JP2022049329A - Medical composite material - Google Patents

Abstract

To provide a medical composite material having high durability while having a high shape recovery rate.SOLUTION: A medical composite material has an Ni-Ti alloy matrix phase, and nickel titanium oxides dispersed in the matrix phase, with the oxygen content of 0.10-0.20 wt.%, the nickel titanium oxides having an average circle equivalent diameter of 1.00 μm or less, the alloy matrix phase containing Ni of more than 50 at% and 53 at% or less, with the balance being Ti and inevitable impurities.SELECTED DRAWING: Figure 1

Description

The present invention relates to medical composites.

Stent placement is a method of expanding the narrowed part of an artery and ensuring blood flow. Most stents are made of metal and can be obtained by braiding wires or laser cutting tubes. Stent materials include stainless steel and cobalt chrome, but especially in the lower limb arteries, blood vessels expand and contract, twist, and compress as they walk, so even if they are deformed, they repeatedly receive the property of returning to their original shape (shape recovery). A superelastic alloy is used as the stent material because durability is required to prevent the stent from breaking due to deformation. Examples of the superelastic alloy include nickel titanium-based shape memory alloys in which titanium and nickel have an equiatomic ratio.

On the other hand, conventionally, catheter treatment of the lower limb artery has been performed by puncturing the iliac artery and inserting the catheter. In recent years, advances in technology have led to catheter treatment using blood vessels in the wrist, which can further reduce the risk. When a blood vessel in the wrist is used, hemostasis is quick because the blood vessel diameter is small, and the risk of complications is reduced.

However, nickel-titanium alloy stents for lower limb arterial blood vessels are difficult to adapt to wrist blood vessels because the stent wall thickness is large in order to maintain the force (radial force) to widen the blood vessels.

Therefore, as an attempt to reduce the thickness of the stent and adapt it to the wrist blood vessel, in Non-Patent Document 1, a sintered body is produced using a Ti—Ni mixed powder in which the amount of Ni is controlled, and the amount of Ni is structured. The effects on the structure, phase transformation temperature, and mechanical and superelastic properties are analyzed. Specifically, the sintered body prepared from the mixture powder of Ti powder and Ni powder shows a structure in which the TiNi phase is used as the parent phase and the Ti ₄ Ni ₂ O phase is dispersed in the mother phase. It has been shown that the increase in the amount increases the precipitation amount of Ti ₃ Ni ₄ , which is effective for improving the superelastic properties, and increases the Ni amount and improves the dynamics and superelastic properties of the alloy.

Non-Patent Document 1 shows that the shape recovery rate when a strain of 8% is applied is 87.3% at the maximum. The shape recovery rate is a very important physical property in maintaining the blood vessel wall at a predetermined diameter during the treatment period, and in this respect, there is room for improvement in the conventional biocomposite material.

In Non-Patent Document 2, a sintered body is produced using a TiNi mixed powder, and the effects of the temperature and conditions of the shape memory heat treatment on the phase transformation temperature, structure, mechanical properties, and superelastic properties are analyzed. Here, it is said that by performing the shape memory heat treatment at a low temperature and for a short time, the effect of suppressing the slip deformation can be obtained by the ultrafine and small amount of precipitates, and the shape recovery rate is improved.

Takayuki Yonezawa, 4 others, "Composition / structure control of Ni-rich TiNi shape memory powder alloy and elucidation of high-strength development mechanism", Proceedings of the Japan Society of Mechanical Engineers (A draft) Vol. 79, No. 808 (2013-12) 1695- 1704 Ryoichi Hayaba, 4 outsiders, "Effects of shape memory heat treatment on the structure and mechanical properties of TiNi shape memory powder alloys", J. Mol. Jpn. Soc. Powder Powder Metallurgy Vol. 65, No. 2,85-90

In a self-expanding stent, the force of the stent to self-expand is restrained and the diameter is reduced, the stent is transported to the indwelling site in a reduced diameter state, the restraint is released at the indwelling site, the stent is expanded, and the stent is placed in a blood vessel. At this time, if the stent does not expand sufficiently to the diameter of the blood vessel, the adhesion to the blood vessel decreases. Therefore, from the viewpoint of ensuring the adhesion of the self-expanding stent to the blood vessel, a high shape recovery rate is required.

In addition, the stent continues to receive various external forces after placement. For example, in the case of a lower limb stent, it is repeatedly subjected to external force due to a person's voluntary movement. The stent is required to be durable so as not to break due to such repeated deformation.

Therefore, an object of the present invention is to provide a medical composite material having a high shape recovery rate and high durability.

The present invention has a Ni—Ti alloy matrix and nickel titanium oxide dispersed in the matrix, has an oxygen content of 0.10 to 0.20% by weight, and is oxidized to nickel titanium. A medical composite material having an average circle equivalent diameter of 1.00 μm or less, the alloy matrix containing more than 50 at% and 53 at% or less of Ni, and the balance being Ti and unavoidable impurities. Is.

According to the present invention, a medical composite material having a high shape recovery rate and high durability is possible.

FIG. 1 is a developed view of a stent which is an example of a medical device. FIG. 2 is a development view of a stent, which is an example of a medical device, when expanded. It is a partially enlarged view of FIG. FIG. 4 is a circle-equivalent diameter histogram of a sample in which the amount of Ni in the example is 51.0 at%.

Hereinafter, embodiments of the present invention will be described. The present invention is not limited to the following embodiments. In the present specification, "X to Y" indicating a range means "X or more and Y or less", and unless otherwise specified, operation and measurement of physical properties are performed at room temperature (20 to 25 ° C.) / relative humidity of 40 to 50% RH. Perform under the conditions of.

The first embodiment of the present invention has a Ni—Ti alloy matrix phase and nickel titanium oxide dispersed in the matrix phase, and has an oxygen content of 0.10 to 0.20% by weight. The average circle equivalent diameter of the nickel titanium oxide is 1.0 μm or less, the alloy matrix contains Ni of more than 50 at% and 53 at% or less, and the balance is made of Ti and unavoidable impurities. , A medical composite material.

The above-mentioned form enables a highly durable medical composite material while having a high shape recovery rate.

The detailed mechanism by which this embodiment exerts the above effects is unknown, but it is presumed as follows. The following inference does not limit the technical scope of the present invention.

In the techniques of Non-Patent Documents 1 and 2, there is still room for improvement in terms of shape recovery rate and durability. As an influence on these physical properties, the present inventor focused on nickel titanium oxide particles in the alloy matrix. Nickel titanium oxide is present as particles in the Ni—Ti alloy matrix obtained by the powder metallurgy method. It is considered that these oxides are formed due to oxygen adhering to the powder raw material, especially when the alloy is produced by the powder metallurgy method. Most of the nickel titanium oxides are Ti ₄ Ni ₂ O. At the interface between Ti ₄ Ni ₂ O and the alloy matrix, dislocations are likely to occur during deformation due to the difference in structure. As a result, it was considered that dislocations caused slip deformation during deformation, resulting in a decrease in shape recovery rate. In addition, since Ti ₄ Ni ₂ O is a hard oxide, if the amount is large or the particle size is large, it cannot follow the deformation of the matrix phase, cracks occur in the oxide itself, and stress is applied to the breaks. Cracks may propagate in a concentrated manner. On the other hand, when the amount of oxygen derived from the raw material is small as in the casting method, the amount of Ti ₄ Ni ₂ O can be controlled to be small. However, it is difficult to control the size, and the uneven distribution of Ti ₄ Ni ₂ O increases the starting point of fracture and reduces the durability. In the present invention, oxygen adhering to the powder raw material is uniformly and finely dispersed.

From the above, it is considered that in the present invention, the presence of a small amount of nickel titanium oxide particles having a small particle size has a high shape recovery rate and durability against deformation when processed into a medical device.

Further, in the technique described in the above non-patent document, the particle size of nickel titanium oxide is large, and it is difficult to perform cold processing or the like. In the present invention, since the particle size of the nickel titanium oxide is small, cracks are less likely to occur as described above, and cold working of wires, tubes and the like is easy. Further, in the heat treatment repeated at that time, Ti ₄ Ni ₂ O exhibits a pinning effect, suppresses the crystal grain growth of the nickel-titanium alloy matrix, and can realize high strength.

Medical composites include Ni—Ti alloy matrix and nickel titanium oxide dispersed in the matrix.

The alloy matrix contains more than 50 at% and 53 at% or less of Ni, and the balance consists of Ti and unavoidable impurities.

The amount of Ni in the Ni—Ti alloy matrix is more than 50 at% and less than 53 at%. Since the amount of Ni is larger than the amount of Ti, it becomes a material in which superelasticity is easily exhibited at the biological temperature. The amount of Ni in the Ni—Ti alloy matrix is preferably more than 50.5 at% and 52.5 at% or less, more preferably 51 to 52.5 at%. As the amount of Ni in the Ni—Ti alloy matrix, the value measured by the method described in the following Examples is adopted.

In a preferred embodiment of the present invention, the medical composite material has a composition represented by the following formula (1).

In the formula (1), A is an unavoidable impurity, and w, x, y, and a represent atomic (at)%, in which case 50 <w ≦ 53, 0 <y ≦ 1.0, and 0 ≦ a ≦ 0.5, and w + x + y + a = 100. It is preferable that the amount of Ni is larger than the amount of Ti, because the material tends to exhibit superelasticity at the biological temperature. More preferably, 50.5 <w ≦ 52.5, 0 <y ≦ 0.7, and 0 ≦ a <0.2, and w + x + y + a = 100, because the superelastic property is further improved. Even more preferably, since the shape recovery rate is further improved, 51 ≦ w ≦ 52, 0 <y ≦ 0.4, and 0 ≦ a <0.15, and w + x + y + a = 100.

In another preferred embodiment of the invention, the medical composite material comprises a Ni—Ti alloy matrix and nickel titanium oxide dispersed in the matrix, from 0.10 to 0.20. It contains weight% oxygen and more than 50 at% and 53 at% or less of Ni, with the balance consisting of Ti and unavoidable impurities, and the nickel titanium oxide has an average circle equivalent diameter of 1.00 μm or less.

In the present specification, the "unavoidable impurity" means a Ni—Ti alloy matrix or a medical composite material that is present in the raw material or inevitably mixed in the manufacturing process. .. Although the unavoidable impurities are originally unnecessary, they are acceptable impurities because they are in trace amounts and do not affect the characteristics of the Ni—Ti alloy matrix and the like. The unavoidable impurities are not particularly limited, but include, for example, carbon.

(Amount of oxygen)
The amount of oxygen in the medical composite is 0.10 to 0.20% by weight. When the amount of oxygen is in such a range, the amount of nickel titanium oxide in the medical composite material becomes an appropriate amount, and high durability can be achieved. Further, when the amount of oxygen is 0.20% by weight or less, the shape recovery rate is improved (for example, the shape recovery rate is 90% or more). The amount of oxygen is preferably 0.10 to 0.15% by weight, more preferably 0.11 to 0.12% by weight. As the amount of oxygen, the value measured by the method described in the following Examples is adopted. The control of the oxygen content in the medical composite material is not particularly limited, but it is preferable to control the oxygen content in the material used in the manufacturing process, the manufacturing atmosphere, and the like. Specifically, for example, as described later, a method for producing Ni powder having a low oxygen content, particularly a method for producing Ni powder having a low oxygen content; a method such as the carbonyl method, which uses Ni powder and Ti powder having a low oxygen content when producing by a powder metallurgy method. Can be mentioned.

(Nickel titanium oxide)
Nickel titanium oxide is a compound composed of Ni, Ti and O, and specific examples thereof include Ti ₄ Ni ₂ O. Nickel titanium oxide is in the form of particles and exists in the Ni—Ti alloy matrix. The particle shape is not particularly limited, and may be any shape such as a spherical shape, a rod shape, a needle shape, a plate shape, a columnar shape, an indefinite shape, a flaky shape, and a spindle shape.

The average circle equivalent diameter of nickel titanium oxide is 1.00 μm or less. When the average circle equivalent diameter is 1.00 μm or less, high durability and high shape recovery rate are obtained. The average circle equivalent diameter of the nickel titanium oxide is more preferably 0.90 μm or less. The lower limit of the average circle equivalent diameter of the nickel titanium oxide is not particularly limited, but is 0.10 μm or more when manufactured by the powder metallurgy method, for example. The control of the average circle equivalent diameter of the nickel titanium oxide is not particularly limited, but it is preferable to control the oxygen content depending on the material used, the manufacturing atmosphere, and the like. Specifically, for example, as will be described later, there are methods such as using Ni powder and Ti powder having a low oxygen content in the production by a powder metallurgy method, particularly using Ni powder having a low oxygen content. Alternatively, the control of the average circle equivalent diameter of the nickel titanium oxide is not particularly limited, and examples thereof include a method such as uniform mixing of powders with a ball mill.

The circle equivalent diameter and the average circle equivalent diameter of the nickel titanium oxide can be measured by the method described in the following Examples. Further, the circle equivalent diameter is calculated up to the second decimal place, the average is calculated up to the third decimal place, and the third decimal place is rounded off to obtain the average circle equivalent diameter.

The specific surface area of the nickel titanium oxide is preferably 1.5 to 3.0%, more preferably 2.0 to 2.5%, from the viewpoint of shape recovery rate and durability. Here, the specific surface area refers to the ratio of the area of nickel titanium oxide to the entire medical composite material.

The specific surface area of the nickel titanium oxide can be measured by the method described in the following Examples. In the image observed by the scanning electron microscope (SEM), it is determined to be nickel titanium oxide from the difference in contrast with the parent phase.

The specific surface area of nickel titanium oxide is usually proportional to the amount of oxygen in the alloy. Therefore, the control of the specific surface area of the nickel titanium oxide is the same as the above description of the amount of oxygen.

(Other compounds)
The Ni—Ti alloy may contain compounds other than nickel titanium oxide. Examples of compounds other than nickel-titanium oxide include compounds composed of titanium, nickel, oxygen, and carbon. The specific surface area of the compound other than the nickel titanium oxide is preferably 0.1 to 0.4%, more preferably 0.1 to 0.35%. Compounds other than nickel titanium oxide are present in the particle shape in the Ni—Ti alloy matrix. Therefore, the specific surface area of the particles can be obtained by the same method as when the specific surface area of the nickel titanium oxide particles is obtained. Here, the particles other than the particles identified as the nickel titanium oxide in the above discrimination method are the particles of the compound other than the nickel titanium oxide. Compounds other than nickel-titanium oxide can be distinguished from nickel-titanium oxide from the difference in contrast of SEM images.

<Manufacturing method>
The method for producing the medical composite material of the present embodiment is not particularly limited, but it is preferable to use the powder metallurgy method because the amounts of nickel, titanium, and oxygen in the alloy can be easily controlled. That is, the medical composite material of the first embodiment is obtained by a powder metallurgy method.

The amount of oxygen in the nickel powder used in the production by the powder metallurgy method is not particularly limited, but is preferably 0.30% by weight or less, preferably 0.05 to 0.30% by weight. It is more preferably 0.10 to 0.20% by weight, and even more preferably 0.10 to 0.20% by weight. It is preferable that the amount of oxygen in the nickel powder used in the production by the powder metallurgy method is in such a range because the amount of oxygen in the obtained alloy can be easily controlled in a specific range of the first embodiment. The amount of oxygen in the nickel powder can be measured by using a method such as ICP.

The amount of oxygen in the titanium powder used in the production by the powder metallurgy method is not particularly limited, but is preferably 0.30% by weight or less, preferably 0.05 to 0.30% by weight. Is more preferable. It is preferable that the amount of oxygen in the titanium powder used in the production by the powder metallurgy method is in such a range because the amount of oxygen in the obtained alloy can be easily controlled in a specific range of the first embodiment. The amount of oxygen in the titanium powder can be measured by using a method such as ICP.

A preferred embodiment of the present invention is to obtain a Ni—Ti alloy by powder metallurgy using nickel powder having an oxygen content of 0.30% by weight or less and titanium powder having an oxygen content of 0.30% by weight or less. A method for producing a medical composite material.

In the powder metallurgy method, titanium powder and nickel powder are usually mixed using a ball mill or the like, and then sintered.

(Sintering)
For sintering the mixed powder, various methods conventionally used in the field of powder metallurgy can be adopted. Specific examples of the sintering method include discharge plasma sintering (SPS), hot press sintering, hot hydrostatic pressure sintering (HIP), millimeter wave sintering, and microwave sintering. Sintering is preferably discharge plasma sintering because alloy formation is likely to be promoted.

Sintering is preferably performed in a vacuum atmosphere or in an atmosphere of an inert gas such as argon gas or nitrogen gas.

The sintering temperature is not particularly limited and is appropriately adjusted depending on the sample size and the like, but is, for example, 900 to 1200 ° C., preferably 950 to 1100 ° C. The sintering time is appropriately adjusted depending on the sample size and the like, but is, for example, 30 to 120 minutes, preferably 45 to 90 minutes. Sintering is preferably performed under pressure, and the conditions at that time are, for example, 10 to 1000 MPa, preferably 10 to 50 MPa.

(Homogenization treatment)
The homogenization treatment is a step of heating the metal material to a predetermined temperature and holding it for a certain period of time so that the diffusion of Ti and Ni in the alloy is promoted and these elements are uniformly distributed in the alloy. The homogenization treatment may be performed before the extrusion processing described below or after the extrusion processing.

The homogenization treatment is preferably carried out in a vacuum atmosphere or an atmosphere of an inert gas such as argon gas or nitrogen gas.

The heating temperature in the homogenization treatment is not particularly limited, but is, for example, 900 to 1150 ° C, preferably 950 to 1100 ° C. The heating time is appropriately adjusted depending on the sample size and the like, but is, for example, 4 to 18 hours, preferably 8 to 14 hours.

(Extrusion)
Further, the sintered body obtained by the above method can be extruded. A rod is obtained by extrusion processing of a sintered body, and a medical device is manufactured using the rod as a material.

The extrusion process may be either hot extrusion, cold extrusion, or warm extrusion, but from the viewpoint of processability, hot extrusion is preferably adopted. The extrusion ratio in extrusion processing is, for example, 5 to 50, and the extrusion ram speed is 1 to 10 mm / sec. The conditions for hot extrusion are not particularly limited, but for example, the preheating temperature is 100 to 400 ° C., and the preheating time is 1 to 30 minutes.

(Soluble treatment)
The solution treatment promotes the diffusion of Ti and Ni in the alloy so that the precipitates coarsely grown by the homogenization treatment are re-dissolved in the parent phase, and these elements are uniformly distributed in the alloy. In addition, it is a step of heating a metal material to a predetermined temperature, holding it for a certain period of time, and then quenching it.

The heating temperature in the solution treatment is not particularly limited, but is, for example, 900 to 1150 ° C, preferably 950 to 1100 ° C. The heating time is, for example, 10 to 180 minutes, preferably 0.5 to 1.5 hours.

(Shape memory heat treatment)
The shape memory heat treatment is a step of heating a metal material to a predetermined temperature so as to promote precipitation of Ti ₃ Ni ₄ and the like and improve mechanical properties. The precipitation of Ti ₃ Ni ₄ or the like may be difficult to observe with a scanning electron microscope (SEM) for observing the nickel titanium oxide described later, and is observed by an observation means such as TEM. The medical composite material of the first embodiment is preferably obtained through shape memory heat treatment, and the medical composite material of the first embodiment preferably contains Ti ₃ Ni ₄ .

The heating temperature in the shape memory heat treatment is not particularly limited, but is, for example, 350 to 600 ° C, preferably 450 to 550 ° C. The heating time is appropriately adjusted depending on the sample size and the like, but is, for example, 5 to 180 minutes, preferably 0.5 to 1.5 hours.

(processing)
The alloy rod obtained by the above method is arbitrarily processed to produce a desired medical device. For example, in the case of a stent, the central part of the rod is hollowed out by machining to form a pipe shape. This can be cut into a stent pattern by laser processing, and further subjected to chemical polishing and electrolytic polishing to prepare a stent.

<Medical equipment>
Another embodiment of the invention is a medical device comprising the composite material of the first embodiment.

Examples of medical devices include stents, stent grafts, guide wires, catheters and the like. Specifically, indwelling needles, IVH catheters, drug solution administration catheters, thermodilution catheters, angiography catheters, vasodilator catheters and catheters inserted or placed in blood vessels such as dilators or introducers; or , Guide wires for these catheters, stylets, etc .; various suctions including gastrointestinal catheters, feeding catheters, tube feeding (ED) tubes, urinary tract catheters, urinary guide catheters, balloon catheters, intratracheal suction catheters, etc. Examples thereof include catheters that are inserted or indwelled in living tissues other than blood vessels such as catheters and drainage catheters. Preferably, the medical device according to the present invention is a stent.

The stent is preferably an annular body formed in an annular shape by linear components, in which a plurality of annular bodies having a plurality of one-sided bending portions and a plurality of ending-side bending portions are arranged in an axial direction and adjacent to each other. Is connected by a connecting portion, and further, as the connecting portion, the central portion of the linear portion connecting the bent portion on one end side and the bent portion on the other end side of the annular body on the adjacent one end side and the annular portion on the other end side. A central apex-to-vertex flexion connecting portion that connects between the vertices of the one-end flexion portion of the body and has at least one one-end flexion portion and an other-end flexion portion, and the other-end flexion of the annular body on the adjacent one-end side. It connects the apex of the portion and the central portion of the linear portion connecting the one end side bent portion and the other end side bent portion of the annular body on the other end side, and has at least one one end side bent portion and the other end side bent portion. It is provided with two types of connecting portions, which are bent connecting portions between the central portions of the vertices.

FIG. 1 represents an example of a stent, which is an example of a medical device. The stent 1 in FIG. 1 is an in-vivo indwelling stent that adheres to an in-vivo tissue by being deformed during an in-vivo indwelling operation.

The stent 1 is a so-called self-expandable stent which is formed into a substantially cylindrical shape, is reduced in diameter when inserted in a living body, and can be restored to a shape before the diameter reduction when placed in a living body. FIG. 1 shows the appearance shape of the stent 1 when compressed (when inserted into a living body). The stent of the present invention is not limited to the self-expandable stent. For example, a balloon-expandable stent that is formed into a substantially tubular body, has a diameter for insertion into a lumen in vivo, and can be expanded when a force that extends radially from the inside of the tubular body is applied. You may.

FIG. 2 shows a stent during expansion. As shown in FIG. 2, the stent 1 is formed in an annular shape by linear components, and has an annular body (wavy linear annular body) 2 having a plurality of one-end side bending portions 2a and a plurality of other end-side bending portions 2b. , A plurality of adjacent annular bodies are arranged in the axial direction, and adjacent annular bodies are connected by a connecting portion.

The number of wavy annular bodies 2 forming the stent 1 varies depending on the length of the stent, but is preferably 3 to 90, and particularly preferably 5 to 80.

As shown in FIG. 2, the annular body located at one end of the stent 1 is further provided with bent linear portions 21, 22, 23, 24 at one end protruding toward one end, and the one end of the stent 1 is provided. , These one end is formed by a bent linear portion. Then, the one end bent linear portion 21 connects the apex of the one end side bent portion of the annular body 2 and the central portion of the linear portion connecting the other one end side bent portion and the other end side bent portion of the annular body 2. At the same time, it has two bent portions on one end side and one bent portion on the other end side. An opening 7 is provided at one end-side bending portion of the one-end bending linear portion 21, and a contrast marker 8 is attached to the opening 7. Further, the one-end bent linear portion 22 connects the apex of the one-ended bent portion of the annular body 2 and the apex of the other one-ended bent portion, and has two one-ended bent portions and one other-ended bent portion. have. An opening 7 is provided at one end-side bending portion of the one-end bending linear portion 22, and a contrast marker 8 is attached to the opening 7. The bent linear portion 23 at one end connects the central portion of the linear portion connecting the bent portion on one end side and the bent portion on the other end side of the annular body 2 and the apex of the bent portion on the other one end side, and also connects the two end sides. It has a bent portion and one bent portion on the other end side. An opening 7 is provided at one end-side bending portion of the one-end bending linear portion 23, and a contrast marker 8 is attached to the opening 7. The bent linear portion 24 at one end is a linear portion connecting the central portion of the linear portion connecting the bent portion on the one end side and the bent portion on the other end side of the annular body 2 and the bent portion on the other end side and the bent portion on the other end side. It is connected to the central portion of the portion and has one bent portion on one end side.

The marker for contrast may be any marker for X-ray contrast, ultrasonic contrast, and the like. The marker is formed by a contrast-enhancing substance such as an X-ray contrast-enhancing substance and an ultrasonic contrast-enhancing substance. As the marker forming material, for example, gold, platinum, tungsten, tantalum, iridium, palladium or an alloy thereof, or a gold-palladium alloy, platinum-iridium, NiTiPd, NiTiAu and the like are suitable.

In the stent 1, as shown in FIGS. 1, 2 and 3, the apex-to-vertex flexion connection portion 31, the central portion-to-center flexion connection portion 32, and the central portion-to-vertex flexion connection portion are between all adjacent annular bodies. It is connected by four types of connecting portions of 33 and the bending connecting portion 34 between the central portions of the vertices.

As shown in FIG. 3, the stent 1 has, as a connecting portion, between the apex of the other end side bending portion 2b of the adjacent one-sided annular body 2 and the apex of the one end side bending portion 2a of the other end side annular body 2. The intervertebral bending connecting portion 31 having at least one one-sided bending portion 3a and the other end-side bending portion 3b, and the one-sided bending portion 2a and the other-end side bending portion 2b of the adjacent one-sided annular bodies 2 are connected to each other. Connect between the central portion 2c of the linear portion connecting the two, the central portion 2c of the linear portion connecting the one end side bending portion 2a and the other end side bending portion 2b of the annular body 2 on the other end side, and at least one one end side bending. The central portion 2c of the linear portion connecting the central portion bending connecting portion 32 having the portion 3a and the other end side bending portion 3b, and the one end side bending portion 2a and the other end side bending portion 2b of the adjacent one end side annular bodies 2. And adjacent to the central apex bending connection portion 33 having at least one one end side bending portion 3a and the other end side bending portion 3b while connecting between the apexes of the one end side bending portion 2a of the annular body 2 on the other end side. At least the central portion 2c of the linear portion connecting the apex of the other end side bent portion 2b of the annular body on the one end side, the bent portion 2a on the one end side of the annular body 2 on the other end side, and the bent portion 2b on the other end side is connected. Of the four types of connecting portions consisting of the bending connecting portion 34 between the apex centers having one bending portion 3a on one end side and the bending connecting portion 3b on the other end side, the bending connecting portion 31 between the apex and the bending connecting portion 32 between the central portions are used. It is provided with at least three types of connecting portions including, and the adjacent annular bodies are connected by at least two different types of connecting portions.

As shown in FIG. 3, the apex-to-vertex bending connection portion 31 is formed between the apex of the other end side bending portion 2b of the adjacent one-sided annular body 2 and the apex of the one-end side bending portion 2a of the other end side annular body 2. It is connected and has two bent portions 3a on one end side and two bent portions 3b on the other end side. By having the two end-side bending portions 3a and the other-end side bending portion 3b, respectively, the apex-to-vertex bending connection portion 31 can surely impart flexibility and compressibility to the stent. Further, the bending connection portion 31 between the vertices has a larger number of bending portions than other connecting portions described later, and has a long length. The bending connection portion between the vertices may have one one end side bending portion 3a and the other end side bending portion 3b, respectively. The apex of the bent portion of the annular body 2 connected to the bent connecting portion 31 constitutes a branch portion. Then, the bent portion 3a on one end side of the bent connecting portion 31 between the vertices has entered between the bent portions (between the bent portions on the other end side) of the annular body 2 on the one end side to which the connecting portion 31 is connected, and is on the other end side. The bent portion 3b has entered between the bent portions (between the bent portions on the one end side) of the other end side annular body 2 to which the connecting portion 31 is connected. For this reason, the stent is provided with a high expansion and retention force.

As shown in FIG. 3, the central portion bending connecting portion 32 is a linear portion connecting the one end side bending portion 2a and the other end side bending portion 2b of the adjacent one end side annular bodies 2 to the central portion 2c and the other end side. It has one end side bent portion 3a and one other end side bent portion 3b while connecting between the central portion 2c of the linear portion connecting the one end side bent portion 2a and the other end side bent portion 2b of the annular body 2. ing. Further, since the bending connecting portion 32 between the central portions connects the intermediate portions of the linear portions of the adjacent annular bodies, the stent has a certain degree of rigidity and contributes to the improvement of the expansion and holding force of the stent. Further, it is preferable that the central portion 2c is substantially an intermediate point of the linear portion connecting the one end side bent portion 2a and the other end side bent portion 2b. The central portion 2c of the annular body 2 connected to the bent connecting portion 32 constitutes a branch portion. Further, the inter-central bending connecting portion 32 is arranged so as not to be continuous with the above-mentioned intervertex bending connecting portion 31 in the circumferential direction of the stent. Further, in the stent of this embodiment, the central-to-central bending connection portion 32 is substantially opposite to the above-mentioned apex-to-vertex bending connection portion 31 with respect to the central axis of the stent. It is preferable that the central bending connecting portion 32 has only one one end side bending portion 3a and the other end side bending connecting portion 3b, respectively. The bent portion 3a on one end side of the bent connecting portion 32 between the central portions also enters between the bent portions of the annular body 2 on the one end side to which the connecting portion 32 is connected, and the bent portion 3b on the other end side is also connected. It has entered between the bent portions of the other end side annular body 2 to which the portions 32 are connected. For this reason, the stent is provided with a high expansion and retention force.

As shown in FIG. 3, the central portion intervertex bending connecting portion 33 is a linear portion connecting the one end side bending portion 2a and the other end side bending portion 2b of the adjacent one end side annular bodies 2 to the central portion 2c and the other end. It connects the vertices of the one end side bent portion 2a of the side annular body 2 and has one one end side bent portion 3a and one other end side bent portion 3b. Further, in order to connect the intermediate portion and the apex of the linear portion of the adjacent annular body, the bending connection portion 33 between the vertices of the central portion is intermediate between the bending connecting portion 31 between the vertices and the bending connecting portion 32 between the central portions. It shows the physical characteristics. The central apex bending connection portion 33 is arranged so as to be between the apex bending connection portion 31 and the central portion bending connecting portion 32 in the circumferential direction of the stent. The apex of the central portion 2c and the bent portion 2a of the annular body 2 connected to the bent connecting portion 33 constitutes a branch portion. It is preferable that the central apex-to-vertex bending connection portion 33 has only one end-side bending portion 3a and the other-end side bending portion 3b, respectively. The bent portion 3a on one end side of the bent connecting portion 33 between the vertices of the central portion also enters between the bent portions of the annular body 2 on the one end side to which the connecting portion 33 is connected, and the bent portion 3b on the other end side also has this. It has entered between the bent portions of the other end side annular body 2 to which the connecting portion 33 is connected. For this reason, the stent is provided with a high expansion and retention force.

As shown in FIG. 3, the bending connection portion 34 between the apex center portions is the apex of the other end side bending portion 2b of the adjacent one end side annular body and the one end side bending portion 2a and the other end of the other end side annular body 2. It is connected to the central portion 2c of the linear portion connecting the side bent portions 2b, and has one one end side bent portion 3a and one other end side bent portion 3b. Further, in order to connect the apex to the intermediate portion of the linear portion of the adjacent annular body, the bending connection portion 34 between the central portions of the vertices is intermediate between the bending connecting portion 31 between the apex and the bending connecting portion 32 between the central portions. It shows the physical characteristics. The bending connection portion 34 between the central portions of the apex is arranged so as to be between the bending connecting portion 31 between the apex and the bending connecting portion 32 between the central portions in the circumferential direction of the stent. Further, in the stent of this embodiment, the bending connection portion 34 between the central vertices is substantially opposite to the above-mentioned bending connecting portion 33 between the central vertices and the central axis of the stent. The apex of the central portion 2c and the bent portion 2b of the annular body 2 connected to the bent connecting portion 34 constitutes a branch portion. It is preferable that the bending connection portion 34 between the apex central portions has only one bending portion 3a on the one end side and the bending portion 3b on the other end side, respectively. The bent portion 3a on one end side of the bent connecting portion 34 between the central vertices also enters between the bent portions of the annular body 2 on the one end side to which the connecting portion 34 is connected, and the bent portion 3b on the other end side also has this. It has entered between the bent portions of the other end side annular body 2 to which the connecting portion 34 is connected. For this reason, the stent is provided with a high expansion and retention force.

As for the connecting portion between the adjacent annular bodies, the central portion inter-vertex bending connecting portion 33 is located on the left side of the circumferential direction of the inter-vertex bending connecting portion 31, and the central portion inter-vertex bending connecting portion 32 is located on the left side. The bending connection portion 34 between the central vertices is located on the left side, and the bending connecting portion 31 between the vertices is located on the left side thereof. 33, the bending connecting portion 32 between the central portions, and the bending connecting portion 34 between the central portions of the apex are arranged so as to be annular in that order in the clockwise direction.

Then, as shown in FIG. 2, the other end annular portion 20a is arranged at the other end portion 20 of the stent 1. The annular portion 20a is a wavy annular body having seven bent portions on one end side and bent portions on the other end side, respectively, like the annular portion 2 described above. Further, a part of the seven other end side bending portions (specifically, the three bending portions) of the other end annular portion 20a is provided with the opening 7 and the contrast marker 8 provided in the opening 7. There is.

The annular body 2 adjacent to the other end annular portion 20a is connected by a plurality of other end annular portions. In the stent 1 of this embodiment, the other end connecting portions 25, 26, 27, 28 are provided between the other end annular portion 20a and the adjacent annular body 2. The other end connecting portion 25 connects the apex of the other end side bent portion 2b of the annular body 2 and the central portion of the linear portion connecting the one end side bent portion and the other end side bent portion of the other end annular portion 20a. It has one one end side bent portion and one other end side bent portion. The other end connecting portion 26 connects the central portion of the linear portion connecting the one end side bent portion and the other end side bent portion of the annular body 2 and the apex of the one end side bent portion of the other end annular portion 20a, and is a bent portion. It is a straight line that does not have. The other end connecting portion 27 connects the central portion of the linear portion connecting the one end side bent portion and the other end side bent portion of the annular body 2 and the apex of the one end side bent portion of the other end annular portion 20a, and 1 It has one one end side bent portion and one other end side bent portion. The other end connecting portion 28 connects and bends the apex of the other end side bent portion of the annular body 2 and the central portion of the linear portion connecting the one end side bent portion and the other end side bent portion of the other end annular portion 20a. It is a straight line without a part.

As shown in FIG. 2, the other end annular portion 20a includes reinforcing bent linear portions 20b and 20c whose start and end are both connected to the other end annular portion 20a. The reinforced bent linear portion 20b connects between the central portions of the linear portion connecting the one end side bent portion and the other end side bent portion of the other end annular portion 20a, and has one one end side bent portion. The reinforcing bent linear portion 20c connects the vertices of the adjacent one end side bent portions of the other end annular portion 20a, and has two one end side bent portions and one other end side bent portion. The other end of the stent has a high shape retention property by having the above-mentioned configuration.

The above-mentioned intervertex flexion connection portion 31 is arranged so as to be spiral with respect to the axial direction of the stent 1. Similarly, the central bending connection portion 32 is also arranged so as to be spiral with respect to the axial direction of the stent. Therefore, the bending connection portion 31 between the vertices and the bending connecting portion 32 between the central portions are not continuous in a straight line in the axial direction of the stent. Similarly, the central apex bending connection portion 33 and the apex central bending connecting portion 34 are also arranged so as to be spiral with respect to the axial direction of the stent. In the stent 1 of this embodiment, the same type of connecting portion is not continuous in a straight line in the axial direction of the stent.

Further, the contrast marker 8 described above is fixed so as to close the opening 7. As the contrast marker 8, for example, a disk-shaped member of a contrast medium having a portion slightly smaller and a portion larger than the opening 7 is arranged in the opening 7 formed in the stent and pressed from both sides to form a rivet. It is preferable that it is attached by caulking.

Stents include stents and stent grafts.

As the thickness of the stent, the conventional general one can be adopted. For example, the thickness of the stent is about 50 to 500 μm, preferably about 60 to 300 μm, and more preferably about 70 to 200 μm from the relationship between supportability and decomposition time. Since the stent substrate according to the present embodiment has excellent mechanical properties (for example, extended holding force), the stent can be made thin.

The size of the stent is also appropriately adjusted according to its purpose and function. For example, the outer diameter (diameter) of the stent after expansion is preferably about 1 to 40 mm, more preferably about 1.5 to 10 mm, and particularly preferably about 2 to 5 mm.

Further, the length of the stent is not particularly limited and can be appropriately selected depending on the disease to be treated. For example, about 5 to 300 mm is preferable, and about 10 to 50 mm is more preferable.

In addition to the above-mentioned stent substrate, the stent may be provided with a coat layer on the stent substrate as long as the object effect of the present invention is not impaired. The constituent material of the coat layer is preferably a biodegradable material, and the biodegradable material is not particularly limited, but for example, polyester, polyacid anhydride, polycarbonate, polyphosphazene, polyphosphate ester, polypeptide, polysaccharide, protein. , A polymer selected from the group consisting of cellulose, and more specifically, polylactic acid, polyglycolic acid, lactic acid-glycolic acid copolymer, polycaprolactone, lactic acid-caprolactone copolymer, polyhydroxybutyric acid, At least one selected from the group consisting of polyapple acid, poly-α-amino acid, collagen, laminin, heparan sulfate, fibronectin, vitronectin, chondroitin sulfate, and hyaluronic acid, which is considered to be decomposed in vivo. Then, a medically safe one is preferable. The molecular weight, degree of purification, and degree of crystallinity of the biodegradable material that coats the outer surface of the stent (outer surface of the stent substrate) can be adjusted to prolong the decomposition period. For example, by increasing the degree of purification of the above biodegradable material to eliminate unreacted monomers and low molecular weight components, or by increasing the degree of crystallinity to suppress the amount of water invading the inside of the stent skeleton. The hydrolysis time can be lengthened. Further, the above-mentioned coat layer-forming biodegradable material and one or more of the above-mentioned agents are mixed in an arbitrary ratio, for example, 1:99 to 99: 1 (w / w), preferably 80:20. The coating layer may be used as a chemical coating layer by containing the mixture in a ratio of ~ 95: 5 (w / w). The method for forming the coat layer is not particularly limited, and a usual coating method can be applied in the same manner or appropriately modified. Specifically, a method of preparing a mixture by mixing a biodegradable material and, if necessary, the above-mentioned drug and an appropriate solvent, and applying the mixture to a stent substrate can be applied.

In another embodiment of the present invention, the durability according to the following durability test method is 100,000 times or more, the stent; durability test method: torsion angle: ± 30 ° / 10 mm, inter-chuck distance: 30 mm, frequency: 2 Hz, temperature: 37 ° C. With such a configuration of the stent, the stent has excellent durability. The durability according to the durability test method is preferably 200,000 times or more, and more preferably 300,000 times or more.

Further, in another preferred embodiment of the present invention, a plurality of annular bodies formed in an annular shape by linear components and having a plurality of bent portions on one end side and a plurality of bent portions on the other end side are arranged in the axial direction. , Adjacent annular bodies are connected by a connecting portion, and further, as the connecting portion, the central portion of the linear portion connecting the one end side bent portion and the other end side bent portion of the annular body on the adjacent one end side and the other. The annular body on one end side adjacent to the central apex-to-vertex flexion connecting portion having at least one one end side bending portion and the other end side bending portion while connecting between the vertices of the one end side bending portion of the annular body on the end side. Connect the apex of the other end side bent portion and the central portion of the linear portion connecting the one end side bent portion and the other end side bent portion of the annular body on the other end side, and at least one one end side bent portion and the other end. It is a stent having two types of connecting portions including a bending connecting portion between the central apex having a side bending portion, and having a durability of 100,000 times or more according to the above durability test method.

The stent of the above embodiment can be obtained, for example, by using the medical composite material of the first embodiment, or can be manufactured by the method for manufacturing the medical composite material of the first embodiment.

The effects of the present invention will be described with reference to the following examples and comparative examples. In the examples, the display of "parts" or "%" may be used, but unless otherwise specified, it represents "parts by weight" or "% by weight". Unless otherwise specified, each operation is performed at room temperature (25 ° C.).

(Example)
(1) A predetermined mixing ratio (Ti-51.0, 51.5, 51.8 at% Ni) of nickel powder (Type-123, manufactured by VALE) and titanium powder (TC-450, manufactured by Toho Tech). After weighing, put in a plastic container, put zirconium oxide balls (φ10 mm) in a plastic container with a powder weight ratio of 10: 1 (powder: balls), and use a tabletop ball mill (AV-2, manufactured by Asahi Rika Seisakusho) to rotate the speed. The mixture was mixed at 90 rpm for 3 hours.
(2) Sintering treatment: The mixed powder obtained in (1) is filled in a carbon container, and a discharge plasma sintering device (SPS-1030S: manufactured by SPS Shintec) is used to obtain a vacuum degree of 6 Pa and a sintering pressure of 30 MPa. The powder was sintered at a sintering temperature of 1000 ° C. and a sintering time of 60 minutes.
(3) Homogenization heat treatment: The powder obtained in (2) was heat-treated at 1000 ° C. for 12 hours under an argon atmosphere.
(4) Extrusion processing: The sintered body obtained in (3) has an extrusion processing ratio of 6 (container inner diameter 37 mm, die diameter 15 mm), extrusion ram speed 6 mm / s, heating temperature 1100 ° C., and mold temperature 300-400 ° C. Extruded with.
(5) Shape memory heat treatment: The obtained processed product was subjected to solution heat treatment (heating and then quenching) at 1000 ° C. for 1 hour, and shape memory heat treatment at 500 ° C. for 1 hour. Then, the extruded material was processed into a tensile test piece and a pipe.

(Comparative example)
A sample was prepared according to the description of Non-Patent Document 1 and Non-Patent Document 2.

[Measurement method of each physical property]
(Measurement of oxygen content)
The amount of oxygen was measured using an inert gas melting-infrared absorption method, nitrogen, oxygen, and hydrogen analyzer EMGA-930 (manufactured by HORIBA, Ltd.).

(Measurement of Ni content in Ni—Ti alloy matrix)
The amount of Ni in the Ni—Ti alloy matrix was measured using a measurement electron probe microanalyzer (FE-EPMA) JXA-8530F (manufactured by JEOL Ltd.).

For the measurement, a pipe (φ6 × t0.2 × L50) obtained by cutting out the extruded material obtained in each Example and Comparative Example by wire electric discharge machining was used, and a cross-sectional sample prepared by polishing and etching was used. Was subjected to Pt spatter coating, measured at N = 3, and the average value was calculated.

(Calculation of average circle equivalent diameter and specific surface area of nickel titanium oxide)
Using a thermal field emission scanning electron microscope (TFE-SEM, JSM-6500F (manufactured by JEOL Ltd.)), the contour was determined from the contrast of the backscattered electron image (BSE), and the particle area was measured. Further, the specific surface area of the nickel titanium oxide was calculated by dividing the total particle area at the imaging location by the SEM measurement area. Furthermore, the equivalent circle diameter is calculated from the particle area from the formula ((4 x particle area) ÷ π) ^1/2 , and the average circle equivalent diameter of the particles (approximately 200 particles) at the imaging location is calculated to form an average circle. The diameter was set to a considerable value. A histogram of the equivalent circle diameter of the sample in which the amount of Ni in the example is 51.0 at% is shown in FIG. Here, particles having a circle-equivalent diameter of more than 0 μm and 0.1 μm or less are defined as a data section of 0.1, particles having a circle-equivalent diameter of more than 0.1 μm and 0.2 μm or less are defined as a data section of 0.2. The number was expressed as the frequency. In this case, the mode of the equivalent circle diameter of the nickel titanium oxide is preferably 1.0 μm or less, and more preferably 0.2 to 1.0 μm.

For the average circle-equivalent diameter and specific surface area of the nickel titanium oxide, a pipe (φ6 × t0.2 × L50) obtained by cutting out the sample obtained in (5) by wire electric discharge machining was used.

[evaluation]
<Tensile test: Plateau stress and shape recovery rate under 8% strain load>
The obtained extruded material was subjected to electric discharge and cutting to obtain a round bar tensile test piece (parallel portion diameter 3 mm, length 15 mm). The tensile test was carried out using AUTOGRAPH AG-X 50 kN (Shimadzu Corporation) at a strain rate of 0.5 ks ^-1 .

In addition, a hysteresis test was performed under the same conditions, and the shape recovery rate at an applied strain of 8% was measured. The shape recovery rate is preferably 90% or more, more preferably 95% or more, and even more preferably 96.5% or more.

The results are shown in Table 1 below.

<Durability test>
A durability test was performed under the following test conditions using a stent having the following stent shape. The test was performed 3 times and the average was taken. The results are shown in Table 2 below.

(Stent shape)
Durability data Measurement sample shape: Stent (Terumo Corporation, Osprey (registered trademark) design / Japanese Patent Laid-Open No. 2011-200705, φ6 × L40)
Stent manufacturing method:
(1) Wire electric discharge machining is performed on the obtained extruded material, and a pipe (φ6 × t0.2 × L50) is cut out.

(2) The pipe was laser-cut, blasted, chemically polished, and electrolytically polished to obtain a stent.

Laser cut: Laser cut using Rofin SC-18 Blast: Surface polishing using Morandum # 700J (Showa Denko) Chemical polishing: Immersed in MicroClean (RD Chemical Company) Electropolishing: Polishing with 10% methanol sulfate.

(Test condition)
Condition: Torsion angle: ± 30 ° / 10mm
Distance between chucks: 30 mm
Frequency: 2Hz
Temperature: 37 ° C
Equipment: Electro Force 3200 (TA Instruments)

From the above results, the medical composite material of the present invention has a high shape recovery rate and high durability.

Stent 1,
Ring 2,
One end side bent portion 2a,
Bent part 2b on the other end side,
Central part 2c,
One end side bent portion 3a,
The other end side bent portion 3b,
Bending connection between vertices 31,
Bending connection between central parts 32,
Central apex-to-vertex flexion connection 33,
Bending connection between the central vertices 34.

Claims (6)

It has a Ni—Ti alloy matrix and nickel titanium oxide dispersed in the matrix.
The amount of oxygen is 0.10 to 0.20% by weight,
The average circle equivalent diameter of the nickel titanium oxide is 1.00 μm or less.
The alloy matrix is a medical composite material containing more than 50 at% and 53 at% or less of Ni, with the balance being Ti and unavoidable impurities. The medical composite material according to claim 1, which is obtained by a powder metallurgy method. The medical composite material according to claim 1 or 2, wherein the nickel titanium oxide has a specific surface area of 1.5 to 3.0%. A medical device using the medical composite material according to any one of claims 1 to 3. Stent with durability of 100,000 times or more according to the following durability test method;
Durability test method: Torsion angle: ± 30 ° / 10 mm, distance between chucks: 30 mm, frequency: 2 Hz, temperature: 37 ° C. A plurality of annular bodies formed in an annular shape by linear components and having a plurality of bent portions on one end side and a plurality of bent portions on the other end side are arranged in the axial direction, and adjacent annular bodies are connected by a connecting portion. ,Moreover,
As the connecting portion, the central portion of the linear portion connecting the one end side bent portion and the other end side bent portion of the annular body on the adjacent one end side and the apex of the one end side bent portion of the annular body on the other end side are connected. At the same time, a central apex-to-vertex flexion connecting portion having at least one one-sided bent portion and an other-ended bent portion, and the apex of the other-side bent portion of the annular body on the adjacent one-sided side and the annular body on the other end side. 2 which connects the central portion of the linear portion connecting the bent portion on one end side and the bent portion on the other end side, and has at least one bent portion on one end side and a bent connecting portion between the central vertices having the bent portion on the other end side. The stent according to claim 5, which comprises a type of coupling.

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