JP3074410B2 - Osteosynthesis device - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention is to fix a portion of a bone until it is formed at the time of bone damage, fracture or bone transplantation.
Auxiliary and prosthetic osteosynthesis devices. More specifically, the present invention relates to an osteosynthesis device in which a molded body of an oxide ceramic or a calcium phosphate ceramic having a composition equivalent to that of a living bone is used as a core material and the molded body is covered with a bioabsorbable polylactic acid.

[0002]

2. Description of the Related Art In surgical fields such as orthopedic surgery, plastic surgery, thoracic surgery, and oral surgery, metal (Cr-Ni alloy, Ti alloy) has been conventionally used as an artificial reduction material for fixing and joining living bone. And inorganic materials made of ceramics (such as oxide ceramics such as alumina and zirconia and calcium phosphate ceramics such as hydroxyapatite and tricalcium phosphate).

[0003] Recently, studies on reduction materials using biodegradable and absorbable materials composed of polylactic acid, polyglycolic acid, polydioxanone or copolymers thereof have been actively conducted, and have been put into practical use through clinical trial stages. It is getting.

[0004]

The above-mentioned metallic materials have a long track record and are often used. However, since the elastic modulus is very high, the strength of the surrounding bone is reduced, and the metal ions are eluted. There is a problem that the living body may be damaged. Furthermore, the biggest disadvantage of metallic materials is that
Once a fracture or bone damage has healed, it must be re-operated to remove it from the body, placing 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 suffer from the disadvantages caused by their high elastic modulus similarly to metal materials. Have left. There is also a problem in that ceramic materials are brittle compared to other materials.

In recent years, studies using bioabsorbable polymers have been actively conducted as such osteosynthesis devices. In particular, osteosynthesis devices are obtained by molding polylactic acid, polyglycolic acid, and glycol-lactic acid copolymer. There are many studies, such as JP-A-59-97654,
198552, JP-A-1-198553, JP-A-3
JP-A-29663 and JP-A-3-103429 are examples thereof. In particular, the present inventors have disclosed Japanese Patent Application Laid-Open No. 1-198.
No. 553, a polylactic acid having a viscosity average molecular weight of 300,000 or more is molded, and then subjected to a stretching operation, whereby the initial strength and the initial elastic modulus are almost the same as those of a living bone, and the strength of a fractured or damaged bone. An ideal osteosynthesis material that maintains strength close to that of living bone until its function is almost restored, and is completely absorbed into the body by the time bone formation is finally completed. Offered. Furthermore, the present inventors
In JP-A-3-29663, the required strength of bone and the strength maintaining period in each part of a living body are clarified, and an osteosynthesis material suitably used for each part is provided.

[0007] These osteosynthesis materials provided by the present inventors satisfies all of the properties required for an osteosynthesis material in terms of strength, and are excellent materials which have no problems up to the present. However, on the other hand, when a thick screw made of polylactic acid or the like is used, the absorption speed is slow, and it takes about 1 to 2 years, or about 3 years in some cases, until it is completely absorbed. I have found something.

[0008] In addition, a composite using a bioabsorbable material has been studied, and JP-A-63-68155 discloses a pin-shaped molded product obtained by mixing hydroxyapatite with polylactic acid and molding by melt extrusion. Have been. However, in this case, as the portion of the absorbent material is decomposed and absorbed, the structure becomes porous, and at some point, the tendency of accelerated decomposition and absorption is inevitable. Therefore, there is a high possibility that the PH locally decreases and inflammation occurs.

Further, in US Pat. No. 4,743,257, a so-called self-rein in which a matrix made of a bioabsorbable polymer is reinforced with a fiber made of the same component.
Bone bonding material composed of a forced composite is shown, but this is also loosened in a fibrous form and the surface area increases.
It is highly likely that a burst of absorption will occur at a certain time, thereby causing inflammation.

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

[0011]

The bone bonding device according to the present invention is characterized in that a molded body of an oxide-based ceramic or a calcium phosphate-based ceramic is used as a core material, and the core material is coated with uniaxially stretched polylactic acid. Features.

The core material used in the present invention may be a molded body of an oxide ceramic or a calcium phosphate ceramic having good biocompatibility. For example, alumina and zirconia may be used as the oxide ceramic. Hydroxyapatite, tricalcium phosphate and the like are preferably used as the base ceramics. After forming these ceramic materials by the conventional method,
What is necessary is just to precision-process and use it in the column shape which has a predetermined outer diameter. In addition to these ceramics, bioactive demineralized bone can be filled, or BMP (Bone Morphor) can be used.
organic protein).

On the other hand, bioabsorbable polylactic acid (hereinafter, referred to as PLA) used as a coating material is prepared from optically active L-form or D-form lactic acid by a conventional method (CE Love,
It is obtained by synthesizing lactide which is a cyclic dimer of lactic acid according to U.S. Pat. No. 2,668,182), and subjecting the lactide to ring-opening polymerization, which is an L-form polylactic acid (hereinafter, referred to as PLLA). Is more preferred. It is important for the PLLA to appropriately adjust the molecular weight and the crystallinity. That is, the higher the molecular weight of PLLA, the higher the strength of the material. However, if the molecular weight is too high, a high temperature and a high pressure are required during melt molding, so that a significant decrease in the molecular weight is caused. The molecular weight is low and, of course, the strength is low. On the other hand, crystalline materials have higher flexural strength than amorphous materials,
The elastic modulus is high, and the penetration of body fluids is slower in the crystalline phase and the apparent hydrolysis is slower. However, when the degree of crystallinity is increased by heat treatment, the strength is improved, but because PLLA is thermally unstable, the deterioration proceeds and the molecular weight decreases,
The hydrolysis rate is increased, and the strength is rapidly deteriorated. For this reason, the PLLA of the coating material has a viscosity average molecular weight of 300,000 to 600,000, preferably 350,000 to 5
Those having a crystallinity of about 50,000 and about 10 to 60% are preferably used.

The PLLA of the coating material may be formed by a known stretching method such as uniaxial stretching after melt molding.
It is desirable that the film is uniaxially stretched at a draw ratio of about twice. The uniaxial stretching increases the strength of the PLLA molded product,
This is because the compression bending strength is 160 to 250 MPa, and the compression bending elastic modulus is tough to show a value of 5500 to 24000 MPa, and a slight return after stretching causes a large increase in the force for tightening the core material. .

The osteosynthesis device of the present invention in which the above-mentioned ceramic core is coated with the stretched PLLA coating material as described above can be used for various rods, screws, pins and the like used in general surgical operations. Used in shapes. In the case of a rod or a pin, the diameter of the core material is about 1 to 3.5 mm (preferably 1.2 to 3 mm), the thickness of the PLLA coating material is about 0.75 to 2 mm (preferably 1 to 1.5 mm),
2.5-8mm (preferably 3-6mm) overall diameter
About the same size is used for the screw, but the screw PL
It is desirable that the thickness of the LA coating material is made slightly thicker in consideration of the groove cut.

The osteosynthesis device of the present invention is, for example, PL
A (PLLA) is melt molded, desirably uniaxially stretched, then drilled to form a hollow pipe into a hollow pipe, which is heated at about 80 ° C. in a nitrogen atmosphere, and the core material is inserted into the hole. Is done. At this time, it is important to take care that heat generated by drilling does not accumulate in the PLLA. The above manufacturing method is merely an example. In addition to this, for example, a PL is applied to the core material using a crosshead mold.
Various manufacturing methods such as a method of coating A can be adopted.

[0017]

When the osteosynthesis device of the present invention is implanted in the body, the surface PLA (PLLA) comes into contact with bodily fluids and gradually begins to hydrolyze, gently progressing from the surface to the inside.
Since the device of the present invention uses PLA only for the coating material portion, the absorption of PLA is completed earlier and the absolute amount absorbed is smaller than that of a conventional device formed entirely of PLA. Therefore, the osteosynthesis device of the present invention has a very low possibility of causing inflammation. After the PLA coating material is completely absorbed, a ceramic core material such as hydroxyapatite, which is excellent in biocompatibility, remains, and is used as an osteosynthesis device until the fracture or damaged part is completely healed. Perform the function of

As described above, the osteosynthesis device of the present invention comprises:
Compared with PLA devices, PLA has a higher absorption rate and a smaller absolute amount is absorbed, so that it is less likely to cause inflammation. Moreover, since the ceramic core material is covered with PLLA, the conventional ceramic material is used. It can sufficiently cover the disadvantages of brittleness found in devices. That is, the initial strength shows an intermediate value between PLA and the core material, and the surface characteristics depend on the properties of PLA. PLA provides toughness as an organic polymer, and ceramics as a core material has advantages of high elastic modulus and high rigidity.
When the ceramic powder used for the core material is mixed,
Such physical strength is not improved.

When PLA is completely absorbed,
Healing of fractures and injured parts has progressed to some extent, and the phenomenon of a decrease in the strength of the surrounding bone, which is a defect of the ceramic material, can be minimized. Furthermore, mixing hydroxyapatite with PLA in powder or flake form,
Compared to fiber reinforced devices, there is no burst-like absorption, and the possibility of inflammation is low, and it is an extremely superior osteosynthesis device compared to currently used or studied osteosynthesis devices I can say.

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

Further, a conventional device made of PLA is X
X-rays with X-rays have the drawback that they are not captured, and there is a problem that it is difficult to grasp the decomposition behavior and the like after implantation. However, in the osteosynthesis device of the present invention, the ceramic molding used as the core material is X X-rays can be taken and can be used as markers during X-ray photography.

[0022]

Embodiments of the present invention will be described below in detail.

A hydroxyapatite (hereinafter referred to as HA) sintered rod having a diameter of 1.5 mm has a viscosity average molecular weight (measured in chloroform at 25 ° C.) of 400,000 P
The LLA is coated by extrusion to form a composite rod of HA / PLLA, and then the coated portion of PLLA is stretched four times in the longitudinal direction at a temperature of 105 ° C., so that the outer diameter is 3.2 mm and the length is 5 mm. A composite rod of 0.5 cm was prepared (Sample 1).

In the same manner, a rod made of crystallized glass containing HA and wollastonite having a diameter of 2 mm is coated with PLLA, and the outer diameter is 6.5 mm and the length is 5 cm.
Was prepared and cut into a cancellous bone screw (screw trough diameter 4 mm, PLLA wall thickness 1 mm at trough diameter portion, 2.25 mm at crest diameter portion) (sample 2).

When these physical strengths were measured, the bending strength and the flexural modulus were dominated by the core material, and Sample 1 had 2400 kg / cm ² and 2100 kg / m ² , respectively.
m ² , 2500 kg / cm ² and 40 for sample 2, respectively
It was 00 kg / mm ² . Further, the surface was dependent on the physical properties of PLLA, and the ceramic had no brittleness and had toughness. In addition, since it does not have the flexibility of PLLA and has the rigidity of the ceramics of the core material, it has a strength that is convenient for inserting the screw. Also, the core material and P
The interface of the LLA coating material is different from the state in which the ceramic rod is simply heat-coated because the interface is once heated at the time of elongating the PLLA and then returned under heating to tighten the core material. The adhesion was so strong that it could not be easily peeled off. This was advantageous because no third material was required as an adhesive to increase the adhesion.

Next, the rod of the sample 1 was experimentally created with a transverse fracture at the center of the shin / fibula shaft of five cats, inserted into the medulla thereof, and reduced and fixed. The outside was equipped with a hardening zone, and each solid was cage-rested.

On the other hand, the screw of Sample 2 was experimentally osteotomized in the proximal part of the tibia of five rabbits and fixed internally. That is, a vertically fractured fracture including about one-third of the joint surface was created in the proximal part of the right tibia of a rabbit weighing about 3 kg, and internally fixed with a single screw. Cage rest was performed without external fixation.

As both controls, the same reduction and fixing were carried out using rods and screws of the same diameter and the same length consisting of PLLA alone.

After the lapse of 25 months, each was sacrificed and the rod hole and the screw hole were observed. As a result, PLLA was decomposed and absorbed by the control rod, and no residual solid was observed. The rod hole was clearly visible and did not reach the point where the new bone was replaced. In the case of the screw, about 5 to 30% of PLLA solid remained, and although the molecular weight was degraded to 2000 to 3000 or less, screw holes were clearly recognized.

On the other hand, in the case of the composite rod of Sample 1 having HA as a core material, PLLA around HA is decomposed,
It disappeared by resorption, and the portion was filled with new bone, and no rod hole remained. Also, in the case of the screw of sample 2 having a bioactive core material, even though a part of PLLA remains in a porous state, the PLA on the outer periphery is formed by the bioactive effect.
A portion of LA was vigorously replaced with new bone, and the outer hole of the screw was fairly filled.

The above facts confirm that the osteosynthesis device achieves the object of the present invention.

Incidentally, in the soft X-ray image in the follow-up observation after the operation, X-ray observation was possible by the core material of the rod and the screw. In addition, at the initial stage from 4 to 8 weeks, a sufficient amount of the fused callus and the bridge-like callus grown from the fracture ends on both sides of the osteotomy were completed.
Therefore, the osteosynthesis device comprising the composite of the present invention also has significance here.

[0033]

As is clear from the above description, the surface of the osteosynthesis device of the present invention is covered with PLA (PLLA) which is biodegradable and absorbable immediately after implantation.
It is possible to alleviate a decrease in the strength of the surrounding bone due to the high elastic modulus of the ceramic core material. In addition, the PLA coating material is gradually decomposed and absorbed from the surface, but the decomposition and absorption are completed in a short period of time because the total amount is smaller than that of the device composed of only PLA, and the absolute amount absorbed is small. Is very unlikely to occur. At the end of this decomposition and absorption process and at the end of the process, the new bone is likely to be buried in a state of bridging the cavity portion thinly. It has the greatest advantage of being filled with new bone in a short period of time without requiring a long period of 3 to 4 years.

After the PLA of the coating material is completely decomposed and absorbed, a ceramic-based core material having excellent biocompatibility is used as an osteosynthesis device until the fracture and the damaged site are completely healed. Perform the function of When the PLA coating material is completely absorbed, the fracture and the healing of the damaged site have progressed to some extent due to the generation of new bone, and the phenomenon of strength reduction of the surrounding bone, which is a drawback of the ceramic device, is minimized. There is also an effect that it can be suppressed.

Furthermore, since the ceramic core material is used as a marker during radiography, the disadvantage that a device consisting of PLA alone cannot be photographed by radiography can be solved. And the stretched PLA used as the coating material is
There is also an effect of accelerating the generation of callus by the piezoelectric effect, and the healing is promoted by the generation of new bone.

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

Continuation of front page (56) References Table 1-501289 (JP, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) A61L 25/00-31/00 A61B 17/58

Claims (1)

(57) [Claims] An osteosynthesis device characterized in that a molded body of an oxide-based ceramic or a calcium phosphate-based ceramic is used as a core material, and the core material is coated with uniaxially stretched polylactic acid.