional area of a plurality of values in this range at a plurality of portions of the mold, or Cold or cold [glass transition point (Tg) and melting temperature (Tm) while pressurizing continuously or intermittently in the cavity of the former two parts including the mold in the case of the same cross-sectional area as the billet). The temperature may be plastically deformed at a suitable temperature (Tc) at which a crystal between the two) is generated, and may be press-filled into the cavity for orientation.

Compression Molding FIGS. 3 and 4 are vertical cross-sectional views schematically showing a molding model by compression molding. FIG. 3 is a state before press-fitting the billet into the cavity of the mold, and FIG. The latter state is shown. The molding die 2 as described above has a thick cylindrical housing tube portion 2a for housing the billet 1 and a thin cylindrical molding cavity 2c into which the billet 1 is press-filled by the pressing means 2b.
And they are vertically coaxially connected to each other via a tapered diameter-reduced portion 20a. A pressurizing means 2b is provided on the upper part of the housing tubular portion 2a, and the billet 1 is continuously or intermittently pressed by the pressurizing means 2b such as a piston (ram). Then, in the bottom of the cavity 2c, very minute air vent holes and gaps (not shown) are formed.

As shown in FIG. 3, the billet 1 is housed in the housing cylinder 2a using the molding die 2 as described above, and the billet 1 is continuously or intermittently pressed by the pressurizing means 2b to form the cavity. In the state of FIG. 4 by cold press-fitting into the 2c while plastically deforming, a large shear due to friction occurs between the inner surface of the reduced diameter portion 20a and the inner surface of the cavity 2c during press fitting, and this is caused by the polymer. Acts as an external force (vector force) in the horizontal or diagonal direction that orients the.

Therefore, the polymer is essentially oriented along the inner surface of the reduced diameter portion 20a, and crystallization proceeds. At the same time, since the speed of press-fitting into the center of the molding cavity 2c is faster than the surroundings, the crystallographic axis of the compression-oriented compact 10 molded according to the shape of the cavity 2c has its longitudinal central axis as shown in FIG. Oriented obliquely with respect to L, the crystal is oriented parallel to many reference axes extending from the circumference to the central axis L. That is, the compression orientation molded body 10 oriented concentrically along the inner peripheral surface of the cavity 2c is obtained. At the same time, the polymer is compressed in the longitudinal direction (machine direction), so that the polymer also exhibits orientation in this direction. Thus, a qualitatively dense, thin columnar compression-oriented compact 10 is obtained.

In such press-fitting and filling molding, by changing the shapes of the accommodating cylindrical portion 2a of the molding die 2 and the cavity 2c having a small cross section similar thereto, it is possible to obtain compression-oriented molded articles of various shapes. it can. For example, FIG.
In order to obtain a plate-shaped compression-oriented molded body such as an osteosynthesis plate as shown in FIG. 2, a housing cylinder portion having a rectangular cross section and a cavity are formed into a reduced diameter portion (a shape in which only two sides in the long side direction are tapered, Alternatively, it is sufficient to use a molding die that is coaxially connected in the up-and-down direction via a shape in which four sides are tapered) and perform pressure orientation in the same manner. Further, by changing the inclination angle θ of the diameter-reduced portion 20a of the molding die 2 over the entire circumference or partially, the axis L or the surface M, which is the mechanical core of the molding, deviates from the center or the middle. Thus, it is possible to obtain a compression-oriented molded body having a crystalline state that is oriented obliquely toward the displaced axis L or plane M.

Forging Molding FIG. 5 is a vertical sectional view schematically showing a molding model by forging molding. The molding die 2 shown in FIG. 5 includes a cylindrical or (multi) -square tubular housing cylinder 2a having a hollow disk shape or a hollow (poly) square having a projected plane area larger than the cross-sectional area of the cylinder 2a. It is provided in the central portion of the cylindrical cavity 2c, and a pressurizing means such as a piston (ram) is provided on the upper portion of the accommodating cylindrical portion 2a. By using such a molding die, the billet 1 made of the above-mentioned polymer system is housed in the housing cylinder portion 2a and continuously or intermittently pressurized by the pressurizing means 2b, so that the billet 1 is cold on the projection plane. The cavities 2c having a large area are pressed and filled from the central portion to the peripheral portion while being expanded to obtain a cylindrical or (multi) square tubular forged oriented molded body.

The forged oriented compact obtained in this embodiment is different from the compression oriented compact in that the molecular axes and crystals are radially oriented with many axes from the central portion to the peripheral portion of the molding cavity 2c. It is a forged oriented molded product that is oriented parallel to many of the reference axes, and is a molded product having a different orientation form from a simple uniaxially stretched product. The method of such an embodiment is particularly effective when manufacturing a bone-bonding material having a hole inside such as a cylindrical shape, a (poly) square tube shape, or a button shape, or an accessory material thereof. In the case of forging, the pressurizing action of press-filling the billet into the cavity of the forming die is basically by casting, but the mechanism of orientation is basically the same as in the case of compression forming. .

According to the method of (ii), the external force at the time of orientation molding acts inwardly toward the material body, which is the opposite of the stretching, so that the material is in a dense state. Therefore, the interface between the bioceramics powder and the matrix polymer changes into a more intimate state, and even the air-containing microvoids existing at the interface during the mixing process are eliminated, so that a high compactness can be obtained. In other words, the two are even more integrated. In addition, the matrix polymer
Since the molecular chain axis and the crystal phase are oriented, the obtained composite material exhibits remarkably high strength. Its form is as shown in the above [particle-reinforced + matrix-reinforced type] (c) diagram of FIG. 6, and the difference from the conventional strengthening method by compounding the material is clear.

In the case of pressure orientation molding, particularly compression orientation molding,
As shown in FIG. 1, since a vector force is applied by “sliding” from the mold surface (molding surface), orientation is parallel to a certain reference axis, unlike uniaxial orientation by simply stretching in the major axis direction. It is in the form of a strong tendency. for that reason,
The feature is that it has little anisotropy due to orientation and is strong against deformation such as twisting.

(Iii) By the pressure molding according to the present invention, a secondary shape such as a block shape, a plate shape, a pin shape, a rod shape, a disk shape, or the like, in which the molecular chain axis or the crystal phase is essentially selectively oriented. Obtain a molded body. After that, if necessary, further milling, cutting, threading, drilling, etc. are performed, and implants of desired shape such as screw shape, pin shape, rod shape, disk shape, button shape, tubular shape, etc. Is finished. However, the method of obtaining an oriented compact by pressure orientation by compression or forging as referred to here is typically,
The diameter, thickness, and
Alternatively, it means a molding method of forcibly and continuously pressurizing and pressing into a narrow space of a molding die whose width is either partially or wholly small. Thus, orientational molding by stretching to stretch the material is essentially a different method and resulting molding.

(Iv) Deformation Deformation R = So / S (where So is the cross-sectional area of the billet,
S is a cross-sectional area of the pressure-oriented molded body) is 3/2 to 5/1
Pressure orientation molding may be performed within the range. If the degree of deformation is less than 3/2, the degree of pressure orientation is low and high strength cannot be obtained, and
When it is larger than 1, deformation is not easy, cracks are generated during molding, or fibrillation occurs and the anisotropy increases, which is not desirable. The range of R that can be most stably molded is 2/1 to 4/1.

(V) Plastic Deformation Temperature The temperature for plastic deformation is cold, that is, an appropriate temperature (Tc) at which a crystal having a glass transition point (Tg) or higher and a melting temperature (Tm) or lower is generated. If T
A temperature (Tc) suitable for crystallization may be selected from g (60 to 65 ° C) to Tm (175 to 185 ° C). Empirically, slippage of molecules occurs at a high temperature of 120 ° C or higher, so that it is difficult to obtain a good pressure orientation state, and at 80 ° C or lower, the ratio of the amorphous phase becomes considerably large, so that the strength is about cortical bone strength. It is difficult to obtain a highly oriented molded product. Therefore, the preferable temperature range is 80 to 120 ° C., more preferably 90 to 120 ° C.
１１０110 ° C. The Tg of the lactic acid-glycol copolymer having the monomer ratio in the above range is 50 to 55 ° C., but the preferable plastic deformation temperature is almost the same as that of the homopolymer.

(Vi) Plastic deformation pressure, etc. The pressure applied during plastic deformation is the deformation degree R, the time required for pressure orientation (deformation speed and heating time), and a mold having an So cross section for accommodating the preform. From the cavity of
Throttle angle (θ) of the path when compressed into a mold cavity having a cross-sectional area of S smaller than So (10 ° to 60 °
It can be arbitrarily selected within the range of °), but it is 3
00-10,000 kg / cm ² , preferably 500-
It is 5000 kg / cm ² . The heating time is 1 to 5 minutes in consideration of crystallization and its growth rate.

(Vii) Action of pressure orientation When plastically deformed under such conditions, for example, in the case of forging,
When pressure-filling a mold having a narrow cavity with a smaller diameter, thickness, or width than a billet, a large shear due to friction occurs between the mold wall and the mold, which causes the polymer to orient laterally and diagonally. External force in the direction (vector force)
And acts as to selectively orient the crystal. Then, the molded body is compressed in the direction of the orientation axis, and the interface between the polymer and the bioceramic powder is brought into a more intimate contact state, so that it becomes qualitatively dense and high strength is obtained. However, in the method of simply orienting the polymer system in the machine direction by extrusion, drawing and stretching, the lateral direction (side surface)
Is free (free width), the thickness becomes thin during the stretching process, and no external force is applied from the side surface. Therefore, a uniaxially oriented molded product in which the molecular chains and crystals are oriented only in the uniaxial (long axis) direction. Since this is a material that is qualitatively thinner than before stretching (a void is also formed) because the molded body is stretched in the orientation axis direction, it is mechanically weak, and the molding of the present invention is also performed. It has greater anisotropy than the body and also has less mechanical strength.

When the billet is pressure-oriented and shaped, crystallization proceeds during orientation during shaping. Although the degree of crystallinity varies depending on the molding time and temperature, in the case of a composite material containing a large amount of bioceramic powder that is a filler as in the present invention, the growth of crystals of matrix polymer is inhibited by bioceramics, Further, since the crystal tends to be finely broken by the pressure during the plastic deformation, the crystallinity is slightly smaller than that when the matrix polymer alone is molded for the same orientation. This is a preferable phenomenon from the viewpoint of the rate of decomposition in the living body and the tissue reaction.

(C) Features such as physical properties of implant material (i) The pressure-orientation-molded body of the present invention is compressed by the pressure at the time of molding to become dense, but its crystal has many reference axes. The strength anisotropy also decreases as much as possible. On the other hand, when the reference axis is uniaxial, the crystals (molecular chains) are uniformly arranged in parallel with the reference axis direction. Therefore, the pressure-oriented molded product of the present invention has improved mechanical properties such as flexural strength, flexural modulus, tensile strength, tear strength, shear strength, torsional strength, and surface hardness in a well-balanced manner, and does not easily break.

(Ii) Physical Properties The implant material of the present invention has a bending strength of 150 to 32.
0 MPa and a flexural modulus of 6 to 15 GPa
It is obtained depending on the filling amount of bioceramics, the degree of deformation, and the size of the molecular weight. Other physical strength ranges are tensile strength 80 to 180 MPa and shear strength 100 to 150.
MPa and a compressive strength of 100 to 150 MPa were obtained, and since these are generally similar to the strength of human cortical bone, it can be said that they are close to ideal as implants.

For example, a homopolymer of L-lactic acid having the above-mentioned initial viscosity average molecular weight range is added to HA having an average particle size of 5 μm.
When 30% by weight is uniformly mixed and dispersed, a pressure orientation molded article obtained by cold pressure orientation molding using a billet so that the deformation degree R = So / S is 1.5 or more is A flexural strength of 250 MPa or more was obtained, which is well above the flexural strength of cortical bone. Increasing the degree of deformation R that changes the degree of orientation improves the mechanical strength of the composite material in the machine direction. At the same time, when the filling amount of the bioceramic powder is large, a material having a high elastic modulus can be obtained.

Bending strength exceeding 300 MPa and elastic modulus close to 15 GPa of cortical bone can be obtained. The elastic modulus range of 6 to 15 GPa does not seem to have much difference in terms of numerical value, but when it is about 10 GPa or more, it is more difficult to bend during insertion as compared with less than that.
Since there is a large difference in the difficulty of bending, the difficulty of deforming the plate, or the rigidity, it is recognized that there is a difference more than the numerical value in the physical usefulness when used as an osteosynthesis material.

(Iii) The pressure-oriented and high-strength composite rod-shaped molded body of the present invention is further cut into a final molded product by a method such as cutting to obtain a medical implant. (Iv) Characteristics of Implant Material The implant material of the present invention contains: fine particles having a size of 0.2 to 50 μm or aggregates (clusters) thereof in a large amount and densely in an amount of 10 to 60% by weight. In the case of cutting by cutting, etc., a large number of bioceramic particles are exposed on the surface, it has good biocompatibility at the initial stage after embedding, and the bioceramics directly bind to the living bone, thus increasing the initial fixing property. .

Since the polymer matrix in which the molecular chains or crystals of the polymer having an appropriate molecular weight and its molecular weight distribution are oriented is made by the novel composite strengthening method in which the orientation is strengthened, the initial high strength is imparted, and , A strength close to that is at least 2-4 required for bone fusion
It can be designed to be maintained for months and then gradually degraded at a rate that does not cause tissue reaction. Since the bioceramic powder continues to exist inside the composite material, it gradually decomposes and is exposed to the surface, thereby contributing to bonding with living bone. Further, since the bioceramic powder promotes osteoinduction and osteoconduction and finally quickly fills the voids in which the polymer has disappeared, living bone can be efficiently replaced.

Since the composite material contains a large amount of bioceramics fine particles, it can be reasonably imaged in a plain X-ray photograph, and the treatment condition and the treatment process, which were not possible in the case of only the polymer, can be obtained. X-ray observation can be performed effectively. Furthermore, matrix polymers and bioceramics have been used clinically in the past, are safe for living organisms, and have excellent biocompatibility. Therefore, it can be said that the composite material for the implant is one of the ideal biomaterials.

[0103]

EXAMPLES The present invention will now be specifically described with reference to examples, but these do not limit the scope of the present invention. The measuring methods for various physical property values will be described below. Compressive bending strength, compressive bending elastic modulus: JIS-K-72
03 (1982). Tensile strength: Measured according to JIS-K-7113 (1981). Shear strength: Method of R.SUURONEN et al. [R.SU RONEN, T.PO
HJONEN et al, J. Mater. Med, (1992) 426]. Density: Measured according to JIS-K-7112 (1980). Crystallinity: Calculated from the enthalpy of the melting peak measured by a differential scanning calorimeter (DSC).

(Example 1) <Compression molding; Example 1> In a solution prepared by dissolving 4% by weight of poly-L-lactic acid (PLLA) having a viscosity average molecular weight of 400,000 in dichloromethane, a maximum particle size of 3 was obtained.
1.0 μm, minimum particle size 0.2 μm, average particle size 1.84 μm
m hydroxyapatite (HA) (calcined at 900 ° C)
The ethyl alcohol suspension of was added and stirred to uniformly disperse HA without secondary aggregation. Furthermore, while stirring, ethyl alcohol was added to co-precipitate PLLA and HA. Then, this was filtered and completely dried, so that HA having the above-mentioned particle size was contained in each of 20, 30, and 4 respectively.
PL uniformly dispersed in a proportion of 0, 50, 60% by weight
LA granules were obtained.

This was melt extruded by an extruder at 185 ° C.,
Diameter 13.0mm, length 40mm, viscosity average molecular weight is 2
50,000 cylindrical billets were obtained. Next, as shown in FIG. 3 and FIG. 4, the billet was heated to 110 ° C. in the accommodating cylinder of the hole having a diameter of 13.0 mm, and the diameter of the billet connected to the accommodating cylinder was reduced by 7 mm. By press-fitting and molding into a cavity having a hole of 0.8 mm and a length of 90 mm,
A compression-oriented molded body having the same shape as the holes of the cavity and having a composite of PLLA and HA in which HA was uniformly dispersed was obtained. However, θ = 15 °.

When the cross-sectional area of the molded body obtained here is S and the cross-sectional area of the billet before plastic deformation is So, the degree of deformation R
= So / S = 2.8. Table 1 shows the obtained composite H
A / PLLA compression orientation molded body (Sample No. 2, 3,
4, 5 and 6) and a PLLA compression-oriented molded article consisting of only PLLA and having a deformation degree of 2.8 (Sample No. 1: Control Example 1),
The physical properties of a non-oriented molded product (Sample No. 3'Control Example 2) containing 30% by weight of HA particles but not compression-oriented were compared.

[0107]

[Table 1]

As shown in Table 1, the mechanical properties of the PLLA compression-oriented molded article containing HA and compounded are remarkably improved. Further, as another contrast example, a force for orientation is applied in a direction away from the material in the direction opposite to the compression orientation of the present invention, and the orientation form is stretched and oriented by a conventional general uniaxial stretching method. Molded product (Sample No.
The physical properties of 7) are shown in Table 1. The stretching was performed by heating in liquid paraffin at 110 ° C. and then stretching.

This molded product is a filler when deformed by stretching.
Since the materials are displaced from each other due to the interface between the polymer and the polymer, the surface of the material is torn into fibrous parts, and the inside is an inferior substance that forms innumerable large and small voids due to the interface between the two. there were. Therefore, reproducible physical property values were not obtained, and the values were low. No. 1 in Table 1. 7
Showed the best value among them. In addition, since it is formed of numerous voids, it is a dilute substance having a low density of 0.924, and it is considered that biological fluid can easily infiltrate from the outside and the hydrolysis rate is high. From this, it was demonstrated that it is impossible to obtain a bone cement having the physical properties intended by the present invention by uniaxial stretching. Moreover, the strength was such that it could not be used as a bone cement.

(Comparative Example 1) <Compression molding> PLLA having a viscosity average molecular weight of 400,000 and a maximum particle size of 100 μm.
Using HA having an average particle size of 60 μm (calcined at 900 ° C.), PLLA granules in which 30% by weight of HA were uniformly dispersed were obtained by the same method and conditions as in Example 1. Then, this was melt-extruded with an extruder in the same manner as in Example 1 to obtain a diameter of 1
A cylindrical billet having a length of 3.0 mm, a length of 40 mm and a viscosity average molecular weight of 250,000 was obtained. Then, this billet was pressed into the holes of the molding die in the same manner and conditions as in Example 1, whereby the HA was uniformly dispersed and the compression orientation molding of the composite HA / PLLA with R = 2.8 was performed. Got the body

Table 2 shows the obtained molded product and HA of Example 1.
The physical properties of the molded product (Sample No. 3) containing 30% by weight were compared.

[Table 2]

Comparative Example 1 in which HA has an average particle size of 60 μm
Example 1 (Sample N) having an average particle size of 1.84 μm.
o. The strength was low as compared with 3). Further, in the bending strength test, Comparative Example 1 reached the yield point and was broken at the time when the maximum load was shown, but Example 1 (Sample No. 3) was not broken. This is because although PLLA is highly oriented, a large number of particles of large HA or large aggregates of brittle HA are distributed, so that the matrix of the orientation of PLLA is interrupted by HA and its strength is not utilized. It is thought to be a tame.

On the other hand, even the maximum particle size is 31.0
Example 1 containing HA that is an aggregated mass of μm (Sample No.
In the case of 3), it did not break even when the maximum load was exhibited. Similarly, the maximum particle size of Example 6 described later is 45
Even in the case of a compression-oriented molded body which is a composite material of unburned hydroxyapatite containing particles of μm or aggregates thereof, there was no breakage.

(Example 2) <Compression molding; Example 2> Using PLLA having a viscosity average molecular weight of 220,000 and 180,000 and the same HA as in Example 1, the same method and conditions as in Example 1 were used. PLLA granules in which HA of HA was dispersed uniformly were obtained and extruded by an extruder to obtain a cylindrical billet having a diameter of 13.0 mm, a length of 40 mm and a viscosity average molecular weight of 150,000 and 100,000, respectively. It was Then, this billet was pressed into the same molding die as in Example 1 in the same manner, whereby HA was uniformly dispersed and HA / PL of R = 2.8.
A LA-composited compression-oriented compact was obtained. In Table 3, the physical properties of the obtained compression-oriented molded article and the compression-oriented molded article having the same molecular weight as PLLA alone as a control example were compared.

[0115]

[Table 3]

The molded product from the billet having a viscosity average molecular weight of 150,000 has a slightly lower strength as compared with Example 1, but the bending strength is sufficiently high enough to be used as a bone cement. In addition, the strength and elastic modulus were increased as compared with the comparative oriented molded product containing only PLLA. On the other hand, the molded product from the billet having a viscosity average molecular weight of 100,000 had a higher flexural strength than that of only PLLA, but was broken at the yield point. However, when the filling amount of the bioceramics particles is 10% by weight, it is possible to obtain the one that is not broken during the descending condition depending on the conditions. Generally, when the molecular weight of a polymer is lowered, its specific strength is also lowered. It is considered that the molded product having a viscosity average molecular weight of 100,000 was ruptured because the toughness of the composite material decreased due to the incorporation of a large amount of HA. Therefore, even if HA is mixed, the lower limit of the viscosity average molecular weight of the billet required to have sufficient strength (rigidity) and toughness is 10
It is judged to be good.

(Example 3) <Compression molding; Example 3> PLLA having a viscosity average molecular weight of 400,000, and the same H as in Example 1
15% by weight under the same conditions and conditions as in Example 1
To obtain PLLA granules in which HA is evenly dispersed and extruded with an extruder to obtain a diameter of 13.0 mm and a length of 40 mm,
A cylindrical billet having a viscosity average molecular weight of 250,000 was obtained. Then, as shown in FIG.
3.0 mm storage cylinder, diameter 7.0 mm, length 113 m
m having a cavity of m.
In a molding die in which a 5 mm accommodating cylinder portion and a cavity having a diameter of 11.8 mm and a length of 57 mm were connected, HA was uniformly dispersed under the same method and conditions as in Example 1, and R = 3.5.
A HA / PLLA composite compression-oriented molded body with R = 1.5 was obtained. However, θ = 15 °. In Table 4,
The physical properties of the obtained molded product and a compression-oriented molded product of RLA = 3.5 and R = 1.5 consisting of only PLLA as a control example were compared.

[0118]

[Table 4]

From these results, the molded product of R = 3.5 has a high strength (rigidity) and a high toughness, which are even higher than the bending strength of the compression-oriented molded product composed of only PLLA which is highly oriented to the same degree. Met. Since the crystallinity is lower than that of the PLLA-only molded product, it is a material having low irritation and irritation to surrounding tissues in the living body. This is H
It is considered that the A particles inhibited the growth of PLLA crystals and acted on the microcrystallization. The molded product of R = 1.5 had a bending strength slightly higher than that of the molded product of only PLLA, but it is an implant material that can be sufficiently used depending on the application.

(Example 4) <Compression molding; Example 4> PLLA having a viscosity average molecular weight of 400,000 and an average particle diameter of 2.7 μm.
m apatite wollastonite glass ceramics (AW-GC) was used, and the same method and conditions as in Example 1 were used, and 35% by weight of AW-GC was uniformly dispersed in the PLL.
A granules are obtained and melt extruded by an extruder to have a diameter of 14.5.
A cylindrical billet having a length of 45 mm and a viscosity average molecular weight of 220,000 was obtained.

Next, as shown in FIG. 3, this billet was inserted into a housing cylinder portion having a diameter of 14.5 mm, a diameter of 9.6 mm, and
AW-GC / PLLA composite of R = 2.3 in which AW-GC is uniformly dispersed by press-fitting and filling in a molding die in which a cavity having a length of 83 mm is connected under the same method and conditions as in Example 1. Thus, a compressed and oriented molded body was obtained. However, θ = 20 °
It is. Table 5 compares the physical properties of the obtained compression-oriented molded article and the PLLA compression-oriented molded article of R = 2.3 consisting of only PLLA as a control example.

[0122]

[Table 5]

The obtained molded product has improved bending strength as compared with the molded product containing only PLLA. When this material is cut to expose AW-GC on the surface, AW-GC vigorously forms a HA layer on the surface several weeks after osteoinduction, which is an extremely effective implant for osseointegration, bone fusion and bone replacement. It can be.

(Example 5) <Compression molding; Example 5> PLLA having a viscosity average molecular weight of 400,000 and a maximum particle size of 22.0.
Using α-type tricalcium phosphate (α-TCP) having a particle size of μm and an average particle size of 7.7 μm, 25% by weight of α-TCP was uniformly dispersed by the same method and conditions as in Example 1. Obtained PLLA granules were melt-extruded by an extruder to obtain a cylindrical billet having a diameter of 13.0 mm, a length of 40 mm and a viscosity average molecular weight of 250,000.

Next, as shown in FIG. 3, the billet was inserted into a housing cylinder portion having a diameter of 13.0 mm and a diameter of 7.5 m.
m, in a mold with 96 mm long cavities connected,
Α-TCP was filled by press fitting under the same method and conditions as in Example 1.
Α-TCP / PLL with R = 3.0 in which are uniformly dispersed
A composite compression-oriented compact of A was obtained. However, θ = 1
5 ° C. In Table 6, the physical properties of the obtained compression-oriented molded product and the molded product of R = 3.0 consisting only of PLLA as a control example were compared.

[0126]

[Table 6]

The obtained molded product has high strength like the HA composite molded product, and its bending strength and elastic modulus are higher than those of PLLA alone. α-TC
Since P has higher bioactivity than sintered HA, it can be a high-strength implant effective for bone replacement.

(Example 6) <Compression molding; Example 6> PLLA having a viscosity average molecular weight of 360,000 and a maximum particle size of 45 μ
PLLA in which 40% by weight of HA was uniformly dispersed by using unbaked hydroxyapatite (wet-HA) having an average particle size of 3.39 μm and the same method and conditions as in Example 1.
The granules are obtained and melt-extruded with an extruder to have a diameter of 10.0.
A cylindrical billet having a length of 40 mm and a viscosity average molecular weight of 200,000 was obtained.

<Measurement of Activity> In order to examine whether the activity is higher than that of the billet 2 containing 40% by weight of calcined HA and uncalcined HA in the PLLA used in Example 6 above, respectively.
Create individual pieces from each billet (10 x 10 x 2 m)
m) was prepared, and both were immersed in the coagulant liquid, and the amount of the calcium phosphate component deposited on the surface was observed.
As a result, in the unbaked HA / PLLA, a large amount of crystals began to be deposited after 3 days, and the crystal layer covered the entire surface after 6 days, whereas in the baked HA / PLLA, the crystal did not cover the entire surface even after 6 days. It was

It has been confirmed that the calcined HA powder is not absorbed by bone cells and does not disappear, and in some cases, the cells may be exhaled again after feeding poorly, and it has been pointed out that the powder may cause a tissue reaction. There is. However, unbaked HA has complete absorbability that is absorbed by the living body and disappears.
Since it is chemically the same as A, there is no such problem. Up to now, no high-strength HA / PLLA high-strength implant has been developed, and this Example forms the basis of the novelty, significance, and invention of the present invention.

Next, as shown in FIG. 3, this billet was inserted into a cylindrical housing portion having a diameter of 10.0 mm and a diameter of 7.0 mm,
A compression mold having R = 2.0 in which unbaked HA was uniformly dispersed was obtained by press-fitting and filling in a molding die having a cavity having a length of 76 mm connected under the same method and conditions as in Example 1. .
However, θ = 30 °. In Table 7, the obtained compression-oriented molded product and R = 2.0 consisting of PLLA alone as a control example are shown.
The physical properties of the molded articles were compared.

[0132]

[Table 7]

The flexural strength of the unfired HA / PLLA composite compression-oriented molded article was similar to that of the fired HA composite compression-oriented molded article of Example 1 compared to the strength of the molded article composed of only PLLA. Also showed a high value. Unfired HA has a much higher bioactivity than fired HA, resulting in a highly bioactive composite high strength implant material.
Since unsintered HA is not sintered, it is an inorganic chemical substance itself and is not a powder with high strength like ceramics, but since it is not chemically modified by sintering, it is closer to hydroxyapatite in living organisms. It is a substance. In the present invention, since the matrix polymer is reinforced, the unsintered HA can also be made into a composite material having the same strength as that of the sintered HA.

(Example 7) <Compression molding; Example 7> PLLA having a viscosity average molecular weight of 400,000 and a maximum particle size of 45 μm.
m and an average particle diameter of 2.91 μm, beta-tricalcium phosphate (β-TCP) was used to uniformly disperse 30% by weight of β-TCP by the same method and conditions as in Example 1. Obtaining PLLA granules, melt-extruding with an extruder,
Diameter 13.0mm, length 40mm, viscosity average molecular weight is 2
50,000 cylindrical billets were obtained. Then, as shown in FIG. 3, the billet is provided with a housing cylinder having a diameter of 13.0 mm and a diameter of 8.6 mm, a length of 74 mm, or a diameter of 7.
In a molding die in which cavities having a length of 8 mm and a length of 90 mm were connected, press-fitting was performed under the same method and conditions as in Example 1, and β-T
R with CP uniformly distributed is 2.3 and 2.8, respectively.
A β-TCP / PLLA composite compression-oriented molded article was obtained. However, θ = 15 °. Table 8 shows the obtained compression-oriented molded body and HA of Example 1 (baked at 900 ° C.) in 3
R = 2.8 composite HA / 0% dispersed by weight
The physical properties of PLLA compression-oriented molded articles were compared.

[0135]

[Table 8]

The obtained molded products had larger Rs shown in Table 5 and Table 1 than the bending strengths of the PLLA-only molded products having 2.3 and 2.8, respectively. Also, for R = 2.8,
Since it has the same bending strength as that of the compression-oriented molded body of the same R, it became clear that a high-strength compression-oriented molded body can be obtained by combining β-TCP.

(Example 8) <Compression molding; Example 8> PLLA having a viscosity average molecular weight of 400,000 and a maximum particle size of 30.0.
PLLA granules in which 15% by weight and 25% by weight of TeCP are uniformly dispersed by using tetracalcium phosphate (TeCP) having an average particle size of 10.0 μm and by the same method and conditions as in Example 1. Was obtained and melted by a compression molding machine to obtain a cylindrical billet having a diameter of 13.0 mm, a length of 40 mm and a viscosity average molecular weight of 250,000. Then, as shown in FIG. 3, this billet containing TeCP in an amount of 15% by weight was in the same mold as in Example 3, and the one containing TeCP in an amount of 25% by weight in the same mold as in Example 5. To the Te by press-fitting under the same method and conditions as in Example 1.
R in which CP is uniformly dispersed is 3.5 and 3.0, respectively.
A TeCP / PLLA compression-oriented molded body of was obtained. However,
θ = 15 °.

In Table 9, the obtained TeCP / PLLA composite compression-oriented molded article and HA (90) of Example 3 are shown.
HA of R = 3.5 with 15% by weight of 0 ° C.) dispersed
/ PLLA composite compression-oriented molded article, and R = 3.0 in which 25% by weight of α-TCP of Example 5 is dispersed.
The physical properties of the compression-oriented molded articles of No. 2 were compared.

[0139]

[Table 9] Although the type of bioceramics contained in the obtained molded body is different from those of Examples 3 and 5, the content rate and R are the same. However, the respective molded products had almost the same strength. When R was 3.5, it exceeded 300 Mpa and showed extremely high bending strength.

(Example 9) <Compression molding; Example 9> PLLA having a viscosity average molecular weight of 600,000 and a maximum particle size of 40.0.
Using anhydrous dibasic calcium phosphate having an average particle size of 5.60 μm (anhydrous phosphoric acid-calcium hydrogen: DCPA), 45% by weight of DCP was prepared by the same method and conditions as in Example 1.
PLLA granules in which A was uniformly dispersed were obtained and melted by a compression molding machine to obtain a cylindrical billet having a diameter of 8.0 mm, a length of 40 mm and a viscosity average molecular weight of 460,000. This billet is then brought to a diameter of 8.0, as shown in FIG.
In a molding die in which an accommodating cylinder part having a diameter of mm and a cavity having a diameter of 5.7 mm and a length of 76 mm are connected to each other by press-fitting and filling under the same method and conditions as in Example 1, DCPA is uniformly dispersed R =
A 2.0 DCPA / PLLA composite compression oriented compact was obtained. However, θ = 45 °.

Table 10 shows the physical properties of the obtained compression-oriented molded product.

[Table 10] Although this molded product had a high viscosity average molecular weight, it could be plastically deformed by press fitting, had high bending strength and elastic modulus, and had high strength and toughness.

(Example 10) <Compression molding; Example 10> PLLA having a viscosity average molecular weight of 400,000 and a maximum particle size of 22.0.
In the same manner as in Example 1, except that octacalcium phosphate (OCP) having an average particle size of 8.35 μm was used.
P in which 0 wt% and 20 wt% OCP are uniformly dispersed
LLA granules were obtained and melted by a compression molding machine to obtain a cylindrical billet having a diameter of 13.0 mm, a length of 40 mm and a viscosity average molecular weight of 250,000. Next, a billet containing 10% by weight of OCP was placed in a molding die in which a housing cylinder having a diameter of 13.0 mm and a cavity having a diameter of 6.1 mm were connected to each other.
A billet containing 20% by weight of CP was press-fitted and filled into a molding die in which an accommodating cylinder portion having a diameter of 13.0 mm and a cavity having a diameter of 6.5 mm were connected by the same method and conditions as in Example 1 to uniformly disperse OCP. A composite compression oriented molded product of OCP / PLLA having R of 4.5 and 4.0 was obtained. However, θ = 15 °.

Table 11 shows the physical properties of the obtained compression-oriented molded product.

[Table 11]

The bending strength of all the molded products was 300MP.
The molded product had a high strength of a or more. Although the molded product of OCP 20% by weight had a lower R than the molded product of OCP 10% by weight, both the strength and elastic modulus were higher. However, the pressure during press-fitting is approximately 10,000 kg / cm ² because of the large R.
Needed pressure.

As a control example, a billet of 10% by weight OCP, which is relatively easy to press-fit, was press-fitted into a molding die having R = 5.5. However, the pressure when press fitting is 1000
A pressure higher than 0 kg / cm ² was required, and the molded body obtained had many cracks. From this, it can be said that the deformation degree R for compressive orientation of PLLA containing bioceramics is preferably 5 or less.

(Example 11) <Compression molding; Example 12> A copolymer of lactic acid-glycolic acid having a viscosity average molecular weight of 380,000 [P (LA-GA)] (molar ratio 90:10) and a maximum HA with a particle size of 31.0 μm and an average particle size of 1.84 μm (900
30 ° C.) by the same method and conditions as in Example 1.
HA of R = 2.8 in which HA of weight% is uniformly dispersed /
A composite compression-oriented compact of P (LA-GA) was obtained. However, θ = 15 °.

Table 12 compares the physical properties of the obtained molded product and the compression-oriented molded product containing only P (LA-GA) as a comparative example.

[Table 12] The obtained molded body was slightly lower in strength than the case of PLLA shown in Example 1. However, it is sufficiently useful as an implant material.

(Example 12) <Forging molding> In a solution prepared by dissolving 4% by weight of poly-L-lactic acid (PLLA) having a viscosity average molecular weight of 400,000 in dichloromethane, a maximum particle size of 3 was obtained.
1.0 μm, minimum particle size 0.2 μm, average particle size 1.84 μm
m hydroxyapatite (HA) (calcined at 900 ° C)
The ethyl alcohol suspension of was added and stirred to uniformly disperse HA without secondary aggregation. Furthermore, while stirring, ethyl alcohol was added to co-precipitate PLLA and HA. Next, this was filtered and completely dried to obtain PLLA granules in which HA having the above-mentioned particle size was uniformly dispersed in the proportion of 30 and 40% by weight.

This was melt extruded at 185 ° C. in an extruder,
Diameter 13.0mm, length 40mm, viscosity average molecular weight is 2
50,000 cylindrical billets were obtained. Then, as shown in FIG. 5, the billet was placed in a cylindrical housing of a disk-shaped molding die having a diameter of 100 mm and a thickness of 10 mm, in which a cylinder having a diameter of 50 mm was protruded in the center, and heated to 100 ° C. HA of the same size as the disk-shaped part of this mold by intermittently forging at a pressure of 3,000 kg / cm ² from
Thus, a composite body of composite forging / pressing orientation of / PLLA was obtained.

Test pieces were cut out from the molded body in the radial direction excluding the cylindrical portion, and the physical properties were measured. As a result, the bending strength was 220 MPa, the bending elastic modulus was 7.4 GPa, the density was 1.505 g / cm ³ , and the crystallinity was 43.0%. It is considered that the forged orientation shaped body is an oriented body in which the crystallographic plane is different from that in the above-mentioned embodiment and the orientation axis is polyaxially oriented from the central portion of the disc shape toward the outer peripheral direction.

(Example 13) <Example of cutting: surface observation and change with time> Each HA / PLLA composite compression-oriented molded body obtained in Example 1 was cut with a lathe to give an outer diameter of 4 A screw having a diameter of 3.2 mm, a root diameter of 3.2 mm and a length of 50 mm, and a pin having a diameter of 3.2 mm and a length of 40 mm were processed. Further, using the PLLA granules in which 30% by weight of HA of Example 1 was dispersed, a billet extruded in a plate shape with an extruder was obtained, and a storage cylinder portion having a rectangular cross section (plate shape) and In a molding die in which cavities each having a smaller cross-sectional area and a rectangular cross section are connected, press-fitting is performed under the same method and conditions as in Example 1, and R =
A plate-shaped molded product of 2.8 was obtained. The surface of this molded body is cut with a slicing machine to give a thickness of 2.0 mm and a length of 20.
A plate having a size of 5 mm and a width of 5 mm was obtained.

The surfaces of the screw, pin and plate were observed with a scanning electron microscope. In each of the cut products, the HA was not aggregated on the surface to form a large aggregate, and the fine particles were exposed in a uniformly dispersed state. It was also observed that the inside was similarly dispersed. The higher the HA content of these, the more HA appeared on the surface. It was also confirmed that such an implant was compact and void-free, and that the bioceramics and the polymer were in good physical contact with each other. This is because the material of the present invention has high mechanical strength, and the biological bone is directly contacted with the bioceramics to bond with the bone and maintain it for a period necessary for bone union, osteoinduction and bone conduction, or bone. It shows the rationale for the effective replacement.

Further, the high-strength polymers obtained in Examples
It was confirmed that the pressure-oriented molded body in which the bioceramics were composited maintained its strength in the simulated liquid at 37 ° C. for 2 to 4 months. After that, it was confirmed in vivo that, although the decomposition behavior was different depending on the composition and structure of the material, it was decomposed and absorbed more quickly after bone union than in the case of only the polymer and bone replacement.

[0154]

As is clear from the above description, the composite high-strength implant material of the present invention has mechanical strength equal to or higher than that of cortical bone, has rigidity and toughness, and has early fracture. Difficult to occur, bio-ceramics bond with living bone, bone conduction, osteoinduction and decomposition / absorption properties in the living body are utilized, and replacement with living bone is performed efficiently.
The strength is maintained until the hard tissue heals, but after that, it gradually decomposes and is absorbed at a speed that does not cause harm to the surrounding bone, and the lost trace is promptly reconstructed by the living body. Together with this, it is an ideal biomaterial that can be imaged by simple X-ray photography after surgery. In addition, the method of the present invention can easily produce the above-mentioned implant material without using special equipment or harsh conditions.

[Brief description of drawings]

FIG. 1 is a schematic view showing a crystalline state of a cylindrical implant material of the present invention. FIG. 1A shows a vertical cross-sectional view.
(B) shows a plan view.

FIG. 2 is a schematic view showing a crystalline state of the plate-like implant material of the present invention. FIG. 2A shows a vertical sectional view.
(B) shows a plan view.

FIG. 3 is a vertical cross-sectional view schematically showing a molding model by compression orientation, showing a state before press-filling a billet.

FIG. 4 is a vertical cross-sectional view schematically showing a molding model by compression orientation, showing a state after a billet is press-fitted and filled.

FIG. 5 is a vertical cross-sectional view schematically showing a forming model by forging orientation.

FIG. 6 is a schematic diagram showing an internal structure of a composite material of the present invention and a conventional composite material in comparison, regarding the strengthening method of the composite material.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 Billet 2 Mold 2a Storage cylinder 2b Pressurizing means 2c Cavity 20a Reduced diameter part 3 Implant material

Claims (17)

[Claims] 1. A bioceramic powder having a size of particles or aggregates of particles of 0.2 to 50 μm in a crystalline thermoplastic polymer matrix that is biodegradable and absorbable.
A composite material comprising a molded body in which 0 to 60% by weight is dispersed substantially uniformly, wherein the crystals of the matrix polymer are oriented by pressure, and the crystallinity is 10 to 70%.
A high-strength implant material, which is a particle and matrix polymer reinforced composite material, characterized in that it comprises a pressure-oriented molded body which is 2. High-strength implant material according to claim 1, characterized in that the crystals of the shaped body are oriented essentially parallel to a plurality of reference axes. 3. A bioceramics powder comprising a surface bioactive sintered hydroxyapatite, bioglass-based or crystallized glass-based biomedical glass, bioabsorbable unsintered hydroxyapatite, dicalcium phosphate, tricalcium phosphate. 3. The high-strength implant material according to claim 1 or 2, which is a single or a mixture of two or more of tetracalcium phosphate and octacalcium phosphate. 4. The biodegradable and absorbable crystalline thermoplastic polymer is either polylactic acid or lactic acid-glycolic acid copolymer, and the initial viscosity average molecular weight thereof is 10 to 6.
The high-strength implant material according to claim 1, wherein the high-strength implant material is 0,000. 5. The high-strength implant material according to claim 1, wherein the thermoplastic polymer is polylactic acid and the bioceramic powder is unfired hydroxyapatite. 6. The high-strength implant material according to claim 1, wherein the molded body is an oriented molded body obtained by pressure orientation by compression molding or forging molding. 7. The oriented molded article has a bending strength of 150 to 150.
The high-strength implant material according to any one of claims 1 to 6, which has a flexural modulus of 320 MPa and a flexural modulus of 6 to 15 GPa. 8. The high-strength implant material according to any one of claims 1 to 7, wherein the oriented molded body is subjected to cutting processing or the like and bioceramic powder is exposed on the surface thereof. 9. A preformed body is prepared by preparing a mixture in which a crystalline thermoplastic polymer which is biodegradable and absorbable in advance and a bioceramic powder are dispersed substantially uniformly, and then melt-molding the mixture. A method for producing a high-strength implant material by pressure orientation, characterized in that the preformed body is cold-press-filled into a cavity of a closed molding die and plastically deformed to form an oriented molded body. 10. The pressure orientation according to claim 9, wherein the pressure orientation is performed by cold press-filling into a cavity of a closed mold having a cross-sectional area smaller than that of the preform. For manufacturing high strength implant materials by. 11. The method according to claim 9, wherein the preform is press-fitted into the cavity of the closed mold so that the crystallinity of the polymer of the pressure-oriented mold is 10 to 70%. A method for producing the high-strength implant material described. 12. A mixture of the polymer and bioceramic powder, wherein the bioceramic powder is substantially uniformly mixed and dispersed in a solvent solution of the polymer, and the bioceramic powder is precipitated with a non-solvent of the polymer. The high-strength implant material manufacturing method according to claim 9, wherein the high-strength implant material is manufactured by: 13. A biodegradable and absorbable crystalline thermoplastic polymer is polylactic acid or a lactic acid-glycolic acid copolymer having an initial viscosity average molecular weight of 150,000 to 700,000,
The method for producing a high-strength implant material according to any one of claims 9 to 12, characterized in that the viscosity-average molecular weight after melt-molding is 100,000 to 600,000. 14. From 2/3 of the area of the cross section of the preform.
The method for producing a high-strength implant material according to claim 9 or 10, wherein the preform is press-filled into a cavity of a mold having a cross-sectional area of ⅕. 15. The high-strength implant material according to claim 9 or 10, characterized in that the plastic deformation temperature of the preform is a crystallizable temperature between the glass transition temperature and the melting temperature of the polymer. Manufacturing method. 16. The method for producing a high-strength implant material according to claim 9, wherein the pressure orientation is a compression orientation or a forging orientation. 17. The method for producing a high-strength implant material according to claim 9, wherein the pressure-oriented molded body is further cut.