JP5380312B2 - Medical device or instrument comprising a porous structure - Google Patents

Description

  The present invention relates to a medical device or instrument that can be used by being placed in a living body for a long period of time, comprising a porous structure having a thrombus anchoring function, and a method for producing and using the same. About.

  In recent years, when heart function is reduced due to a disease such as heart failure, an artificial heart or the like is used to assist systemic blood circulation. For an auxiliary artificial heart device, heart disease, trauma or heart attack The importance of maintaining a patient's life as a temporary replacement of cardiac function or replacement of permanent cardiac function while recovering cardiac function lost due to the above or waiting for a heart transplant is recognized.

  In particular, the left ventricular assist device is widely known to be very effective in improving symptoms in patients with congestive heart failure. Left ventricular assist devices have been developed as the last treatment for patients with severe congestive heart failure requiring long-term circulatory support, eg, patients who cannot temporarily or permanently receive heart transplants. The left ventricular assist device can replace the function of the left ventricle that takes oxygen back into the lungs and sends it back to the whole body. When attached to the patient's heart and blood vessels, the natural heart recovers. It is possible to remove it.

  A general auxiliary artificial heart device is mainly composed of a blood pump, a controller, a battery, a cannula, and an apparatus / instrument such as an outflow graft. These are surgically implanted in the patient's chest cavity, with the cannula inserted into the ventricle (left or right ventricle) or atria (left or right atrium), deflated, and flowed with a blood pump. And return the blood to the aorta through the outflow graft. As a result, it is possible to ensure blood circulation in a patient whose cardiac function has deteriorated.

  Here, since the artificial heart and the auxiliary artificial heart device are indwelled in the living body for a long period of time, the mechanical devices capable of maintaining a stable structure in the living body for a long period of time for each device and instrument constituting them. Strength is required. Such mechanical strength is strictly guaranteed, as some parts of these devices / instruments are damaged, and if the broken pieces fall into the blood, they can cause embolism. Must be.

  Furthermore, in the case of using an artificial heart or an auxiliary artificial heart device for a long period of time, in addition to the above mechanical strength, a blood circulation disorder due to a thrombus is also a serious problem. For example, when a thrombus is generated or grows in a blood pump, the blood flow path is blocked or the pump is stopped. Even if the generated thrombus is very small, It may occlude peripheral blood vessels and pose a serious risk to human life. In order to avoid these problems, conventionally, a device having an antithrombogenic property or a material having antithrombogenic means on the surface is used for an apparatus or an instrument constituting an artificial heart or an auxiliary artificial heart device. I came.

  However, even if such a material is used for a device or instrument constituting an artificial heart or an auxiliary artificial heart device, for example, a thrombus is formed on the cannula inserted into the heart, that is, on the outer peripheral surface of the inflow cannula. It tends to be easy to do. This is because the inflow cannula protrudes into the ventricle (left or right ventricle) or the atrium (left or right atrium), creating a space between the outer surface of the inflow cannula and the inner wall of the self-heart, This is because blood stays there, and it is due to the nature of blood that it is easy to clot at a slow flow place. In fact, when a titanium inflow cannula having a smooth surface, i.e., a smooth surface that has been smoothed by polishing or the like, is inserted into the heart and used in a short time, It has been found that a thrombus can form on the cannula surface. If a blood clot falls into the left ventricle etc., it immediately rides on the bloodstream and flows to the whole body, which may cause infarction where the diameter of the blood vessel is narrow, which has a profound effect on patients with cerebral infarction and renal infarction. May cause illness. Other devices / instruments other than the inflow cannula constituting the artificial heart or the auxiliary artificial heart device, such as a blood pump (particularly, the inner surface of the pump that comes into contact with blood) or a connector, are also placed in a region where blood tends to stay. Similar problems may arise with respect to those.

  Regarding such a problem, in the auxiliary artificial heart device, the blood contact surface of the device or instrument constituting the auxiliary artificial heart device is a textured surface, that is, a surface on which irregularities or holes are formed. Alternatively, by placing and fixing a textured surface structure separately on the blood contact surface of the above devices / instruments, etc., it is possible to stabilize the thrombus using the textured surface irregularities and holes, especially voids created by the holes Attempts have been made to anchor. Due to the anchoring of the thrombus, it is possible to prevent the thrombus from dropping into the blood, and depending on the site where the textured surface is provided, it can be expected that the endothelial cells will further settle on the anchored thrombus. Here, endothelial cells are known to exhibit extremely high antithrombotic properties. From the viewpoint of preventing thrombus formation, ultimately, all blood contact surfaces in the auxiliary artificial heart device are covered with endothelial cells. Is also considered ideal.

As an example of adopting such a textured surface for an auxiliary artificial heart device, Non-Patent Document 1, for example, describes a pulsatile blood pump whose surface is coated with sintered titanium alloy beads. In the blood pump of Non-Patent Literature 1, a textured surface made of sintered titanium alloy beads is formed on the blood pump by sintering a number of titanium alloy beads on the surface of the blood pump, and the particle size distribution is It has been observed that the best anchoring effect can be obtained when using titanium alloy beads in the range of 75-150 μm. In addition, when using a large number of beads having such a particle size range, the opening area of the holes formed between the beads is assumed to be all regularly arranged, and the minimum particle size is further reduced. When the beads having (75 μm) are densely arranged, the above-mentioned hole is approximately 0.22 × 10 ⁻³ mm ² or more when calculated as the number of holes formed between the beads is minimized. (This is about 17 μm in terms of a circle diameter).

  Patent Document 1 describes a blood pump that employs a textured surface for some parts. In this case as well, as in Non-Patent Document 1, titanium beads are sintered on the surface of the part. The sintered titanium bead layer formed by doing so is used as a textured surface.

  Furthermore, Patent Document 2 describes a blood pump in which a structure having a sintered titanium bead layer is arranged on the outer peripheral surface of a blood pump in contact with blood, with respect to an axial flow pump of the type in which the blood pump is directly inserted into the left ventricle. Has been. In this case as well, the sintered titanium bead layer plays a role as a textured surface. However, in the case of the blood pump described in Patent Document 2, the titanium beads are placed on a member called a wall shell. It is sintered separately from the blood pump, and then a wall shell having this sintered titanium bead layer is fitted on the outer peripheral surface of the blood pump.

  As mentioned above, it is ideal to cover all blood contact surfaces in the auxiliary artificial heart device with endothelial cells via a textured surface in consideration of antithrombogenicity. Since the number of times is limited, the endothelial cells do not extend to a site separated from the living tissue, and therefore it is impossible to cover the entire blood contact surface in the auxiliary artificial heart device with the endothelial cells. Close to. Therefore, if a textured surface is employed on the entire blood contact surface, a part of the blood contact surface is covered with endothelial cells but the other parts are not covered. . The part of the textured surface that is not covered with endothelial cells becomes a hotbed of bacteria if bacteria are mixed in the blood, and once that becomes a hotbed of bacteria, that part can be normalized. The sex is extremely low, and it is difficult to remove bacteria even with antibiotics, etc., which eventually causes sepsis.

  Therefore, in reality, a textured surface is adopted only in a necessary part of the blood contact surface of the auxiliary artificial heart device, and the state where the thrombus is anchored only in the part and / or only the part is the endothelium. It can be said that the best design for assistive heart devices at the present time is to create a cell-covered state and apply a mirror finish and / or anti-thrombotic coating for the rest of the site. And in consideration of this, it is possible to manufacture by selecting either a smooth surface or a textured surface as appropriate for each device / apparatus or part constituting the auxiliary artificial heart device. It is also necessary to be able to manufacture a device / apparatus or component in which the textured surface portion and the smooth surface portion are mixed in the device or component.

US Pat. No. 6,050,975 US Patent Application Publication No. 2007/0299297

H. Harasaki et al,. Powdered Metal Surface for Blood Pump. Trans Am Soc Artift Organ Organs, 1979; 25; 225-230.

  The first problem of the present invention is that it has a robust structure, has a thrombus anchoring effect, thereby enabling endothelial cell colonization, and is free from deformation and dimensional accuracy reduction during the manufacturing process. An inflow cannula for an auxiliary device is provided.

  The second subject of the present invention further comprises a textured surface formed by pores having a uniform opening area and shape, thereby improving the thrombus anchoring effect and hence more stable endothelial cells Providing an inflow cannula that results in the establishment of

  The third object of the present invention is to provide the inflow cannula having higher mechanical strength and improved ease of insertion into an application site.

  The fourth problem of the present invention is to provide an inflow cannula for a blood circulation assisting device that can successfully suppress the excessive proliferation of cells to the tip of the inflow cannula.

A fifth object of the present invention is to provide a method for manufacturing an inflow cannula that does not cause deformation of the structure during the manufacturing process and ensures high dimensional accuracy.
The sixth object of the present invention is to connect a blood pump and a conduit in a blood circulation auxiliary device having a robust structure, having an effect of anchoring a thrombus, and further, having no deformation in the manufacturing process and a decrease in dimensional accuracy. It is to provide a connector.

  It is a further object of the present invention to provide a conduit assembly and auxiliary artificial heart device comprising the inflow cannula and a method of making and using the inflow cannula.

  Other problems of the present invention will be apparent from the following description.

  As a result of intensive studies to achieve the above object, the present inventors have found that the above-mentioned problems can be achieved by forming a porous structure from filaments or using a porous molded body.

  Accordingly, the present invention is an inflow cannula for a blood circulation assisting device which is partially or entirely made of a porous structure in response to the first problem, and the porous structure is formed from a filament. The inflow cannula is made of a porous molded body.

  Furthermore, in the present invention, in response to the second problem, the porous structure is formed by spirally winding one or more filaments so that a hollow tubular body is formed. Inflow cannula.

  Furthermore, the present invention relates to the inflow cannula further provided with a non-porous support on the radially inner side in response to the third problem.

  Further, in response to the fourth problem, the present invention further includes a non-porous support on the radially inner side, and the non-porous support is abutted against one end portion (rim) of the non-porous support. The above-mentioned inflow cannula having a portion.

Furthermore, the present invention, in response to the fifth problem, the following step, that is, (a) a step of spirally winding the filament from one end to the other end around the tubular core material,
(B) a step of spirally winding the same or another filament so as to intersect with the spiral wound in step (a),
(C) a step of sintering the tubular structure obtained by steps (a) and (b);
(D) A step of extracting the core material from the sintered tubular structure obtained in the step (c), and in addition to the above (a) to (d), the following (e) and / or Or (f):
(E) Tubular with an outer diameter adapted to fit inside the structure and thus to support the structure inside the tubular structure obtained in step (d) in the radial direction. And / or (f) a tubular structure obtained in step (d) or an entire tubular structure with a nonporous support obtained in step (e). Applying a thrombotic coating,
A method of manufacturing an inflow cannula.

Further, according to the fifth problem, the present invention provides the following process, that is, (a) in a mold frame comprising a pedestal, and an inner mold frame and an outer mold frame arranged concentrically thereon. In addition, the step of irregularly putting the filaments and then fixing them to obtain a tubular structure composed of a non-woven body, if necessary, in addition to the above (a), the following (b) and / or (c):
(B) Tubular outer diameter adapted to fit inside the structure and thus to support the structure inside the tubular structure obtained in step (a) in the radial direction And (c) the tubular structure obtained in step (a) or the entire tubular structure with the nonporous support obtained in step (b). Applying a thrombotic coating,
A method of manufacturing an inflow cannula.

  Furthermore, the present invention is a connector for connecting an inflow cannula or an artificial blood vessel and a blood pump in a blood circulation assistance device in response to the sixth problem, and is porous on the radially inner surface thereof. The present invention relates to the connector, wherein the structure is joined or fitted, and the porous structure is formed from a filament or is made of a porous molded body.

  Furthermore, the present invention relates to a conduit assembly including the inflow cannula and / or the connector, and an auxiliary artificial heart device including the conduit assembly.

  Furthermore, this invention relates to the method of using the said inflow cannula for blood circulation assistance apparatuses by connecting to a blood pump directly or indirectly.

  Furthermore, the present invention provides a symptom selected from the group consisting of congestive heart failure, dilated cardiomyopathy, ischemic heart disease, cardiac sarcoidosis, and cardiac amyloidosis by the assistive artificial heart device including the inflow cannula for the blood circulation assist device. Relates to a method for ameliorating or treating a disease or disorder.

  Other invention forms and preferred embodiments according to the present application corresponding to the above problems are described below and in the dependent claims.

  As used herein, “blood circulation assisting device” means a device that substitutes or assists the pumping function of the heart that is responsible for blood circulation when cardiac function is reduced due to a disease such as heart failure.

  As used herein, “auxiliary artificial heart device” means a device for assisting blood circulation of a patient in a state where the self-heart is left among the blood circulation assistance devices. The auxiliary artificial heart device is mainly composed of a blood pump, a controller for adjusting the function thereof, a battery as a power supply source, and various conduits such as an inflow cannula, an outflow graft, and an artificial blood vessel. By attaching the blood pump directly to a part of the heart or indirectly through an inflow cannula or the like, blood is pumped from the blood pump into the body with a sufficient amount and pressure.

  As used herein, an “inflow cannula” is a conduit that is inserted into the heart's ventricle or atria, preferably the left ventricle, for blood removal, either via an artificial blood vessel or directly. A tubular device connected to a blood pump and serving to supply blood from the ventricle or atrium (preferably the left ventricle) to the blood pump. Here, an inflow cannula that is used directly or indirectly connected to a blood pump of an auxiliary artificial heart device is particularly referred to as an inflow cannula for an auxiliary artificial heart device.

  As used herein, “connector” means an instrument that becomes a joint for connecting a blood pump and a conduit (an inflow cannula, an outflow graft or an artificial blood vessel) in an auxiliary artificial heart device.

  When the inflow cannula is directly connected to the blood pump, the connector connects the inflow cannula and the blood pump, and when the inflow cannula is indirectly connected to the blood pump via an artificial blood vessel. The connector connects the artificial blood vessel and the blood pump. And this connector can be used also as a coupling which connects an outflow graft and a blood pump similarly to connecting an inflow cannula or an artificial blood vessel, and a blood pump.

  As used herein, a “conduit assembly” consists of a set of conduits and related components that make up the area of the ventricular assist device from the heart's ventricle or atria to the blood pump. By assembly is meant an inflow cannula and connector as essential components.

  Thus, when the inflow cannula is indirectly connected to the blood pump via an artificial blood vessel, the conduit assembly includes the inflow cannula and the artificial blood vessel, a connector connecting them to the blood pump, and a cuff, sleeve, If the inflow cannula is connected directly to the blood pump, the conduit assembly comprises the inflow cannula and it. It can also be composed of only a minimum component called a connector for connecting the to the blood pump. When the conduit assembly is composed of an inflow cannula and a connector in this way, the conduit assembly may be directly connected by screwing or the like, or has the function of an inflow cannula. It may be integrally manufactured as one instrument composed of both the part and the part having a connector function.

  In any case, the conduit assembly has the functions of blood removal from the heart by the conduit, supply of blood to the pump, and connection of the conduit to the blood pump. This is ensured by placing the cannula and connector continuously (although via an artificial blood vessel) in the same conduit assembly.

  The inflow cannula of the present invention consists of a specific porous structure, part or most or all of which has open pores on the surface. The connector of the present invention comprises this specific porous structure joined or fitted radially inward as part of the connector.

  In one embodiment of the present invention, the porous structure is formed from filaments.

  When the porous structure is formed from filaments, the porous structure includes a porous texture including one or two or more filaments as its constituent elements. In this case, this structure is formed by intersecting and / or contacting one or more filaments, and these or these filaments are mutually connected on the surface of the porous structure. A hole can be formed in a region surrounded by a line connecting adjacent intersections and / or contact points. That is, one or more filaments may be wound, woven or knitted, or irregularly arranged or entangled to form a nonwoven, etc. Forming a porous texture. At this time, the filaments intersect and / or contact the same filaments or different filaments several times on the surface of the structure, or on the structure surface and in the thickness direction. As a result, the region surrounded by the line connecting the adjacent intersections and / or contact points among the intersections and / or contact points of the generated line is various, such as a square, a triangle, a rhombus, a parallelogram, a polygon, etc. Presenting any shape or any combination thereof, this can be a hole in the structure.

  In another aspect of the present invention, the porous structure comprises a porous molded body.

  In the porous structure of the present invention, blood flows into the structure from such a hole on the surface, but the flow of blood slows toward the inside of the structure. Thrombus anchoring is achieved by solidifying inside the body to form a thrombus having an appropriate size, and this thrombus is firmly held in the structure (in this specification, the structure of such a thrombus is achieved). This is called “thrombus anchoring”).

The above-mentioned “hole” only needs to allow blood cells to pass through the hole, and usually has an opening area of about 1.9 × 10 ⁻⁵ mm ² (about 5.0 μm in terms of circular diameter) or more. On the other hand, the upper limit can be generally about 20 mm ² (about 5.0 mm in terms of circular diameter) so that the mechanical strength of the porous structure is maintained. In addition, in the above-mentioned range of about 1.9 × 10 ⁻⁵ mm ² to about 20 mm ² , the larger the opening area, the easier the blood flow into the structure. On the contrary, the smaller the opening area, The stability of thrombus anchoring is increased because the thrombus is held more firmly inside the structure. Moreover, when an opening area is large, the advantage that the process at the time of manufacturing the said porous structure becomes easy can also be enjoyed. Therefore, considering these points comprehensively, in one embodiment, the hole is about 0.22 × 10 ⁻³ mm ² to about 0.80 mm ² (about 17 μm to about 1.0 mm in terms of a circular diameter). ), For example, an opening area of about 3.0 × 10 ⁻² mm ² to about 15 × 10 ⁻² mm ² (about 0.20 mm to about 0.44 mm in terms of a circular diameter). Is preferred.

Here, the opening area of the hole in the porous structure of the present invention is determined by measuring each dimension of the hole from the front enlarged photograph of the structure, and correcting each dimension related to the magnification and the geometric shape of the hole. It is possible to obtain mathematically based on All of the holes formed in the structure need not have an opening area in the range of 1.9 × 10 ^-5 mm ² ~20mm ² above, to the extent that the intended purpose of the present invention are achieved It is sufficient if a part of the holes to be formed is open within this range, but it is desirable that the main proportion, preferably all or substantially all have the above-mentioned hole size. Will.

  In the porous structure of the present invention, “pores” can also be formed in the thickness direction. That is, when the porous structure is formed from filaments, depending on the number of layers, the diameter of the filaments, and the manufacturing method, the filaments are on a plane that is horizontal in the thickness direction of the structure. In the region surrounded by the line connecting the intersections and / or the contact points adjacent to each other, the “hole” as described above can be formed. Further, even when the porous structure is made of a porous molded body, “pores” can be formed in the thickness direction depending on the thickness of the structure and the manufacturing method.

  Such a mode in which “holes” are formed in the thickness direction is also included as a matter within the scope of the present invention. Such a hole in the thickness direction increases anchoring space in order to increase the space in which the thrombus can be retained in the structure.

  As used herein, “porous structure” means a rod-like porous structure having a hollow inside, and the cross-sectional shape thereof is not particularly limited. This structure includes, for example, those whose cross-sectional shape is circular, elliptical or polygonal (for example, a triangle or a quadrangle), and those whose cross-sectional shape is generally circular or elliptical. Furthermore, the structure of the present invention does not necessarily have a constant diameter, thickness, and cross-sectional shape throughout the structure. Therefore, the shape required for the device / apparatus and the shape of the device / apparatus for arranging the structure, etc. Can be matched.

  Whether the porous structure is used as an inflow cannula or as a part of a connector, the internal diameter of the porous structure is a ratio that occupies the heart or chest cavity if it is too large. Is unnecessarily large. On the other hand, if the inner diameter is too small, there is a possibility that a sufficient blood removal amount may not be ensured, so that it is generally 6 to 30 mm, particularly 10 to 20 mm.

  The thickness of the porous structure depends on, for example, the diameter of the filament and how the structure is formed from the filament, but the space for thrombus anchoring and endothelial cell colonization is sufficient in the thickness direction. In view of the fact that the structure can be secured, even when used as an inflow cannula or as a part of a connector, generally within a range of 0.2 to 5 mm, In particular, it should be in the range of 0.5 to 2 mm.

  When the porous structure is used as an inflow cannula, the length of the porous structure passes through the apex wall and is exposed in the heart (for example, the left ventricle). Although it can be set as appropriate in consideration of the possibility of securing a sufficient amount of blood removal, if the exposed part is too short, there is a possibility that the tip opening of the structure will be blocked by growth in surrounding tissues or muscles. is there. Considering these, the length of the structure is usually in the range of 10 mm to 50 mm, particularly 15 to 35 mm.

  Moreover, when using this structure as a part of connector, the length is suitably set so that it may correspond with the form of a connector.

  As used herein, “strip” means a metallic linear material and a non-metallic linear material.

  As the filament used in the porous structure of the present invention, for example, a metal material filament, a polymer material filament, or carbon fiber can be used.

  Examples of the metal material include stainless steel, pure titanium, or a titanium alloy, and examples of the polymer material include, but are not limited to, polyester, polyamide, polypropylene, and fluororesin.

  However, when comprehensively considering the strength, biocompatibility, ease of processing, etc. of the material itself, it is preferable to use a filament made of pure titanium or a titanium alloy. In the porous structure of the present invention, the cross-sectional shape of the porous structure when it is cut along a plane perpendicular to the length direction of the filaments is in principle arbitrary, but blood flows into the structure through the pores. From the viewpoint of smoothing the flow of time, it is preferable to use a filament having a smooth surface without having corners.

  Furthermore, in the manufacturing process of the porous structure, in order to increase the mechanical strength of the structure obtained after sintering, when the structure made from the filament is fixed using means such as sintering. In addition, it is preferable to use a filament that increases the contact area at the intersection and / or contact point of the filament.

  Considering these points, it is preferable to use a flat elliptical filament (hereinafter abbreviated as a flat filament) in the porous structure of the present invention, and such a flat filament has, for example, a circular cross section. It can manufacture by rolling of the wire which has. In the present invention, a flat filament having a flattening ratio of 1.1 to 10 is usually obtained by rolling a filament having a circular cross section.

  As used herein, “flatness” means the ratio of the minor axis to the major axis in the cross-sectional shape of the flat filament, that is, the value obtained by dividing the major axis of the cross-sectional shape by the minor axis (major axis / minor axis). ). In the present invention, in order to increase the contact area between the filaments, it is preferable to use a flat filament having a flattening ratio of 1.1 to 5, particularly a flattening having a flattening ratio of 1.5 to 2.5. It is particularly preferred to use filaments.

  The diameter of the filament used in the porous structure of the present invention is 20 μm to 500 μm because if the diameter is too small, the mechanical strength decreases, and conversely if too large, the workability decreases. It is preferable to use a filament having a diameter, and considering the ease of handling of the porous structure (for example, if the unevenness of the surface of the structure is too large, a surgical glove during an implantation operation to a patient) In particular, it is preferable to use a filament having a diameter of 30 μm to 200 μm. This diameter corresponds to the diameter of the circle when the cross-sectional shape is a circle, the short diameter when the cross section is an ellipse or a flat ellipse, and the short side when the cross section is a rectangle.

  Examples of the filaments used in the porous structure of the present invention include, for example, ASTM F67-95-Gr. Pure titanium wire that meets the standards of No. 2 (a wire having a diameter of 85 ± 20 μm rolled to a thickness of 50 ± 20 μm), Ti-6Al-4V alloy ELI, Ti-6Al-7Nb, Ti-13Zr-13Nb , Ti-15Mo-5Zr-3Al or Ti-6Al-2Nb-1Ta, a titanium alloy wire (a wire having a diameter of 85 ± 20 μm rolled to a thickness of 50 ± 20 μm), polyester fiber It is done.

  In addition, when the porous structure of the present invention is formed from filaments, the structure can mainly be made using one or two or more filaments, but two or more When using a filament, all the filaments of the same material may be used, or the filaments of different materials may be used in combination. Whether one line is used to produce one porous structure or two or more lines are used, blood flow unevenness on the surface of the structure is reduced, and blood is In order to smooth the flow as the liquid flows into the structure through the holes, it is preferable to use a filament having a seamless and smooth surface.

  As a form, the porous structure of the present invention can be formed by winding one or more filaments into a hollow tube.

  In this case, for example, one or two or more filaments are wound around a ceramic tubular core material at random or spirally so as to form the above-mentioned holes, sintered, and finally sintered. The porous structure can be produced by extracting the core material.

  When the porous structure is manufactured by spirally winding, the winding of the filament can include both S winding and Z winding, for example, both can be included alternately.

  Specifically, for example, a single filament is wound around a tubular core material in a spiral shape at an appropriate pitch from one end to the other end (winding direction: S winding) and wound to the other end. The wire is then folded back and wound in a spiral at an appropriate pitch so as to intersect with the spiral wound in this way (winding direction: Z winding). Then, by repeating the winding of the filaments until a desired number of layers (structure thickness) is obtained, a structure in which the filaments are wound in a spiral manner can be obtained.

  In the case of using a plurality of filaments, for example, one filament is wound around a tubular core material in a spiral shape from one end to the other end at an appropriate pitch, and another one from above. A tubular structure in which the above-mentioned filaments are spirally wound using a separate filament for each layer, such as spirally winding the other filaments at an appropriate pitch with the winding direction reversed. Can also be manufactured.

  In the porous structure obtained in this manner, as shown in FIG. 1A, holes are formed from the intersection of the filaments, and are surrounded by lines connecting the intersections adjacent to each other on the plane among the intersections of the filaments generated. The region to be formed (shaded portion in FIG. 1A) forms a hole in the structure.

  In addition, “S winding” and “Z winding” have the same meanings as “from S” and “from Z” described in JIS G3525 “wire rope”. Winding the wire in the same direction as “From S”, “Z winding” means winding the wire in the same direction as “From Z”. “Pitch” refers to the distance traveled in the axial direction during one revolution of the spiral when the filament is wound in a spiral, for example, in the range of 10 to 20000 μm.

  Sintering is performed at a temperature below the melting point of the filament material used, but at a temperature and for a time sufficient to ensure a sufficiently strong bond at the intersection of the filaments and / or at the contact points. For example, when a pure titanium wire is used, sintering can be usually performed at 1200 to 1300 ° C. for about 0.5 to 5 hours. As the sintering furnace, an infrared radiation type or induction heating type vacuum heating furnace is usually used, but is not limited thereto. Since the intersection and / or contact portions of the filaments are completely bonded by this sintering process, the filaments are not peeled off, and a structure having high mechanical strength can be obtained.

  Further, the porous structure of the present invention comprises a pedestal and an inner mold frame and an outer mold frame arranged concentrically thereon, and the filaments are irregularly placed in, for example, a ceramic mold frame. Then, by fixing, it can be produced as a sheet-like non-woven body having the above-mentioned holes and having a tubular shape, or in another aspect, the filament is woven or knitted. The sheet-like knitted body or woven body having the above-mentioned holes is produced from the line by joining the filaments by sintering or the like, and the obtained sheet-like knitted body or woven body is rolled into a tube or After winding on a tubular core material, it can also be manufactured by welding between both ends and, if a core material is used, then extracting the core material. At this time, two or more of these sheet-like knitted bodies, woven bodies, or non-woven bodies can be stacked to form the porous structure.

  “Fixed” means that the filaments irregularly placed in the above-mentioned formwork are processed so that the structure of the nonwoven body is fixed. Examples of such a fixing process include pressing, sintering, welding, pressure bonding, adhesion, and the like, but are not limited to these as long as the process can fix the filament.

  “Knitted body” means a fabric knitted while creating a stitch with the line defined above, and “woven fabric” combines the line defined above vertically and horizontally. Means a sheet that has been interlaced according to certain rules and finished into a sheet. “Nonwoven body” means a material that is formed by irregularly arranging or tangling these as defined in the above, and the filament is unidirectional or random. It is oriented to These are joined between the filaments by sintering or the like.

  In a porous structure manufactured from a sheet-like non-woven body, as shown in FIG. 1B, the stripes intersect and / or contact each other, and the resulting intersections and / or contact points of the resulting stripes are mutually connected on a plane. A region surrounded by a line connecting adjacent intersections and / or contact points (shaded portion in FIG. 1B) forms a hole in the structure.

  Furthermore, the structure produced in this way is used in an alkaline aqueous solution of 7N or less, preferably 5N or less, preferably an aqueous sodium hydroxide solution for the purpose of increasing the surface area per unit volume and improving the mechanical strength. It can be used after being immersed for 1 to 8 hours at a temperature of 100 ° C., preferably 60 ° C., and washed with distilled water at room temperature for 0.5 to 5 minutes.

  The fixing process can be performed by any conventionally known method related to pressing, sintering, welding, pressure bonding, adhesion, and the like. Specifically, for example, when sintering is performed as the fixing process, Can be sintered under the above conditions.

  As used herein, the term “porous molded body” refers to a metal material, a resin-based material or the like molded into a hollow tubular body, and has a large number of pores on the surface thereof or on the surface and inside thereof. It means what you have.

  For example, stainless steel, pure titanium, a titanium alloy, a fluororesin, or the like can be used as the metal material or the resin-based material, but is not limited thereto.

  However, considering comprehensively the strength, biocompatibility, workability, etc. of the material itself, it is preferable to use pure titanium or a titanium alloy as the material of the porous molded body. For example, ASTM F67-95-Gr. Titanium alloy that satisfies the standards of pure titanium, Ti-6Al-4V alloy ELI, Ti-6Al-7Nb, Ti-13Zr-13Nb, Ti-15Mo-5Zr-3Al, or Ti-6Al-2Nb-1Ta Used.

  For example, in the case of using a metal material, the above porous molded body is formed by mixing a metal powder and a spacer material powder that evaporates at a low temperature to form a hollow tubular body, and then heating to the evaporation temperature of the spacer material powder. After the spacer material is evaporated, the metal powder can be manufactured by sintering at a higher sintering temperature than the spacer material. A metal material in which pores are formed by positively introducing voids on the surface and inside thereof by means of using such a spacer material is generally also referred to as “porous metal”.

  Here, as the spacer material, for example, ammonium hydrogen carbonate, urea, polyoxymethylene resin, urea resin, foamed polystyrene resin or foamed polyurethane resin can be used, and these are, for example, spherical, columnar, and fibrous. It can be used as a powder.

  Sintering can be performed under the same conditions as when the filaments are used. For example, when pure titanium is used as the metal material and polyoxymethylene resin is used as the spacer material, it is usually used for evaporation of the spacer material. After heating at 300 to 500 ° C. for 0.5 to 5 hours, sintering can be usually performed at 1200 to 1300 ° C. for about 0.5 to 5 hours.

  Further, an antithrombogenic coating can be applied to the surface of the filament or the surface of the porous molded body in the porous structure produced as described above. By applying the antithrombogenic coating, it is possible to suppress the thrombus anchored in the structure from becoming excessively large, and therefore, it is possible to suppress the thrombus anchoring from becoming unstable. . For example, an MPC polymer coating can be used as the antithrombogenic coating. Since the MPC polymer has MPC (2-methacryloyloxyethyl phosphorylcholine) having the same structure as the polar group of phosphatidylcholine constituting the cell membrane as a constituent unit, when coated with this, the surface of the structure is cell membrane-like. A structure is formed, and this cell membrane-like structure exhibits antithrombogenicity by suppressing adhesion of platelets and the like. In addition, MPC can obtain a commercially available thing.

The antithrombogenic coating can be performed by any conventionally known method in relation to a coating for imparting antithrombogenicity to the material surface. For example, if the antithrombogenic coating is an MPC coating, it can be performed as follows:
-MPC is diluted with ethanol to prepare 0.1-10 wt%, preferably 0.5 wt% MPC ethanol solution,
-Immersing the produced porous structure in the solution at room temperature for 1 to 60 minutes, preferably 5 to 10 minutes;
-The structure is removed from the solution and dried at room temperature.

The porous structure of the present invention usually has a volume of 5 to 90 volumes in consideration of the balance between securing the space for thrombus retention and / or endothelial cell colonization and the mechanical strength of the entire structure. %, Preferably 30 to 80% by volume. Here, “porosity” means the ratio (volume%) of the volume of the space to the total volume of the structure. This porosity can be approximated as follows:
-Mathematically calculating the volume (V ₁ ) of the geometric shape assuming an average geometric shape of the porous structure (eg, a hollow cylinder having a uniform thickness in the radial direction);
-Measuring the weight of the structure actually produced using the filament or the actual porous molded body;
-The volume (V ₂ ) of the filament or porous molded body part of the structure is obtained from the above weight and the specific gravity of the filament or the molded body.
The total void volume (V ₃ ) in the structure is determined by subtracting the volume (V ₂ ) of the filament or shaped part from the assumed geometric volume (V ₁ ),
-A value obtained by dividing the total void volume (V ₃ ) in the structure by the assumed geometric volume (V ₁ ) and multiplying by 100 is defined as a void ratio (% by volume).

  For example, when the structure is produced by winding the filament in a hollow tube, the porosity is mainly the diameter of the filament to be used, the pitch for winding the filament, and the number of layers wound with the filament. In the case of manufacturing the porous structure from a sheet-like non-woven body made of a filament and having a hollow tubular shape, the density of the filament is mainly adjusted. By doing so, control is possible.

  Further, when the porous structure is composed of a porous molded body, the porosity can be controlled by adjusting the mixing ratio of the metal powder and the spacer material powder and the average particle diameter of the spacer material powder. Is possible.

  Thus, the porous structure of the present invention made of a filament or made of a porous molded body is robust, and part of the structure material peels off during use in a living body and enters the bloodstream. There is very little risk of falling out. Therefore, the porous structure of the present invention has a very high mechanical strength, and can be safely placed in a living body for a long period of time, for example, several months to several years.

  In the porous structure of the present invention, the layer structure of the structure is, for example, in the case of a structure produced by winding a filament, in the production process, for example, the form of the filament (particularly the diameter), the filament For example, in the case of a tubular structure made of a sheet-like non-woven body manufactured from a filament, in the production process, for example, It can be easily controlled by appropriately selecting the form (particularly the diameter), the thickness for laminating the filaments, and the like. And also when the said porous structure consists of a porous molded object, the thickness of this structure can be easily controlled by selection of the formwork used in a shaping | molding process. Therefore, in the porous structure described above, not only in the planar direction but also in the thickness direction, a large number of holes are formed to adjust the porosity, and a three-dimensional structure having a reasonably large void in the thickness direction, that is, a thrombus is retained. In order to easily obtain a three-dimensional structure that can sufficiently secure a space for fixing and / or fixing endothelial cells, a high anchoring effect is achieved, and the three-dimensional structure is arranged at a site adjacent to the living tissue. In some cases, stable endothelial cell colonization is achieved.

  In particular, in the case of a porous structure manufactured by spirally winding a filament at a constant pitch, the structure has a uniform opening shape / opening area of the formed holes, and further, the entire structure The three-dimensional structure is also uniform and has moderately large voids. And the dispersion | variation between the bodies of the structure finally manufactured becomes also very small.

  In the porous structure manufactured so that the opening shape and area of the hole are uniform and the three-dimensional structure as a whole structure is uniform and has a moderately large void, an extremely stable thrombus anchor is provided. When a ring is achieved and used in a place adjacent to living tissue, for example, in the heart, fibroblasts that have entered through the pores of the structure settle in the voids of the structure and grow from the myocardium, etc. It was confirmed that the same endothelial cells as the living body were formed on the surface of the structure very uniformly over the entire surface by the riding of the endothelial cells.

  This is presumably because in such a porous structure, the initial thrombus adherence state before the formation of endothelial cells in the voids in the structure is stabilized. That is, when the thrombus adheres to the structure, it is reduced by the fibrinolysis system. In the structure, this initial thrombus attachment / reduction process proceeds uniformly throughout the structure. When the initial thrombus adheres in this way, the endothelial cells enter and settle into the adhering portion of the initial thrombus, so that the formation of the endothelial cells proceeds uniformly throughout the entire body, and as a result, This is probably because a uniform and stable endothelial cell tissue is formed.

  Specifically, when the porous structure is used, for example, as an inflow cannula in the left ventricle (or as a part thereof), endothelial cells extend from the inner surface of the left ventricle toward the outer surface of the inflow cannula. To do. Usually, about 50 to 100 cell divisions occur for each endothelial cell, which is sufficient to cover the entire outer peripheral surface of an inflow cannula having a normal size with cells.

  When the porous structure is covered with endothelial cells, there is no risk of blood coagulation, and it exhibits extremely high antithrombogenicity. This is because vascular endothelial cells themselves control so that thrombi never occur on or around vascular endothelial cells, or can be quickly lysed even if thrombosis occurs for some reason. It is believed that there is. Such control is the ability that vascular endothelial cells exert mainly by regulating the expression level of t-PA (tissue plasminogen activator) or PAI-1 (plasminogen activator inhibitor 1). Generally called anti-thrombogenicity of vascular endothelial cells, it is a particularly important function among many functions of vascular endothelial cells.

  Further, when covered with such endothelial cells, invasion of foreign substances such as bacteria into the porous structure is also prevented, so that an indwelling medical device such as an artificial heart or an auxiliary artificial heart device can be used. This is a problem that often occurs when used, and the risk of developing an infectious disease that is a fatal problem for patients is also reduced.

  Moreover, when the site | part to which the said porous structure is detained is a site | part far from a myocardium, or when the patient into whom the said structure is detained is elderly, when endothelial cells do not grow over the whole surface of the said structure Even so, the benign granulation covers the structure and the granulation inhibits thrombus growth, so that the structure can acquire a high degree of antithrombogenicity.

  In addition, since the porous structure of the present invention is made of filaments or made of a porous molded body, unlike the case of sintered titanium beads described in Non-Patent Document 1, etc., Even if it does not use a member, it has the advantage that it is possible to manufacture the said structure alone.

  Therefore, the porous structure can be independently manufactured as a device / apparatus having a textured surface, or the porous structure is separately manufactured and then used in an auxiliary artificial heart device. It is also possible to arrange and fix on a desired part of the blood contact surface. In this case, it is not necessary to introduce the apparatus / apparatus and the like where the porous structure is to be placed into the sintering furnace, and it is only necessary to place the separately manufactured structure at a site where the textured surface is desired. These devices / instruments and the like are not deformed or roughened, and the dimensional accuracy is not lowered. For example, there is no need to perform additional machining using polishing powder or cutting powder. Accordingly, it is possible to easily manufacture an apparatus / apparatus or the like in which a smooth surface portion and a textured surface portion are mixed.

  And since the porous structure of the present invention can be produced independently as described above, the porous structure itself is not likely to have a reduced dimensional accuracy due to deformation / distortion of other members during sintering. Furthermore, since it is not subject to design restrictions caused by other members such as the above-mentioned wall shell, it can be accurately incorporated in each device / apparatus or component.

  Furthermore, in one aspect of the present invention, the inflow cannula of the present invention is adapted to fit within and so support the structure radially inward of the porous structure. It further comprises a tubular non-porous support having an outer diameter adapted to obtain.

  In one aspect, this support body can be composed of a support body body portion at the center, an abutting portion at one end, and a threaded portion at the other end. The trunk portion is a portion that supports the porous structure, the length of which corresponds to the length of the structure, and the abutting portion is a rim portion provided at one end of the support, It serves as a stopper when fitting the support to the structure, and a threaded portion is provided at the other end of the support to attach other inflow cannula members and to an artificial blood vessel or blood pump. Is for.

  In addition to the role as a stopper, the support abutting portion also plays a role of suppressing excessive tissue / cell growth. Due to the effect of the structure, endothelial cells and the like enter and settle inside the structure, but if they grow excessively, they form a blood retention area and may increase the risk of infarction. For this reason, by disposing a non-porous support butting portion on the distal end side of the structure to suppress excessive growth of endothelial cells and the like, the inflow cannula is prevented from being blocked, so that sufficient blood removal is possible. The amount can be maintained.

  In order to maximize the effect of suppressing such excessive tissue / cell growth, the abutting portion of the support, particularly the outer peripheral surface thereof, is preferably polished and smoothed. If Ra on the outer peripheral surface of the support abutting portion is 1 μm or less, it is considered that excessive growth of tissue / cells on the outer peripheral surface is suppressed, and Ra on the outer peripheral surface is 0.1 μm or less. Is particularly preferred.

  “Ra” means arithmetic average roughness Ra defined by JIS B 0601, and Ra can be measured using various commercially available devices of contact type or non-contact type. Specifically, for example, by using a stylus type surface roughness meter, setting the cutoff value to 0.25 mm, the evaluation length to 1.25 mm, and the measurement speed to 0.5 mm / s. , Ra can be measured.

  Here, the total length of the support, the width of the support body, the width of the support abutment and the support thread, the outer diameter, the inner diameter, the thickness, and the like match the form of the porous structure. It is appropriately set in consideration of the inner diameter of the entire inflow cannula and the like.

  However, as described above, the support abutting portion also plays a role of suppressing excessive tissue / cell growth. Therefore, when the width of the support abutting portion is too short, such a suppression effect is obtained. In contrast, if the length is too long, the portion not covered with the endothelial cells increases, and the effect exerted by the structure is reduced. Considering such a point, the width of the support abutting portion is preferably 0.5 mm to 15 mm, particularly 1 mm to 5 mm.

  In addition, the step between the outer peripheral surface of the porous structure and the outer peripheral surface of the support abutting portion gives a force necessary for inserting or removing the inflow cannula into the heart (ventricle or atrium). It should be small and as small as possible to reduce tissue damage in the body. Specifically, the difference in the outer diameter is preferably in the range of 0 to 1 mm, particularly in the range of 0 to 0.5 mm.

  In the inflow cannula having such a support, the inner diameter of the support corresponds to the inner diameter of the inflow cannula. Therefore, the preferred inner diameter can be the same as described above for the porous structure.

  In this case, the outer diameter of the inflow cannula as a whole (diameter obtained by adding the thickness of the porous structure to the outer shape of the support body) is usually in the range of 6 mm to 30 mm without any problem. Can be used in vivo.

  As the material for the support, for example, pure titanium, stainless steel, titanium alloy, or the like can be used in consideration of mechanical strength, biocompatibility, workability, and the like.

For example, the inflow cannula including the support is assembled as follows.
-Fitting the support radially inside the porous structure until the abutment of the support hits the porous structure;
-The porous structure is fixed on the support by passing the sleeve and cuff sequentially through the support, and finally screwing the cuff holding screw with the support thread.

  At this time, the anti-thrombogenic coating can also be applied to the non-porous support. In this case, the antithrombogenic coating may be applied to the nonporous support in advance, or the nonporous support may be applied to the porous structure and then applied to the antithrombogenic coating together. .

  In addition, in the inflow cannula equipped with the above-mentioned non-porous support on the radially inner side, the porous structure according to the present invention can be additionally arranged on the radially inner side of the support. .

  The porous structure of the present invention is, for example, each device / apparatus or part constituting an auxiliary artificial heart device or as a part of each device / apparatus or part, or each device / apparatus constituting an auxiliary artificial heart device or It can be used by being placed on a part. In particular, when it is used at a site in contact with blood in an auxiliary artificial heart device, the effect is maximized.

  Specifically, the porous structure of the present invention is provided, for example, on the inner surface of a connector for connecting a blood pump of an auxiliary artificial heart device and an inflow cannula or an artificial blood vessel, or as an inflow cannula (or inflow cannula). As part of the cannula). Furthermore, the porous structure of the present invention can also be applied to the blood pump inner wall and impeller of an auxiliary artificial heart device.

FIG. 1 shows the pores in the porous structure of the present invention. (A) A hole (shaded portion) in a porous structure produced by winding a filament in a spiral shape. (B) The hole (shaded part) in the porous structure manufactured using the sheet-like nonwoven material. FIG. 2 shows an inflow cannula of the present invention. FIG. 3A is a perspective view of the inflow cannula shown in FIG. FIG. 3B is an exploded view of the inflow cannula shown in FIG. FIG. 4 is a perspective view of a conduit assembly including the inflow cannula shown in FIG. FIG. 5 is a cross-sectional view of the inflow cannula shown in FIGS. FIG. 6 shows an inflow cannula partially having a two-layer structure as a modification of the inflow cannula of the present invention. FIG. 7 shows an inflow cannula having a single layer structure as a modification of the inflow cannula of the present invention. FIG. 8 is a front view of a patient showing a connection state of a typical auxiliary artificial heart device to the patient's heart. FIGS. 9A and 9B are front views of a patient showing a connection state of a typical auxiliary artificial heart device to the patient's heart. FIG. 10 shows a state in which a part of the auxiliary artificial heart device is stored in a shoulder bag. FIG. 11 is a perspective view of a connector having the structure of the present invention. FIG. 12 is a cross-sectional view of a connector having the structure of the present invention. FIG. 13 shows a photograph of the state of the inflow cannula when the inflow cannula of the present invention was implanted in the living body of an animal and inserted into the left ventricle for 65 days and an autopsy was performed. Tissue growth can be confirmed on the outer peripheral surface of the inflow cannula. FIG. 14 shows a photograph of the state of the inflow cannula when an inflow cannula having a conventional smooth surface is implanted in the living body of an animal and inserted into the left ventricle for 65 days and then necropsied. It can be seen that a large thrombus is formed on the outer peripheral surface of the inflow cannula.

  FIG. 2 shows a diagram of an inflow cannula of the present invention provided with a non-porous support as an example of the present invention.

  In FIG. 2, reference numeral 1 denotes an inflow cannula having a support for an auxiliary artificial heart device, which is inserted into a patient's ventricle, most preferably the left ventricle. It consists of an inflow cannula body 2 in the form of a tubular porous structure and a support 3 (nonporous pure titanium tubular body with a smooth surface). In FIG. 2, 4 is a sleeve made of pure titanium, and 5 is a cuff made of PTFE fiber.

  The outer peripheral surface of the support abutting portion 3 has an Ra of 0.1 or less.

  The main body 2 is obtained by spirally winding a single titanium wire on a tubular core material (made of ceramics), repeating S winding and Z winding, and then sintering and removing the core material after sintering. It is a thing.

As shown in FIG. 2, the main body 2 includes an intersection of the wires formed from pure titanium wires, and holes are formed. The main body 2 (length: 24 mm, outer diameter: 20 mm, inner diameter: 18.6 mm, thickness: 0.7 mm) has an area of each hole of 3.9 × 10 ⁻² mm ² to about 13.4 × 10 ^−2. in the range of mm ^2, having a porosity of about 40 to 70% by volume as a whole.

  FIG. 3 is a schematic view (FIG. 3A) and an exploded view (FIG. 3B) of the inflow cannula 1 shown in FIG. 2.

  As shown in FIGS. 3A and 3B, in the inflow cannula 1, the support body 3 is fitted inside the main body 2 in the radial direction, and the overall length L1 (FIG. 3A) of the inflow cannula 1 is 30 mm. .

  The support 3 (total length: about 50 mm) includes a support body 3a (outer diameter: 18.6 mm, inner diameter: 16 mm), an abutting portion 3b (outer diameter: 20 mm, inner diameter: 16 mm), and a screw portion 3c (outer diameter: 18 mm, inner diameter: 16 mm), and the support body portion 3 a has an outer diameter slightly smaller than the inner diameter of the main body 2, so that it can be fitted in the main body 2 in an appropriate manner. Further, the support body 3 is provided with an abutting portion 3b having an outer diameter larger than the outer diameter of the support body barrel portion 3a. Since the abutting portion 3b functions as a stopper when fitted into the main body 2, The main body 2 can be firmly fixed on the support by sandwiching the main body 2 with the abutting portion 3b and the sleeve 4 (and / or the cuff 5 and the cuff holding screw 6). And the inflow cannula 1 is connected to the artificial blood vessel or the blood pump through the screw part 3c.

  The main body 2 and the support 3 are MPC polymer coated over the entire surface.

  As shown in FIG. 4, the inflow cannula 1 is connected to the artificial blood vessel 7 through the support thread portion 3c. The artificial blood vessel 7, the outer clamp 8, the inner clamp 9, the connector 18 and the retaining ring 19 (FIG. 5, 11 and 12) together to form a conduit assembly 10 that is ultimately connected to a blood pump.

  FIG. 5 is a cross-sectional view of the inflow cannula 1 shown in FIGS. The inflow cannula 1 in the present invention may take other forms in addition to the structure shown in FIG. 5, and such examples are shown in cross-sectional views in FIGS. 6 and 7.

  5-7, 1 (or 1b) is an inflow cannula with a nonporous support for an auxiliary heart prosthesis, 1c is an inflow cannula without a nonporous support, and 2 is a porous structure. A body inflow cannula body, 3 is a support, 4 is a sleeve, 5 is a cuff, 6 is a cuff holding screw, 7 is an artificial blood vessel, 8 is an outer clamp, and 9 is an inner clamp.

  In the inflow cannula 1 in FIG. 5, the main body 2 is disposed so as to cover the outer peripheral surface of the support 3 except the abutting portion 3 b, whereas in the inflow cannula 1 b in FIG. A short-length support 3 is used, and most of the portion inserted into the heart (ventricle or atrium) has a single layer structure of the main body 2. In addition, in the inflow cannula 1b of FIG. 6, considering that there is a tendency that thrombus and endothelial cells tend to settle in an unstable state at the boundary between the support 3 and the main body 2 on the inner surface thereof. The length of the support 3 is adjusted so that such a boundary is generated at a site where the blood flow is fast, and the above-described unstable fixation can be suppressed. Moreover, in the inflow cannula 1c of FIG. 7, the support body is not used and the whole cannula has a single layer structure of the main body 2 only.

  Any of the above inflow cannulas 1, 1b and 1c can be used as an inflow cannula for an auxiliary artificial heart device, but the mechanical strength of the inflow cannula as a whole, to the heart (ventricle or atrium) Considering comprehensively the ease of insertion and the prevention of cell overgrowth at the tip of the inflow cannula, it is preferable to use an inflow cannula having a two-layer structure as shown in FIGS. .

  Since blood flows at a large flow rate inside the inflow cannula for the auxiliary artificial heart device and there is a low possibility that the blood stays in this portion, the inside of the inflow cannula is shown in FIGS. Even if a support having a normal smooth surface such as an inflow cannula is disposed, a thrombus is not usually formed. However, when a support having a smooth surface is disposed as shown in FIGS. 5 and 6, it is possible in some cases to further dispose the porous structure of the present invention on the radially inner side of the support. is there.

  Thus, in the case where the porous structure is disposed on the radially inner side of the support, when the inflow cannula is directly connected to the connector, the length of the porous structure can be covered up to the connector. By adjusting the length as possible, it is also possible to continuously cover the radially inner surfaces of both the inflow cannula and the connector with a single porous structure.

  Hereinafter, an example of attaching the auxiliary artificial heart device to the left ventricle will be described with reference to FIGS. Here, the auxiliary artificial heart device refers to the entire circulation assist device including the conduit assembly 10 to which the inflow cannula 1 is connected, the blood pump 11, the pump cable 12, the controller 13, the battery 14, and the like.

  FIG. 8 is a view of the auxiliary artificial heart device as an example, and shows a partial front view of the patient 16. Surgically, a blood pump 11 of the auxiliary artificial heart device is implanted in the chest cavity 17 of the patient. The auxiliary artificial heart device introduces blood from the patient's left ventricle into the blood pump 11 by the conduit assembly 10 with the inflow cannula 1, and carries the blood from the blood pump 11 to the patient's ascending aorta via the outflow graft 15. doing.

  The inflow cannula 1 is inserted into the left ventricle through the apical wall of the heart (actually, since it is inserted into the left ventricle, it cannot be seen from the outside, but in FIG. The shape is indicated by a solid line at the position where the cannula is inserted), and is fixedly connected to the patient's heart by sewing a cuff 5 placed at the distal end to the heart. It is connected to the aorta by sewing the end to the ascending aorta.

  The pump cable 12 extends from the blood pump 11 through the patient's body and extends to a compact controller 13 as shown in FIGS. 9A and B. The power source is a battery 14 and is connected to the controller 13.

  The controller 13 and the battery 14 connected to the pump cable 12 are stored compactly in a shoulder bag as shown in FIG. 10, for example, and can be carried by the patient himself / herself.

  Further, as another example of the present invention, a connector having the porous structure of the present invention is shown in FIGS. FIG. 11 is a perspective view of the connector, and FIG. 12 is a cross-sectional view of the connector. As shown in FIGS. 11 and 12, the connector 18 connects the blood pump and the artificial blood vessel together with the retaining ring 19. 12a of FIG. 12 is the porous structure of the present invention, and is fitted inside the connector 18 in the radial direction.

  EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, it cannot be overemphasized that this invention is not limited at all by these Examples, and is specified by a claim.

  Two animal experiments were performed using the inflow cannulas shown in FIGS. 2-5 (two inflow cannulas with two cows (age 3 months, male, body weight 86.5 kg when implanted; and age 3 Month, male, weight 88.8 kg when implanted). They were selectively sacrificed at POD65 (65 days after surgery) and POD63 (63 days after surgery), respectively. Implantation was performed with left thoracotomy and left ventricular pulsation. The inflow cannula was inserted into the left ventricle, the blood pump was placed in the thoracic cavity, and the outflow graft was end-to-side anastomosed to the descending aorta. After implantation, the blood pump was stably driven at a rotation speed of 1864-1897 rpm and power consumption of 4.4-6.1 W. The cows were in good health, and blood test results showed no decline in renal function, and no signs of infarction due to thrombus formation. Necropsy confirmed that tissue had grown on the textured surface of the inflow cannula placed in the left ventricle (FIG. 13). Further, as seen in FIG. 13, it was also confirmed that the growth of the endothelial cells was stopped at the abutting portion.

  In contrast, when an inflow cannula having a conventional smooth surface was used, a thrombus generated at the root of the cannula was often seen (FIG. 14), but was not seen in this experiment. This phenomenon was confirmed in the two cases conducted. As a result of pathological evaluation, it was found that the surface of the tissue on the textured surface was covered with endothelial cells. From this experiment, it was suggested that the endothelial cells of the left ventricular wall grew in a direction extending on the textured surface. Endothelial cells have a function of controlling blood coagulation, and it has been proved that high antithrombotic properties are obtained.

Furthermore, the inflow cannula produced in the example maintains a stable structure even when inserted into the left ventricle of a bovine in the above animal experiment, and no breakage or peeling is confirmed even at the time of necropsy. It was.
[Effect of the invention]
The porous structure in the present invention has a high mechanical strength, and furthermore, a large number of pores are formed not only on the surface but also in the thickness direction to obtain a three-dimensional structure having moderately large voids in the thickness direction. Therefore, a high anchoring effect is achieved, and stable placement of endothelial cells is achieved when placed at a site adjacent to a living tissue. Therefore, the structure of the present invention can be left for a long period of time even in a region where blood in a living body is likely to stay. It is possible to prevent inflow.

  Further, since the porous structure of the present invention can be produced independently, it can be produced independently as a device / tool having a textured surface, or the structure is produced separately, It is also possible to place and fix on a desired part of the blood contact surface of the auxiliary artificial heart device. And in this case, it is not necessary to introduce the apparatus / apparatus etc. where the porous structure is to be placed into the sintering furnace, and it is only necessary to place the separately manufactured structure at the site where the textured surface is desired. Therefore, it is possible to easily manufacture devices / instruments that have both a smooth surface portion and a textured surface portion without any deformation or roughening of these devices / instruments, dimensional accuracy, etc. .

DESCRIPTION OF SYMBOLS 1 Inflow cannula 1b with nonporous support body Inflow cannula 1c with nonporous support body Inflow cannula 2 which does not have a nonporous support body 3 Support body 3a Support body trunk | drum 3b Support body butting part 3c Support screw part 4 Sleeve 5 Cuff 6 Cuff holding screw 7 Artificial blood vessel 8 Outer clamp 9 Inner clamp 10 Conduit assembly 11 Blood pump 12 Pump cable 13 Controller 14 Battery 15 Outflow graft 16 Patient 17 Thoracic cavity 18 Connector 18a Porous structure 19 retaining ring

Claims (12)

A connector for connecting an inflow cannula or an artificial blood vessel and a blood pump in a blood circulation assistance device, wherein a porous structure is joined or fitted on a radially inner surface thereof, and the porous structure The connector as described above, wherein the body is formed of a metal material filament or a porous molded body made of a porous metal . The porous structure is formed by intersecting and / or contacting one or more metal material filaments, and these or these filaments are formed on the surface of the porous structure, The connector according to claim 1, wherein a hole is formed in a region surrounded by a line connecting the intersections and / or contact points adjacent to each other. The connector according to claim 1, wherein the porous structure is formed by spirally winding one or more metal material filaments so that a hollow tubular body is formed. The connector according to any one of claims 1 and 2, wherein the porous structure is made of a non-woven body formed of one or more metal material filaments. The connector according to claim 1, wherein the metal material of the metal material filament is selected from stainless steel, pure titanium, or a titanium alloy. The connector according to the porous structure, containing pores with an open area of ^{1.9 × 10 -5 mm 2 ~20mm 2} , any one of the preceding claims.   The connector according to any one of claims 1 to 6, wherein an antithrombogenic coating is applied to the surface of the filament or the surface of the porous molded body.   The connector according to claim 1, wherein the blood circulation assist device is an assistive artificial heart device.   A conduit assembly comprising a connector according to any one of claims 1-8.   An assistive artificial heart device comprising the conduit assembly according to claim 9. The next step, that is, (a) a step of spirally winding the filament from one end to the other end around the tubular core material,
(B) a step of spirally winding the same or another filament so as to intersect with the spiral wound in step (a),
(C) a step of sintering the tubular structure obtained by steps (a) and (b);
(D) A step of extracting the core material from the sintered tubular structure obtained in the step (c), and in addition to the above (a) to (d), the following (e):
(E) applying an antithrombogenic coating to the tubular structure obtained in step (d);
The method of manufacturing the connector as described in any one of Claims 1-3 and 5-8 containing this. In the next process, that is, (a) a pedestal, and an inner mold frame and an outer mold frame arranged concentrically thereon, the filaments are irregularly placed and then fixed, A step of obtaining a tubular structure in the form of a body, if necessary in addition to the above (a), the following (b):
(B) applying an antithrombogenic coating to the tubular structure obtained in step (a);
A method of manufacturing a connector according to any one of claims 1, 2, and 4-8.