JP5899864B2 - Embolization coil - Google Patents

Description

  The present invention relates to an embolization coil that is indwelled at a predetermined portion of a living body lumen and closes the living body lumen, and more particularly to an embolization coil for blocking a blood vessel or an aneurysm formed in the blood vessel. is there.

  Currently, as a less invasive treatment method for aneurysms and the like, vascular embolization is known in which an indwelling device for embolization is placed in an aneurysm. In this vascular embolization, the indwelling device for embolization placed in the aneurysm becomes a physical obstacle to the blood flow, and a thrombus is formed around the indwelling device for embolization. The risk of aneurysm rupture can be reduced. Here, there is an embolization coil made of a metal material as an indwelling device for embolization that is placed at a predetermined site in a blood vessel such as an aneurysm.

  Such an embolization coil is introduced into a predetermined site via an appropriate catheter by an extruding means (inductor) removably connected to an end of the embolization coil, and is detached at the predetermined site. The function is demonstrated by being indwelled. Such an embolization coil is required to have various characteristics such as the following characteristics.

  (1) Necessary for performing an indwelling operation without causing a problem such as breaking through the wall surface of a blood vessel or an aneurysm by applying an excessive load to an application site such as a blood vessel or an aneurysm. Have high flexibility. In addition, for example, after performing vascular embolization, a gap is generated due to a shape change over time, and reperfusion is prevented (compaction). From the viewpoint of increasing the embolization rate per unit volume (occupation rate of the embolization coil at a predetermined site) as much as possible, it is necessary to have high flexibility. The

  (2) The coil body is prevented from extending indefinitely so that it can be reliably pushed out after being pushed out of the catheter and once placed at a predetermined site, and then repositioning it. That is, it has a function of suppressing, that is, for example, when the coil body is stretched by being caught on the distal end edge of the catheter, it is difficult to collect the coil body, or the application site may be damaged. Therefore, it is required to have a configuration that does not cause such a problem.

  Then, after such vascular embolization is performed, it is necessary to perform a periodic examination in order to confirm whether there is an increase in aneurysm or deviation of the coil to the parent blood vessel. An increase in the aneurysm leads to rupture, and deviation of the coil to the parent vessel leads to ischemia and cerebral infarction. Angiography, CT, MRI, or the like is used for postoperative examination, but MRI is the best from the viewpoint of observing blood flow.

If the nuclear spin satisfying the MRI principle is a nucleus other than 0, it is possible to make all images, but in medical MRI, almost all signals of the hydrogen atom ¹ H are observed. Since the human body contains a lot of hydrogen atoms in the water and other fats that make it up, ¹ H exists everywhere. By looking at the ¹ H signal, the intensity reflects the tissue. It is imaged. In terms of% by weight relative to body weight, hydrogen atoms are 10%, oxygen atoms are 61%, and carbon atoms are 23%. However, since ¹⁶ O and ¹² C have no nuclear spin, no signal can be obtained by MRI. In principle, MRI for measuring the isotope ¹³ C of a carbon atom having a nuclear spin is possible but is not used clinically.

Water is a weak diamagnetic material, and its volume magnetic susceptibility is χ _v = −9.05 × 10 ⁻⁶ (= −9.05 ppm). In normal medical MRI, the sensitivity is adjusted with respect to detection of water, and the image is adjusted so as not to be distorted. Therefore, there is a problem that an MRI image artifact becomes large for a substance that is significantly different from the volume magnetic susceptibility of water, and a living body part in the vicinity of the substance cannot be imaged. In particular, when an embolization coil is placed in an aneurysm, if the volume magnetic susceptibility of the coil is significantly different from the volume magnetic susceptibility of water, the arteries near the aneurysm cannot be clearly imaged due to the influence of artifacts.

  Patent Document 1 discloses a coil made of an alloy wire containing 80% by weight or more of any one of platinum, gold, silver, and tantalum, but does not mention an artifact in an MRI image. Patent Document 2 refers to a binary alloy of gold (Au) and platinum (Pt) as a metal material having high biocompatibility and MRI compatibility. The magnetic susceptibility of gold is negative and the magnetic susceptibility of platinum is There is a disclosure that it is positive and non-magnetization can be realized by mixing the two at a predetermined ratio and alloying them. And it has been reported that the magnetic susceptibility of Au-28Pt is −13 ppm (Δχ = −4 ppm), but the binary alloy of gold and platinum is in terms of physical properties such as strength and hardness. Since it cannot be applied to various medical devices in general, he proposed a ternary alloy of gold, platinum and niobium (Nb). Therefore, it cannot be said that Patent Document 2 discloses an alloy having a specific ratio of gold and platinum as an embolization coil. The magnetic susceptibility of the Au—Pt alloy is reported in Non-Patent Document 1.

JP 2004-097719 A WO2010 / 084948A1

Zeitschrift fur Physikalische Chemie Neue Folge, Bd. 144, S. 233-229 (1985)

  Therefore, in view of the above-mentioned situation, the present invention is intended to be solved while having practical mechanical properties as an embolization coil that is indwelled at a predetermined site of a biological lumen and closes the biological lumen. An object of the present invention is to provide an embolization coil that does not cause artifacts during MRI imaging.

In order to solve the above-mentioned problems, the present invention provides an embolization coil that is placed in a predetermined part of a living body lumen and used to close the living body lumen, and the coil wire is Au _x Pt _100-x. The embolization coil is characterized in that it is an alloy (X = 60 to 90), and its volume magnetic susceptibility has an absolute value of difference (Δχ) from water volume magnetic susceptibility of 15 ppm or less.

Here, the coil strand is preferably an Au _x Pt _100-x alloy (X = 70 to 75), and the coil strand is an Au _x Pt _100-x alloy (X = 71.5 to 72). More preferably.

  Moreover, it is also preferable that the diameter of the said coil strand is 35-120 micrometers, and the said coil strand does not heat-process after a wire drawing process.

  The embolization coil of the present invention as described above is placed at a predetermined site of a living body lumen and has practical mechanical properties as an embolization coil that closes the living body lumen, and has a predetermined wire diameter from the ingot. It is easy to manufacture a coil wire, and no artifacts are generated during imaging by MRI, or artifacts are suppressed, so that there is no practical problem with the parent vessel without being affected by the embolization coil. Clear imaging is possible, and further less heat is generated, so there is less invasion of the living body.

It is a graph of magnetic susceptibility χ (ppm) with respect to the composition in the Au—Pt alloy. It is a graph which shows the relationship between the artifact length and magnetic susceptibility in a MRI image (Spin Echo). It is a graph which shows the relationship between the artifact length and magnetic susceptibility in a MRI image (Gradient Echo). It is a coronal-section MRI image of the ingot sample of the Au-Pt binary alloy of various mixing ratios. It is an MRI image (the upper stage is Spin Echo and the lower stage is Gradient Echo) of the ingot sample of the Au-Pt binary alloy of various mixing ratios. These are MRI images (Spin Echo) and artifact images of six types of samples. These are an MRI image (Spin Echo) and an artifact image of an aneurysm model made of silicone rubber (diameter 7 mm) filled with fine lines of various compositions. It is a graph which shows the change of the compression load with respect to the compression displacement of the secondary coil created with the coil strand of Au-28Pt and Pt-8W. This is an MRI image obtained by placing an Au-28Pt coil and a Pt-8W coil in a rabbit blood vessel and picking up an image by an MRI imaging method (T2 star imaging method) suitable for blood vessel imaging. Using a model animal in which an Au-28Pt alloy coil inserted into a silicon hollow body (Example) and a Pt-8W alloy coil inserted (Comparative Example) are sutured into the outer membrane of a rabbit abdominal aorta It is the acquired TOF-MRA image. Using a model animal in which an Au-28Pt alloy coil inserted into a silicon hollow body (Example) and a Pt-8W alloy coil inserted (Comparative Example) are sutured into the outer membrane of a rabbit abdominal aorta It is the angiography result acquired by the digital subtraction method.

  The embolization coil of the present invention is placed in a predetermined part of a living body lumen and used to close the living body lumen, and in particular, a blood vessel or an aneurysm formed in the blood vessel, in particular, a brain. It is used to occlude an aneurysm, and is produced using a binary alloy of Au—Pt that is formulated to a composition that does not cause or significantly reduces the generation of artifacts that distort MRI images.

In the Au _x Pt _100-x alloy (X = 60 to 90), the α phase and the β phase are mixed. Gold is a metal with excellent malleability, and the higher the gold content, the more advantageous is the wire drawing process when manufacturing the coil wire. FIG. 1 is a graph of magnetic susceptibility χ (ppm) with respect to composition in an Au—Pt alloy, which is cited from Non-Patent Document 1 described above.

  First, FIG. 2 (Spin Echo) and FIG. 3 (Gradient Echo) show the results of examining the relationship between the artifact length and the magnetic susceptibility in the MRI image. These are the results of producing cylindrical samples with eight types of materials having different magnetic susceptibilities, acquiring MRI images, and measuring the artifact lengths. From this graph, it can be confirmed that the artifact length is minimized when the magnetic susceptibility is about -9 ppm. In other words, the closer the magnetic susceptibility of the material is to the magnetic susceptibility of water, the smaller the artifact length, which means that there is no distortion in the MRI image.

  Next, Au—Pt binary alloys with various mixing ratios were prepared, and MRI imaging of the ingot was evaluated according to the MRI conformity test method (F2119 test) of medical devices proposed by the US FDA. The composition of the ingot of the produced Au—Pt binary alloy is such that Pt is in the range of 20 to 80% by weight. Specifically, the weight percentage of Pt is 20, 25, 28, 28.3, 28.5, 29, 29.5, 32, 35, 40, 60, 80. The coronal cross-sectional MRI images of these ingot samples are shown in FIG. In FIG. 4, the left side is an image of Spin Echo and the right side is an image of Gradient Echo. The ratio of Pt is described beside each MRI image in FIG. As shown in this MRI image, the artifact disappeared when the weight percentage of Pt was 28.5-28%. In addition, 28Y in FIG. 4 is an ingot produced using a material that is considered to have impurities mixed therein, and is not helpful. FIG. 5 shows MRI images of Au-Pt binary alloy ingot samples having various mixing ratios with Pt weight percentages of 0, 25, 28, 30, 60 (upper row is Spin Echo, lower row is Gradient Echo). It can be seen that the artifact is minimized in the vicinity of the Pt ratio of 28% by weight.

It is well known that artifacts can be reduced (or no artifacts are generated) as the difference (Δχ) from the magnetic susceptibility (−9 ppm) of water is closer to zero. 2 and 3, it is known that if the absolute value of Δχ is 15 ppm or less, the artifact length can be suppressed within several mm. That is, the magnetic susceptibility of the material may be adjusted to a range of approximately −24 ppm <χ <+6 ppm. From FIG. 1, the composition in which the magnetic susceptibility of the Au—Pt alloy falls within this range is an Au _x Pt _100-x alloy (X = 60 to 90). The boundary of this numerical range has no critical meaning. Furthermore, it is preferably an Au _x Pt _100-x alloy (X = 70 to 75), and the coil wire is more preferably an Au _x Pt _100-x alloy (X = 71.5 to 72). Was determined from the results of FIG. An alloy having 28% by weight of Pt is represented as Au-28Pt. Unless otherwise specified, since it is a binary alloy, the composition of the alloy is expressed only by the ratio of Pt (for example, 28 Pt).

  Actually, a coil wire is manufactured from an ingot by wire drawing, and then a coil having a predetermined diameter (primary and secondary) is produced. When the coil is implanted in the vicinity of a living blood vessel, the coil is affected. It must be ensured that an MRI image of the blood vessel can be acquired without it.

  As the previous step, F2119 test (MR image artifact test) is performed in the US FDA medical device MRI conformity test method, and image processing software for data mapping and artifact extraction is created from the obtained data to extract the artifact. Quantified (see FIG. 6). The alloy used here is (1) a material subjected to aging treatment of 500 ° C. × 24 h after homogenization of 28 Pt, (2) a material subjected to aging treatment of 1000 ° C. × 48 h after homogenization of 28 Pt, ( 3) Material obtained by subjecting 28 Pt to a homogenization treatment of 1000 ° C. × 48 h, (4) Material obtained by subjecting 29 Pt to a homogenization treatment of 1000 ° C. × 48 h, (5) A material as dissolved in 28 Pt, (6) 28 6 types of materials that remain as 5Pt melt. The arrangement of the sample is described on the left side of FIG. 6, the MRI image (Spin Echo) is shown in the center, and the artifact image processed by the artifact extraction image processing software is shown on the right side together with the artifact length. . As a result, it has been found that it is better to treat the ingot as a melted material and not perform any subsequent treatment, rather than performing homogenization or aging treatment.

  Similarly, an Au-Pt fine wire having a Pt weight percentage of 28.5-28% was prepared, and a commercially available aneurysm coil (a thin wire of W (tungsten) 8% with a Pt weight percentage of 92%: Pt-8W) was filled into a silicone rubber (diameter 7 mm) aneurysm model, and MRI imaging and image processing were performed according to the conformity test method standard to extract and quantify artifacts ( (See FIG. 7). The arrangement of the sample is shown on the upper left side in FIG. 7. From the upper left side of the arrangement, only empty silicone rubber, Pt-8W (filling rate (VER): 15%), Au-28Pt (drawing up, VER: 15%) ), Pt-8W (VER: 26%), Au-28Pt (drawing, VER: 26%), Au-28Pt (aging treatment (TA) 800 ° C., VER: 26%) from the lower left. 7 shows an MRI image (Spin Echo) on the upper right side and an artifact image corresponding to the lower right side. And the artifact measurement result is shown as a list on the lower left side in FIG. In FIG. 7, Au72-Pt28 is the same as Au-28Pt, and Pt92-W8 is the same as Pt-8W.

  Next, physical properties of the Au-28Pt alloy were examined. It has also been found that the drawing of the primary thin wire, the primary coil processing, and the secondary coil processing are possible without any significant problems. In addition, the physical properties of the prototype coil and the same coil (Pt-8W) currently used clinically in Japan were compared and verified. Table 1 below shows the wire strength, primary coil yield strength, and primary coil breaking strength measured for the material of the present invention (Au-28Pt) and the commercially available material (Pt-8W), respectively. The material (Au-28Pt) of the present invention has sufficient strength as an embolization coil, although its mechanical strength is slightly inferior to that of a commercially available product.

  Next, the flexibility of the coil was evaluated as follows. A coil sample (composition: Au-28Pt, wire diameter: 35 μm, primary coil diameter: 0.25 mm, secondary coil diameter: 2.0 mm) of the present invention provided with a secondary coil shape is compressed by 1 mm in the radial direction. The load required for this was measured. The load per pitch was calculated and compared with existing products (composition: Pt-8W, wire diameter: 35 μm, primary coil diameter: 0.25 mm, secondary coil diameter: 2.0 mm). Two samples were measured for Au-28Pt. The measurement results are shown in Table 2 below.

  In addition, the following coil samples having different wire diameters and secondary coil diameters were prepared. A coil sample of the present invention having a secondary coil shape (composition: Au-28Pt, wire diameter: 45 μm, primary coil diameter: 0.25 mm, secondary coil diameter: 2.5 mm) is 0.7 mm in the radial direction. The load required for compression was measured. Calculate the load per pitch, the most flexible existing product (ED coil ES (manufactured by Kaneka Corporation), composition: Pt-8W, wire diameter: 35 μm, primary coil diameter: 0.25 mm, secondary coil diameter : 2.5 mm). The measurement results of the flexibility of this sample are also shown in Table 2 together with n = 3.

  As a result of the above, it became clear that both of the two types of samples of Au-28Pt (drawn wire, 400 ° C. TA product) showed higher flexibility than existing products.

  It has been clarified that the tensile strength of the Au-28Pt φ35 μm strand is lower than that of the existing Pt-8W 35 μm strand. After estimating the Au-28Pt strand diameter expected to show the same tensile strength as that of existing products, the flexibility was estimated by computer simulation. As a result, the tensile strength of the 35 μm strand of Au-28Pt is 1.25 N (average of n = 2), whereas the tensile strength of the 35 μm strand of Pt-8W is 2.00 N (average of n = 2). ). As a result of assuming that the tensile strength of the same material is proportional to the cross-sectional area of the wire, changing the wire diameter of Au-28Pt to 45 μm makes the tensile strength 2.07 N, which is equivalent to the existing product. This result agrees with the measured values shown in Table 1. Further, for each of Au-28Pt and Pt-8W, the secondary coil flexibility (primary coil diameter: 0.25 mm, secondary coil diameter: 3.0 mm) when the wire diameter is 35 μm or 45 μm is a finite element. It was evaluated by analysis. For the analysis, a 1/4 model of the secondary coil was used. The change of the compressive load with respect to the compressive displacement is shown in FIG. By changing the strand diameter from 35 μm to 45 μm, it was recognized that the flexibility tends to decrease in both Au-28Pt and Pt-8W. Further, it was found that Au-28Pt is more flexible at the same wire diameter. It can be seen that the mechanical strength and flexibility of the existing product can be approximated by making the diameter of the coil wire of the present invention slightly larger than the diameter of the existing product.

  From Table 2, it was confirmed that the coil sample (n = 3) using the wire diameter of 45 μm is slightly inferior in flexibility to the ED coil ES and agrees with the above simulation result. On the other hand, the difference in flexibility is slight, and existing products using thicker wires (ED coil S (manufactured by Kaneka Corporation), composition: Pt8-W, wire diameter: 45 μm) are used for aneurysm embolization treatment. Since it is used, the flexibility of the coil sample (n = 3) is considered to meet the clinical needs well.

  The diameter of the coil wire can be appropriately selected according to the required physical properties, but the diameter of the coil wire is practically in the range of 35 to 120 μm. The coil element wire is preferably not heat-treated after wire drawing from the viewpoint of ease of manufacture and reduction of artifacts, but homogenization treatment and aging treatment may be performed as necessary.

  The Au-28Pt coil of the present invention was placed in a rabbit blood vessel, and an artifact evaluation was performed by an MRI imaging method (T2 star imaging method) used for blood vessel imaging in clinical practice. The target blood vessel was an external aneurysm of the common carotid artery, in which the coil was placed on the side of the internal carotid artery by sealing the external carotid artery with a coil. Since the vascular meridians of the rabbits themselves were small, the coil was cut into approximately 5 mm (primary coil length) and cut into small pieces, which were placed in the external carotid artery for a total of approximately 20 mm, and the starting portion was ligated. A commercially available aneurysm coil made of Pt-8W was used for the right external carotid artery, and a coil made of Au-28Pt of the present invention was used for the left external carotid artery. When the artifacts were compared, the right external carotid artery (Pt-8W coil implantation) became larger than the left external carotid artery (Au-28Pt implantation), and the tissue around the coil was blackened due to the influence of the artifact (FIG. 9).

  A spherical hollow body having an inner diameter of 6 mm and a wall thickness of 0.3 mm was prepared using two-component curable silicon. A straight coil having an outer diameter of 0.25 mm, which was produced by winding a 0.035 mm diameter wire of an Au-28Pt alloy, was inserted into the hollow body from the opening. The number of straight coils used is 1 and the length is 81 cm. The embolization rate calculated from the ratio of the volume of the aneurysm and the volume of the straight coil used (approximate the straight coil as a cylinder having an outer diameter of 0.25 mm) was 35%. An example in which the opening was sealed using a sheet prepared from two-part curable silicon was used. What was produced like the Example except having used Pt-8W alloy was made into the comparative example.

  A rabbit (New Zealand White, male, weight 3.5 kg) was opened under anesthesia to expose the abdominal aorta. Each of the examples and comparative examples was sutured to the outer membrane of the abdominal aorta and then closed, and the indwelling was terminated. Three days after indwelling, a TOF-MRA image was obtained by a maximum value projection method using a superconducting magnet type whole body MR apparatus having a static magnetic field strength of 1.5 Tesla using this model animal. The result is shown in FIG. FIG. 11 shows the result of angiography performed by the digital subtraction method.

  From the angiographic image, it can be seen that there is no stenosis in the abdominal aorta near the example and the comparative example, and a good blood flow is obtained. In the TOF-MRA image, an artifact is generated in the abdominal aorta near the comparative example, whereas no artifact is generated in the vicinity of the example.

Claims (4)

An embolization coil that is placed in a predetermined portion of a living body lumen and used to close the living body lumen, and the coil wire that has been drawn is an Au _x Pt _100-x alloy (X = 60 to 90) , and the embolization coil, characterized in that the volume magnetic susceptibility is the absolute value of the difference between the volume magnetic susceptibility of water (Δχ) is 15ppm or less. The embolization coil according to claim 1, wherein the coil wire is an Au _x Pt _100-x alloy (X = 70 to 75). The embolization coil according to claim 1, wherein the coil wire is an Au _x Pt _100-x alloy (X = 71.5 to 72). The embolization coil according to any one of claims 1 to 3, wherein the coil wire has a diameter of 35 to 120 µm.