JPH05237180A - Bone joining device - Google Patents

Abstract

PURPOSE:To provide the bone joining device which has excellent initial strength and initial modulus of elasticity and with which the part coated with polylactic acid is absorbed in about several months after implantation into a living body, the probability of inducing an inflammation is extremely low, the cavity after absorption by the neobone is filled in an early period and the core material adapts itself to the biotissue, thereby the re-operation to draw out a mail is no need. CONSTITUTION:This bone joining material is constituted by using a molding of biode gradable polymer contg. 75 to 95wt.% respective independent materials of hydroxy apatite (HA), tricalcium phosphate (TC) and crystallized glass contg. HA and wallastonite or the mixture composed thereof as a core material and coating this core material with the polylactic acid.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an osteosynthesis device for fixing and assisting and prolonging bone parts during bone damage, fracture or bone transplantation. More specifically, as a core material, a molded body obtained by adding a biodegradable polymer to a component having a composition equivalent to that of living bone or bioactive ceramics is used, and this is coated with biodegradable and absorbable polylactic acid. For devices.

[0002]

In the field of surgery such as orthopedic surgery, plastic surgery, thoracic surgery and oral surgery, it has been conventionally used as an artificial reduction material for fixing and joining biological bones (Cr-Ni alloy type, Ti alloy type). Etc.) and ceramics (oxide ceramics such as alumina and zirconia, and calcium phosphate ceramics such as hydroxyapatite and tricalcium phosphate) have been used.

[0003] Recently, research on a reduction material using a biodegradable and absorbable material composed of polylactic acid, polyglycolic acid, polydioxanone or a copolymer thereof has been actively conducted, and put into practical use after the stage of clinical trials. It's starting.

[0004]

The above-mentioned metallic materials have a long-term track record and are often used. However, due to their extremely high elastic modulus, the strength of the surrounding bone is reduced, and the elution of metal ions causes It has a problem that it may damage the living body. Furthermore, the biggest drawback of metallic materials is
When a fracture or bone damage is healed, it must be re-operated to remove it from the living body, which imposes a physical and economic burden on the patient.

On the other hand, ceramic materials have been actively used in recent years because of their good biocompatibility. However, these materials also have the problem of having a high elastic modulus like metal materials. I have left. Another problem is that ceramic materials are more brittle than other materials.

As such an osteosynthesis device, researches using a bioabsorbable polymer have been actively conducted in recent years, and in particular, the osteosynthesis device is formed by molding polylactic acid, polyglycolic acid, or glycolic acid-lactic acid copolymer. There are many researches to obtain the method, and the methods are disclosed in JP-A-59-97654 and JP-A-1.
Examples thereof include JP-A-198552, JP-A-1-198553, JP-A-3-29663, and JP-A-3-103429. Among them, the present inventors have disclosed in Japanese Patent Application Laid-Open No. 1-19
No. 8553, polylactic acid having a viscosity average molecular weight of 300,000 or more is molded, and then stretched,
The initial strength and elastic modulus are similar to those of living bones, and the strength and function of the bones that have been fractured or injured are almost restored until the strength and function of the bones are almost restored. By the time the formation was completed, it provided an ideal bone cement that would be completely absorbed in the living body. Furthermore, the present inventors
In Japanese Patent Laid-Open No. 3-29663, the required strength and strength retention period of the bone in each part of the living body are clarified, and a bone bonding material suitable for use in each part is provided.

These bone-bonding materials provided by the present inventors satisfy all the properties required as a bone-bonding material in terms of strength, and are excellent materials that have no problems even now. However, on the other hand, when a large diameter screw made of polylactic acid or the like is used, its absorption rate is slow, and it takes one and a half to three years, and sometimes three years or more to be completely absorbed. It turns out that there is something.

Further, research on a composite using a bioabsorbable material has also been conducted, and Japanese Patent Laid-Open No. 63-68155 discloses a pin-shaped molded product obtained by mixing polylactic acid with hydroxyapatite and molding the mixture by melt extrusion. Has been done. However, there are problems that the strength cannot be improved and that the structure becomes porous when stretched. In addition, it is inevitable that a part of the absorptive material has a porous structure as it is decomposed and absorbed, and that the decomposition and absorption is accelerated more rapidly at a certain point. Therefore, the pH locally rises,
It is highly likely to cause irritation.

Further, in US Pat. No. 4,743,257, a so-called self-rein structure in which a matrix made of a bioabsorbable polymer is reinforced with fibers made of the same component.
An osteosynthesis material composed of a force-complexed composite material is shown, but this also loosens into a fibrous shape to increase the surface area.
It is highly possible that bursty absorption will occur at a certain time, which may cause inflammation.

The present invention has been made in view of the above problems, and is excellent in initial strength and initial elastic modulus, and the polylactic acid-coated portion around it is absorbed within a few months after implantation in a living body. After that, since the ceramic core material is compatible with living tissue, there is no need for re-operation for nail extraction, and since the proportion of bioabsorbable polylactic acid is low, the absolute amount absorbed is small and inflammation is reduced. Very unlikely to cause
It is an object of the present invention to provide an ideal osteosynthesis device in which the cavity after being absorbed by new bone is filled early.

[0011]

In order to achieve the above object, the device of the present invention comprises a hydroxyapatite (H
A) and tricalcium phosphate (TCP) and H
A molded body of a biodegradable polymer containing 75 to 95% by weight of each crystallized glass containing A and wollastonite or a mixture thereof is used as a core material, and the core material is coated with polylactic acid. Characterize.

The core material used in the present invention is mainly composed of calcium phosphate ceramics such as hydroxyapatite and tricalcium phosphate and oxide ceramics such as crystallized glass containing HA and wollastonite. It is obtained by adding a biodegradable polymer such as polylactic acid, gelatin or collagen, and heating and pressing.

For the crystallized glass containing hydroxyapatite, tricalcium phosphate, HA and wollastonite, powders thereof are used alone or in combination, and a biodegradable polymer such as polylactic acid is used in an amount of 5 to 25% by weight.
In addition, a thin rod-shaped core material is manufactured by a known molding means such as extrusion molding or press molding. Further, as another manufacturing method of the core material, a method of dissolving the polymer component in a solvent, adding the above-mentioned powder, mixing and removing the solvent can also be adopted. In this case, the amount of the polymer to be dissolved may be small, and there is an advantage that a polymer having a high molecular weight can be used.

In the device of the present invention, a molded article of biodegradable polymer containing 75 to 95% by weight of hydroxyapatite and tricalcium phosphate and 75 to 95% by weight of crystallized glass containing HA and wollastonite, respectively. The reason is that when the content of the above-mentioned ceramics is 75% by weight or less, the physical strength of the ceramics does not increase so much, and when it is 95% by weight or more, the polymer component is too small and there is a problem in fluidity and moldability. Is. The amount of this ceramic added depends on the particle size of each component.

On the other hand, the bioabsorbable polylactic acid (hereinafter referred to as PLA) used as the coating material is prepared from the optically active L- or D-form lactic acid by a conventional method (CE Love,
It is obtained by synthesizing a lactide which is a cyclic dimer of lactic acid according to U.S. Pat. No. 2,668,182) and then subjecting the lactide to ring-opening polymerization to obtain L-form polylactic acid (hereinafter referred to as PLLA). Is more preferable. It is important to adjust the molecular weight and crystallinity of this PLLA appropriately. That is, PLLA has a higher strength as the molecular weight is higher. However, if the molecular weight is too high, high temperature and high pressure are required in the melt molding, resulting in a large decrease in the molecular weight. The molecular weight is low, and naturally the strength is also low. On the other hand, crystalline materials have a higher bending strength than amorphous materials,
The elastic modulus is high, the penetration of body fluid is slower in the crystalline phase, and the apparent hydrolysis is slower. However, if the crystallinity is increased by heat treatment, the strength is improved, but the deterioration of the molecular weight is caused by the deterioration of PLLA due to thermal instability.
The hydrolysis rate becomes faster, and the strength deteriorates rapidly. For these reasons, the coating material PLLA has a viscosity average molecular weight of 300,000 to 600,000, and above all 350,000 to 5
Those having a crystallinity of about 50,000 and a crystallinity of about 10 to 60% are preferably used.

Further, it is preferable that the coating material PLLA is uniaxially stretched at a stretching ratio of about 2 to 5 after the melt molding. When the uniaxially stretched as described above, the strength of the PLLA molded product is improved, the flexural strength becomes 160 to 250 MPa, and the flexural modulus of compression becomes 5500 to 24000 MPa. This significantly increases the force for tightening the core material.

The osteosynthesis device of the present invention in which the core material containing ceramics as a main component is coated with the stretched or non-stretched PLLA coating material as described above is a rod used in general surgery. It is used in various shapes such as screws, screws, and pins. In the case of rods and pins, the diameter of the core material is about 1 to 3.5 mm (preferably 1.2 to 3 mm), P
The thickness of the LLA coating material is 0.75 to 2 mm (preferably 1
.About.1.5 mm), and an overall diameter set to about 2.5 to 8 mm (preferably 3 to 6 mm) is used.
Further, in the case of a screw, those having almost the same size are used, but it is desirable that the thickness of the PLLA coating material of the screw is slightly thicker in consideration of the groove cut portion.

The osteosynthesis device of the present invention is manufactured as follows. One method is to mix PLLA with ceramic powder such as hydroxyapatite and use an extruder for molding a core material, attach a crosshead die to the tip of the core material, and simultaneously extrude the core material from the side surface of the die. P
In this method, only LLA is melt extruded, and the core material is coated with the tip of the die. In another method, PLLA is melt-molded, uniaxially stretched, and then a hole is formed by drilling to form a hollow pipe, and the core material is inserted into the hole while being heated in a nitrogen atmosphere at about 80 ° C. Is the way. On this occasion,
It is necessary to take care so that the heat generated by drilling does not accumulate in the PLLA.

[0019]

When the osteosynthesis device of the present invention is implanted in the body, PLA (PLLA) on the surface comes into contact with the body fluid and gradually starts to hydrolyze, and gently progresses from the surface to the inside.
In the device of the present invention, PLA is used as the coating portion, and a very small amount of PLA is used as the binder of the ceramic in the core material portion. , PLA
Absorption is completed early and the absolute amount absorbed is small. Therefore, the osteosynthesis device of the present invention is extremely unlikely to cause inflammation. After the PLA coating material is completely absorbed, the ceramic core material such as hydroxyapatite, which has excellent biocompatibility, remains, and as a device for osteosynthesis until the fracture or damaged portion is completely healed. Fulfill the function of.

As described above, the osteosynthesis device of the present invention is
Compared to PLA devices, PLA has a faster absorption rate and a smaller absolute amount of absorption, so it is less prone to inflammation, and PLA covers a ceramic-rich core material with a ceramic component of 75 to 95% by weight. Therefore, it is possible to sufficiently cover the defect of brittleness that is found in the conventional ceramic device. That is,
The initial strength shows an intermediate value between PLA and the core material, and its surface characteristics depend on the properties of PLA. PLA provides toughness as an organic polymer, and the core material provides the advantages of high elastic modulus and high rigidity. PLA added with a small amount of ceramics does not show improvement in physical strength as in the core material of the present invention.

Further, when the coated PLA is completely absorbed, the healing of the fracture and the damaged site has progressed to some extent, and the phenomenon of the strength decrease of the surrounding bone, which is a defect of the ceramic material, can be minimized. .. In addition, PLA is mixed with a small amount of hydroxyapatite in powder form, or is mixed in the form of flakes, or even when compared with fiber reinforced ones, there is no burst absorption and there is less possibility of causing inflammation. It can be said that it is an extremely excellent osteosynthesis device as compared with the osteosynthesis devices currently used or studied.

The present inventors have also found out that stretching PLA, which is preferably used as a covering material, causes piezoelectricity. It has been known that the generation of callus is promoted by this piezoelectric effect, and from this point, it can be said that the osteosynthesis device of the present invention is ideal.

In addition, the conventional device consisting of PLA is X
Although there is a problem that it is difficult to grasp the decomposition behavior after embedding and the like because the X-ray imaging with a line does not appear, it is difficult to grasp the decomposition behavior after implantation. However, in the osteosynthesis device of the present invention, the ceramic-based molding used as the core material is X-ray. It can be used for X-ray photography and can also serve as a marker during X-ray photography.

[0024]

EXAMPLES Examples of the present invention will be described in detail below.

Hydroxyapatite (HA) powder was mixed with PLLA having a viscosity average molecular weight (measured in chloroform at 25 ° C.) of 400,000 at a weight ratio of 80:20,
A molded product having a diameter of 1.5 mm manufactured by melt extrusion was cut into a predetermined length to obtain a core material. On the other hand, the above-mentioned molecular weight 4
Melting and extruding 0,000 PLLA into a rod, then stretching it 4 times, cutting it to a predetermined size, and drilling in the long axis direction with a drill to make a rod with an outer diameter of 3.2 mm and a length of 5 cm. did. Then, the core material was inserted into the rod at about 80 ° C. in a nitrogen atmosphere to prepare a composite rod (Sample 1).

In the same manner, a core material was prepared by mixing tricalcium phosphate powder and PLLA in a weight ratio of 80:20, and PLLA was covered in the same manner as above to prepare a composite rod. The diameter of the core of this rod is 2mm, PL
The outer diameter after coating LA was 6.5 mm, and the length was 5 cm. This is cut and processed for cancellous bone screw (screw root diameter is 4 mm, PLLA wall thickness is 1 m at the root diameter part)
m, 2.25 mm in the portion of the mountain diameter) was produced (Sample 2).

Similarly, a core material was prepared by mixing alumina wollastonite powder and PLLA in a weight ratio of 80:20, and PLLA was covered in the same manner as above to prepare a composite rod. The diameter of the core material of this rod is 2 mm, PLLA
The outer diameter after coating was 6.5 mm and the length was 5 cm.
By cutting this, a screw having the same diameter and the same length as the sample 2 was produced (sample 3).

Further, hydroxyapatite, tricalcium phosphate and alumina wollastonite are mixed in equal amounts, 20% by weight of PLLA is added thereto, and this is put into an extruder for core material and extruded for coating. PL in the machine
LA was introduced and a crosshead die was used to prepare a composite rod having a core material diameter of about 2 mm and a coating material thickness of about 4 mm (Sample 4).

When the physical strengths of these materials were measured, the bending strength and bending elastic modulus were dominated by the core material, and the average measured values were as follows. Flexural strength (kg / cm2) Flexural modulus (kg / mm2) Sample 1 2800 2500 Sample 2 2400 2300 Sample 3 2450 2300 Sample 4 2500 2200

The surface depended on the physical properties of PLLA, and the ceramic had no brittleness and had toughness. Moreover,
It was not as flexible as PLLA and had the rigidity of the core material, so it had a strength suitable for embedding a screw.

Next, an osteotomy was experimentally performed on the tibia proximal parts of five rabbits, and internally fixed using the screws of Sample 2 and Sample 3. That is, a longitudinal fracture containing a joint surface of about 1/3 is made in the proximal portion of the right tibia of a rabbit weighing 3 kg,
It was fixed with one screw. It was performed at the cage rest without external fixation. As a control, the same reduction and fixation were performed using a screw of the same diameter made of only PLLA.

After 25 months, each was slaughtered and the screw holes were observed. As a result, about 5 to 30% of PLLA remained in the control screw, and its molecular weight was 2%.
000 to 3,000. In addition, the screw hole was clearly recognized, and it was not completely replaced by the new bone. In the case of the screw of sample 2, the PLLA on the surface was decomposed, absorbed, and disappeared, and the part was replaced by new bone. Further, the core portion has a porous structure as the PLLA is decomposed and absorbed, and the contact area with the body fluid increases, so that it tends to be decomposed and absorbed earlier than the control. As a result, although a small amount of PLLA remained in the core part, it was almost replaced with new bone.

As in the case of the screw of Sample 2, the screw of Sample 3 had the surface PLLA decomposed and absorbed, and that portion was almost replaced by the new bone. Although the residual amount of PLLA was also recognized in the core material, the amount was much smaller than the residual amount in the case of the control, and the portion in which PLLA was absorbed was almost completely replaced by the new bone.

[0034]

As is apparent from the above description, the osteosynthesis device of the present invention has a smaller total amount of PLA (PLLA) than a device composed of only PLA (PLLA), and therefore decomposition and absorption can be completed in a short period of time. However, since the absolute amount absorbed is also small, the risk of causing inflammation is extremely low. Therefore, there is also an advantage that a plurality of devices can be used in a limited local area. Then, during this decomposition and absorption process and its final stage, the new bone is apt to be buried in a state that it is thinly bridged to the hollow portion, so if the whole is an absorbable material, the new bone is completely buried for 2-3 years or Has the advantage of filling with new bone in a short period of time without requiring a long period of 3 to 4 years.

Further, after the PLA of the coating material is completely decomposed and absorbed, the core material containing ceramics having excellent biocompatibility is used as an osteosynthesis device until the fracture and the damaged site are completely healed. Fulfill the function of. And PLA
When the covering material etc. of is completely absorbed, the healing of the fracture and damaged site has progressed to some extent due to the generation of new bone,
There is also an effect that it is possible to minimize the phenomenon of strength deterioration of the surrounding bone, which is a drawback of the ceramic-based device.

Further, since the core material containing ceramics serves as a marker during radiography, it is possible to eliminate the drawback that a device consisting of PLA is not captured during radiography. When the stretched PLA is used as the coating material, there is also an effect that the generation of callus is promoted by the piezoelectric effect, and the promotion of healing due to the generation of new bone can be seen.

As described above, the osteosynthesis device of the present invention is extremely ideal.

Claims (2)

[Claims] 1. A biodegradable polymer containing 75 to 95% by weight of hydroxyapatite (HA) and tricalcium phosphate (TCP) and crystallized glass containing HA and wollastonite alone or in a mixture thereof. A bone-bonding device, characterized in that the molded body of 1. is used as a core material, and the core material is coated with polylactic acid. 2. The osteosynthesis device according to claim 1, wherein polylactic acid is uniaxially stretched.