JP3239127B2 - Composite high-strength implant material and method for producing the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

FIELD OF THE INVENTION The present invention relates to an extremely high strength composite material comprising a novel particle and matrix polymer reinforced composite of surface bioactive bioceramics and a biodegradable and absorbable crystalline thermoplastic polymer. High implant materials and methods for their manufacture. More specifically,
The present invention is a new and useful artificial bone, artificial joint, artificial root, which is biodegradable and absorbable in vivo, is replaceable with a living body, and at the same time has binding and tissue inducing properties with a living body and is bioactive. The present invention relates to a more ideal biomaterial useful for applications such as a bone filling material, an osteosynthesis material, and a bone prosthesis material.

[0002]

2. Description of the Related Art It is safe without toxicity, temporarily exists in a living body, and mechanically and physiologically functions until healing.
After achieving its purpose, it is gradually made up of materials that are gradually decomposed and disintegrated, absorbed by the living body, and excreted outside the body through the metabolic circuit of the living body. An implant that replaces a living body and reconstructs the original state of the living body can be said to be one of ideal biomaterials.

In recent years, artificial bones, artificial joints, artificial tooth roots, bone fillers, and bone prostheses for replacing living bones and cartilage, which are hard tissues, or for the purpose of fixing cartilage or bone at each site. Osteosynthesis materials have been made using various metals, ceramics, and polymers. Among them, the metal osteosynthesis material has much higher mechanical strength and elastic modulus than that of the living bone, and thus has a problem that the strength of the surrounding bone is reduced by stress protection after the treatment. In addition, the ceramic bone bonding material has excellent hardness and rigidity, but has a fatal defect that it is easily broken because of its brittleness. Also, efforts are being made to increase strength, as polymers are usually less strong than bone. On the other hand, bioactive bioceramics that can be directly bonded to bone have been used more frequently by being directly implanted or brought into contact with the human body for the purpose of restoring or enhancing biological functions.

[0004] In addition, it strongly binds directly to living organisms,
Since bioceramics that are gradually replaced by living organisms have unknown potential, further research is being continued. However, although bioceramics generally have high rigidity and hardness, they have the fragile nature of being easily chipped or cracked by instantaneous impact force compared to metal, so their use as implants is limited. The development of a material having toughness without brittleness is desired.

On the other hand, at present, polymers used for implanting around the hard tissue of a living body include a silicone resin used as a substitute for cartilage, a curable acrylic resin as a dental cement, and a ligament. Some examples are known, such as braids of polyester or polypropylene fibers for use. However, inert, high strength ultra-high molecular weight polyethylene used to replace the hard tissue of the living body,
Polypropylene, polytetrafluoroethylene, etc.
There is a considerable lack of strength to replace living bone by itself. Therefore, if these are used alone as a substitute bone or a screw, a pin, or a plate for joining bones, the bone is easily broken, broken, twisted, or broken.

Therefore, attempts have been made to produce a high-strength implant using a plastics compounding technique. For example, carbon fiber reinforced plastic is one example of this. When embedded in a living body for a long period of time, peeling may occur between the fiber and the matrix plastic, or the peeled carbon fiber may break and break the living body. It is not practical because it causes irritation and inflammation. In recent years, attention has been drawn to polyorthoesters (butylene terephthalate-polyethylene glycol copolymer) which are said to bind to bone, but the strength of this polymer itself is lower than that of living bone, and The question remains whether the physical behavior in the living body can be synchronized with the living bone. Unlike the above polymers, which are non-absorbable in vivo, polylactic acid, polyglycolic acid, lactic acid-glycolic acid copolymer and polydioxanone, which are biodegradable and absorbable, have been used as absorbable sutures for a long time. Clinically used. If each polymer used in this suture can be used as an osteosynthesis material, re-operation after healing is not necessary, and after the polymer has been absorbed and disappeared, the living tissue is reconstructed. The idea that an osteosynthesis material with a Under such circumstances, researches using the above-mentioned biodegradable and absorbable polymer as an osteosynthesis material have been actively conducted.

For example, a self-reinforced osteosynthesis device fused with polyglycolic acid fibers has been proposed (US Pat. No. 4,968,317) and used clinically.
It has been pointed out that it is degraded quickly, and the peeling between the fused fibers and the disintegration of the fibrous strips irritate, but rarely, the surrounding organisms to cause inflammation. JP-A-59-97654 discloses a method for synthesizing polylactic acid and a lactic acid-glycolic acid copolymer which can be used as a biodegradable and resorbable osteosynthesis device. It is the polymerization product itself that is mentioned as the osteosynthesis material, and nothing is described about the molding process of this material, and no attempt has been 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 formed, and then heated in the longitudinal direction. For producing an osteosynthesis pin stretched and oriented in a polymer (Japanese Patent Application Laid-Open No. 63-68155), and a high molecular weight polylactic acid or lactic acid-glycolic acid copolymer having a viscosity average molecular weight of 200,000 or more after melt molding. (Japanese Patent Application Laid-Open No. 1-198553) has been proposed. The osteosynthesis material or pins obtained by these manufacturing methods essentially have a uniaxial orientation of the crystal axis (molecular axis) of the polymer material in the major axis direction, so that bending strength and tensile strength in the major axis direction are improved. I do. In particular, in the case of a bone bonding material having a viscosity average molecular weight of 200,000 or more after melt molding as in the latter case, it is practical because the strength is high even in a low-magnification stretching that does not cause fibrillation.

However, in a bone bonding material obtained by stretching essentially only in the long axis direction, 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 transverse direction perpendicular to the major axis direction is large, and the transverse strength is relatively weak.
According to Japanese Patent Application Laid-Open No. 63-68155, H
162M by stretching a mixture containing 5% by weight of A
Although the maximum bending strength of Pa was obtained, the bending strength, which is 20% by weight of HA, was a value when the bending strength was not stretched.
The pressure drops to 74 MPa, which is slightly higher than MPa.

However, this maximum strength value still does not sufficiently exceed that of cortical bone, and voids generated by stretching become a porous heterogeneous body that exists at a large number at the interface between the filler and the matrix polymer. However, it cannot be used for implants requiring high strength such as replacement of living bone or osteosynthesis. The publication also discloses 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 lactic acid mixture is merely melt-pressed, and there is no concept aimed at increasing the strength in consideration of the orientation.

[0011]

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

[0012]

Means for Solving the Problems As a result of various studies on the above-mentioned problems, the present inventors have found that a surface bioactive bioceramic powder having a size of particles or aggregates of particles of 0.2 to 50 μm is used in vivo. Particles, which are substantially uniformly dispersed in a decomposable crystalline, thermoplastic polymer (hereinafter simply referred to as a polymer), and in which the crystals of the polymer are oriented under pressure, and The present inventors have found that the above problems can be solved by forming a novel composite material by reinforcing a matrix polymer and using the composite material as an implant material, thereby completing the present invention.

[0013] That is, the present invention provides: [1] Implant material In a crystalline thermoplastic polymer matrix which is biodegradable and absorbable, the size of particles or aggregates of particles is not more than 0.1%.
A composite material comprising a molded product in which 10 to 60% by weight of a surface bioactive bioceramic powder of 2 to 50 μm is substantially uniformly dispersed, wherein the matrix polymer crystals are formed by press molding by press-fitting. Crystallized and oriented
And a high-density pressure with a crystallinity of 10 to 70%.
Provided is a high-strength implant material which is a matrix polymer-reinforced composite material and particles composed of a press-oriented molded product by filling and filling . In addition, the particles or aggregated particles
High-strength implantation according size is 1-10 μm
It also has a feature in the point of material of the paint . In addition, the surface raw
Mixing ratio of bioactive ceramic powder is 20-5
0% by weight, and the density of the molded body is 1.4 to 1.8.
It is also characterized in terms of certain or described high-strength implant materials . Also,

[0014]The crystals of the above-mentioned molded body are essentially composed of a plurality of groups.
Oriented parallel to the quasi-axis~ofHigh described in any
Strength implant materialofpointIt also has features. Also,
The above-mentioned reference axis is an axis serving as a mechanical core of the molded body or
High strength described diagonally inclined toward a continuous surface
Degree implant materialofpointIt also has features. Also,
From the center of the compact to the periphery of the compact
High strength described, radially oriented with many axes
Implant materialofpointIt also has features. Also,Up
The shape of the compact is cylindrical, and crystals of the compact are formed.
Tilt obliquely from the outer peripheral surface toward the axis that becomes the mechanical core of the body
Oriented or described in parallel with multiple reference axes
High strength implant materialofpointIt also has features. Ma
WasThe shape of the molded body is a flat plate,
The crystal contains an axis that is the mechanical core of the compact and
Oblique from both sides toward the plane parallel to the opposite sides
Oriented parallel to multiple reference axes inclined for
High strength implant material as describedofpointAlso has features
You. Also,  Surface bioactive bioceramic powder
But calcined hydroxyapatite, bioglass
Or crystallized glass-based biological glass alone or
It is a mixture of two or moreAny ofStated high strength
It also has characteristics in terms of implant material. Also,(Ten) A crystalline thermoplastic polymer that is biodegradable and absorbable
Is polylactic acid or lactic acid-glycolic acid copolymer
And its viscosity average molecular weight is 100,000 to 600,000.
~One ofIn terms of the described high-strength implant material
Also have features. Also,(11) The thermoplastic polymer is polylactic acid,
Bioceramic powder is fired hydroxyapater
It isTo any of (10)High strength implants described
It also has a feature in the point of material of the paint. Also,(12) The molded body has a bending strength of 150 to 320MP.
a, the flexural modulus is from 6 to 15 GPa(11)Nozomi
It is also unique in terms of the high-strength implant materials described in
I do. Also,(13) The oriented molded product has a tensile strength of 80 to 180MP.
a, shear strength 100-150 MPa, compressive strength 100-
High strength according to any one of (1) to (11), which is 150 MPa.
Implant material ofpointIt also has features. Also,(14) The oriented molded body is cut and the like, and the surfacetable
BioactiveBioceramics powder is manifesting
~(13)High strength implant material according to any of the above
It also has features.

[11] Method for producing implant material  Crystalline thermoplastic polypreviously bioabsorbable
With maSurface bioactiveReal with bioceramic powder
To form a homogeneously dispersed mixture, and then dissolve the mixture.
Melt molding to make a preformed body, and closing the preformed body
Cold press-fit into the mold cavity to plastically deform
To form an oriented molded body,By press-fit fillingPressure orientationWas doneHigh
Provided is a method for manufacturing a strength implant material. Also,
Preparing by cold press-fitting and plastic deformation
By applying an external inward force to the molded body, the thermoplastic polymer and
Press-fitting described in close contact with ceramics powder
Of press-oriented high-strength implant material by filling
MethodIt also has a feature in the point. Also,  the aboveFor press-fit filling
AccordingClosed with pressure orientation smaller cross-sectional area than preform
By cold press-fitting the cavity of the chain mold
Or describedPressed orientation by press-fit filling
WasAnother feature is the method of manufacturing high-strength implant materials.
I do. Also,The pressure orientation by the above press-fit filling is preliminary
Large cylindrical housing tube for housing the compact and preforming
A cylindrical molding cavity that is thinner than
Lower part, that is, a narrow diameter part having a taper of constriction
It is done by a closed mold ~ Press fitting described in any of
Production of press-oriented high-strength implant material by filling
Construction methodIt also has a feature in the point. Also,Housing of mold
The cross section of the cylindrical portion is cylindrical or square cylindrical, and
For cavities larger than area, small in thickness, width and space
The storage cylinder is provided at the center, and
And press-fit filling
High-strength implant material oriented under pressure by press-fit filling
Manufacturing methodIt also has a feature in the point. Also,

[0016]  Crystallinity of polymer in press-oriented molded product
Of the preform so that the preform becomes 10 to 70%.
Press-fit into cavityAny ofStated
It is also unique in the method of manufacturing high-strength implant materials.
You. Also,  The polymer and the surface bioactive biose
The mixture with Lamix powder is a solvent solution of the polymer.
The above bioceramic powder is mixed substantially uniformly
Dispersing and precipitating this in a non-solvent of the polymer
Created by~High strength imp described in any of
It also has a feature in the method of producing a runt material. Also,
 A crystalline thermoplastic polymer that is biodegradable and absorbable
Polylactic acid having an initial viscosity average molecular weight of 150,000 to 700,000
Is a lactic acid-glycolic acid copolymer, after melt molding
Has a viscosity average molecular weight of 100,000 to 600,000~Any of
The method for producing high-strength implant materials described in
Has features. Also,  Of the cross-sectional area of the preform
Mold mold mold having a cross-sectional area of 2/3 to 1/5
Press-fit the preform into the tee~Any of
The method of manufacturing high-strength implant materials described in
Have signs. Also,(Ten) The plastic deformation temperature of the preform is the glass of the polymer.
Crystallizable temperature between the transition temperature and the melting temperature
To~, Any of ~High strength implan described
It also has a feature in the method of manufacturing the material. Also,(11) By press-fit fillingPressure orientation is compression orientation or forging orientation
Made in~, Any of ~High strength b
It is also unique in the method of producing implant materials. Ma
Was(12) Further cutting the pressed orientation molded body Written in
In terms of the method of manufacturing the high-strength implant material
Have.

Hereinafter, the present invention will be described in detail, but before that, from the aspect of the composite material, it will be clarified that the present invention is a composite material by a novel reinforcing method. <Characteristics of Composite Material of the Present Invention> 1) In the case where a large number of microscopic materials are dispersed therein for the purpose of improving the characteristics of a certain material, the former is referred to as a base material (matrix) and the latter is referred to as a dispersant. A composite material is created by mixing these two types of substances into macroscopic rather than microscopic mixtures at the molecular level so as to have excellent properties not found in a single substance.

As described above, a method of producing a material having more excellent properties (higher strength) by compounding different kinds of materials depends on the form of the dispersant (reinforcement) 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 according to the present invention belongs to the composite materials of. The polymer as the matrix is polylactic acid or a copolymer thereof, which is a thermoplastic and crystalline biodegradable and absorbable polymer, and the dispersing material is the surface bioactivity of the fine particle powder described above.
Such is the bio-ceramics.

2) By the way, conventionally, from the viewpoint of material engineering, an implant which is a composite material made of a combination is considered to be promising, and such studies have been tried many times at one time. However, in the method of reinforcing by filling short fibers of bioceramics as a dispersing material, good results were not obtained because the fiber fragments stimulate the living body and cause inflammation. In addition, the above-mentioned self-reinforcement type method in which fibers of polylactic acid or polyglycolic acid having the same form as the fiber-reinforced ones were surface-fused was considered, but the fusion interface between fibrils was not microscopic. Since it is homogeneous and easily peels off between the fibers, there is a disadvantage that the decomposed strip rarely causes irritation to a living body. Biomaterials must be safe, biocompatible, non-toxic (harmful) to living organisms, and are disqualified from this point.

3) Even in the case of the filler-filled composite material, if the bioceramic powder and the matrix polymer are simply mixed according to a conventional method, a high-strength composite material of the present invention can be obtained. Is not easy to obtain. In general, the properties of the filler-filled composite material include the form of the filler (shape (powder, spherical, plate-like, etc.) and the size and surface area of the particles), and the functionality (in this case, bonding with bone, bone Hard tissue-inducing ability such as conductivity and bioabsorbability), and the nature of the polymer.
The mechanical properties are determined by the matrix polymer and filler.
Greatly depends on factors such as the content, morphology, orientation, and interfacial force. Since many of these factors are intricately entangled with each other, it is necessary to fully understand the influence of a certain factor on the overall characteristics in order to achieve the desired structural characteristics and functional characteristics.

4) This point will be described in some detail. In the composite material filled with the filler, the characteristics that exhibit remarkable effects are elastic modulus, tensile strength, elongation characteristics, toughness, hardness and the like. In the case of the filler-filled composite material of the present invention, since the L / D (length / particle diameter) of the bioceramic is selected to be extremely small, the elasticity of the composite material reflecting the high rigidity of the bioceramic is selected. The percentage can be more effectively increased by increasing the filler loading than the strength of the matrix polymer itself. However, the tensile strength, elongation, toughness, and the like tend to decrease as the filling amount increases. Thus, the challenge is how to increase the modulus of elasticity and other properties beyond the strength of the original matrix polymer.

That is, it can be said that the compounding is a technique for synergistically extracting the excellent properties of the dispersant and the matrix and canceling out the defects. The elastic modulus is a value in a region where the degree of deformation is small, whereas mechanical characteristics 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 various physical properties are greatly influenced by the latter. Thus, it will be noted that increasing the interfacial adhesion will provide better latter physical properties.

5) An aggressive method for increasing the interfacial adhesion is as follows:
The purpose is to combine a polymer as a matrix and a bioceramic as a dispersant with a coupling agent.
Some coupling agents represented by silicones and titaniums are used in composite materials for industrial use. Therefore, these may be used. But,
At present, it is hard to say that the safety of this kind of compound for living organisms has been deeply studied. Although these coupling agents are used in non-absorbable dental bone cement, which is a high-filling material, safety is not known because there is no actual application to biodegradable and absorbable medical materials. At present it is unknown and should be avoided for use in the present invention. That is, the method of increasing the interfacial force by chemically bonding the matrix polymer and the bioceramic fine particles is not suitable for a hard tissue implant which is decomposed and absorbed in the living body to replace the tissue as in the present invention. Unlike implants, the coupling agent is gradually exposed during the degradation process and should not be used at this time as safety issues remain unresolved. In addition, the surface activity of the bioceramic 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 having the same concentration are mixed, the impact strength, tensile strength and elongation at break are relatively improved when the degree of dispersion of the fine particles is generally improved. Similarly, the size of the fine particles greatly affects the physical properties of the composite material. When the size is reduced at the same concentration, the impact strength, tensile strength, compressive strength, elastic modulus, and the like generally increase relatively. The reason is that when the size is reduced, the surface area is relatively increased, so that the surface energy is relatively increased. Further, when the contact area with the polymer is also increased, it effectively functions as a nucleating agent for crystallization of the polymer. Yes, as a result, the physical bond between the dispersant and the matrix is enhanced. In view of the above facts, it is only necessary to mix the ceramic fine powder as small as possible within a certain concentration range with as good a dispersion as possible.

7) However, as in the present invention, bioceramics having surface bioactivity are mixed with a thermoplastic, crystalline biodegradable and absorbable polymer so as to have an extremely high strength equal to or higher than that of cortical bone. In addition, when a composite material having a complex function of being able to quickly heal and replace living bone by bone induction and conduction is required, these problems can be easily solved only by simple mixing as described above. Not something.

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

9) By the way, it is known that the strength when not accompanied by a large deformation such as a notch Charpy impact does not depend on the size of the aggregate, but depends on the maximum diameter of each particle. In addition, when the composite material is greatly deformed and is subjected to a force such as bending, tension, or torsion that eventually leads to destruction, the composite material becomes a matrix polymer.
It usually breaks at the point of smaller deformation than it breaks itself. These phenomena are caused by the fact that relatively large particles and aggregates different from the polymer present in the matrix behave differently from the matrix due to deformation. That is, 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 move as it is, so that the fracture occurs at the interface between the two.

10) However, when the particles are finely and uniformly dispersed, unlike the case where large particles or aggregates are present, the barrier for energy propagation is small, so that the deformation energy is low. Because less is propagated throughout the system, the matrix polymer of the composite material alone breaks down at the amount of deformation closer to the point at which the polymer deforms. In other words, poorly dispersed filler-filled composites with large particles present (even if they are evenly dispersed) or with small particles forming large aggregates are large. It can be said that the strength at the time of breaking due to deformation is rather smaller than the strength at the time of breaking of only the matrix polymer containing no dispersed particles.

11) For this reason, it is possible to form a uniform dispersion system composed of only particles having a small particle size that does not significantly affect the deformation amount and strength at the time of deformation failure and that does not form a large aggregate. It is absolutely necessary when high mechanical strength is required. That is, the fine particles of the surface bioactive 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 115
0 ° C., 1400 ° C.], and then mechanically pulverized and knotted to obtain a particle having a particle size of about 0.2 to 50 μm, more preferably 1 to several tens of μm. It is necessary to use a system which is uniformly dispersed so as to have the following diameter. Of course, even in the case of bioceramics, in the case of non-calcined bio-absorptive wet HA (wet HA), there is no need to calcine and pulverize, and crystal particles in this range obtained by precipitation during synthesis can be used as they are. The size of the particles is not only necessary to satisfy the above-mentioned physical strength, but also has an important relationship with the reactivity of surrounding osteoblasts, as described later. A system that satisfies such conditions is the strength at the time of receiving a small deformation, impact strength, surface hardness,
The modulus of elasticity has been improved, and the strength such as bending, tension, and torsion, which are the strength when subjected to large deformation, maintains the matrix polymer itself. is there.

12) Here, one effective method for mixing bioceramics, such as HA, which relatively easily aggregates, particularly bioactive ceramics having surface bioactivity, such as calcined HA, without secondary aggregation in a matrix. A good measure is to add the bioceramics to the polymer dissolved in the solvent, disperse the mixture well, and precipitate the dispersion with a non-solvent. That is, the polymer and the surface bioactive biose
The mixture with Lamix powder is a solvent solution of the polymer.
The above-mentioned bioceramics powder is mixed substantially uniformly inside
Dispersing and precipitating this in a non-solvent of the polymer
Created by Surface bioactive bioceramics /
The weight ratio of the polymer can be mixed from a low ratio of 10% or less to a high ratio of more than 60%. If the amount of surface bioactive bioceramics is less than 10%, the volume ratio of bioceramics is small, so that direct bonding with bone, which is expected for surface bioactive bioceramics,
Osteoconductivity is hardly exhibited, and replacement with living bone is slow.
On the other hand, if it exceeds 60%, the fluidity of the mixed system at the time of thermoforming becomes insufficient, so that molding becomes difficult. And, since the amount of polymer in the molded product is insufficient and the binder effect does not reach,
Since the filler and the polymer are easily separated, they are brittle in strength. Therefore, the surface bioactive biocera according to the present invention
The mixing ratio of the mix is preferably 20 to 50% by weight .
More preferably, it is 30 to 40% by weight . Within this range, the desirable properties of both the dispersant and the polymer matrix as a composite material are significantly exhibited in both structure and function. The conditions, purpose and method for obtaining uniform dispersion have been described above from the viewpoint of obtaining a mixed system of bioceramics and polymer having surface bioactivity.

13) However, even if the composite material of polymer and filler uniformly dispersed in this way is processed by a usual thermoforming method, it exceeds the strength of high-strength plastic, and furthermore, the strength (bending) of cortical bone. Biomaterials having a strength exceeding 150 to 200 MPa) cannot be obtained. Generally, a polymer containing a large amount of filler is difficult to thermoform because of poor flowability. Furthermore, in order to consider the safety to a living body as in the present invention, thermoforming is more difficult when a titanium-based coupling agent that is extremely effective in improving fluidity cannot be used. When the composite of the polymer having low fluidity and the ceramic powder is kneaded and thermoformed by extrusion molding, which is a molding method in which a shear force is applied during melting, the polymer itself deforms and flows with its original flow characteristics, Since the filled inorganic filler does not have the property of plasticizing and flowing due to heat, cleavage occurs at the interface between the polymer and the filler particles due to flow deformation and the voids are interposed, resulting in a coarse density. Molded products can be obtained. The strength of a porous molded product containing many voids is low. Therefore, in molding such a polymer filled with a large amount of filler, a molding method of a pressurizing method such as injection molding or press molding is generally used in order to prevent voids from being formed.

14) However, in such a usual molding method, the polylactic acid and the copolymer thereof of the present invention are easily thermally degraded by shearing force, or remarkably hydrolyzed by a small amount of contained water. Due to the deterioration, a molded article having a high strength 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 little degradation of the polymer, but the polymer itself has a molecular structure or higher order. Because it is not reinforced at the structural level, it still does not have strength beyond the cortical bone.

15) Stretching is one method of increasing the strength of a polymer that is crystalline and thermoplastic, such as poly-L-lactic acid and its copolymer. This means that at a specific temperature (below the temperature Tm at which the polymer melts and flows), both ends of the rod or the like which is the primary molded product, or the other end where one end is fixed, are pulled outward from the molded product. This is plastic working in which uniaxial stretching is performed in the major axis direction to orient the molecular chains and the resulting crystal phase in the tensile direction (MD) to obtain a secondary molded product having higher strength. Although the purpose and method are different from the present invention,
A method of mixing a small amount of HA of 1 to 15% and uniaxially stretching the primary molded body in the major axis direction is described in Japanese Patent Publication No. 3-639.
No. 01 publication. However, when the polymer filled with the filler is stretched in this way, the polymer itself moves in the machine direction with the plastic deformation of the polymer as described above, but the filler particles themselves undergo plastic deformation of the polymer. Since the particles do not move completely synchronously, it is unavoidable that a boundary is formed at the interface between the particles and the polymer during stretching, and that voids are generated there. In particular, in the 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 material per unit volume is thinned due to the force exerted by the stretching. When the stretching ratio is increased, the polymer changes from microfibril to fibrillated state. In this state, a micro discontinuous space is generated between the fibrils, and the density of the material is further reduced.

16) According to this fact, the stretched product of the composite material in which the filler is dispersed in a large amount has a larger number of voids as the filling amount of the filler is larger, and the larger the amount of deformation due to the stretching, the larger the amount of deformation. The larger the stretching ratio, the larger the voids. Furthermore, in a system in which the size of the particle size of the filler is not adjusted, the dispersion is poor, and the system contains large agglomerates, the number and the size of the voids are even more uneven. In fact, such a voided composite material is easily cut in the middle of stretching, so that the desired stretched product cannot be obtained. Thus, with a stretched composite material containing voids, the high-strength molded product required by the present invention cannot be obtained at all.

17) Therefore, the present inventor has earnestly accomplished the object by the following molding method. That is, as described above, a billet of the polymer containing a large amount of uniformly dispersed surface bioactive bioceramics is melt-molded by a method such as extrusion or compression molding under conditions where thermal degradation is minimized, and the billet is further processed. This is a method of forming an oriented molded article by compression molding or forging molding for the purpose of pressurized orientation by press-fitting and filling a polymer. According to this method, the external force during the orientation molding acts inward toward the material body, which is opposite to the stretching, so that the material becomes dense. for that reason,
The interface between the particles and the matrix changes to a more intimate state, and even microvoids intervening at the interface during the mixing process disappear, so that a high density can be obtained.
That is, both are further integrated. In addition, the resulting composite exhibits significantly higher strength because the matrix polymer is oriented in the molecular chain axis and the crystalline phase. In this case, the orientation of the crystal obtained by press-fitting the billet, which is the primary molded product, into a cavity of a mold having a cross-sectional area smaller than the cross-sectional area of the billet partly or entirely by press-fitting is given by Because the force is applied by "shear" from the mold surface, it has a strong tendency to be plane oriented parallel to a certain reference axis, unlike uniaxial orientation by simple stretching in the longitudinal direction. Can be considered. For this reason, a characteristic that anisotropy due to orientation is small and resistance to deformation such as twisting is exhibited. However, the degree of orientation is essentially suppressed to such an extent that the molecular chain lamellas are oriented, and is not high enough to generate voids due to microfibril and fibril structures observed when the stretching ratio is high.

18) The method of strengthening the composite material of the present invention has been described above. When this is compared with that of the conventional composite material, the difference in the form is clear as shown in FIG. In other words, the conventional particle reinforced type (a) and fiber reinforced type (b) simultaneously express the physical strength of the filled particles and the fibers themselves in the system by increasing the packing ratio as much as possible, This method aims to essentially increase the strength depending on the chemical and physical bonding force with the matrix polymer. In the fiber reinforced type (b), the entanglement of the fibers effectively acts to improve the strength. In this case, if a matrix polymer having a relatively high strength is used, a higher strength can be obtained.

19) However, as in the present invention, an example in which the matrix of this system is strengthened by performing a specific secondary processing for crystal (molecular chain) orientation has not been found so far.
In the present invention, in addition to the particle-reinforced type (a) reinforcing method, the crystals (molecular chains) are oriented by pressing and filling the matrix polymer by press-fitting as described above, and the interface between the particles and the matrix polymer is formed. By making it more intimate,
This is a strengthening method (c), which strengthens by creating a more dense system (particle strengthening + matrix strengthening type). In other words, it relates to a novel method of strengthening the matrix polymer by a unique secondary molding process physically cold, which has not been done conventionally, and the composite system obtained by it, and the difference from the conventional method is clear It is.

(A) High-Strength Implant Material The implant material of the present invention is basically composed of a crystalline thermoplastic polymer which is biodegradable and absorbable and has a particle or aggregated particle size of 0.2 to 50 μm. A composite material in which 10 to 60% by weight of the surface bioactive bioceramic powder is substantially uniformly dispersed.
The particles and matrix polymer formed from a press -aligned molded article by press-fitting , which are crystallized and oriented by press-filling and have a crystallinity of 10 to 70%.
Characterized in that it is a high-strength implant material that is a composite material . Here, `` Press-fitting into a closed mold and adding
The molded product obtained by pressure- oriented compression molding or forging molding is simply referred to as " press molded product by press-fitting and filling ".

Hereinafter, the contents will be described in detail. (a) Bioceramics 1) The bioceramics used in the present invention are surface-active bioceramics. Examples of the surface bioactive bioceramics include fired hydroxyapatite (HA), bioglass-based or crystallized glass-based biomedical glass, and diopside alone or a mixture of two or more. Among them, calcined hydroxyapatite (H
A), bioglass based bioglass, serabital,
Crystallized glass-based A-W glass ceramics or crystallized glass-based Bioberit-1, implant-1,
β-crystallized glass and diopside can be suitably used.

2) Other Bioceramics The bioceramics used in the present invention are limited to the above-mentioned surface bioactive bioceramics. Of course, other bioceramics such as bioabsorbable bioceramics can be similarly used. It goes without saying that it can be used.
Examples of bioabsorbable bioceramics include unfired hydroxyapatite, dicalcium phosphate, tricalcium phosphate, tetracalcium phosphate, octacalcium phosphate, calcite and the like, or a mixture of two or more thereof.
Among them, unfired HA (unfired HA), dicalcium phosphate, α-tricalcium phosphate (α-T
CP), β-tricalcium phosphate (β-TC
P), tetracalcium phosphate (TeCP), octacalcium phosphate (OCP), dicalcium phosphate hydrate octacalcium phosphate (DCPD OCP), dicalcium phosphate −
T-anhydride tetracalcium phosphate (DCPA / TeCP), calcite and the like can be suitably used.

The bioceramics 1) and 2) described above differ in the degree of bioactivity, resulting in a difference in the speed and morphology of new bone formation. The above components are used as appropriate. Therefore, the term “surface bioactive bioceramics” used herein refers to surface bioactive bioceramics alone,
Alternatively, a mixture mainly containing the surface bioactive bioceramics and a small amount of bioabsorbable bioceramics is also included. The unfired HA which is bioabsorbable bioceramics in 2) is very similar to HA in a living body, unlike the fired HA in 1) according to the present invention.
It is one of the most effective bioabsorbable active powders because it is completely absorbed and lost in the living body, has high activity, is safe, and has a track record of practical use.

(B) Particle Size of Bioceramics Powder Here, the bioceramics powder is a general term for primary particles of bioceramics or secondary particles that are aggregates (aggregates) of the particles. 1) The particle size of surface bioactive bioceramic powder is
In order to obtain a high-strength composite material based on the above-mentioned reasons, it is preferable to use a high-strength composite material.
Those having a particle size of primary particles or secondary aggregates (agglomerated) of 2 to 50 μm, preferably 1 to 10 μm are used. The particles having the above-mentioned particle size are also preferable from the viewpoint of dispersing uniformly with a crystalline thermoplastic polymer that is degradable and absorbable in a living body. When the particle size of the surface bioactive bioceramic powder is at the upper limit close to 50 μm, it is preferable that the size of the aggregated mass when primary particles of about 10 μm are secondary aggregated. When the size of the independent primary particles is close to 50 μm, it is not desirable because the composite material breaks (breaks) at the time of yielding. Press-fit
The press-oriented molded product by filling is finally finished into an implant material having various precise shapes by a method such as cutting. If the particle size is large, the fine and finely-shaped product is chipped or broken at the interface of the powder, so that it becomes difficult to process. Therefore, it can be said that the particle size of 50 μm is an upper limit for determining the fineness of the shape of the implant material.

2) The lower limit of the particle diameter of 0.2 μm corresponds to, for example, the size of unfired HA primary particles. In addition,
It was confirmed that the calcined HA, which is the surface bioactive bioceramic of the present invention, was almost equivalent to the size of the primary particles of unbaked HA. Usually, these fine particles aggregate to form secondary aggregated particles of several μm to several tens μm. If a system is obtained in which particles or aggregates of surface bioactive bioceramics having an apparent average particle size within the above range are uniformly dispersed in a polymer matrix, high strength can be obtained, and absorption of the biomass can be achieved by absorption. Both properties of the immediate replacement of the bone with the implant are simultaneously satisfied. Then, an implant composite material having a fine shape is obtained.

3) When the implant material containing such surface bioactive bioceramics is embedded in a living body, the surface bioactive bioceramics powder that appears on the surface is bonded to the surrounding living bone by fibrous bonding. Since the binding is performed directly without using the tissue or indirectly via the HA deposited on the surface, initial fixation between the two can be obtained early. This property is used for pins and screws for bonding and fixing fractures.
Preferred for implant materials such as. Conventionally,
Plates, deformed bone substitutes, and osteosynthesis materials that could not be used mainly due to lack of strength can also be applied because of their bonding properties with bone.

4) The implant material used as a fracture fixation material in the bone maintains the strength necessary for fixation for at least 2 to 4 months required for bone fusion, and thereafter, from the surface in contact with body fluid. It takes a process in which hydrolysis gradually progresses and deteriorates. In this process, the surface bioactive ceramic powder contained therein is gradually exposed to body fluid. Thereafter, the bodily fluid penetrates further into the implant along the interface between the surface bioactive powder and the polymer. As a result, the hydrolysis of the polymer and the absorption of the decomposed product into the living body are faster than in the case of the polymer alone containing no surface-active bioceramics. In this process, the exposed surface bioactive bioceramic powder promotes the invasion of new bone and sometimes forms a nucleus of bone formation to form trabecular bone. Then, in some cases, it is discharged from the bone hole. In this way, the penetration and replacement of living bone into the bone hole where the implant material has disappeared is effectively performed.

5) The process and morphology of the replacement of bone holes with living bone by the implant material of the present invention vary considerably depending on the type of surface bioactive bioceramics contained therein and the shape, size or content of granules. Compared with an implant material made of a bioabsorbable polymer alone, the implant material of the present invention has a smaller amount of polymer by the proportion filled with the surface bioactive bioceramic powder. It is possible to avoid the risk of an inflammatory response due to a foreign body reaction caused by the temporary occurrence of a large number of polymer fragments. In addition, the speed of bone hole repair can be arbitrarily adjusted by selecting the type, size, and amount of the surface bioactive bioceramic.

(C) Composition of Polymer The polymer is not particularly limited as long as it is a crystalline thermoplastic polymer that is biodegradable and absorptive. Among them, biosafety and biocompatibility have been confirmed. Polylactic acid and various polylactic acid copolymers (eg, lactic acid-glycolic acid copolymer) are preferably used. As the polylactic acid, a homopolymer of L-lactic acid or D-lactic acid is preferable, and as the lactic acid-glycolic acid copolymer, those having a molar ratio in the range of 99: 1 to 75:25 are selected from glycols. 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 other homopolymers and copolymers compatible with the biodegradable and absorbable biodegradable polymer A small amount,
Mixing may be performed to facilitate plastic deformation or to impart toughness to the obtained oriented molded article by pressure orientation. Of course, in consideration of the reaction rate with the living body or the decomposition rate, it is preferable to use a polymer in which unreacted monomers and catalyst residues are removed and purified to reduce the amount.

(D) Molecular weight of raw material polymer and preformed body 1) The above-mentioned polymer must have at least a certain value of physical properties such as strength as an osteosynthesis material. Since the polymer is inevitably reduced at the stage of melt molding into a body, the polymer is polylactic acid or lactic acid-
In the case of a glycolic acid copolymer, it is important to use a copolymer 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. That is, crystals that are biodegradable and absorbable
Thermoplastic polymer has an initial viscosity average content of 150,000 to 700,000
Polylactic acid or lactic acid-glycolic acid copolymer having a molecular weight
Having a viscosity average molecular weight of 10 to 60 after melt molding.
It is ten thousand.

2) The polymer is then filled by press-fitting.
That the plastic deformation of the cold for orientation pressurization orientation by molecular chains (crystals), can be a composite material for implant materials of high strength, set the well conditions in the course of this plastic deformation If the above operation is performed, a 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 surface bioactive bioceramics is different from the range of the implant obtained by molding only the polymer by the same method. The reason for this is that since a large amount of bioceramic powder is contained, there is a difference in the apparent melt viscosity and the degree of deterioration during the process. When the polymer according to the present invention has a molecular weight in this range and the molecular chains (crystals) are oriented by a pressurizing operation, when the molded body is actually used in a living body, for example, as an osteosynthesis material, bone fusion occurs. The average period required for at least 2
Maintains the same strength as that of living bone for 4 months or more, and then gradually removes the osteosynthesis material at a rate that does not produce an inflammatory response due to the debris produced by the decomposition of the osteosynthesis material and surrounding tissue cells. Decompose into In this process, the surface bioactive properties of the bioceramics are developed, so that an initial bond with the bone is obtained, and thereafter, the replacement with the bone proceeds moderately.

3) The polymer has an initial viscosity average molecular weight of 15
If it is less than 10,000, there is an advantage that molding is easy because the melt viscosity is low, but a high initial strength cannot be obtained. Further, since the strength of the living body decreases rapidly, the strength maintenance period is shorter than the period required for bone fusion. Then, 1.
Since a large amount of low-molecular-weight debris may be generated in a short period of time within 5 to 2 years, inflammation may be caused by the foreign body reaction. The polymer has an initial viscosity average molecular weight of 70.
If the temperature is too high, the polymer becomes difficult to flow when heated, and high temperature and high pressure are required when producing a preformed body by melt molding, so that the polymer is generated due to high shear stress and frictional force during processing. The heat causes a significant decrease in molecular weight,
The molecular weight of the final implant material is rather 7
Since the strength is lower than that of the case of using less than 100,000, the strength is smaller than the expected value.

A polymer having a low initial viscosity average molecular weight of 150,000 to 200,000 can be filled with a relatively large amount of 30 to 60% by weight of a surface bioactive bioceramic powder. Is lower, it is easy to break (yield fracture) when yielded by receiving an external force such as bending deformation. Therefore, it is better to suppress the filling amount to a low amount of 10 to 30% by weight. It is better to keep it small. 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.
It is even more difficult to fill and melt-mold a large amount of surface bioactive bioceramic powder of 60% by weight. Therefore, the bioceramic powder having surface bioactivity should be reduced to 20% by weight or less, and the degree of deformation R should be necessarily kept small. In short, if the initial viscosity average molecular weight is about 200,000 to 550,000, a relatively wide range of filling amount and deformation degree R can be selected. Further, the strength maintenance period in the living body 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. Therefore, in order to lower the melt viscosity and facilitate molding, the viscosity average molecular weight is 100,000 or less, and in some cases, 10,000 or less. A low molecular weight polymer 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 the residual monomer in the polymer used is large, the molecular weight is reduced in the course of processing, and the decomposition in vivo is accelerated. Therefore, it is desirable to suppress the amount to about 0.5% by weight or less. When the filler is highly filled at 40% by weight or more, in order to increase the interfacial bonding force between the two, a soft bioabsorbable polymer or a complex comprising optical isomers of D-form and L-form of polylactic acid is used. Surface treatment. The subsequent operation of molecular (crystal) orientation by press-fitting into a mold gives a high-strength pressure-oriented molded body, that is, a material for an implant, without substantially reducing the molecular weight. Then, by cutting, milling, punching, secondary processing such as drilling, high-strength screw, pin, rod, disk, button,
A osteosynthesis material having a cylindrical shape or another desired shape is manufactured. That is,
The above-mentioned oriented molded body is cut and the like, and the surface
Active bioceramic powders have been revealed .

(E) Crystallinity The pressure- oriented molded product of the present invention by press-fitting has a high mechanical strength and a good hydrolysis rate. 10 degree range
７０70%, preferably 20-50%. When the degree of crystallinity exceeds 70%, the apparent rigidity is high, but the brittleness is lacking due to lack of toughness, and it is easily broken when stress is applied in the body. Also, disassembly is slower than necessary,
It takes a long time for absorption and disappearance in a living body, which is not desirable. Conversely, if the crystallinity is as low as less than 10%, no improvement in strength due to crystal orientation can be expected. Considering the mechanical strength and the speed of extinction due to decomposition and absorption or low irritation to a living body, an appropriate crystallinity is 10 to 7 as described above.
0%, preferably 20 to 50%. Even at a low crystallinity of 10 to 20%, the strength is improved by the effect of the filler as compared with the case of non-filling. In addition, even if the degree of crystallinity is as high as 50 to 70%, microcrystals are less likely to be generated in the course of plastic deformation by pressurization and adversely affect in vivo decomposition and absorption. That is, the crystallinity of the oriented molded product is 10 to 70.
% Is desirable .

(F) Density Since the implant material of the present invention is a molded article which is three-dimensionally press-oriented, its density is higher than that of a conventional stretch-oriented molded article. It depends on the degree of deformation,
Surface bioactive bioceramics mixed in the 20% range are 1.4-1.5 g / cm ³ , those mixed in the 30% range are 1.5-1.6 g / cm ³ , and those mixed in the 40% range are A mixture of 1.6 to 1.7 g / cm ³ , in the order of 50%, is 1.7 to 1.8 g / cm ³ . This high density is also an index indicating the denseness of the material, and is one of the important factors supporting high strength.

(G) Crystal Form Since the implant material of the present invention was produced by press-fitting by press-fitting , the crystals (molecular chains) of the molded body are essentially oriented parallel to a plurality of reference axes. . In general, as the reference axis increases, the strength anisotropy of the formed body decreases, so that the material is less likely to be broken by a relatively weak force from a certain direction as in a directional material. The fact that the crystals of the molded body in the implant material of the present invention are essentially oriented in parallel to a plurality of reference axes will be described with reference to FIGS. That is,
FIGS. 1 (a) and 1 (b) are a longitudinal sectional view and a plan view, respectively, showing the state of a crystal when a round rod is press- aligned by a press-fitting filling method as a typical example of the press- orientation. .

As shown in FIGS. 1 (a) and 1 (b), the morphology of the crystal of the pressure-oriented molded product by press-fitting is basically as shown in FIGS. L), that is, along a number of reference axes N obliquely inclined from the outer peripheral surface toward an axis L of a continuous center of a mechanical point where external forces are concentrated during molding, as shown in FIG. Are oriented in parallel continuously from below. That is, the reference axis is the mechanical
Tilted toward the axis or the continuous surface of the axis
It is inclined . In other words, a large number of reference axes N, which take a radially oblique orientation around the central axis L, form a substantially conical shape continuously in the circumferential direction as shown in FIG. As described above, and are oriented parallel to the reference axis N to form a continuous phase having a substantially conical surface. The conical crystal faces continuous in a vertical direction of the central axis L, and the crystal plane toward the center from the periphery can be considered as orientation structure which forms a state of being oriented in the direction of the central axis. That is, of the molded body
The shape is cylindrical, and the crystals of the compact
Multiple slanted from the outer circumference toward the axis
Are oriented parallel to the reference axis .

In such a crystal state, the billet 1 is subjected to a large shear due to friction during compression molding by press-fitting , and as the crystallization progresses, the billet 1 is inclined obliquely from the outer peripheral surface toward the central axis L. This is done by orienting. Fig. 1 (a), (b)
In has described a cylindrical like a round rod, pressurized-pressure countercurrent moldings of the press-fitting packing such as flat rather than cylindrical, as shown in FIG. 2 (a), (b), from both sides thereof The axis that becomes the mechanical core under the high shear forces is not the centerline, but forms a plane M that contains this axis and is parallel and equidistant (middle) to the opposing sides of the plate. Therefore, the crystals of the plate-shaped press- formed body formed by press-fitting are oriented parallel to the oblique reference axis N from the opposite side surfaces of the plate toward the surface M. That is, the shape of the molded body is a flat plate,
The crystal of the molded body includes an axis serving as a mechanical core of the molded body; and
Both sides towards the plane parallel to the opposite sides of the plate
Oriented in parallel to multiple reference axes that are oblique to the plane.
You . 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 external force concentrates, the press-fitting is performed.
By adjusting the force from the surrounding or both sides at the time of pressurized orientation by filling, the point where the external force concentrates deviates from the center or the center, and the crystal moves to the off-center axis L or the center from either the left or right. A crystal state oriented toward the deviated plane M is obtained.

(B) Manufacture of Implant Material The manufacture of the implant material of the present invention is basically carried out by (a) combining a crystalline thermoplastic polymer which is biodegradable and absorbable in advance and a surface bioactive bioceramic powder. Producing a substantially homogeneously mixed and dispersed mixture, (b) then melt molding the mixture to form a preform (eg, a billet),
(c) by press-fitting (in the case of compression orientation) the preform into the cavity of a closed mold having a narrow space of the mold essentially closed at the lower end, or by the thickness or width of the cross-sectional area Either partly or wholly in the narrow space of the mold smaller than that of the preform, or in the cavity of the mold in which the space of the mold is smaller than the space for accommodating the preform (forging In the case of orientation), the preform is formed into a pressure-oriented compact while plastically deforming the preform by cold press-fitting. That is,
The manufacturing method is made of crystalline thermoplastic, which is pre-
Polymer and surface bioactive bioceramic powder
Forming a substantially uniformly dispersed mixture, and then
Is melt-molded to form a preform, and the preform is closed
Plastic deformation due to cold press-fitting into cavity of mold
It is made to be an oriented molded article .

(A) Preparation of a mixture of a polymer and a surface bioactive bioceramic powder 1) A surface bioactive bioceramic powder which is relatively easily aggregated is substantially uniformly mixed and dispersed in a matrix polymer. To do this, for example, bioceramic powder having a surface bioactive is added to a matrix polymer dissolved in a solvent such as dichloromethane or chloroform, and the mixture is dispersed well. It is desirable to adopt a method of forming a mixture. In this case, the dissolution concentration of the polymer and the ratio between the solvent and the non-solvent may be adjusted according to the type of the polymer and the degree of polymerization. That is, the polymer and the surface bioactive bioceramic
Mixture with the polymer powder in a solvent solution of the polymer.
Mix and disperse the above bioceramics powder substantially uniformly
By precipitation with a non-solvent of the polymer.
Created .

2) The mixing ratio of bioceramic powder / matrix polymer having bioactive surface is from 10% by weight to 60% by weight.
%, Preferably 20 to 50% by weight, more preferably 30 to 40% by weight. That is, the surface bioactive
When the mixing ratio of the ioceramic powder is 20-50% by weight
It is desirable. When the mixing ratio is less than 10% by weight, the volume ratio of the surface bioactive bioceramic powder occupies a small amount, and thus the properties of direct bonding with bone, osteoconduction, and osteoinduction expected from the surface bioactive bioceramic powder. Is difficult to develop, and the replacement with living bone is relatively slow, much like the case of the polymer alone. On the other hand, if the content exceeds 60% by weight, the fluidity during thermoforming of the mixed system is insufficient, so that molding becomes difficult, and the amount of polymer in the molded product is insufficient, so that the binder effect cannot be obtained. -And the polymer are easily separated, so that they are brittle in strength. In addition, during the decomposition process in the living body, surface bioactive bioceramic powder is exposed from the surface of the bone bonding material quickly, which may cause harm to the living body. When the mixing ratio is within this range, the desirable properties of both the surface bioactive powder and the polymer matrix can be remarkably exhibited in both the structure and the function of the composite material.

(B) Melt molding 1) The composite material of the present invention belongs to a particle-reinforced composite material.
As in the case of the implant material of the present invention, a polymer system containing a large amount of surface bioactive bioceramic powder is generally difficult to thermoform due to poor flowability. Furthermore, it is necessary to consider the safety of the implant in the living body, and it is more difficult to form the implant under the condition that a titanium-based coupling agent that is extremely effective in improving the fluidity cannot be used. When this composite material with poor fluidity is kneaded and thermoformed by general extrusion molding or the like where shearing force is applied at the time of melting,
Although the polymer itself deforms and flows with its original flow characteristics, the filled surface bioactive bioceramic powder does not have the property of plasticizing and flowing due to heat, so it can be molded at the interface between the polymer and the bioceramic particles. As a result of the formation of cleavages at the time of movement due to the accompanying flow deformation and the inclusion of voids, a compact having a low density is formed, and the strength of the compact tends to be inevitable.

2) Primary molding of a polymer system containing a large amount of filler such as bioceramic powder having surface bioactivity as in the present invention (melt molding to form a preform).
For this purpose, a ram (plunger) type melt extrusion molding method is advantageous, but a special injection molding method or a compression molding method, such as a compression molding method, that takes into account the above-mentioned problems, is used so that voids are not easily formed. It is good to use. In short, the melt molding for obtaining the billet may be performed at a temperature condition higher than the melting point of the polymer.However, if the temperature is too high, the molecular weight is remarkably reduced. It is desirable to carry out melt molding so as not to interpose voids. For example, the polymer has an initial viscosity average molecular weight of 1
When about 50,000 to 700,000 of the above-mentioned polylactic acid is used, a temperature condition of not less than its melting point and not more than 200 ° C., preferably about 190 ° C. is selected. The viscosity average molecular weight after molding can be maintained at 100,000 to 600,000. Similarly, regarding the pressure condition, in order to suppress a decrease in molecular weight due to heat generation due to friction, a minimum pressure at which melt molding is possible, for example, 300
kg / cm ² or less, preferably 150 to 250 kg / c
It is desirable to use m ² . However, this varies considerably depending on the composition and size (thickness, diameter, length) of the preform (billet), and may be changed depending on the situation.

3) The billet is desirably melt-molded so as to have a cross-sectional shape similar to the cross-sectional shape of the cavity of the mold for press- orientation molding by press-fitting . If the cavity has a circular cross-sectional shape, The billet is melt-molded so as to have a cylindrical body having a larger circular cross-sectional shape. If the cross-sectional shape of the billet is similar to the cross-sectional shape of the cavity as described above, the billet can be plastically deformed while being uniformly compressed from the surroundings and press-filled into the cavity to obtain a homogeneous press-aligned molded product. Can be.

[0064] 4) At that time, the billet is the cross-sectional area of the molding
It is desirable to perform melt molding so that the cross-sectional area of the cavity of the mold is 1.5 to 5.0. That is, the crossing of the preform
Molding with a cross-sectional area of 2/3 to 1/5 of the surface area
The preform is press-filled into the mold cavity. After passing through the secondary process by pressure orientation by press-fitting, a desired shape is cut out by tertiary processing such as cutting. 5) In some cases (particularly in the case of a complicated cross-sectional shape), the billet as a pre-formed body is press-fitted in the next step.
It may be cut out into a desired shape suitable for secondary orientation by pressure orientation by filling , for example, forging orientation or compression orientation.

(C) Pressure forming by press-fitting into a closed mold (i) Multiaxially oriented forming by pressing and forming a billet as a primary molded product by press-fitting and filling in a closed mold for secondary forming The body is obtained. That is, for example, using the technology of ram extrusion method or compression molding method, the billet is
A closed mold having a cross-sectional area of 2/3 to 1/5 of the cross-sectional area (however, if the mold has any single value of 2/3 to 1/5 over the entire mold, it is partially (Including molds where the cross-sectional area of any of the ranges has more than one section at multiple locations of the mold, or where the rest of the former have the same cross-sectional area as the billet) While being pressurized continuously or intermittently by press-fitting, it is plastically deformed at a cold temperature (appropriate temperature (Tc) at which crystals between the glass transition point (Tg) and the melting temperature (Tm) occur) to be pressed into the cavity. What is necessary is just to fill and orient.

[0066] pressed filled compression molded Figure 3 by, 4 is a longitudinal sectional view schematically showing a molded model by compression molding by press fitting packing, pre 3 is press-fitted filling a billet into a mold cavity FIG. 4 shows a state after press-fitting and filling. Such a mold 2 includes a billet 1
And a pressurizing means 2b.
And a thin cylindrical molding cavity 2c into which the billet 1 is press-fitted, and which are connected coaxially up and down via a tapered portion 20a having a tapered lower portion. A pressurizing means 2b is provided on the upper part of the housing cylinder 2a, and the billet 1 is provided with a pressurizing means 2b such as a piston (ram).
Pressurized by continuously or intermittently pressed filled with.
At the bottom of the cavity 2c, extremely minute holes for venting air and gaps (not shown) are formed. That is,
The pressure orientation by press-fitting is large enough to accommodate the preform.
Cylindrical housing tube and a cylindrical
Shaped cavities and the taper of the constriction connecting them
And a small-diameter portion having the following .

As shown in FIG. 3, the billet 1 is housed in the housing cylinder 2a by using such a molding die 2, and the billet 1 is continuously or intermittently pressurized by the pressurizing means 2b. 4 is press-fitted while being plastically deformed in a cold state to form the state shown in FIG. Acts as an external force (vector force) in a lateral or oblique direction for orienting. for that reason,
The polymer is essentially oriented along the inner surface of the reduced diameter portion 20a, and crystallization proceeds. At the same time, since the press-fitting speed into the center of the molding cavity 2c is faster than that of the surroundings, the compression-oriented molded body 1 formed by press-fitting and filling according to the shape of the cavity 2c.
As shown in FIG. 1, the crystal axis of 0 is oriented obliquely with respect to its longitudinal center axis L, and the crystal is oriented parallel to many reference axes from the circumference toward the center axis L. In other words, for press-fit filling, which is oriented concentrically along the inner peripheral surface of the cavity 2c.
Thus, a compression-oriented molded body 10 is obtained. At the same time, since the polymer is compressed in the machine direction (machine direction), the polymer also exhibits orientation in this direction. And qualitatively dense narrow cylindrical press-fitting
The compression-oriented molded body 10 obtained by filling is obtained. Immediately
That is, the shape of the molded body is a columnar shape, and the crystal of the molded body is
Is inclined from the outer peripheral surface toward the axis that is the mechanical core of the compact.
Oriented parallel to a plurality of reference axes inclined .

In the press-fitting molding by such press-fitting, by changing the shape of the accommodating cylindrical portion 2a of the molding die 2 and the cavity 2c having a small cross-section similar to this, compression-oriented molded articles of various shapes can be formed. Obtainable. For example, as shown in FIG. 2, in order to obtain a plate-shaped compression-orientation molded body such as an osteosynthesis plate, the accommodating cylindrical portion having a rectangular cross section and the cavity are reduced in diameter (a taper is applied only to two sides in the long side direction). Pressing and filling may be performed in the same manner by using a molding die which is coaxially connected in the up-down direction through a given shape or a shape having four sides tapered). Also,
By changing the inclination angle θ of the reduced diameter portion 20a of the molding die 2 over the entire circumference or partially, the axis L or the surface M serving as the mechanical core of the molded body deviates from the center or the center, and is deviated. It is possible to obtain a compression-orientation molded product by press-fitting, which has a crystalline state obliquely oriented toward the aligned axis L or plane M.

[0069] forging diagram 5 by press fitting packing is a longitudinal sectional view schematically showing a molded model by forging by press fitting packing. The molding die 2 shown in FIG.
The cylindrical or (multi) square cylindrical housing cylindrical portion 2a is connected to the cylindrical portion 2a.
Provided at the center of a hollow disk-shaped or hollow (multi) prismatic cavity 2c having an area of a projection plane larger than the cross-sectional area of
A pressurizing means such as a piston (ram) is provided on the upper part of the housing cylinder 2a. By using such a mold, the billet 1 made of the polymer is accommodated in the accommodating cylinder portion 2a and continuously or intermittently pressed by the pressurizing means 2b, so that the billet 1 is coldly projected on the projection plane. The cavity 2c having a large area is press-filled while being spread from the central portion to the peripheral portion to obtain a forged oriented molded body by press-fitting a cylindrical or (multi) rectangular tube. That is, the housing of the mold
The cross section of the portion is cylindrical or rectangular cylindrical, and the cross section of the housing cylinder portion
Inside a cavity that is larger than the product, and has a small thickness, width, and space
The storage cylinder is provided in the center, and from almost the center of the cavity
The peripheral area is spread and spread by press-fitting .

[0070] <br/> forged oriented moldings of the press-fitting packing obtained in this embodiment is different from the compression orientation molding body by the press-fitting packing, molecular axis and crystals from the central portion to the peripheral portion of the molding cavity 2c It is a forged oriented compact formed by press-fitting and oriented parallel to many reference axes oriented radially with many axes, and has a different orientation from a simple uniaxial stretch. That is, the crystal of the molded product is
Radial with many axes from the center to the periphery
Oriented . The method of such an embodiment is particularly effective when manufacturing a bone-joining material having a hole therein such as a cylindrical shape, a (multi) square tube shape, a button shape or the like, or an accessory thereof. In the case of forging, the pressurizing action of cold press-fitting the billet into the cavity of the mold is basically by casting, but the mechanism of orientation is basically the same as in the above-mentioned compression molding. .

According to the method (ii), the external force at the time of orientation molding acts inward toward the material body opposite to the stretching, so that the material is in a dense state. As a result, the interface between the surface bioactive bioceramic powder and the matrix polymer changes to a more intimate state, and even microvoids intervening at the interface disappear during the mixing process, resulting in higher densities. Can be That is,
Both are more integrated. In addition, the resulting composite exhibits significantly higher strength because the polymer of the matrix is oriented in the molecular chain axis and the crystalline phase. The form is as shown in the above-mentioned FIG. 6 [Particle strengthening + matrix strengthening type] (c), which is clearly different from the conventional strengthening method by compounding materials. In the case of pressure orientation molding by press-fit filling , especially in the case of compression orientation molding by press-fit filling ,
As shown in FIG. 1, since a vector force is applied by "shear" from a mold surface (molding mold surface), unlike a uniaxial orientation by merely stretching in a major axis direction, the orientation is parallel to a certain reference axis. Has a strong tendency to do. for that reason,
The characteristic that the anisotropy due to orientation is small and that it is resistant to deformation such as twisting is exhibited.

(Iii) By pressure molding by press-fitting and filling according to the present invention, blocks, plates, pins, rods in which the molecular chain axis or crystal phase is essentially selectively oriented. To obtain a disk-shaped secondary molded body. After that, if necessary, milling, cutting, threading, drilling, etc. are performed, and implants of desired shape such as screw, pin, rod, disk, button, and cylinder are formed. Finished. However, where the method of obtaining an oriented molded body by pressure orientation I by the pressure <br/> condensation or forging molding by press-fit filling say, typically, than itself the billet is melt-molded product Any one of the diameter, thickness, or width is partially or wholly small in the narrow space of the mold,
It refers to a molding method in which continuous or intermittent forcible pressure is applied. Therefore, the method and the obtained molded product are essentially different from the orientation molding by stretching in which the material is stretched.

(Iv) Deformation degree Deformation degree R = So / S (where So is the sectional area of the billet,
S is the cross-sectional area of the molded article oriented under pressure) is 3/2 to 5/1
The pressure orientation molding by press-fitting may be performed within the range described above. When the degree of deformation is less than 3/2, the degree of pressure orientation by press-fitting is low, and high strength cannot be obtained. As a result, the anisotropy increases, which is not desirable. The range of R that can be most stably formed is 2/1 to 4/1.

(V) Plastic deformation temperature The plastic deformation temperature is cold, that is, [appropriate temperature (Tc) at which a crystal having a glass transition point (Tg) or higher and a melting temperature (Tm) or lower] is formed. In the case of T
A temperature (Tc) suitable for crystallization between g (60-65 ° C) and Tm (175-185 ° C) may be selected. That is,
The plastic deformation temperature of the preform is the glass transition temperature of the polymer
This is the temperature at which crystallization can be performed between the melting point and the melting point . Empirically, at a high temperature of 120 ° C. or higher, molecular slip occurs, so that it is difficult to obtain a good pressure alignment state.
In the following, since the ratio of the amorphous phase becomes considerably large, it is difficult to obtain an oriented molded body having a strength as high as that of cortical bone. Therefore, the preferable temperature range is 80 to 120 ° C, more preferably 9 to 120 ° C.
0-110 ° C. Further, the Tg of the lactic acid-glycol copolymer having the monomer ratio in the above range is 50 to 55 ° C.
However, the preferred plastic deformation temperature is almost the same as that of the single polymer.

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

(Vii) Effect of Pressing Orientation by Press-Filling If plastic deformation occurs under such conditions, for example, press-fitting
In the case of forging, when a mold having a narrow cavity having a smaller diameter, thickness or width than a billet is pressure-filled, a large shear due to friction occurs between the mold wall and the polymer. The crystal is selectively oriented by acting as an external force (vector force) in the horizontal and oblique directions. Then, the compact is compressed in the direction of the orientation axis, and the interface between the polymer and the bioceramics powder becomes more closely contacted, so that the compact becomes qualitatively dense and high strength is obtained. That is, plastic deformation is performed by cold press-fitting.
By applying an inward external force to the preform,
The conductive polymer and the bioceramic powder
You . In the case of forging by press-fitting, the orientation
External force at the time of forming is inward toward the material body opposite to the stretching
As it works, the material is in a dense state . for that reason,
Surface bioactive bioceramic powder and matrix
The polymer interface changes to a more intimate state,
Micro voids with air existing at the interface
Since the fly disappears, a high density can be obtained. In other words, both
Is even more integrated. In addition, the matrix
Is obtained because the molecular chain axis and the crystal phase are oriented.
The composite material shows significantly higher strength . However, in the method in which the polymer system is simply oriented in the machine direction by extrusion, drawing, or stretching, the lateral direction (side surface) is free (free width), the thickness is reduced in the stretching process, and No external force is applied. Therefore, a uniaxially oriented product in which the molecular chains and crystals are oriented only in the uniaxial (long axis) direction. Since the molded body is stretched in the direction of the orientation axis, the material is qualitatively a thinner material (voids are also formed) than before stretching, and is mechanically weak. It has greater anisotropy and less mechanical strength than the body.

When the billet is subjected to pressure orientation molding by press-fitting , crystallization proceeds during orientation during molding. The degree of crystallinity varies depending on the molding time and temperature. In the case of a composite material containing a large amount of surface bioactive bioceramic powder as a filler as in the present invention, a matrix polymer is used.
Crystal growth is inhibited by the bioceramics, and the crystal tends to be finely broken by the pressure at the time of plastic deformation. Slightly smaller. This is a preferable phenomenon from the viewpoint of the speed of decomposition in a living body and the tissue reaction.

(C) Characteristics of the physical properties of the implant material and the like (i) The press- oriented molded product of the present invention by press-fitting is compacted by compression at the time of molding. As the number of axes increases, the strength anisotropy also decreases. On the other hand, when the reference axis is uniaxial, the crystals (molecular chains) are arranged uniformly parallel to the reference axis direction. Therefore, the press- oriented molded product by press-fitting 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.
Hard to break.

(Ii) Physical properties The implant material of the present invention has a bending strength of 150 to 32.
0 MPa, the one having a flexural modulus of 6 to 15 GPa,
The surface is obtained depending on the amount of the bioactive bioceramics, the degree of deformation and the size of the molecular weight. That is, the above molding
The body has a bending strength of 150 to 320 MPa and a flexural modulus of elasticity.
It is 6 to 15 GPa . Other physical strength ranges are tensile strength of 80 to 180 MPa and shear strength of 100 to 150.
MPa and a compressive strength of 100 to 150 MPa are obtained, which are almost ideal as implants because they generally resemble the strength of human cortical bone. That is, on
The oriented molded product has a tensile strength of 80 to 180 MPa and a shear strength.
Degree 100-150MPa, compressive strength 100-150MPa
a . For example, a homopolymer of L-lactic acid having the above-mentioned initial viscosity average molecular weight range is added to HA3 having an average particle size of 5 μm.
When 0% by weight is uniformly mixed and dispersed, a pressure-oriented molded product obtained by cold pressure-oriented molding using a billet so that the degree of deformation R = So / S becomes 1.5 or more is: A material having a bending strength of at least 250 MPa is obtained, which sufficiently exceeds the bending strength of cortical bone. Increasing the degree of deformation R that changes the degree of orientation increases the mechanical strength of the composite material in the machine direction. At the same time, if the amount of bioceramic powder that is bioactive on the surface is large, a material having a high elastic modulus can be obtained. Then, those having a bending strength exceeding 300 MPa and those having an elastic modulus close to 15 GPa of cortical bone can be obtained. This range of elastic modulus of 6 to 15 GPa does not seem to be much different from the numerical value. Since there is a large difference in the difficulty of deformation or the rigidity, a difference of more than a numerical value is recognized in the physical usefulness when used as an osteosynthesis material or the like.

(Iii) A high-strength composite rod-shaped molded article that has been oriented under pressure by press-fitting and filling according to the present invention is further cut out into a final molded article by a method such as cutting to obtain a medical implant. it can. (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 clusters thereof in a large amount of 10 to 60% by weight and densely. In the material cut by cutting, etc., a large number of surface bioactive bioceramic particles are prominent on the surface, and at the initial point after implantation, biocompatibility is good, and the bioceramic is directly bonded to living bone Increase initial fixation. In other words, the results are
Particles or particles in a crystalline thermoplastic polymer matrix
Agglomerates with a size of 0.2-50 μm
Substantially 10 to 60% by weight of bioceramic powder
It is a composite material consisting of a uniformly dispersed molded body .

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 a novel composite strengthening method enhanced by orientation, the initial high strength is imparted, and A strength close to that is at least 2 to 4 necessary for bone fusion
It can be designed to be maintained for a period of months and then be gradually degraded at a rate that does not cause a tissue reaction. Since the surface bioactive bioceramic powder is continuously present inside the composite material, it gradually decomposes and exposes to the surface, thereby contributing to bonding with the living bone. In addition, the surface bioactive bioceramic powder promotes osteoinduction and osteoconduction, and finally quickly fills the voids where the polymer has disappeared, so that the replacement of living bone is performed efficiently.
Since the composite material contains a large amount of surface bioactive fine particles of bioceramics, it can be adequately projected on a plain X-ray photograph, and the treatment condition and treatment process that was impossible with only a polymer alone X-ray observation can be effectively performed. Furthermore, matrix polymers and surface bioactive bioceramics have been used in clinical practice in the past, and are safe for living organisms and have excellent biocompatibility. Therefore, this composite material for an implant can be said to be one of ideal biomaterials.

[0082]

EXAMPLES The present invention will be described in more detail with reference to the following Examples, which do not limit the scope of the present invention. Measurement methods for various physical property values will be described below. Compression bending strength, compression bending elastic modulus: JIS-K-7203 (198
It was measured according to 2). Tensile strength: Measured according to JIS-K-7113 (1981). Shear strength: R.SUURONEN et al. [R.SUURONEN, 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 by press-fit filling ;
Example 1> In a solution obtained 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 31.0 μm as a surface bioactive bioceramic was obtained.
Ethyl alcohol suspension of hydroxyapatite (HA) (calcined at 900 ° C.) having a minimum particle size of 0.2 μm and an average particle size of 1.84 μm was added and stirred to disperse HA uniformly without secondary aggregation. . Further, while stirring, ethyl alcohol was added to co-precipitate PLLA and HA. Then, it is filtered and dried completely, inside which HA having the above particle size is 20, 30, 40, 50, 6 respectively.
PLLA granules uniformly dispersed at a ratio of 0% by weight were obtained. This was melt-extruded at 185 ° C. with an extruder to obtain a diameter of 1 mm.
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, as shown in FIGS. 3 and 4, the billet was heated to 110 ° C. in a housing cylinder having a hole having a diameter of 13.0 mm, and the billet was connected to the housing cylinder via a reduced-diameter portion. By press-fitting into a cavity having a hole having a length of 0.8 mm and a length of 90 mm, P is formed in the same shape as the hole of the cavity and HA is uniformly dispersed.
A compression-oriented molded product obtained by press-fitting in which LLA and HA were combined was obtained. However, θ = 15 °. Assuming that the cross-sectional area of the obtained compact 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 HA / PLLA.
Compressed orientation molded product by press-fitting (Sample Nos. 2, 3,
And 4,5,6), compression orientation molding body according to press-fit filling of PLLA modification degree 2.8 composed only PLLA (sample No.
1: Control Example 1) and containing 30% by weight of HA particles but at a pressure
The physical properties of a non-oriented compact (sample No. 3 ′, control example 2) that was not compression-oriented by filling and filling were compared.

[Table 1]

As shown in Table 1, the mechanical properties of the compression-orientation molded article obtained by press-fitting the PLLA containing HA and being compounded are remarkably improved. In addition, as another control example, a force for orientation is applied in a direction away from the material in the direction opposite to the compression orientation by press-fitting according to the present invention, and a conventional general uniaxial stretching method in which the form of orientation is also different. Table 1 shows the physical properties of the stretch-oriented molded product (Sample No. 7). The stretching was performed after heating in liquid paraffin at 110 ° C. In this molded product, when the material is deformed by stretching, the material shifts from each other due to the interface between the filler and the polymer, so that the surface of the material becomes fibrous and is torn.
The inside was a poor substance forming countless large and small voids at the interface between the two. 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. Also, because of the formation of countless voids, the density is 0.924, which is a dilute substance that is low, and the invasion of biological fluid from the outside is easy,
The hydrolysis rate seems to be fast. From this, it was proved that it was impossible to obtain an osteosynthesis material having the properties intended by the present invention by uniaxial stretching. Further, the strength was such that it could not be used as a bone bonding material.

(Comparative Example 1) <Compression Molding by Press-Filling > Using PLLA having a viscosity average molecular weight of 400,000, and HA having a maximum particle size of 100 μm and an average particle size of 60 μm (baked at 900 ° C.) as a surface bioactive bioceramic. Under the same method and conditions as in Example 1, PLLA granules in which 30% by weight of HA were uniformly dispersed were obtained. This was melt-extruded with an extruder in the same manner as in Example 1 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, the billet was pressed into the hole of the mold under the same method and conditions as in Example 1 to obtain a composite HA / PL of R = 2.8 in which HA was uniformly dispersed.
A compression-oriented molded product was obtained by press-fitting LA.

Table 2 shows the obtained molded articles and the HA of Example 1.
The physical properties of the compact (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
In Example 1, the average particle size was 1.84 μm (sample N
o. The strength was lower than that of 3). Further, in the bending strength test, Comparative Example 1 was broken when reaching the yield point and showing the maximum load, but Example 1 (Sample No. 3) was not broken. This is because, although PLLA is highly oriented, a large number of large HA particles or large lumps of brittle HA are distributed, so that the matrix of PLLA orientation is interrupted by HA and its strength cannot be utilized. It is considered that On the other hand, in the case of Example 1 (sample No. 3) containing HA which is an aggregate lump having a maximum particle size of 31.0 μm, no breakage occurred even when the maximum load was exhibited. Similarly, as a bio-absorbable bioceramic in Reference Example 2 described later, particles having a maximum particle size of 45 μm or press-fitting, which is a composite material with unfired hydroxyapatite containing an aggregated mass thereof, are used .
In the case of the compression-oriented molded body, no breakage occurred.

(Example 2) <Compression molding by press-fit filling ;
Example 2> PLLA having a viscosity average molecular weight of 220,000 and 180,000 and 30% by weight of HA were obtained by using the same HA as in Example 1 as a surface bioactive bioceramic in the same manner and under the same conditions as in Example 1. PLLA granules which are uniformly dispersed are obtained, extruded by an extruder, and have a diameter of 13.0 mm, a length of 40 mm,
Cylindrical billets having a viscosity average molecular weight of 150,000 and 100,000, respectively, were obtained. Then, the billet was pressed into the same mold as in Example 1 in the same manner as described above, so that the HA was uniformly dispersed, and the compressed orientation was obtained by press-fitting the compounded HA / PLLA of R = 2.8. A molded article was obtained.

[0090] Table 3, a compression oriented moldings of the press-fitting packing obtained were compared with the physical properties of the compression orientation molding body according to press-fit filling the same molecular weight as each consisting of only PLLA as a control example.

[Table 3] A molded article made of a billet having a viscosity average molecular weight of 150,000 is slightly lower in strength than Example 1, but has a sufficient bending strength to be used as a bone bonding material. Also,
The strength and the elastic modulus were increased as compared with the comparative orientation molded article containing only PLLA. On the other hand, a molded article made of a billet having a viscosity average molecular weight of 100,000 had a higher flexural strength than that of PLLA alone, but broke at the yield point. However, when the filling amount of bioceramic particles having surface bioactivity is 10% by weight, a material which does not break at the time of descending is obtained depending on conditions. Generally, the lower the molecular weight of a polymer, the lower its inherent strength. It is considered that the molded article having a viscosity average molecular weight of 100,000 was broken because the toughness of the composite material was reduced by 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 or less.
It is determined to be ten thousand.

(Example 3) <Compression molding by press-fit filling ;
Example 3> Using PLLA having a viscosity average molecular weight of 400,000 and the same HA as in Example 1 as a surface bioactive bioceramic,
PLLA granules in which 15% by weight of HA were uniformly dispersed were obtained by the same method and under the same conditions as in Example 1 and extruded with an extruder to obtain a diameter of 13.0 mm, a length of 40 mm, and a viscosity average molecular weight of 25. Ten thousand cylindrical billets were obtained. Next, as shown in FIG. 3, the billet is formed by connecting a housing cylinder having a diameter of 13.0 mm to a cavity having a diameter of 7.0 mm and a length of 113 mm, or a housing cylinder having a diameter of 14.5 mm and a diameter of 14.5 mm. A mold having a cavity connected to a cavity having a length of 11.8 mm and a length of 57 mm.
Are uniformly dispersed, respectively, R = 3.5 and R = 1.
No. 5 was obtained by press-fitting the compounded HA / PLLA to obtain a compression-oriented molded product. However, θ = 15 °.

Table 4 shows the obtained compacts and, as a control, P = 3.5 and R = 1.5 consisting of PLLA only.
The physical properties of the compression-orientation molded product obtained by press-fitting only LLA were compared.

[Table 4] From these results, it can be seen that the molded body with R = 3.5 has a higher strength (rigidity) that exceeds the flexural strength of the compression-oriented molded body formed by press-fitting only consisting of PLLA having the same high degree of orientation.
It had high toughness. Crystallinity is PLLA
Since it is lower than that of only a molded body, it is a material that is less irritating and irritating to surrounding tissues in a living body. this is,
It is considered that the HA particles inhibited the growth of PLLA crystals and acted on microcrystallization. The molded product with R = 1.5 has a bending strength slightly higher than that of the PLLA-only molded product, but is a sufficiently usable implant material depending on the application.

Example 4 <Compression molding by press-fit filling ;
Example 4> PLLA having a viscosity average molecular weight of 400,000 and apatite wollastonite glass ceramic (AW-GC) having an average particle size of 2.7 μm as a surface bioactive bioceramic
To obtain PLLA granules in which 35% by weight of AW-GC is uniformly dispersed in the same manner and under the same conditions as in Example 1.
Melt extruded with an extruder, diameter 14.5mm, length 45
mm, and a cylindrical billet having a viscosity average molecular weight of 220,000 was obtained. Next, as shown in FIG. 3, the billet was placed in a housing cylinder having a diameter of 14.5 mm, a diameter of 9.6 mm, and a length of 83 mm.
AW-GC / PLLA with R = 2.3, in which AW-GC is uniformly dispersed, is press-fitted and filled into a mold having cavities connected to each other in the same manner and under the same conditions as in Example 1. A compression-oriented molded product was obtained by press-fitting . Where θ =
20 °.

Table 5 shows that the obtained compression-oriented molded product by press-fitting and, as a control, R =
The physical properties of the compression-orientation molded product obtained by press-filling PLLA with 2.3 were compared.

[Table 5] The obtained molded body has improved bending strength as compared with the molded body of PLLA alone. AW-
When GC was exposed, AW-GC became H
Since the layer A is actively formed on the surface, it can be an extremely effective implant for osteointegration, bone fusion and bone replacement.

(Reference Example 1) <Compression molding by press-fitting ; Example 5> PLLA having a viscosity-average molecular weight of 400,000 and a bio-absorbable bioceramic having a maximum particle size of 22.0 μm and an average particle size of 7.7 μm Alpha-type tricalcium phosphate
(Α-TCP), and a PL in which 25% by weight of α-TCP is uniformly dispersed in the same manner and under the same conditions as in Example 1.
LA granules were obtained and melt extruded with an extruder 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. Next, as shown in FIG. 3, this billet was placed in a mold having a 13.0 mm diameter cylindrical housing and a 7.5 mm diameter, 96 mm long cavity connected to each other by the same method and conditions as in Example 1. And press-fit
α-TC of R = 3.0 in which α-TCP is uniformly dispersed
A compression-oriented molded product obtained by press-fitting with a composite of P / PLLA was obtained. However, θ = 15 ° C.

Table 6 shows the obtained compression-oriented molded product by press-fitting and, as a control, R = 3.
The physical properties of the molded articles of No. 0 were compared.

[Table 6] The obtained molded body has a high strength similarly to the HA composite molded body, and its bending strength and elastic modulus are PLL.
It exceeds the molded product of only A. α-TCP is sintered HA
Therefore, it can be a high strength implant that is effective for bone replacement.

(Reference Example 2) <Compression molding by press-fitting ; Example 6> PLLA having a viscosity-average molecular weight of 360,000 and a bio-absorbable bioceramic having a maximum particle size of 45 μm and an average particle size of 3.39 μm Calcined hydroxyapatite (wet −
Using HA), PLLA granules in which 40% by weight of HA were uniformly dispersed were obtained in the same manner and under the same conditions as in Example 1.
Extrusion with an extruder, diameter 10.0mm, length 4
A cylindrical billet having 0 mm and a viscosity average molecular weight of 200,000 was obtained.

<Measurement of Activity> In order to check whether the activity is higher or less, the PLLA used in the above-mentioned Reference Example 2 was baked HA (surface bioactive bioceramic) and unfired HA (in vivo), respectively. Two billets containing 40% by weight of absorptive bioceramics were prepared, and a small piece (10 × 10 × 2 mm) was prepared from each billet.
Were immersed in a pseudo-body fluid, and the amount of calcium phosphate component deposited on the surface was observed. As a result, in the unfired 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 fired HA / PLLA, the crystal did not cover the entire surface even after 6 days. Was. It has been confirmed that the calcined HA powder is not absorbed by the bone cells and does not disappear. In some cases, it is confirmed that the cells exhale again after poor eating, and it has been pointed out that the powder may cause a tissue reaction. However, unfired HA is
Such a problem does not occur because it has complete absorbability to be absorbed by the living body and disappears and is chemically the same as HA of the living body. To date, no high strength HA / PLLA implants have been developed. Next, as shown in FIG. 3, the billet was placed in a mold having a 10.0 mm diameter housing cylinder and a 7.0 mm diameter, 76 mm long cavity connected by the same method and conditions as in Example 1. Press-fitting, press-fitting of R = 2.0 with unsintered HA uniformly dispersed
A compression-oriented molded product by filling was obtained. However, θ = 30 °.

Table 7 compares the physical properties of the obtained compression-oriented molded article and a molded article of R = 2.0 composed of only PLLA as a control.

[Table 7] The flexural strength of the uncompressed HA / PLLA composite press-fitted molded product by press-fitting is the same as that of the compressed orientation molded product of press-filled baked HA composite of Example 1, as in the case of the compression-oriented molded product.
The value was higher than the strength of the molded body composed of only LLA. Unfired HA has significantly higher bioactivity than fired HA, resulting in a highly bioactive composite high strength implant material. Since unfired HA is not sintered, it is an inorganic chemical substance itself and is not a powder having high strength like ceramics. However, since there is no chemical modification due to sintering, it is closer to biological hydroxyapatite. Is a substance. In the present reference example 2, since the matrix polymer was strengthened, the unfired HA was also fired HA.
It was possible to obtain a composite material having the same strength as in the case of (1).

(Reference Example 3) <Compression molding by press-fitting ; Example 7> PLLA having a viscosity average molecular weight of 400,000 and a bioabsorbable bioceramic having a maximum particle size of 45 μm and an average particle size of 2.91 μm PLL in which 30% by weight of β-TCP is uniformly dispersed in the same manner and under the same conditions as in Example 1 using tri-type tricalcium phosphate (β-TCP).
A granule was obtained and melt-extruded with an extruder to obtain a diameter of 13.
A cylindrical billet having a length of 0 mm, a length of 40 mm, and a viscosity average molecular weight of 250,000 was obtained. Then, as shown in FIG.
This billet is accommodated in 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 7.8 mm.
A 90 mm long cavity is connected to a mold by press-fitting under the same method and conditions as in Example 1, and β-TCP in which β-TCP is uniformly dispersed is 2.3 and 2.8, respectively. T
A compression-oriented molded product obtained by press-fitting a composite of CP / PLLA was obtained. However, θ = 15 °.

Table 8 shows the obtained compression-oriented molded product by press-fitting and the composite HA / PLL of R = 2.8 in which 30% by weight of the HA of Example 1 (fired at 900 ° C.) is dispersed.
The physical properties of the compression-oriented molded articles obtained by press-fitting and filling A were compared.

[Table 8] The obtained molded product has a larger flexural strength than the molded product of PLLA only in which R shown in Table 5 and Table 1 is 2.3 and 2.8, respectively. In the case of R = 2.8, the same R is press-fitted.
Since it has the same bending strength as the compression-orientation molded product due to filling , it has been clarified that a high-strength compression-orientation molding can be obtained by combining β-TCP.

(Reference Example 4) <Compression molding by press-fit filling ; Example 8> PLLA having a viscosity average molecular weight of 400,000 and a bioabsorbable bioceramic having a maximum particle size of 30.0 μm and an average particle size of 10.0 μm Of tetracalcium phosphate (Te
CP) in which 15 wt% and 25 wt% of TeCP are uniformly dispersed using the same method and conditions as in Example 1.
LA granules were obtained and melted by a compression molding machine 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. Next, as shown in FIG. 3, the billet containing 15% by weight of TeCP was placed in the same mold as in Example 3, and the billet was 25% by weight of TeCP.
The inclusions were pressed into the same mold as in Example 5 under the same method and conditions as in Example 1 so that TeCP with uniformly dispersed TeCP was 3.5 and 3.0, respectively.
/ PLLA was obtained by press-fitting and filling . However, θ = 15 °.

Table 9 shows that the obtained TeCP / PLLA composite-compressed molded product by press-fitting and the R of Example 3 in which 15% by weight of HA (baked at 900 ° C.) are dispersed.
= 3.5 HA / PLLA combined press-fit filling
Compression orientation molding body that, and alpha-TCP Reference Example 1 were compared with the physical properties of the pressure <br/> contraction oriented green body by press-fitting the filling of R = 3.0 which is dispersed 25% by weight.

[Table 9] The obtained molded article has a different bioceramic content from those of Example 3 and Reference Example 1, but the content and R are the same. However, each molded article had almost the same strength. 300Mp when R is 3.5
a, and exhibited extremely high bending strength.

(Reference Example 5) <Compression molding by press-fitting ; Example 9> PLLA having a viscosity-average molecular weight of 600,000, and a bioabsorbable bioceramic having a maximum particle size of 40.0 μm and an average particle size of 5.60 μm Of anhydrous dibasic calcium phosphate (calcium anhydrous-hydrogen phosphate: DCPA) in the same manner and under the same conditions as in Example 1 to obtain PLLA granules in which 45% by weight of DCPA is uniformly dispersed, and 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. Next, as shown in FIG. 3, the billet was placed in a molding die having a housing cylinder having a diameter of 8.0 mm and a cavity having a diameter of 5.7 mm and a length of 76 mm connected by the same method and conditions as in Example 1. DCP of R = 2.0 which is press-filled and DCPA is uniformly dispersed
A compression-molded article was obtained by press-fitting the composite of A / PLLA. However, θ = 45 °.

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

[Table 10] Although the molded article had a high viscosity average molecular weight, it could undergo plastic deformation by press-fitting, had high bending strength and elastic modulus, and had high strength and toughness.

(Reference Example 6) <Compression molding by press-fit filling ; Example 10> PLLA having a viscosity average molecular weight of 400,000 and a bioabsorbable bioceramic having a maximum particle size of 22.0 μm and an average particle size of 8.35 μm Octacalcium phosphate (OC
Using P), 10% by weight and 2% in the same manner as in Example 1.
PLLA granules in which 0% by weight of OCP is uniformly dispersed are obtained, melted by a compression molding machine, and have a diameter of 13.0 m.
m, a length of 40 mm, and a cylindrical billet having a viscosity average molecular weight of 250,000. Then, a billet containing 10% by weight of OCP was connected to a housing cylinder having a diameter of 13.0 mm and a cavity having a diameter of 6.1 mm, and a billet containing 20% by weight of OCP was contained in a cylinder having a diameter of 13.0 mm. And a cavity having a diameter of 6.5 mm connected to each other by press-fitting under the same method and conditions as in Example 1, and OCPs in which OCP is uniformly dispersed are 4.5 and 4.0, respectively.
/ PLLA to obtain a compression-oriented molded product by composite press-fitting and filling . However, θ = 15 °.

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

[Table 11] Each molded product was a high-strength molded product having a bending strength of 300 MPa or more. The molded body of 20% by weight of OCP is
Although the R was lower than that of the molded article of 10% by weight of CP, both the strength and the elastic modulus exceeded. However, the pressure at the time of press-fitting required a pressure of about 10,000 kg / cm ² because R was large. As a control example, a billet of 10% by weight of OCP, which is relatively easy to press-fit, was press-fitted into a mold having R = 5.5. However, the pressure at the time of press-fitting is 1000
A pressure higher than 0 kg / cm ² was required, and the obtained molded article had many cracks. From this, press-fitting of PLLA containing bioceramics
Deformation degree R for compression orientation by it can be said that not more than 5 desirable.

(Example 5) <Compression molding by press-fit filling ;
Example 12> Lactic acid-glycolic acid copolymer [P (LA-GA)] (molar ratio 90:10) having a viscosity average molecular weight of 380,000, and a maximum particle size of 31.0 μm as a surface bioactive bioceramic
m, an HA having an average particle size of 1.84 μm (calcined at 900 ° C.) and 30% by weight of HA in the same manner and under the same conditions as in Example 1.
Are uniformly dispersed in HA / P (LA-G of R = 2.8).
A composite oriented compression-molded article obtained by press-fitting was obtained. However, θ = 15 °. Table 12 shows that the obtained molded body was subjected to press-fitting filling with only P (LA-GA) as a comparative example.
Properties of the compression orientation molding body by comparing.

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

(Example 6) <Forging by press-fit filling ;
> In a solution in which 4% by weight of poly-L-lactic acid (PLLA) having a viscosity average molecular weight of 400,000 is dissolved in dichloromethane, a maximum particle size of 31.0 μm is obtained as a surface bioactive bioceramic.
Ethyl alcohol suspension of hydroxyapatite (HA) (calcined at 900 ° C.) having a minimum particle size of 0.2 μm and an average particle size of 1.84 μm was added and stirred to disperse HA uniformly without secondary aggregation. . Further, 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 particle diameter was uniformly dispersed at a ratio of 30, 40% by weight. This is extruded at 185
Melt extruded at a temperature of 13.0 mm in diameter, 40 mm in length,
A cylindrical billet having a viscosity average molecular weight of 250,000 was obtained. Next, as shown in FIG.
Is placed in a cylindrical housing of a disk-shaped mold having a diameter of 100 mm and a thickness of 10 mm protruding from the center of the cylinder.
After the heating, the forging is carried out intermittently from above with a pressure of 3,000 kg / cm ² , whereby the HA / PLLA of the same size as the disc-shaped part of this molding die is press-fitted.
A compact was obtained by forging and press orientation. A test piece was cut out from the molded body in a radial direction excluding a cylindrical portion, and physical properties were measured. As a result, the flexural strength was 220 MPa, the flexural modulus was 7.4 GPa, the density was 1.505 g / cm ³ , and the crystallinity was 43.0%. The compact formed by forging orientation by press-fitting is considered to be an oriented body in which the crystal plane is different from the above-described embodiment and the orientation axis is multiaxially oriented from the center of the disk to the outer periphery.

(Example 7) <Example of Cutting: Surface Observation and Change with Time> The HA (surface bioactive bioceramics) / PLLA composite obtained in Example 1 was subjected to press-fitting by each press-fitting. The shrink-oriented molded body was cut with a lathe to form a screw having an outer diameter of 4.5 mm, a valley diameter of 3.2 mm, a length of 50 mm, and a pin of 3.2 mm in diameter and 40 mm in length. Further, a billet extruded in a plate shape by an extruder was obtained using the PLLA granules in which 30% by weight of HA of Example 1 was dispersed, and a rectangular cylindrical (plate-shaped) storage cylinder was formed. A press-fitting is performed by a method and under the same conditions as in Example 1 into a mold in which cavities having a smaller cross-sectional area and a rectangular cross-section are connected.
A 2.8 plate-like molded product was obtained. The surface of this molded body was cut with a slicer to a thickness of 2.0 mm and a length of 20 mm.
A plate having a width of 5 mm and a width of 5 mm was obtained.

The surfaces of the screws, pins and plates were observed with a scanning electron microscope. Each of the cut workpieces was exposed in a state in which the fine particles were uniformly dispersed without secondary aggregation of HA on the surface to form a large aggregate. It was also observed that the inside was similarly uniformly dispersed. And these higher content of the HA increases, the more HA had appeared on the surface. Such implants were dense and free of voids, and it was also confirmed that the bioceramics and polymer were in good physical contact with each other. This has the mechanical strength of the material having a high present invention, living bone binds to bone by direct contact with the bioceramics, it was time maintaining required bone union, osteoinductive and osteoconductive, or This shows the basis for effective bone replacement. In addition, the pressure- oriented molded body by press-fitting in which the high-strength polymer / bioceramic obtained in the example or the reference example is compounded,
It was confirmed that the strength was substantially maintained for 2 to 4 months in the analog solution at 37 ° C. Thereafter, it was confirmed in vivo that although the decomposition behavior was different depending on the composition and structure of the material, the bone was heavily decomposed and absorbed and replaced by bone after bone fusion, as compared with the case of the polymer alone.

[0112]

As is apparent 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 can be destroyed at an early stage. It is hard to occur, and the surface bioactive ceramics is used for the bonding with living bone, osteoconductivity and in vivo decomposition / absorption properties. While maintaining strength during the period, it is gradually decomposed and absorbed at a speed that does not cause harm to the surrounding bone, and the disappeared traces are immediately reconstructed by the living body, and after operation, simple X-ray It is an ideal biomaterial that can be captured by photography. Further, the method of the present invention can easily produce the above-mentioned implant material without employing special equipment or severe conditions.

[Brief description of the drawings]

FIG. 1 is a schematic view showing a crystalline state of a columnar implant material of the present invention. FIG. 1A shows a longitudinal sectional view, and FIG.
(B) shows a plan view.

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

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

FIG. 4 is a longitudinal sectional view schematically showing a molding model by compression orientation by press-fitting , and shows a state after billet press-filling.

FIG. 5 is a longitudinal sectional view schematically showing a forming model by forging orientation by press-fitting .

FIG. 6 is a schematic diagram showing an internal structure of a composite material strengthening system, in which the composite material of the present invention is compared with a conventional composite material.

[Explanation of symbols]

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

──────────────────────────────────────────────────続 き Continuation of the front page (56) References JP-A-63-68155 (JP, A) JP-A-63-89166 (JP, A) JP-A-61-68054 (JP, A) 168647 (JP, A) JP-A-2-89599 (JP, A) JP-A-1-501289 (JP, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) A61L 27/14-27 / 57 A61F 2/28 A61B 17/56-17/92 B29C 43/00-43/58 B29C 45/02

Claims (26)

(57) [Claims] 1. A bioactive bioceramic powder having a size of 0.2 to 50 μm in the size of a particle or an aggregate of particles in a crystalline thermoplastic polymer matrix which is biodegradable and absorbable. %, A composite material comprising a molded body in which the matrix polymer is substantially uniformly dispersed, wherein the crystals of the matrix polymer are crystallized by pressure molding by press-fitting and filling.
Oriented by, and its high crystallinity is 10% to 70%
A high-strength implant material, which is a composite material reinforced with particles and a matrix polymer, characterized by comprising a press- oriented molded product obtained by press-fitting with high density . 2. The method according to claim 1, wherein the size of the particles or the aggregate of the particles is one.
2. The method according to claim 1, wherein the diameter is from 10 to several tens of micrometers.
High strength implant material. 3. The surface bioactive bioceramics
A powder mixture ratio of 20 to 50% by weight;
Has a density of 1.4 to 1.8.
Item 3. The high-strength implant material according to item 1 or 2. 4. The method according to claim 1, wherein the crystals of the compact are essentially a plurality of criteria.
Characterized in that they are oriented parallel to an axis.
4. The high-strength implant material according to any one of 3 . 5. The reference axis serves as a mechanical core of the molded body.
Inclined obliquely toward the axis or a continuous surface of the axis
The high-strength implant according to claim 4, characterized in that:
material. 6. The crystal of the compact is formed from the center to the periphery of the compact.
Radially oriented with many axes towards the sides
The high-strength implant according to claim 4, characterized in that:
material. 7. The molded article has a columnar shape.
The crystals of the form move outwards towards the axis that is the mechanical core of the compact.
Orientated parallel to multiple reference axes that are inclined obliquely from the peripheral surface
The high-strength material according to claim 4, wherein
Implant material. 8. The molded article has a flat plate shape.
Form crystals are formed Including the axis that is the mechanical core of the
Both sides towards the plane parallel to the opposite sides of the plate
Oriented parallel to more oblique reference axes
The high-strength imp according to claim 4 or 5, wherein
Runt material. 9. surface bioactive bioceramics powder, wherein the sintered hydroxyapatite, is any one or two or more mixtures of biological glass bioglass-based or crystallized glass system, wherein Item 1
8. The high-strength implant material according to any one of 8 . 10. The crystalline thermoplastic polymer that is biodegradable and absorbable is either polylactic acid or lactic acid-glycolic acid copolymer, and has a viscosity average molecular weight of 10 to 60.
The high-strength implant material according to any one of claims 1 to 9, wherein the material is 10,000. 11. The thermoplastic polymer is polylactic acid,
Wherein a surface bioactive bioceramics powder is sintered hydroxyapatite, claim 1-1
0. The high-strength implant material according to any one of the above items . 12. The molded product having a bending strength of 150 to 3
The high-strength implant material according to any one of claims 1 to 11 , wherein the high-strength implant material has a bending elastic modulus of 20 to 15 GPa. 13. The method according to claim 13, wherein the oriented molded product has a tensile strength of 80 to 1
80MPa, shear strength 100-150MPa, compressive strength
The pressure is 100 to 150 MPa.
12. The high-strength implant material according to any one of 1 to 11. 14. The oriented green body is machined such, high strength according to its, wherein the surface bioactive bioceramics powder is manifested to a surface, either of claims 1 to 13 Implant material. 15. A mixture in which a crystalline thermoplastic polymer that is biodegradable and absorbable and a surface bioactive bioceramic powder are substantially uniformly dispersed in advance, and then the mixture is melt-molded to obtain a preliminary mixture. the compact build, on the preform closed mold cavity, characterized in that the oriented green body by plastically deforming press-fitted filled cold, pressure
A method for producing a high-strength implant material that is pressure-oriented by filling and filling . 16. A method of plastically deforming by cold press-fitting.
By applying an inward external force to the preform,
Adhesion between polymer and bioceramic powder
The high-strength implant according to claim 15, wherein
Method of manufacturing paint materials . 17., characterized in that pressurization orientation by the press-filling is made by being pressed filled cold into a closed mold cavity having a smaller cross-sectional area than the preform according to claim 15 or 16 A method for producing the high-strength implant material as described above. 18. The pressure orientation by the press-fitting and filling
Large cylindrical housing tube for housing the compact and preforming
A cylindrical molding cavity that is thinner than
Closure consisting of a tapered narrow portion with a constriction
18. The method according to claim 15, wherein the shape is determined by a shape.
Method for producing high-strength implant material according to any of the above
Law . 19. A cross section of a housing cylindrical portion of a molding die is cylindrical or
It is a square tubular shape, larger than the cross-sectional area of the housing tubular portion, thickness,
The housing cylinder is installed in the center of a cavity with a small width and space.
From the center of the cavity to the periphery.
16. The method according to claim 15, characterized by spreading and press-fitting.
Method for producing the high-strength implant material described above . 20. The pre-molded product is press-fitted into a cavity of a closed mold so that the degree of crystallinity of the polymer of the pressure-oriented molded product is 10 to 70%.
20. The method for producing a high-strength implant material according to any one of 15 to 19 . 21. A mixture of the polymer and a surface bioactive bioceramics powder substantially uniformly mixes and disperses the bioceramics in a solvent solution of the polymer, characterized in that it is prepared by precipitation in a solvent, according to claim 15 to 20
The method for producing a high-strength implant material according to any one of the above. 22. The crystalline thermoplastic polymer that is biodegradable and absorbable 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 15 to 21 , wherein the viscosity-average molecular weight after the melt molding is 100,000 to 600,000. 23. ２ to 2/3 of the area of the cross section of the preform
The preform is press-fitted into a cavity of a mold having a cross-sectional area of 1/5.
A method for producing a high-strength implant material according to any one of 15 to 18 , 20 to 22 . Plastic deformation temperature of 24. preform characterized in that it is a crystallizable temperature between the glass transition temperature or less than the melting temperature of the polymer, according to claim 15 to 23 Neu
A method for producing a high-strength implant material according to any of the preceding claims. 25. The method for producing a high-strength implant material according to claim 15, wherein the pressure orientation by press-fitting is performed in a compression orientation or a forging orientation. 26. The method for producing a high-strength implant material according to claim 15 , wherein the pressure-oriented molded body is further subjected to cutting or the like.