JP2002306518A - Indwelling implement - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a indwelling implement, which is light in weight, has superior mechanical physical properties and improves the characteristics of bonding with invivo tissues. SOLUTION: In the indwelling implement provided with a metallic portion in one part at least, at least one part of the metallic portion is configured by using a porous metal.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an indwelling device which can be indwelled (or placed) in a body by an operation such as transplantation, and can be typically used in, for example, a surgical area (orthopedic surgery, brain surgery, etc.) or a dental area. Medical tools (eg, artificial bones that can be implanted into hard tissue such as bones, fracture fixing plates, medical tools that can be used in the orthopedic field such as screws and wires, etc .; clips for cerebral aneurysm ligation and brain Medical tools such as a coil for filling an aneurysm, which can be used in the field of brain surgery; and medical tools which can be used in a dental field, such as an artificial tooth root).

The indwelling device according to the present invention is stable for a long period of time while achieving weight reduction and compatibility with internal tissues (preferably, further promoting healing, preventing infection, etc.) without reducing strength. It is possible to leave it in the body in the state of being done.

[0003]

2. Description of the Related Art The application site and application method of the indwelling device of the present invention are not particularly limited, but for convenience of explanation, the conventional technology will be described by taking an example of "implanted device" which is a typical usage method of the indwelling device in recent years. State. With respect to implantable devices in orthopedic and dental fields, many such devices are made of metal. Metals are used for these because of the expectation of mechanical strength for metal materials. In response to these expectations, metallic materials have greatly contributed to the treatment of many diseases that were considered difficult to treat.

[0004] In the area of metal plates, screws, wires, and the like that can be used for artificial joints, artificial bones, artificial dental roots, and fracture treatments, metallic materials have been the main material. Metallic materials have also been used for cerebral aneurysm ligation clips and cerebral aneurysm filling coils used in the cerebral vascular region in terms of stability in the body, excellent mechanical strength, and good workability. Was. As metal materials to be left in the body, stainless steel, titanium, platinum, tantalum, a shape memory alloy which is an alloy of nickel / titanium, and the like have been mainly used.

[0005] In today's medical care, however, further expectations are placed on metallic materials, such as strength, suppleness, durability against continuous stimulation, stealth in the body, corrosion resistance, and non-irritability. In addition, higher-functional elements such as biological functions and physical properties equivalent to body tissue materials, and interoperability at the cell level with body tissue are required. Was.

However, it is impossible for today's metal materials to meet these requirements. In addition, metallic materials also typically show large differences in balance in terms of volume, weight, mechanical properties, etc. compared to those of body tissue, so that simple conditions required today (for example,
The problem of creating materials closer to body tissue remains unsolved.

[0007] In the past 30 years, a problem that has been imposed on metal materials is the affinity for tissue in the body, and the affinity for cells has been improved by using titanium or the like and improving surface treatment such as ceramic processing by plasma irradiation. Was. However, no further improvements have been made. It is believed that the main reason was that the metal material did not have an improved means for fundamentally solving many of these problems. This leaves some clinically inconvenient phenomena.

For example, a plate, a bolt, and a wire for fixing an artificial hip joint, an artificial head, or a fracture in an elderly person are too strong and too heavy to wear or destroy the patient's own bone. Inconvenience such as breaking or breaking. In addition, in the conventional artificial root abutment, the gingival fibers did not bond with the abutment, and bacteria could easily enter.

[0009] Furthermore, since it is impossible for tissue of the body to invade into the metal material, when inserted into the body,
The body tissue surrounds the entire metal material with the body tissue, and performs a foreign substance treatment by a phenomenon called “encapsulation”. This phenomenon represents an extraterritorial territory within one country. Therefore, when an infection or the like occurs, it is difficult to enter the area even if a drug such as an antibiotic is used, and the therapeutic effect is uncertain.

[0010] In addition, when an infection occurs in a very small part of the metal part, the infection spreads quickly to the entire surface of the material at the boundary area between the inner surface of the encapsulating tissue and the material, so that the metal material becomes extremely infected. It also results in weakness. On the other hand, for a metal material that has been used conventionally, it has a property to positively act on the body tissue, for example, to impart properties of promoting healing, antibacterial, coagulation, anticoagulation, etc. It was almost impossible. For example, platinum or the like has been used as a medical device that is inserted into a blood vessel such as a filling coil in a cerebral aneurysm and used as an embolizing agent, but the inside of the aneurysm is closed by a thrombus formed on the surface of the platinum coil. However, the process by which the formed thrombus becomes a matrix and is covered by vascular endothelial cells (vascular endothelialization) is extremely slow and cannot be said to be complete treatment.
There was a major problem that the risk of blood clots being released into the cerebral arteries would last forever.

Of course, the conventional metal material is replaced with the above-described artificial bone,
Even when used as a fracture plate, artificial root, or the like, it has not been possible to positively act on body tissue to promote treatment or prevent infection.

[0012]

SUMMARY OF THE INVENTION It is an object of the present invention to provide a device for indwelling a living body which has solved the above-mentioned disadvantages of the prior art. Another object of the present invention is to provide an in-dwelling device having the same mechanical properties as the tissue around the body, excellent strength and light weight.

It is still another object of the present invention to provide a device for indwelling the body in which the device for indwelling the body is given an affinity and a binding property with surrounding body tissue. Still another object of the present invention is to provide an in-dwelling device provided with positive functions such as healing promotion, antibacterial, blood coagulation, and anticoagulant effects.

[0014]

Means for Solving the Problems As a result of earnest studies, the present inventors have found that it is extremely effective to impart a porous structure to the metal itself constituting the indwelling device in order to achieve the above object. I found it. The metal indwelling device of the present invention is based on the above findings, and is an indwelling device including a metal portion in at least a part thereof, wherein at least a part of the metal portion contains a porous metal. Things.

The indwelling device of the present invention having the above-described structure is not only lightweight because the porous metal material constituting the device is porous, but also has a sufficient bonding strength because the contact area with the body tissue is significantly increased. Can be easily obtained. Further, in the embodiment using a porous metal having an anisotropic pore structure described later, not only the indwelling device has excellent mechanical strength, but also it is easy to exhibit the same toughness as hard tissue in the body.

Further, in the indwelling device of the present invention having the above-mentioned structure, since the metallic material constituting the device is porous (especially in the case of an anisotropic pore structure as described later), the body tissue invades inside. It is easy to strengthen the bond between the metal material and the surrounding body tissue. In this case, it is possible to control the degree of invasion of the body tissue particularly by the size of the pore.

When the pore size is 8 to 15 μm, a body tissue such as collagen fiber enters the pore, when the pore size is 40 to 100 μm, the bone-like tissue enters, and when the pore size is 150 to 200 μm, the bone tissue enters the pore. It is said that. Therefore, accurate control of the pore size is very important to enhance the connection between the indwelling device and the surrounding body tissue.

As described above, when the connection between the indwelling device and the surrounding body tissue can be strengthened, even if bone resorption, osteoporosis, deterioration of bone re-performance, etc. occur, the medical device can be stabilized in the body. Is held. For example, in the case of an artificial tooth root, it is easy to obtain bonding strength enough to withstand occlusal force.
In the case of a fracture plate, a bolt, a wire, and the like, it is easy to obtain a sufficient joint strength.

Furthermore, as described above, even if infection occurs on a very small portion of the metal surface, if the connection between the metal surface and the surrounding tissue is strong, the infected portion is limited to a local area and does not cause a major obstacle. . In addition, in the case of an artificial tooth root, if the bonding between the artificial tooth root and the surrounding tissue is strong, the adhesion of food plaque (plaque), bacteria and the like to plaque (plaque) on the surface of the artificial tooth root is suppressed, Prevent peri-implantitis.

Further, since the metal material constituting the indwelling device of the present invention having the above-mentioned structure is porous, various functional substances (for example, agents such as a coagulant, an anticoagulant and an antibacterial agent, A biologically active substance such as a cell growth inhibitor or a promoter or a cell, etc., in combination with a polymer compound if necessary)
Is extremely easy to fill. Therefore, the functional substance can be gradually released from the surface of the medical device into the surrounding tissue, and healing promotion, antibacterial, blood coagulation, and anticoagulant action can be positively imparted to the medical device. It is possible.

Particularly, in an embodiment using a porous metal having an anisotropic pore structure described later, since the pores are open, it is necessary to fill a large amount of a functional substance inside the porous metal and to release the porous metal gradually. But easier. When a cell growth promoting substance is used as the above functional substance,
For example, by slowly releasing the substance from the indwelling device of the present invention in the form of a filling coil in a cerebral aneurysm, it is possible to remarkably promote the delay of vascular endothelialization, which was conventionally a critical problem. It is.

Further, the sustained release of a cell growth promoting factor or the like from the indwelling device of the present invention in the form of a plate for fixing a fractured portion or an artificial tooth root can significantly improve the promotion of healing. In addition, when an antibacterial agent or the like is used as a functional substance, it is possible to positively prevent infection, which is a major problem of artificial joints and artificial roots. In the present invention, when the pore direction of the porous metal is aligned in one direction (Smax / Smin ≧ 2) and the shape of the pore cross section in a direction perpendicular to the direction is almost circular, the strength of the porous metal material is reduced. Maintaining the artificial joint, the plate for fixing a fractured part, the screw, the artificial tooth root and the like of the present invention further facilitates the maintenance.

In the embodiment of the present invention, in which the pore inner surface of the porous metal is formed by the solid solution strengthening layer or the ceramic layer, the strength of the porous metal can be further improved. In the embodiment of the present invention, the porous metal is produced using a difference in solubility of gas atoms in a molten state and a solidified state of the metal using a metal-gas system, while maintaining the strength of the porous metal, It is extremely easy to obtain pores. In such an embodiment, the solid solution strengthening layer can be easily formed on the inner surface of the pore by the reaction between the metal atom and the gas atom in the production process of the porous metal.

In the present invention, if necessary, a ceramic layer can be formed on the inner surface of the pores of the porous metal by a chemical vapor deposition method or a physical vapor deposition method. Such a ceramic layer on the inner surface of the pore
It can also be formed by an ion plantation method.

[0025]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, the present invention will be described more specifically with reference to the drawings as necessary. In the following description, “parts” and “%” representing the quantitative ratios are based on mass unless otherwise specified. (In-vivo indwelling device) In the present invention, the "in-vivo indwelling device" refers to a medical device that is temporarily or (semi) permanently indwelled or placed in the body by an operation such as transplantation. As used herein, the term "medical device" refers to a device or device intended to be used for diagnosis, treatment or prevention of human or animal diseases, or to affect the structure or function of the human or animal body. Say

The term "body" refers to a human or animal body. As long as the indwelling body has a meaning (for example, preservation of the body tissue and prevention of deterioration), it includes not only the body tissue but also the body of a dead body. In the present invention, as long as at least a part of the indwelling device can be indwelled in a body tissue by invasion, insertion, or the like, the device is referred to as an “in-vivo” indwelling device. The “medical device” in the present invention is not particularly limited as long as the use of the porous metal is effective. "Medical device" in the present invention
As typical examples, for example, artificial joints (FIG. 1), fracture fixing plates (FIG. 2), screws (FIG. 3), wires,
Artificial roots (FIG. 4), cerebral aneurysm filling coils, etc. are included. (Metal having porous structure) The porous metal constituting the indwelling device of the present invention is not particularly limited as long as it has porosity, but those having the following physical properties can be particularly preferably used. (Pore Size) The porous metal constituting the stent of the present invention has an average pore size (pore diameter) of 0.1 to 1000 μm.
m, more preferably about 0.5 to 500 μm. Such pore sizes are, for example,
The measurement can be suitably performed using a measuring device (trade name: Automated Perm-Porometer) manufactured by Materials, Inc. (Porosity) The porous metal constituting the stent of the present invention has a porosity (porosity or porosity) of 5 to 80.
%, More preferably about 10 to 40%. Such porosity is, for example, the US Porous Mat
It can be suitably measured using a measuring device (trade name: Automated Perm-Porometer) manufactured by erials, Inc. (Direction of Pore) The porous metal constituting the indwelling device of the present invention preferably has a pore directionality (Smax / Smin) of 2 or more. Furthermore, this direction (Smax /
Smin) is preferably 10 or more, more preferably 20 or more (especially 50 or more). The directionality of such pores can be suitably measured by the following method. <Method of Measuring Pore Directivity> A porous metal tube having a hollow cylindrical shape along the axial direction of the porous metal as shown in the schematic perspective view of FIG.
mm).

The porous metal tube obtained above is cut at one position along the pore axis direction, and a porous metal plate (thickness: about 1 mm, size: about 1 mm) as shown in the schematic perspective view of FIG.
(About 2 mm × about 20 mm). The porous metal plate obtained above is cut at a thickness of about 1 mm along a direction perpendicular to the pore axis to obtain a porous metal fragment. Approximately ten such metal fragments are arranged and adhered to each other using an epoxy resin, and a sample for measuring the directionality of pores made of porous metal fragments as shown in the schematic perspective view of FIG. 7 is prepared. This sample is cut out in an appropriate size (for example, a disk having a diameter of about 10 mmφ) and used for the following measurements.

Using an apparatus as shown in the schematic cross-sectional view of FIG. 8, P = 133 × 10 ⁵ P was added to water retained above the sample.
The pressure of a (= 100 mmHg) is applied, and the amount of water passing through a predetermined area (for example, a disk having a diameter of about 7 mmφ) of the sample is measured for about 5 minutes. The measurement is repeated about three times, and the average is obtained. The measured value of the sample surface A (that is, the surface through which water permeates in the direction in which the directionality of the pore is maximum) is Smax, and the sample surface B (that is, the water permeation in the direction in which the directionality of the pore is minimum) Smin
, The directionality of the pore (Smax / Smin) is calculated. (Mechanical Strength) The porous metal used in the present invention preferably has the following mechanical strength characteristics from the viewpoint of durability and reliability (particularly important in medical fields).

For example, the tensile strength (σ) in the direction parallel to the direction of the pores of the porous metal and the tensile strength (σ ₀ ) when the porosity of the porous metal is zero, ie, when the porous metal is solid (no pores) are measured. I do. The ratio (A) between the relative tensile strength (σ / σ ₀ ) and the porosity (P%) of the porous metal can be used as an index of the mechanical strength.

A = {(σ / σ ₀ ) / (100−P)} × 100 In the present invention, A represented by the above formula may be 0.8 or more, and more preferably 0.9 or more. preferable. (Embodiment of indwelling device) The embodiment of the indwelling device of the present invention is not particularly limited as long as the use of the porous metal is effective. The indwelling device of the present invention typically includes, for example, an artificial joint (FIG. 1), a plate for fixing a fractured part (FIG. 2), a screw (FIG. 3), a wire, an artificial root (FIG. 4), a cerebral aneurysm. And an inner filling coil. (Embodiment of Artificial Joint) FIG. 1 is a schematic perspective view showing an example in which the indwelling device of the present invention is in the form of an artificial joint. This figure is an example of a so-called Chanley type artificial hip joint. The hip prosthesis includes a pelvis-side socket 1 using high-density polyethylene (HDP), ultra-high-density polyethylene (UH-MWPE), or the like as an artificial cartilage; a metal bone tip (ball) portion 2 on the femur side; And a stem 3 made of stainless steel. In FIG. 1, for example, when a porous metal (for example, a porous titanium alloy) is used as the stem, the weight of the base material is reduced, the impact force is absorbed, the affinity with the living body is increased, the infection is prevented, and the healing is promoted. Advantages such as can be obtained. (Aspect of Fracture Repair Plate) FIGS. 2A and 2B are a schematic plan view and a schematic cross-sectional view, respectively, showing an example of the in-vivo indwelling device of the present invention as a fracture repair plate. The fracture repair plate of FIG.
A slightly flat elongated member 4 having a desired number of holes 5
Having. In FIG. 2, for example, when a porous metal (for example, a porous titanium alloy) is used as the elongated member 4, the fixing screw is prevented from loosening due to the absorption of the impact force and the stress, and the affinity with the living body is increased. Advantages such as prevention of infection and promotion of healing can be obtained. (Embodiment of Fracture Repair Screw) FIG. 3 is a schematic plan view showing an example in which the indwelling device of the present invention is an embodiment of a fracture repair screw. 3 has a handle 7 having a thread 6. In FIG. 3, for example, when a porous metal (for example, a porous titanium alloy) is used as the handle portion 7, the screw is prevented from being loosened by absorbing an impact force, and the infection is prevented by improving affinity with a living body.
Benefits such as accelerating healing can be obtained. (Embodiment of Artificial Root) FIG. 4 is a schematic perspective view showing an example in which the indwelling device of the present invention is used as an artificial root (implant). The artificial dental root shown in FIG. 4 has a fixture 11 for fixing the artificial dental root to the gingiva 10, an abutment 12 for supporting engagement, and an upper structure 13 having a shape similar to the shape of a human tooth. In FIG.
For example, as an abutment, a porous metal (for example,
When a porous titanium alloy is used, advantages such as prevention of infection and promotion of healing due to strong bonding with gingival fibers can be obtained. (Method for Producing Porous Metal) The method for producing the porous metal is not particularly limited as long as the porous metal having the above-described characteristics can be produced. In general, as a method for producing a porous metal, methods such as a casting method, a plating method, a powder metallurgy method, and a sputter deposition method described below have been developed. Casting methods Casting methods include a molten metal foaming method, an interparticle infiltration method, and an investment casting method. The molten metal foaming method is a physical method in which an inert gas or carbon dioxide gas is injected into a molten metal, stirred, foamed, and solidified, or a foaming agent such as a titanium hydride compound or a zirconium hydride compound is added to the molten metal to form a hydrogen compound. There is a chemical method of foaming and solidifying with hydrogen gas generated by a decomposition reaction. The porous structure obtained by these methods has a strong tendency to consist of independent pores, and it is relatively difficult to obtain a porous metal having anisotropic pores.

The interparticle infiltration method is a method in which molten metal is impregnated into gaps between small spheres packed in a mold and solidified.
For the small spheres, hollow glass spheres or sodium chloride are often used. The globules of sodium chloride can be dissolved with water after solidification. On the other hand, in the investment casting method, a void portion of a polyurethane foam is filled with a refractory slurry, dried, and then fired to produce a mold. After casting the molten metal there under reduced pressure, the mold is removed to produce a porous metal.

Although the porous metal having a large pore diameter can be produced by the interparticle infiltration method or the investment casting method, the pore diameter of the porous metal suitable for the stent of the present invention, that is, the small pore diameter of several μm to several tens μm is used. It is relatively difficult to make metal. In addition, the porous metal produced by the above method has a strong tendency that the pores become random and the mechanical properties deteriorate, and it is relatively difficult to process the obtained porous metal into a stent. Plating method The surface of the skeleton of the polyurethane foam is coated with graphite or the like by a chemical method, and this is used as a cathode.
After the cathode is plated with nickel or the like in an electrolytic bath, the polyurethane foam is removed by firing to produce a porous metal. Also in this method, it is relatively difficult to produce a porous metal having a pore size suitable for the present invention and good mechanical strength. Powder metallurgy method A foaming agent is mixed with a slurry of an organic medium and a metal powder, foamed, solidified, and then fired, without using the slurry foaming method, HIP (hot isostatic pressure treatment) or CIP (cold isostatic processing). There are a normal pressure sintering method in which metal powder is sintered at normal pressure, a sponge method in which a polyurethane foam is immersed in a slurry of metal powder and dried, and then the polyurethane foam is thermally decomposed and sintered. Sputter deposition A metal is sputter-deposited on a water-cooled substrate in an inert gas using a sputtering method to synthesize a thin film. Such a thin film usually contains about 20 to 2000 ppm of an inert gas. When the thin film is heated just below the melting point, bubbles formed by the mixed gas atoms grow and grow, and the volume of the bubble is increased by the heating to form a foamed metal.

[0033] In the above, an overview of various methods for producing a porous metal or a foamed metal has been given.
There is a metal-gas method described later. An open pore that can be suitably used for the porous metal for indwelling device of the present invention can be easily obtained, or the uniformity of the pore diameter, the directionality of the pore and the control of the small pore diameter of several μm to several hundred μm are easy. From a certain point of view, the metal-gas method can be particularly preferably used among the various methods described above.

Further, the porous metal obtained by the metal-gas method is of an open type and can easily provide anisotropic pores. By utilizing the characteristics of such pores, weight reduction can be achieved while maintaining mechanical strength. Further, as described above, the body tissue can penetrate into the pore, and a strong bonding layer can be obtained between the metal material and the surrounding tissue. Further, by filling the pores with functional substances (drugs or physiologically active substances, etc.),
It is easy to impart a sustained release function, and it is possible to impart functions such as promotion of healing and antibacterial properties to the indwelling device of the present invention. (Metal-gas method) Hereinafter, a method (metal-gas method) of imparting a porous structure that can be most preferably used in the present invention will be described.

In this method, using a metal-gas system, a porous metal is produced by utilizing the difference in solubility of gas atoms between a molten state and a solidified state of a metal (Japanese Patent Laid-Open No.
-88254, Japanese Patent Application No. 10-227624, Japanese Patent Application No. 11-42575, Japanese Patent Application No. 11-195260; Production and Technology, Vol. 51, No. 3, page 60 (199)
9)). When a metal is melted in a gas (hydrogen, oxygen or nitrogen) atmosphere, a large amount of gas atoms dissociate and dissolve in the metal. Thereafter, when the molten metal is solidified, supersaturated gas atoms are precipitated, and pores are formed in the metal. Increasing the gas pressure when melting a metal in a gas atmosphere increases the solubility of gas atoms in the molten metal and increases the porosity.

On the other hand, the hole diameter and the direction of the pores can be controlled by the cooling speed and cooling system of the molten metal. In this method, since the pore formation is based on the precipitation of supersaturated gas atoms, for example, it is extremely easy to make the shape of the pore cross section of the porous metal substantially circular. In such a porous metal having a substantially circular pore cross section, unlike a conventional porous metal having an irregular pore cross section, stress concentration does not occur around the pore during deformation, and when a tensile stress is applied. It has been demonstrated that the "specific strength" of stress divided by substantial cross-sectional area does not depend on porosity (eg, SK Hyun et al. "Mec
hanical properties of porous copperfabricated by u
nidirectional solidification under high pressure h
ydrogen ", Proceedings of the International Confere
nce on Solid-Solid Phase Transformation '99 (JIMIC
-3), p. 341, edited by M. Koiwa et al., The Ja
pan Institute of Materials, 1999). In other words, even if the porosity of the porous metal having a substantially circular pore cross section is increased to some extent, it is easy to maintain the mechanical strength of the porous metal.

The pores of the porous metal formed by the metal-gas method can be easily formed as open pores (that is, the pores are formed on the surface of the porous metal). Unlike a conventional porous metal, such a porous metal having an open-type pore is easy to fill a drug or a physiologically active substance into the pore and release the same gradually. The pores of the porous metal formed by the metal-gas method can be easily formed into a pore shape in which the directions of the pores are aligned in the axial direction, that is, a so-called "lotus root type pore". It has been demonstrated that such a “lotus root type pore” has a higher torsional strength and an axial compressive strength than a solid (no pore) rod-shaped sample (for example, the literature “for mechanical design”). Material selection ", 149
153 pages, translated by Junichi Kaneko and Masahisa Otsuka, published by Uchida Lao Tsuruho,
1997).

Further, according to the experiments of the present inventor, the tensile strength of porous copper (porosity of about 30%) produced by using the metal-gas method is reduced by only 20 to 30%, It has been found that when porous copper having a porosity of about 30% is produced by the powder metallurgy method described above, the tensile strength tends to decrease by as much as 60 to 90%. FIG. 9 shows σ / σ ₀ (relative tensile strength) of “Renkon type” porous copper manufactured using the metal-gas method,
It is a graph which shows an example of the relationship with porosity. As is clear from this graph, the above-mentioned "Ronkon-type" porous copper is superior in strength at the same porosity as compared with the conventional sintered metal or foamed metal. (Material of Porous Metal) The material of the porous metal is not particularly limited as long as a porous metal having the above-described characteristics can be manufactured. In the present invention, for example, iron, nickel, aluminum,
Copper, magnesium, cobalt, tungsten, manganese, chromium, beryllium, titanium, silver, gold and alloys thereof (Hideo Nakajima, “Creation and Application of Porous Metals”, Material Integration 12 , 37, 1999). Stainless steel, nitinol, and the like, which can be suitably used as a material for the stent, can also be made porous using, for example, a metal-gas method. (Inner Pore Surface of Porous Metal) In the present invention, a modified layer (for example, a solid solution strengthening layer or a ceramic layer) may be formed on the inner surface of the pore of the porous metal as needed. For example, by using the modified layer to increase the hardness of the inner surface of the pore of the porous metal, the strength (tensile strength, compressive strength, bending strength, etc.) of the porous metal can be significantly improved.

As a method for forming the modified layer on the inner surface of the pore of the porous metal, the following two methods can be suitably used. (1) As described above, the porous metal in the present invention can be produced, for example, by utilizing the difference in solubility of gas atoms in a molten state and a solidified state in a metal-gas system (metal-gas). Law). In this embodiment, when the molten metal is cooled and solidified, the solubility of gas atoms such as hydrogen, oxygen, and nitrogen in the metal is reduced, and the gas phase and the metal phase are separated to form pores. The solid solution strengthening layer can be easily formed by diffusing the gas atoms from the inner wall of the pore into the metal. By forming the solid solution strengthening layer, the hardness and the like of the inner surface of the pore can be improved.

(2) After preparing the porous metal of the present invention by various methods (for example, metal-gas method), if necessary, a ceramic layer may be formed on the inner surface of the porous metal pore by a known ceramic forming method. Can be formed. As such a ceramic formation method, a chemical vapor deposition method (chemical vapor deposition) or a physical vapor deposition method (physical vapor deposition; for example, an ion plantation method) can be suitably used.

For the purpose of increasing the hardness of the inner surface of the pore, it is effective to form a ceramic layer such as titanium nitride (TiN) or titanium carbide (TiC). For example, TiN or TiC can be formed on the inner surface of a porous metal by using titanium as an evaporation source and using nitrogen or acetylene as a reaction gas element by an ion plating method. When such a ceramic layer is formed on the inner surface of the porous metal, for example, the thickness of the ceramic layer can be controlled in the range of 100 ° (angstrom) to several μm by controlling the vapor deposition conditions. It is possible. (Preparation of in-vivo indwelling device using porous metal) The method for imparting the in-vivo indwelling device shape to the porous metal described above is not particularly limited, and a known method can be used.

For example, in the above-described embodiment using the metal-gas method, a supersaturated gas is deposited in a solid phase in a process of dissolving a gas in a molten metal material, and then solidifying and transforming the solid into a solid. A porous metal is produced using the property of being used as a base material for indwelling devices.
Examples of a method for producing an indwelling device using the porous metal include a method using a linear porous metal and a method of finishing a desired shape by cutting a plate-shaped or rod-shaped porous metal. From the former, a fracture part fixing wire, a cerebral aneurysm ligating clip, a cerebral aneurysm filling coil, and the like can be produced by the latter method, and a fracture part fixing plate, a screw, an artificial root, and the like, respectively. (Part Using Porous Metal of Indwelling Device) All or a part of the metal part constituting the indwelling device of the present invention is
Basically, it can be made of a porous metal.
In the following embodiment of the device for indwelling in a body, a portion particularly preferable to be made of a porous metal is exemplified as follows.

Artificial joint (as in FIG. 1, etc.): metal stem portion 3 Fracture fixing plate (as in FIG. 2, etc.): plate body 4 Fracture fixing screw (as in FIG. 2, etc.) ): Screw body 7 having thread portion 6 Wire for fixing fracture part: Wire body Artificial dental root (as in FIG. 3, etc.): Fixture 11 and abutment 12 Clip for ligating cerebral aneurysm: Clip body Filling cerebral aneurysm Coil for use: coil body (Method for producing linear porous metal) FIG. 10 is a schematic cross-sectional view showing an example of an apparatus for producing a linear porous metal.

Referring to FIG. 10, in a ceramic crucible 21 having a nozzle 21a, stainless steel, tantalum,
A material such as titanium, an alloy of titanium and nickel (Nitinol) is filled, and heat is applied from the periphery by means such as high frequency heating 22 to heat and melt. At that time, the atmosphere is hydrogen, oxygen,
Hydrogen, oxygen, or nitrogen gas atoms are dissolved in a molten metal (or alloy) 24 using nitrogen or a mixed gas 23 of them and an inert gas such as argon or helium. Thereafter, by applying a slight pressure to the crucible 21 to cause the molten metal to flow out from the nozzle 21a, and by bringing the molten metal into contact with the cooling unit 25 installed at the lower part of the nozzle 21a,
While maintaining the shape of the linear molten metal discharged through the nozzle, the molten metal is solidified at a predetermined solidification rate to produce the fine wire 26. By reducing the diameter of the nozzle 21a, it is possible to manufacture a considerably long thin wire 26. By changing the diameter of the nozzle, the thickness of the porous fine metal wire 26 can be easily changed. The solidification rate can be controlled by controlling the temperature and flow rate of the cooling medium circulating in the cooling unit, or by installing a heating unit in the cooling unit 25, and thereby the size and length of the pores can be controlled. It is possible to freely control the aspect ratio (pore aspect ratio), the porosity, the angle between the linear busbar and the pore growth direction, and the like. Since the surface of the fine porous metal wire 26 generated in this manner has an extremely high cooling rate, pores cannot normally be generated on the surface of the fine wire, and a nonporous surface is formed. Therefore, if necessary, the nonporous surface of the fine wire may be removed by a chemical polishing method such as corrosion etching using an acid solution, or a physical or mechanical polishing method such as sand polishing or mechanical cutting.

The final shape of the porous fine metal wire 26 after such a treatment is, for example, as shown in FIG.
The pores are exposed on the surface and grow with a slight inclination in the direction of the fine line bus. In order to smooth the surface of the fine wire 26, drawing plastic working may be performed as needed to form a fine wire having a uniform diameter. This process is not only for making the thickness uniform, but also for thin lines 2
6 has the advantage that crystal grains can be refined by introducing new plasticity, and the strength of the fine wire can be enhanced by introducing plastic strain. (Production method of plate-shaped or rod-shaped porous metal) FIG.
It is a schematic cross section which shows an example of the manufacturing apparatus of a cylindrical porous metal. Referring to FIG. 12, ceramic crucible 32
Is filled with a starting material 31a such as stainless steel, tantalum, titanium, or an alloy of titanium and nickel (Nitinol), and heat is applied from the periphery by means of a high-frequency heating coil 33 or the like to be heated and melted. The crucible 32 is surrounded by a heat insulator 34, a heat shield 35, and a pressure vessel 36.

When the above-mentioned starting material 31a is heated and melted, hydrogen, oxygen, nitrogen or a mixed gas thereof and an inert gas such as argon or helium is used as the atmosphere 31c to convert the molten metal (or alloy) 31b into hydrogen. Dissolves oxygen, or nitrogen gas atoms. Thereafter, the apparatus is inclined by 90 degrees, and the molten metal 31b is poured into the mold 38 via the pouring funnel 37. Since the cooling part 39 is provided on the bottom part of the mold 38, solidification of the molten metal is performed from above the bottom part (the cooling part 39 side) (the pouring funnel 37 side).
Proceed toward. In other words, by using such an apparatus, upward "unidirectional solidification" can be caused as solidification of the molten metal. In such unidirectional solidification, it is extremely easy to change the pore size, length, porosity, and the like by controlling the solidification speed and the atmospheric gas pressure.

The bulk porous metal of the above-prepared raw material prepared as described above is cut into a plate or a rod, for example, and cut and plastically processed. In this case, if necessary, bulk porous metal or, at the stage of cutting into a plate or rod shape, can be rolled and subjected to plastic working to refine the crystal grains and strengthen the base material by plastic strain. is there.

As described above, in the above-described process for producing a porous metal (metal-gas method), gas atoms such as oxygen or nitrogen usually react with the metal to form solid solution oxygen on the inner surface of the pore of the porous metal. Alternatively, since a nitrogen-enriched layer is formed, the inner surface hardness of the pore is improved, and a porous metal having high strength as a whole can be easily obtained. Further, after the porous metal is produced by the above-described method, if necessary, the inner surface of the pore of the porous metal is excellently formed by using a chemical vapor deposition method or a physical vapor deposition method (such as an ion plantation method). By forming a ceramic layer such as titanium nitride or titanium carbide having a high hardness, a porous metal having more excellent mechanical properties can be obtained.

As shown in the graph of FIG.
When the gas method is used, the growth amount and morphology of the pores in the porous metal, that is, the formation of the pore direction, size, porosity, etc., are determined by melting temperature, molten gas pressure, solidification gas pressure, cooling temperature, solidification cooling rate. , Parameters such as the mixing volume ratio with an inert gas and the pressure can be freely and accurately controlled and determined. The graph of FIG. 13 shows the porosity (%) of porous iron in which a nitrogen gas was solidified in iron melted at about 1650 ° C. under a predetermined mixed gas pressure of nitrogen and argon to form a unidirectional multicore pore. ) And the partial pressures of nitrogen gas (P-N ₂ ) and argon gas (P-Ar).

FIGS. 14 to 17 are optical micrographs (magnification: magnification) of cross sections of porous iron obtained by the ratio of the partial pressures of nitrogen gas and argon gas shown in the graph of FIG.
2.6 times). According to these figures, the porosity changes depending on the ratio between the partial pressure of nitrogen gas and the partial pressure of argon gas.
It can be seen that the porosity increases as the pressure of the nitrogen gas increases relative to the pressure of the argon gas. (Non-metallic substance) The in-vivo indwelling device of the present invention comprising the above-described porous metal can be filled with various non-metallic substances as necessary. As such a non-metallic substance,
Using functional materials that can exhibit various functions,
By supporting and / or sustained release in the pore,
A useful function can be imparted to the indwelling device.

The nonmetallic substance to be filled in the pores of the porous metal is not particularly limited as long as the function of the indwelling device of the present invention comprising a porous metal is not substantially impaired. It is preferable that the non-metallic substance contains an organic substance from the viewpoint of easy filling into the pores and easy provision of functionality. Examples of such an organic substance include a drug or a physiologically active substance. By filling the pores of the porous metal with the organic substance, the indwelling device of the present invention can carry a drug or a physiologically active substance and / or sustained release. The drug or physiologically active substance to be filled in the pore is not particularly limited, and one or more known drugs or physiologically active substances can be appropriately selected or used in combination.

Examples of such drugs or physiologically active substances include thrombus formation suppression, thrombolysis, platelet adhesion / aggregation suppression, infection prevention, anticancer properties, ability to suppress proliferation of fibroblasts / smooth muscle cells, blood vessels, and the like. Substances having the ability to promote the growth of endothelial cells and the like can be mentioned. (Cell) For fracture plate or artificial root,
If necessary, the patient's own bone cells and the like can be suitably used. In the case of an aneurysm-filled coil or the like, vascular endothelial cells or stem cells that can be differentiated into vascular endothelial cells can be suitably used to promote vascular endothelialization. (Polymer material) In the embodiment of filling the above-mentioned drug or physiologically active substance into the pores of the indwelling device of the present invention comprising a porous metal, in order to release these at a desired dissolution rate for a predetermined period, It is preferable to combine a drug or a physiologically active substance with a polymer material. The solubility of the drug or physiologically active substance to be filled in blood,
It is possible to select a suitable polymer material depending on the physiological activity concentration, release period and the like.

In the present invention, one of the polymer materials suitable for such purpose is a polymer material having biodegradability. Examples of the biodegradable polymer material include biodegradable polyesters represented by polyglycolic acid, polylactic acid, various polylactones, and the like. Also, in order for the drug or physiologically active substance incorporated in the polymer material to elute from the surface of the material, the porous polymer material, particularly the hydrogel (substantially loses the hydrated liquid to be held inside, (Including so-called "xerogel" state)
Alternatively, a hydrogel-forming polymer can be suitably used. Examples of the hydrogel include collagen gel, gelatin gel, fibrin gel, matrigel, alginate gel, chitosan gel, hyaluronic acid gel, and other natural polymer gels, and various synthetic polymer hydrogels.

On the other hand, as a polymer material for immobilizing cells (eg, bone cells for promoting bone formation or vascular endothelial cells for promoting vascular endothelialization), the activity of cells inside the polymer material is maintained. It is highly preferred that nutrient replenishment and removal of waste products be easy so that they can be divided and propagated. From this point, hydrogel can be particularly preferably used as a polymer material for immobilizing cells. In particular, the above-mentioned natural product hydrogel and a gelling thermoreversible hydrogel at the time of heating, which becomes a solution state at a low temperature and a gel state at a high temperature (Yoshioka, H. et al, "Preparation of poly (N-iso-
propylacylacrylamide) -block-poly (ethylene glycol)
and calorimetric analysis of its aqueous solutio
n ”, J. Macromol. Scis, A31 , 109, 1994). (Method of filling non-metallic substance into porous metal pore) In the pore of the porous metal indwelling device made of the porous metal of the present invention. The method of filling a nonmetallic substance (for example, a drug, a physiologically active substance, or a cell) in combination with a polymer material as necessary is not particularly limited, and can be appropriately selected or combined from known methods. For example,
As a method of combining a drug or a physiologically active substance with a polymer material, a mixed solution in which both are dissolved or dispersed in water or an organic solvent is prepared, and the in-vivo indwelling device made of the porous metal of the present invention is prepared in the mixed solution. The dipping method is most generally feasible. In this case, for example, by replacing the air and the mixture in the pores of the in-vivo device under negative pressure, removing the in-vivo device and drying to remove water or an organic solvent, the in-vivo device made of porous metal Can be filled with a non-metallic substance.

On the other hand, as a method of combining cells and the like with the above-mentioned hydrogel, for example, in the case of collagen,
After dispersing the cells in a solution containing a hydrogel-forming polymer and introducing the dispersion into the pore of the indwelling device,
By changing the pH or temperature, the hydrogel-forming polymer can be gelled and the cells can be immobilized in the gel. In the case of alginate gel, cells are dispersed in a medium solution of sodium alginate, and the dispersion is introduced into the pores of the indwelling device, and then, for example, by contacting with a concentrated calcium chloride solution, the sodium alginate is gelled. The cells can be immobilized within the pore.

In the case of the above-mentioned thermogelling thermoreversible hydrogel at the time of heating, the cells are dispersed in a solution of the hydrogel-forming polymer dissolved at low temperature, and the cell dispersion is placed in the body. After filling the pores of the device, the temperature can be increased to gel the hydrogel-forming polymer, thereby immobilizing the cells. The sol-gel transition temperature of the gelling thermoreversible hydrogel at the time of temperature rise is preferably within the physiological temperature range of cells.

[0057]

As described above, the indwelling device of the present invention not only has excellent strength and light weight because the porous metal material constituting the device is porous, but also has a remarkable contact area with the body tissue. Sufficient bonding strength can be easily obtained because of the increase. Further, in the embodiment of the present invention using the porous metal having the above-described anisotropic pore structure, not only the indwelling device has excellent mechanical strength, but also it is easy to exhibit the same toughness as hard tissue in the body. Becomes

Further, in the indwelling device of the present invention having the above structure, since the metal material constituting the device is porous (especially in the case of the above-described anisotropic pore structure), the body tissue invades inside. It is easy to strengthen the bond between the metal material and the surrounding body tissue. In this case, since the size of the pore can be controlled so that the body tissue can enter the pore, the degree of penetration of the body tissue can be controlled by the size of the pore. When the indwelling device is firmly held in the body in this way, infection that may occur at the joint can be effectively prevented.

It is also easy to carry various physiologically active substances in the porous metal pores of the present invention and release them gradually, which makes the in-dwelling device of the present invention highly functional (eg, healing promoting action, antibacterial action). Action, antithrombotic action, thrombus forming action, etc.).

[Brief description of the drawings]

FIG. 1 is a schematic perspective view showing an example in which the indwelling device of the present invention is in the form of an artificial joint.

FIG. 2 is a schematic plan view and a schematic cross-sectional view showing an example in which the indwelling device of the present invention is in the form of a plate for fixing a fractured part.

FIG. 3 is a schematic perspective view showing an example in which the indwelling device of the present invention is in the form of a screw for fixing a fractured part.

FIG. 4 is a schematic perspective view showing an example in which the indwelling device according to the present invention is in the form of an artificial tooth root.

FIG. 5 shows pore directionality of porous metal (Smax / Smin)
It is a schematic perspective view which shows an example of the manufacturing method of the hollow cylindrical sample for a measurement.

FIG. 6 is a schematic perspective view showing an example of a method for producing a plate-like sample for measuring the pore directionality of a porous metal.

FIG. 7 is a schematic perspective view showing an example of a method for producing a laminated sample for measuring the pore directionality of a porous metal.

FIG. 8 is a schematic cross-sectional view showing an example of a measurement method for measuring pore directionality of a porous metal.

FIG. 9: “Rotkon type” manufactured using a metal-gas method
5 is a graph showing an example of the relationship between porosity and σ / σ ₀ (relative tensile strength) of porous copper.

FIG. 10 is a schematic cross-sectional view showing an example of an apparatus for producing a linear porous metal.

FIG. 11 shows an embodiment of a linear porous metal, and a pore direction,
It is the typical perspective view and typical cross section which show an example of the relationship of a cooling direction.

FIG. 12 is a schematic cross-sectional view showing another example of an apparatus for producing a linear porous metal.

FIG. 13 is a graph showing an example of a relationship between a nitrogen partial pressure and an argon partial pressure of a mixed gas in a porous metal production method by a metal-gas method.

14 is a micrograph (magnification: 2.6 times) of a cross section of a porous metal obtained corresponding to one condition of the graph in FIG.

15 is a micrograph (magnification: 2.6 times) of a cross section of a porous metal obtained corresponding to another condition of the graph in FIG.

16 is a micrograph (magnification: 2.6) of a cross section of a porous metal obtained according to still another condition of the graph of FIG.
Times).

FIG. 17 is a micrograph (magnification: 2.6) of a cross section of a porous metal obtained according to still another condition of the graph of FIG.
Times).

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 21 ... Crucible 22 ... Heating part 23 ... Mixed gas 24 ... Molten metal 25 ... Cooling part 26 ... Solidification porous metal wire 31a ... Starting material 31b ... Molten metal 31c ... Atmosphere 32 ... Crucible 33 ... Heating coil 34 ... Thermal insulator 35 ... Heat shield plate 36 ... Pressure vessel 37 ... Pouring funnel 38 ... Mold 39 ... Cooling unit

 ──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Hideo Nakajima 5-6-40 Hiyoshidai, Takatsuki-shi, Osaka (72) Inventor Yasuharu No Isshiki 2-6-11 Namiki, Kanazawa-ku, Yokohama-shi, Kanagawa-ken (72) Inventor Yuichi Higuchi 4-2-16 Komakawa, Higashisumiyoshi-ku, Osaka-shi, Osaka (72) Inventor Shigeki Honda 12-25, Muranomotocho, Hirakata-shi, Osaka F-term (reference) 4C059 AA02 4C060 DD03 DD19 DD29 LL14 4C081 AB03 AC03 BA13 CG01 CG02 CG03 CG05 DA01 DA03 DB03 4C097 AA01 BB01 BB04 CC01 CC03 DD09 DD10 SC03

Claims (16)

[Claims] 1. An in-vivo indwelling device including a metal part at least in a part thereof, wherein at least a part of the metal part includes a porous metal. 2. The indwelling device according to claim 1, wherein the porous metal has anisotropic pores. 3. The indwelling device according to claim 2, wherein the porous metal has an anisotropic pore having a maximum value / minimum value ratio (Smax / Smin) indicating pore directionality of 2 or more. 4. The indwelling device according to claim 2, wherein the pores of the porous metal are mainly open pores. 5. The indwelling device according to claim 2, wherein pore directions of the porous metal are aligned in one direction. 6. The indwelling device according to any one of 2 to 5, wherein a shape of a pore cross section orthogonal to a direction of the porous metal is substantially circular. 7. The indwelling device according to claim 1, wherein an inner surface of the porous metal pore is formed of a solid solution strengthening layer or a ceramic layer. 8. The indwelling device according to claim 1, wherein a nonmetallic substance is filled in the pores of the porous metal. 9. The indwelling device according to claim 8, wherein the non-metallic substance is a drug, a physiologically active substance, or a cell. 10. The indwelling device according to claim 8, wherein the non-metallic substance is filled in a state of being combined with a polymer material. 11. The body according to claim 1, wherein the porous metal is produced by utilizing a difference in solubility of gas atoms between a molten state and a solidified state of the metal using a metal-gas method. For indwelling medical use. 12. An inner surface of a pore of the porous metal is a solid solution strengthening layer, and the solid solution strengthening layer is formed by a reaction between the metal atom and a gas atom in a step of manufacturing the porous metal. 2. The indwelling device according to claim 1. 13. The indwelling device according to claim 7, wherein an inner surface of the porous metal pore is a ceramic layer, and the ceramic layer is formed by a chemical vapor deposition method or a physical vapor deposition method. 14. The indwelling device according to claim 7, wherein an inner surface of the pore of the porous metal is a ceramic layer, and the ceramic layer is formed by an ion plantation method. 15. The indwelling device in the body is in the form of an indwelling device in hard tissue selected from an artificial bone, a fracture fixing plate, a fracture fixing screw, a fracture fixing wire and an artificial dental root. 15. The indwelling device according to any one of claims 14 to 14. 16. The indwelling device according to any one of claims 1 to 14, wherein the indwelling device is in the form of a cerebral artery indwelling device selected from a cerebral aneurysm ligation clip and a cerebral aneurysm filling coil. Tools.