JP5636857B2 - Flexible metal foil tape for bonding biological tissue and bonding method thereof - Google Patents

Description

  INDUSTRIAL APPLICABILITY The present invention is used for treating a diseased part or a damaged part of a living tissue, can adhere to the living tissue, and has a significantly higher adhesion to the living tissue than conventional medical jigs (stents, stent grafts, etc.). The present invention relates to an improved flexible metal foil tape for bonding biological tissue and a bonding method thereof.

  Stenosis is a disease in which a part of a defect contracts, and vascular dilation using a stent is used to treat the stenosis. An aortic aneurysm is a disease in which a part of a blood vessel expands, and a stained grant interpolation is used to treat an aortic aneurysm. The treatment using stents and stent grants is very minimally invasive because it does not require thoracotomy as in the case of artificial blood vessel replacement.

  Such stents or stent grants are not only those with optimized shapes and molding processes, but also metal stents coated with a polymer carrying a therapeutic agent, or biocompatible, especially antithrombotic. What formed the film | membrane which is excellent in the property on the base-material surface is known. Patent Documents 1 and 2 disclose a stent coated with a polymer that holds a therapeutic agent on the surface of a metal stent, and Patent Document 2 discloses a metal that is a stent base material and a polymer coating material. A method for improving the adhesiveness of is described. Patent Documents 3 to 7 disclose stents coated with a polymer such as tetrafluoroethylene or those surface-treated with diamond-like carbon as stents having excellent antithrombogenicity. Furthermore, Patent Documents 5 to 7 propose various surface treatment techniques for preventing diamond-like carbon from peeling from the stent substrate.

  However, conventional stents or stent grants are not intended for suturing or bonding when treating a diseased or damaged part existing in a living tissue (for example, a blood vessel or the like). The property is not taken into consideration and does not have sufficient adhesion. Therefore, when a conventional stent or stent grant is used for suturing or the like, blood leakage into the aneurysm (endoleak) resulting from incomplete adhesion with the artery, deviation from the installation location due to blood flow, etc. There is a problem that arises. The techniques disclosed in Patent Documents 5 to 7 described above are for suppressing the removal of diamond-like carbon from the stent base material, and are described, suggested, or anything about the adhesiveness with living tissue. The effect is completely unknown.

  Therefore, there is a strong demand for a stent that can be firmly bonded to a living tissue in the field of medical devices. Patent Document 8 discloses a stent in which a metal base material is coated with an organic material (for example, wet collagen, polyurethane, vinylon, gelatin, or a composite material thereof) that can adhere to a living tissue. Moreover, as a base material having a biocompatible substance on its surface, as shown in Patent Documents 9 and 10, a cell-adhesive base material having a surface coated with titanium oxide on a base material, and calcium phosphate or titanium oxide and a base material There are known hybrid complexes in which at least a part of a complex formed by chemically bonding with each other is further coated with a soft tissue affinity improving substance having an affinity for soft tissue.

JP 2005-65981 A JP 2007-236399 A JP-A-7-24072 Japanese Patent Laying-Open No. 2005-40219 JP 2006-521 A Japanese Patent Laid-Open No. 11-313884 JP 2001-29447 A JP 2007-229271 A Japanese Patent Laid-Open No. 2002-253204 JP 2006-130007 A

  However, although the stent described in Patent Document 8 can easily enhance the adhesion to living tissue, since the organic substance is coated on the surface of the base material, the above-mentioned stent is bonded at high temperature, ultrasonic vibration or high pressure. There remains a problem that the stent is easily displaced with respect to the living tissue due to the melting, flow and thickness variation of the organic matter. In addition, since the organic matter is interposed between the living tissue and the stent base material, it is necessary to finely adjust the bonding device and set conditions in terms of heat conduction, vibration transmission or pressurization. In some cases, the work required skill. The same problem also occurs in the hybrid complex disclosed in Patent Document 10 due to the presence of the soft tissue affinity improving substance.

  Moreover, the cell-adhesive base material obtained by surface-coating titanium oxide on the base material described in Patent Document 9 is a technique for solving the problem that the coating film is easily peeled off from the glass surface as a base material. There is no description or suggestion about the adhesiveness to the tissue, and it is completely unknown whether it can be applied as a stent material used for suturing or bonding biological tissues.

  On the other hand, according to the adhesion method described in Patent Document 8, using a stent material made of a metal base material having no coating film on the surface, or a stent material coated with diamond-like carbon described in Patent Documents 5-7. Although it is conceivable to adhere to a living tissue, the influence on the adhesion to the living tissue has not been studied at all. For this reason, almost no stent for living tissue adhesion by such a method has been known, and no actual application has been made.

  The present invention has been made to solve such a problem, and is used when performing adhesion by applying at least one of heat, vibration and pressure in order to treat a diseased or damaged part of a living tissue. As a base material for bonding, it does not shift to a living tissue, can perform an efficient bonding in a short time, and has a superior adhesiveness to a living tissue than before. An object of the present invention is to provide a flexible metal foil tape and an adhesion method thereof.

  As a result of intensive investigations on materials and properties that enable efficient bonding by applying at least one of heat, vibration and pressure, the inventor has determined a predetermined range for the bonding base material for living tissue. It was found that the above-mentioned problems can be solved by using a metal foil having a thickness and a surface roughness of the present invention, and the present invention has been reached.

That is, the configuration of the present invention is as follows.
(1) The present invention is used to adhere to a living tissue by applying at least one of heat, vibration, and pressure, and has a thickness of 5 to 300 μm and adheres to the living tissue. A flexible metal foil tape comprising a metal foil having a surface roughness of 0.05 to 5.0 μm in terms of arithmetic average roughness (Ra), wherein the flexible metal foil tape has a plurality of pores. It is provided avoiding a part that directly contacts a diseased part or damaged part of the living tissue, and an area ratio of all of the plurality of holes to the flexible metal foil tape is 50% or less. A flexible metal foil tape for bonding a living tissue is provided.
(2) The flexible metal foil tape for bonding a living tissue according to (1), wherein the present invention has a thickness of 10 to 100 μm, and the surface roughness of the bonding surface with the living tissue is an arithmetic average roughness ( Provided is a flexible metal foil tape for bonding a living tissue, characterized by comprising a metal foil having a thickness of Ra) of 0.07 μm or more and less than 2.0 μm.
(3) The tissue-bonding flexible metal foil tape according to (1) or (2), wherein the metal foil is a stainless steel foil or a NiTi alloy foil. Providing flexible metal foil tape.
(4) In the flexible metal foil tape for bonding a living tissue according to any one of (1) to (3), the present invention provides an antithrombogenic and / or anti-thrombogenic property on the bonding surface of the metal foil with the living tissue. Alternatively, the present invention provides a flexible metal foil tape for bonding to living tissue, wherein a highly adhesive coating is formed by surface treatment.
(5) The flexible metal foil tape for bonding to living tissue according to the above (4), wherein the coating is a diamond-like carbon film or a titanium oxide film. Provide metal foil tape.
(6) The present invention provides the flexible metal foil tape for bonding biological tissue according to (5), wherein the diamond-like carbon film uses a mixed gas of CH4 and CF4 with a composition ratio of CF4 of 70% or more. There is provided a flexible metal foil tape for bonding a living tissue, characterized in that it is a fluorine-containing diamond-like carbon (F-DLC) formed by a high-frequency plasma CVD method.
(7) The present invention, said during (4) to said metal foil in flexible metal foil tape biological tissue adhesive according to any one of (6) and the coating is Si, W, Ti, Provided is a flexible metal foil tape for bonding a living tissue, characterized in that an intermediate layer made of any one of Cr and a carbonized compound thereof is formed.
(8) The present invention provides the flexible metal foil tape for bonding biological tissue according to any one of (1) to (7), wherein the flexible metal foil tape is cylindrical so as to wrap biological tissue. A flexible metal foil tape for adhesion to living tissue is provided that is processed into a shape or a bag shape having at least one opening.

  According to the present invention, the material and structure of the stent for living tissue adhesion is made of a metal foil having a specific thickness and surface roughness, in particular, an adhesive tape made of stainless steel foil or NiTi alloy foil. In addition, the body can be freely deformed and bent according to the shape of the living tissue, and a high adhesive force can be obtained when efficient bonding is performed by applying at least one of heat, vibration, and pressure.

  In addition, according to the present invention, an antithrombogenic and / or highly adhesive film, particularly a diamond-like carbon or titanium oxide film is formed on the surface of the metal foil by the surface treatment, and thus has an adverse effect on living tissue. Can be suppressed, and at the same time, the adhesive force can be improved.

  The flexible metal foil tape for bonding a living tissue of the present invention is processed into a shape that can be easily laminated or contacted with a living tissue and can be firmly fixed to each other. Can be facilitated, and a significant improvement in adhesion to living tissue can be achieved.

It is a block diagram of the flexible metal foil tape for biological tissue adhesion | attachment used by embodiment of this invention, and the biological tissue adhesion | attachment apparatus. FIG. 2 is a cross-sectional view showing a configuration around a sample to be bonded particularly in the bonding apparatus for bonding a flexible metal foil tape for bonding a living tissue and a human tissue of the present invention. FIG. 2 (a) shows the flexible metal foil tape for biological tissue adhesion of the present invention in which the surface coating film is not formed, and FIG. 2 (b) shows the surface modified by the surface coating film being applied. The flexible metal foil tape for biological tissue adhesion of this invention is each shown. It is sectional drawing which shows the structure at the time of adhere | attaching the flexible metal foil tape for biological tissue adhesion | attachment and biological tissue which become embodiment of this invention using a lever. FIG. 3 (a) shows the flexible metal foil tape for biological tissue adhesion according to the present invention in which the surface coating film is not formed, and FIG. 3 (b) shows that the surface coating film has been applied to modify the surface. The flexible metal foil tape for biological tissue adhesion of this invention is each shown. It is a figure which shows the shape of the metal foil tape for biological tissue adhesion | attachment which provided the several void | hole which is another embodiment of this invention. It is a figure which shows the flexible metal foil tape for biological tissue adhesion which has various shapes which are another embodiment of this invention. FIG. 5A shows a cylindrical shape, and FIG. 5B shows a bag shape having one opening. By changing the ratio of CF ₄ is a Raman spectrum when performing coating of diamond-like carbon (DLC) on the substrate. X-ray photoelectron spectroscopy results showing C1s of C-C bonds peaks when changing the proportion of CF _4. X-ray photoelectron spectroscopy results indicating CF bond peak of F1s when changing the proportion of CF _4. It is a figure which shows the adhesive strength of the flexible metal foil tape for biological tissue adhesion | attachment of this invention surface-coated with DLC (F-DLC) and titanium dioxide which added the fluorine (F), and the blood vessel. It is an image photograph of the result of having observed the vascular tissue which remained on the stainless steel foil tape in which the coating film was formed after the peeling test with the scanning electron microscope (SEM).

  In the present invention, a metal foil is used as a base material for a flexible tape for bonding biological tissue. Since the bonding operation is performed by applying at least one of heat, vibration, and pressure, the organic material such as plastic is deformed, softened or melted during the bonding operation, and the living tissue is sewn. There arises a problem that it is easy to deviate from. In addition, since the thickness of the adhesive base material is likely to fluctuate, there is also a problem that an adhesive thickness sufficient to increase the adhesive strength cannot be secured. This is because an organic substance generally used for bonding has a property of being easily deformed by heating because its glass transition temperature, melting point or softening point is 150 ° C. or lower. In addition, since the hardness (or hardness) defined by the modulus of elasticity is inferior to inorganic materials such as metals and ceramics, even if vibrations or pressure such as ultrasonic waves are applied, the applied energy is lost. A sufficient adhesive strength cannot be obtained. In particular, when the bonding operation is performed by simultaneously applying heat and vibration (or pressure), this effect becomes significant. On the other hand, a base material made of an inorganic material such as ceramic or glass not only has heat resistance, but also can sufficiently secure energy transmission during application of vibration and pressure, and thus can improve adhesive strength. However, since these inorganic substances are very hard and brittle, even if the thickness is reduced, sufficient followability of the shape cannot be obtained with respect to soft biological tissue, and there is also a problem in handling property, It is difficult to apply as a substrate.

  The metal foil used as the base material of the flexible tape for bonding tissue of the present invention is not limited as long as the shape of the foil can be obtained. For example, steel, stainless steel, copper, nickel, titanium, aluminum, cobalt, zinc, nickel titanium alloy (NiTi alloy), etc. can be mentioned, but metals that are less likely to adversely affect biological tissues include steel, stainless steel. Nickel, titanium, aluminum or NiTi alloy can be used. Among them, stainless steel or NiTi alloy is most preferable because of excellent workability, low cost, excellent corrosion resistance, and high safety against living tissues.

  In this invention, the metal foil used as a base material of the flexible tape for biological tissue adhesion | attachment, more preferable stainless steel or NiTi alloy is the thing by which the organic substance or inorganic substances, such as ceramic and glass, are not coated on the surface. The metal foil with organic material coated on the surface is difficult to adhere as described above because the adverse effect of organic material cannot be completely removed during the adhesion work performed by applying at least one of heat, vibration and pressure. It becomes. In addition, the metal foil whose surface is coated with an inorganic material such as ceramic or glass is not only inferior in flexibility, but also has a problem in handling because the surface-coated ceramic is easily peeled off during the bonding operation. However, as will be described in detail later, a metal foil that has been surface-modified by surface treatment may be able to improve adhesion and antithrombotic properties, and as a base material for a flexible tape for adhesion to biological tissue, This is an effective configuration for producing the effect.

  The flexible metal foil tape for bonding biological tissue of the present invention is adapted to adhere to the biological tissue by applying at least one of heat, vibration and pressure after adapting to various shapes of the biological tissue. Therefore, it must not only be flexible enough to match the shape of the living tissue, but also be easy to handle. When the flexible metal tape for bonding biological tissue becomes thick, the flexibility is lost, and a gap is easily generated between the metal foil tape and the biological tissue after being attached. If the voids are present, the thermal conductivity or vibration transmission property deteriorates when applying at least one of heat, vibration, and pressure, and uniform pressurization becomes difficult, so that the bonding operation becomes difficult. In addition, if heat, vibration, or pressure energy is added more than necessary to obtain sufficient adhesion, the body tissue may be greatly damaged. Therefore, it is necessary to make the thickness of the flexible metal tape for bonding biological tissue of the present invention thinner than a predetermined value, but conversely, if it is too thin, the metal foil is likely to bend / wrinkle and handling is difficult. In the worst case, the metal foil tape is damaged during the bonding operation. In addition, when the living tissue is moved after bonding, the metal foil tape has no strength and is liable to be broken or cut, which may adversely affect the stitched portion. Therefore, the flexible metal tape for bonding biological tissue of the present invention needs to have a thickness of 5 to 300 μm, preferably 10 to 100 μm.

  The surface roughness of the flexible metal foil tape for bonding a living tissue of the present invention is an indispensable factor for enhancing the adhesion to the living tissue. That is, when the surface of the metal foil is smooth like a mirror surface, there is no anchor effect for adhesion to a living tissue, so that sufficient adhesion cannot be obtained. Further, if the surface of the base material is too smooth, it is likely to be displaced from the position of alignment with the living tissue during the bonding work, so that a process such as temporary fixing to the base material becomes an essential process, and the bonding work becomes complicated. On the other hand, if the surface roughness is too large, when at least one of heat, vibration, and pressure is applied, the thermal conductivity, vibration transmission, or uniform pressurization of pressure will be inferior, resulting in a decrease in adhesive strength. To do. In addition, there is a problem that it is very difficult to set conditions during the bonding operation, and efficient bonding cannot be performed.

  As physical quantity which prescribes | regulates the surface roughness of a base material, arithmetic roughness (Ra), the maximum roughness (Ry), or ten-point average generally measured based on the method described in JIS-B-0601 Although there is a roughness (Rz), in the present invention, the surface roughness of the flexible metal foil tape for bonding a biological tissue is defined by using the arithmetic roughness (Ra) capable of obtaining a strong relationship with the adhesiveness. . As for the flexible metal foil tape for biological tissue adhesion of this invention, surface roughness is 0.05-5.0 micrometers by arithmetic roughness (Ra), More preferably, it is the range of 0.07 micrometer or more and less than 2.0 micrometers. When the surface roughness Ra is less than 0.05 μm, there is no anchor effect on the surface of the metal foil, so that sufficient adhesion with a living tissue cannot be obtained. On the other hand, when the surface roughness Ra exceeds 5.0 μm, application by at least one of heat, vibration and pressure cannot be achieved as expected, and the adhesion cannot be improved. In addition, even if the application condition by at least one of heat, vibration, and pressure is finely adjusted, it is difficult to make the application of energy uniform across the entire surface of the adhesive, resulting in variations in the adhesive force with the living tissue.

  In the present invention, it is required by setting the thickness and the surface roughness Ra of the flexible metal foil tape for biological tissue adhesion to 10-100 μm and 0.07 μm or more and less than 2.0 μm which are more preferable ranges. Not only can reliable bonding be performed for biological tissue bonding applications, but the application can be expanded to biological tissues having various forms.

  The flexible metal foil tape for adhesion to living tissue of the present invention can form a film having a function of improving adhesion to living tissue and / or imparting antithrombogenicity on the surface by surface treatment. Specifically, it is a diamond-like carbon (DLC) coating film or a titanium oxide (TiOx) coating film. Also in the flexible metal foil tape for biological tissue adhesion which has these coating films, in order to maintain adhesiveness, surface roughness (Ra) is 0.05-5.0 micrometers, More preferably, it is 0.07 micrometer or more 2 Must be in the range of less than 0.0 μm.

  Diamond-like carbon (DLC) film is contained in amorphous carbon, and has high hardness, high wear resistance, low friction coefficient, insulation, high chemical stability, high corrosion resistance, high gas barrier properties, and high thermal conductivity. It has characteristics such as high biocompatibility and high infrared transparency. DLC films are widely used in electrical and electronic equipment, cutting tools, molds, automotive parts, optical parts, medical base materials (artificial bones, intraocular lenses, etc.), oxygen barrier films in polyethylene terephthalate (PET) bottles, etc. It is also known to have a function of imparting antithrombogenicity to living tissue.

  This amorphous carbon includes those that contain an element to be added (doped) and those that do not. The present invention includes both. Examples of elements added (doped) to amorphous carbon include Si, Ti, Cr, Al, Fe, Ni, Cu, Ag, Mo, W, F, H, and N.

  Examples of the DLC film forming method include an arc ion plating method, a sputtering physical vapor deposition method (PVD method), a high-frequency plasma CVD method, an ionization vapor deposition method, and the like. The characteristics of the DLC film differ depending on these film forming methods. In the present invention, a high-frequency plasma CVD method, which is a method capable of forming a denser film, is used to increase antithrombogenicity and prevent adverse effects on living tissues. However, the present invention is not limited to the high-frequency plasma CVD method. By optimizing various film formation conditions (flow rate, pressure, power, etc. of carbon-hydrogen gas), the other film formation methods described above can be used. It may be adopted.

  In the present invention, it is necessary to prevent or suppress the DLC film coated on the surface of the flexible metal foil tape for bonding to living tissue from being peeled off from the metal foil tape during bonding work and during use after bonding to living tissue. is there. The cause of the peeling is due to the internal stress of the DLC film. As a method for controlling and reducing the stress of the DLC film, the metal foil base material and the surface-coated DLC film of the flexible metal foil tape for biological tissue adhesion are used. An intermediate layer may be formed at the boundary. Since this intermediate layer can relieve high internal stress that is likely to occur when the DLC film is formed, the adhesion between the substrate and the DLC film is improved. Si, W, Ti, C and carbonized compounds thereof are used as the material of the intermediate layer.

  As another method for intentionally relieving the internal stress of the DLC film, addition of other elements to the DLC film is effective. In the present invention, in order to reduce the internal stress to the DLC film and suppress the peeling of the DLC film, the DLC film to which fluorine (F) is added among the elements to be added (doped) described above (F -DLC). Since the DLC film (F-DLC) to which fluorine (F) is added not only lowers the stress of the film but also softens than conventional DLC, the adhesion and followability of the metal foil tape to the metal foil base material improves.

This F-DLC film can not only prevent the DLC film from peeling, but also can improve the adhesion to living tissue by adjusting the amount of fluorine element added. In the F-DLC film, as the fluorine content increases, the contact angle in surface wettability increases and the surface energy decreases. Generally speaking, as the fluorine content increases, the surface energy decreases, the contact angle with the substrate decreases, and the adhesive strength tends to decrease. However, the flexible metal foil tape for bonding to living tissue of the present invention has been made on the basis of a new finding that adhesion to living tissue can be improved by forming an F-DLC film on the surface. Specifically, fluorine-doped diamond-like carbon (F-DLC) formed by a high-frequency plasma CVD method using a mixed gas of CH ₄ and CF ₄ in which the composition ratio of CF ₄ is 70% or more is doped. It has higher adhesion to living tissue than diamond-like carbon (DLC). The F-DLC film thus manufactured corresponds to an F / C ratio in the film of 30% or more.

In the metal foil tape for bonding tissue of the present invention, titanium dioxide (TiO ₂ ), which is exemplified as another example of the surface coating material, is typically titanium dioxide (TiO ₂ ). It is known that titanium dioxide is excellent in affinity to living tissue. Moreover, it is disclosed in the said patent document 9 that it has adhesiveness with respect to a cell. However, it is hardly known that it is a coating film capable of imparting high adhesiveness to such an extent that a biological tissue can be sutured, and the present invention has been made based on this new finding.

  A bonding apparatus used when bonding to a living tissue using the flexible metal foil tape for bonding a living tissue of the present invention will be described. FIG. 1 is an example of a bonding apparatus used in the bonding method of the present invention. In FIG. 1, the bonding apparatus 1 has a mounting body 1b having an L-shaped cross section and having a protruding base 1a at the bottom. A load cell 2 (load converter) is placed on the upper part of the projecting base 1a of the apparatus body 1b, and a vibrator (piezo actuator) 3 is placed on the upper part of the load cell 2. A ceramic heater 4 is disposed above the vibrator 3.

  Between the vibrator 3 and the ceramic heater 4, a sample S 1 having a laminated structure of a living tissue (for example, blood vessel) 6 and a flexible metal foil tape 7 for bonding a living tissue of the present invention is interposed via a sample contact portion 5. Placed. FIG. 2 is a cross-sectional view of an enlarged configuration of this situation. In the sample S1 shown in FIG. 2, (a) is the flexible metal foil tape for adhesion to living tissue of the present invention in which the surface coating film is not formed, and (b) is the surface coating film 7a is applied to the surface. 1 shows a modified flexible metal foil tape for bonding a living tissue according to the present invention.

  As shown in FIG. 2, the living tissue 6 and the flexible metal foil tape 7 for bonding to the living tissue are arranged on the upper part of the sample contact portion 5 in a state of being overlapped and brought into contact with each other. The flexible metal foil tape 7 is disposed and sandwiched between the vibrator 3 and the ceramic heater 4 in a state of being overlaid and brought into contact with each other. That is, the vibrator 4 and the ceramic heater 4 serve as a supporting means for laminating and supporting the living tissue 6 and the flexible metal foil tape 7 for bonding to living tissue between them.

  The tip of the ceramic heater 4 is in contact with the upper part of the flexible metal foil tape 7 for bonding biological tissue of the present invention. The flexible metal foil tape 7 for living tissue adhesion and the living tissue 6 receive heat and / or pressure from the ceramic heater 4. The vibrator 3 gives a predetermined vibration to the sample contact portion 5, the living tissue 6, and the flexible metal foil tape 7 for bonding the living tissue. The flexible metal foil tape 7 for living tissue adhesion, the living tissue 6, and the sample contact portion 5 are sandwiched between the vibrator 3 and the ceramic heater 4, and in this case, low energy vibration, heat and pressure are simultaneously applied. Yes. That is, the vibrator 3 (or the sample contact portion 5) and the ceramic heater 4 serve as application means for applying pressure to the laminated structure of the living tissue 6 and the flexible metal foil tape 7 for bonding to the living tissue. This is a means for applying heat to the laminated structure.

  Thus, the above-described bonding apparatus 1 has a structure and a mechanism capable of applying at least one of heat, vibration, and pressure, and can be used by combining those applying means as necessary. In particular, when any one of heat, vibration and pressure is used alone, even if low energy that cannot cause protein denaturation of living tissue is used, the vibration, heat and pressure should be combined into a composite energy. By this, protein denaturation is caused, and the living tissue 6 and the flexible metal foil tape 7 for bonding to living tissue can be bonded.

  As shown in FIG. 1, the ceramic heater 4 is connected to a ceramic heater controller 8 that controls the temperature of the ceramic heater 4. The ceramic heater controller 8 keeps the ceramic heater 4 at a set temperature. The vibrator 3 is connected to a piezo actuator driver 9 that controls the vibration of the vibrator 3. The piezo actuator driver 9 determines the vibration frequency and vibration amplitude of the vibrator 3.

  Further, a capacitance displacement meter (capacitance gap detector) 10 is disposed on the side surface of the ceramic heater 4. The capacitance type displacement meter 10 detects a gap between the vibrator 3 and the four ceramic heaters.

  Further, the bonding apparatus 1 includes an oscilloscope 11 that measures the voltage of the ceramic heater 4 and the like. Further, the bonding apparatus A has a thermography 12, and the thermography 12 measures and images the surface temperature of the flexible metal foil tape 7 for living tissue adhesion and the living tissue 6, whereby the operator can The temperature state of the surface of the flexible metal foil tape 7 for living tissue adhesion and the living tissue 6 can be diagnosed. In this way, the vibration amplitude, temperature, and pressure are measured using the oscilloscope 11, the thermography 12, and the load cell 2.

  The above-described bonding apparatus 1 includes an AD conversion device 13, and the AD conversion device 13 converts data of the load cell 2 into data such as voltage. The thermography 12 and the AD conversion device 13 are connected to a personal computer 14.

  In the configuration of FIG. 2, the adhesive strength between the living tissue 6 after bonding and the flexible metal foil tape 7 for bonding to living tissue (the coating film 7a in FIG. 2B) is required to be high. This adhesive strength can be improved by using the flexible metal foil tape 7 for bonding biological tissue of the present invention.

  On the other hand, at least one of heat, vibration, and pressure is not only applied to the interface between the living tissue 6 and the flexible metal foil tape 7 for bonding to living tissue, but also a part of the bonding apparatus 1, for example, FIG. 2 is also applied to an interface between the ceramic heater 4 and the metal foil tape 7 for bonding a biological tissue shown in FIG. In particular, when the interface between the living tissue 6 and the sample contact portion 5 is bonded to increase the bonding strength, the structure in which the living tissue 6 and the flexible metal foil tape 7 for bonding to the living tissue are bonded to each other. It becomes difficult to separate from the bonding apparatus 1. In the worst case, the living tissue 6 may be damaged. Therefore, it is necessary to minimize the adhesive strength at the interface between the living tissue 6 and the sample contact portion 5 so as not to adhere them. For this reason, the sample contact portion 5 is made of a fluororesin processed plate (for example, PTFE (polytetrafluoroethylene) plate) having low adhesion to the living tissue 6 or an organic surface treated with a fluororesin or a fluorosilane coupling agent. An inorganic plate or the like can be used. In the present invention, what can be used as the sample contact portion 5 is not limited to the above-mentioned fluororesin processed plate or the like, but a plate whose adhesive strength with the living tissue 6 is smaller than that of the flexible metal foil tape 7 for bonding to living tissue, Although a sheet may be used, it is preferable to select a sheet that maximizes the difference in adhesive strength between the two.

  In the bonding method for bonding to a living tissue using the flexible metal foil tape for bonding a living tissue of the present invention, each condition of heat, vibration and pressure applied by the bonding apparatus shown in FIG. It is the range of 250 degreeC, vibration frequency 1-60kHz, and pressure 1-150Mpa. Moreover, the conditions of the vibration total amplitude at the time of vibration provision are the range of 1-300 micrometers. When the temperature at the time of heating is less than 50 ° C., the vibration is less than 1 kHz, and the pressure is less than 1 MPa, not only in the case of single application, but also in the case where the vibration, heat and pressure are combined and applied as composite energy, Adhesive strength with living tissue cannot be sufficiently increased. Even if both appear to be bonded after the bonding operation, the flexible metal foil tape for bonding the living tissue easily peels off from the living tissue during use. Must be greater than or equal to the lower limit shown in. Further, when the temperature during heating exceeds 250 ° C., the vibration exceeds 60 kHz, or the pressure exceeds 150 MPa, damage to the living tissue increases. In addition, local peeling easily occurs due to stress generation or heat generation at the bonding portion of the living tissue, and the bonding strength to the living tissue is reduced as a whole, and there is a problem in terms of durability and reliability. Therefore, the vibration, heat, and pressure conditions must be equal to or lower than the upper limit values shown above.

  Further, the present invention has a feature that the bonding work time can be made in a short time. Although the bonding time varies depending on the above bonding conditions, the bonding time in the bonding method of the present invention is in the range of 2 to 60 sec, and preferably in the range of 10 to 300 sec.

  Even if the bonding apparatus 1 shown in FIGS. 1 and 2 is not used in the present invention, as shown in FIG. . 3A shows the flexible metal foil tape 22 for bonding a living tissue according to the present invention in which the surface coating film is not formed, and FIG. 3B shows that the surface coating film 22a is applied to modify the surface. The flexible metal foil tape 22 for biological tissue adhesion of this invention is shown, respectively. At least one of heat, vibration and pressure is applied through the lever 23. In FIG. 3, the surface of the jaw 23 arranged at the lower part so as to be in direct contact with the living tissue 21 is surface-treated with a fluororesin or a fluorinated coupling agent so as not to adhere to the living tissue 21. Is good. In addition, for the cantilever 23 arranged on the upper stage so as to be in direct contact with the flexible metal foil tape 22 for adhering to the living tissue, the upper cantilever 23 or the cantilever 23 for touching the cantilever 23 so as not to adhere to each other. A coating film that lowers the adhesiveness can be formed on the surface of the flexible metal foil tape 22.

  The flexible metal foil tape for bonding a living tissue of the present invention can be provided with a plurality of pores in the flexible metal foil tape in order to further increase the adhesive strength with the living tissue. FIG. 4 shows an example of the metal foil tape for bonding a biological tissue of the present invention provided with a plurality of holes. In the metal tissue tape 25 for bonding a biological tissue shown in FIG. 4, a plurality of holes 26 are formed so as to avoid a portion that directly adheres to a diseased part or damaged part 24 of the biological tissue. The plurality of vacancies 26 are for imparting an anchor effect to the metal tissue tape 25 for bonding a biological tissue, and a living tissue denatured or deformed by application of heat, vibration and / or pressure at the time of bonding is a plurality of vacancies 26. The contact area is increased by penetrating into the film, thereby producing an effect of increasing the adhesive strength. However, when the plurality of vacancies 26 are formed in a portion of the living tissue that is in direct contact with the diseased or damaged portion 24, even if heat, vibration and / or pressure are applied, the energy of the vacancies is not reduced. Since it becomes easy to escape from, the effect with respect to adhesiveness improvement becomes small.

The plurality of holes 26 shown in FIG. 4 can be formed in any shape such as a sphere, an ellipse, or a rectangle such as a rectangle, a square, or a polygon, and can be formed by a punching method using a press or an etching method. It can be easily processed into a predetermined shape. In the present invention, the area ratio occupied by all of the plurality of pores with respect to the flexible metal foil tape for adhesion to living tissue is required to be 50% or less. When this area ratio exceeds 50%, heat, vibration, or pressure energy tends to escape during the bonding operation, and the bonding strength cannot be increased with respect to the living tissue. In addition, the variation in the adhesive strength is increased, which may cause peeling or detachment of the flexible metal foil tape for bonding a living tissue. In the present invention, the area ratio occupied by all of the plurality of holes with respect to the flexible metal foil tape for biological tissue bonding is 50% or less, and at the same time, the area of all the holes needs to be 1 cm ² or less. It is. When the area of the pores exceeds 1 cm ² , heat, vibration, or pressure energy easily escapes during the bonding operation.

  The flexible metal foil tape for bonding biological tissue of the present invention can be processed into a cylindrical shape or a bag shape having at least one opening so that not only the planar shape shown in FIG. it can. In FIG. 5, the flexible metal foil tape for biological tissue adhesion processed in that way is shown. 5A is a cylindrical shape, and FIG. 5B is a bag shape having one opening.

  When a biological tissue such as a blood vessel is sutured, as shown in FIG. 5 (a), after the two blood vessels 29 are encapsulated by the cylindrical metal tissue flexible metal foil tape 28, the cylindrical shape Two blood vessels can be bonded and sutured at once using an adhesive jig. In that case, in order to prevent the fusion of the blood vessel tissues, a thin rod made of a material that is difficult to adhere to the blood vessel is inserted, and the rod inserted after the bonding shown in FIG. 2 is used. A sampling method may be adopted. Further, the flexible metal foil tape for bonding biological tissue can be used even when one blood vessel having a diseased part or a damaged part is sutured. In this method, since both sides of the blood vessel are adhered, adhesion is performed at the same time on a portion that is not a diseased part or a damaged part. However, since the flexible metal foil tape for bonding a biological tissue of the present invention is thin, Even if a flexible metal foil tape remains in a non-damaged part, it is considered that it does not become a major obstacle in practical use.

  Further, when it is desired to close only the end of the blood vessel, as shown in FIG. 5 (b), the use of a bag-like flexible metal foil tape 31 for adhering to biological tissue having a single opening assures secure stitching. Can do. In the present invention, the number of openings is not limited to one. According to the shape of the living tissue, a flexible metal foil tape for bonding a living tissue having two or more openings is used. Also good. For example, a bag-like flexible metal foil tape for bonding tissue, which has two openings, can be used for the same application as in FIG.

  EXAMPLES Next, although an Example demonstrates this invention, the scope of the present invention is not limited to these Examples.

[Examples 1 to 5, Comparative Example 1]
Using the bonding apparatus shown in FIG. 1, the living tissue was bonded with stainless steel foil or NiTi alloy foil. A fluororesin processed plate (PTFE plate) 5 was laid on the vibrator 3 in FIG. 2, and a stainless steel foil (SUS) or NiTi alloy foil 7 and a blood vessel 6 which is a living tissue were placed thereon in that order. The stainless steel foil (SUS) or NiTi alloy foil 7 had a thickness of 30 μm, a surface roughness (Ra) of 0.07 μm, and a strip shape of 8 mm × 20 mm. This stainless steel foil or NiTi alloy is not surface-coated. The blood vessel 6 was an 8 mm × 20 mm strip, and the stainless steel foil 7 and the blood vessel 6 were overlapped and contacted with each other by 5 mm. The size of the pressing surface of the ceramic heater 4 was 4 mm × 1 mm. As described above, adhesion between the PTFE plate 5 and the blood vessel 6 did not occur. Further, as Comparative Example 1, in place of stainless steel foil (SUS) or NiTi alloy foil, 30 μm-thick wet collagen (a type 1 collagen made by Koken is cross-linked with glutaraldehyde) is used to adhere to a blood vessel. It was.

  In the case of no vibration addition, the bonding conditions are an adhesion temperature of 130 ° C. or 200 ° C., an adhesion pressure of 15 MPa or 10 MPa, an adhesion time of 120 sec, and in the case of vibration addition, an adhesion temperature of 230 ° C., an adhesion pressure of 2.5 MPa, adhesion 120 seconds. The vibration frequency was 12 kHz and the vibration amplitude was 2 μm.

Table 1 shows the adhesion test results of stainless steel foil (uncoated). The adhesive strength was evaluated by holding a test piece in which a stainless steel foil, NiTi alloy foil or collagen foil and a blood vessel were bonded with a check fixed to a load transducer, and then applying a shear tensile load at a shear tensile speed of 4 mm / min. The maximum tensile load at room temperature was measured. Since the adhesive area is 1 mm × 4 mm, the adhesive strength was obtained by dividing the maximum tensile load at room temperature by 4 mm ² .

  As shown in Table 1, each of Examples 1 to 5 has a sufficient adhesion to blood vessels. The difference between SUS and NiTi alloy as metal foil did not appear as a difference in adhesive strength, and both showed high adhesive strength (contrast with Example 2 and Example 4). Example 3 shows that adhesiveness with blood vessels can be further improved by using a composite energy combining heat, pressure, and vibration. In addition, the order of the test pieces was changed, and when the blood vessel was placed on the stainless steel foil (SUS), it was adhered (Example 5), and when the stainless steel (SUS) was placed on the blood vessel (Example) 2) Higher adhesive strength than On the other hand, Comparative Example 1 in which adhesion to the blood vessel was performed with a foil made of an organic substance had a lower adhesive strength than Example 2. Furthermore, in Comparative Example 1, since a deviation from the overlapped bonding distance of 5 mm was observed as 1.5 mm, it was found that it was difficult to bond a fine portion under the bonding conditions employed. On the other hand, in Examples 1-5, the shift | offset | difference of an adhesion location is less than 0.2 mm, and the significant improvement effect is seen with respect to shift | offset | difference suppression.

[Examples 6 to 13, Comparative Examples 2 to 7]
Using stainless steel foil (SUS) having a different thickness and surface roughness (Ra), adhesion to a blood vessel was performed in the same manner as in Example 2, and the adhesion was evaluated based on adhesion strength. Stainless steel foils having different surface roughness Ra were obtained by changing the surface roughness of the forging roll during processing, or by performing a new roughening treatment such as shot blasting or etching after the processing. The evaluation results are shown in Table 2. Table 2 also shows the bonding conditions when the actual bonding operation was performed.

  If the surface roughness Ra of the stainless steel foil is in the range of 0.05 to 5.0 μm, the adhesive strength with the blood vessel can be increased and the adhesiveness can be maintained. No peeling occurred (Examples 6 to 13). In particular, Examples 7 to 11 having a surface roughness Ra of 0.07 μm or more and less than 2.0 μm exhibit an adhesive strength of 0.28 MPa or more and have excellent adhesiveness. On the other hand, in Comparative Example 2 having a surface roughness Ra of 0.03 μm, the adhesive strength was significantly reduced to less than 0.02 MPa, and peeling occurred. Even if the bonding conditions were changed, as shown in Comparative Example 3, sufficient bonding strength could not be obtained. Further, as shown in Comparative Examples 4 to 5, even when the surface roughness Ra was 5.3 μm, no improvement in adhesive force was observed. The surface of the stainless steel foil becomes too rough, so that the sufficient anchoring effect for enhancing the adhesive force cannot be obtained, and in addition, the energy of heat, pressure and / or vibration is efficiently applied to the interface between the stainless steel foil and the blood vessel. It is thought that it was not transmitted. Furthermore, the improvement of the adhesiveness was examined according to the bonding conditions in which the heat and pressure and / or vibration application energy was higher than those in Comparative Examples 4 to 5, but when the application energy was increased, the local minute portion of the adhesion surface was browned. Spots were observed and the adhesion could not be improved. Since peeling occurred at the minute portion, the adhesive strength could be improved only slightly even when the bonding conditions were changed. The cause of this is thought to be due to local concentration of heat, pressure, and vibration energy, but details are unknown.

  In Comparative Example 6 shown in Table 2, since the thickness of the stainless steel foil is 3 μm, the flexibility is high and the adhesive strength is also high. However, the operability was extremely poor because creases and wrinkles occurred during the bonding operation. Therefore, the stainless steel foil of Comparative Example 6 is not suitable for suturing to a complex-shaped living tissue. In addition, the stainless steel foil of Comparative Example 7 is not sufficiently flexible because the thickness is very thick at 400 μm. In addition, since the heat and pressure were not sufficiently transmitted to the interface between the stainless steel foil and the blood vessel, the adhesive strength was low. The stainless steel foil of Comparative Example 7 may be used for adhesion of a flat biological tissue, but is not suitable as a metal foil tape for adhesion to a biological tissue having a curved surface or a complicated shape. In addition, in order to obtain a sufficient adhesive strength using the stainless steel foil of Comparative Example 7, it is necessary to increase the energy of application of heat, pressure and / or vibration, or to increase the bonding time. Can not do.

[Example 14]
Using a surface-coated stainless steel foil (SUS), adhesion to a blood vessel was performed in the same manner as in Examples 1 to 5, and the adhesiveness was evaluated by the adhesive strength. As a coating material, of (1) DLC (fluorine (F) without _{doping), (2) CF 4 20} % F-DLC with raw material gas (CH80%), (3) CF 4 40% (CH60%) F-DLC using source gas, (4) F-DLC using CF ₄ 60% (CH 40%) source gas, (5) F-DLC using CF ₄ 70% (CH 30%) source gas , (6) F-DLC using a raw material gas of 80% CF ₄ (CH 20%), and (7) titanium dioxide (TiO ₂ ). A stainless foil tape having a DLC film, an F-DLC film, and a TiO ₂ film was prepared as follows.

DLC film size 20 mm × 8 mm, a thickness of 30 [mu] m, surface roughness (Ra) of 0.07μm stainless steel (SUS316) to the surface of the foil, using a high-frequency plasma CVD apparatus, the ratio of CF ₄ Coating was carried out by adjusting the total flow rate (CH ₄ + CF ₄ ) to 0%, 20%, 40%, 60%, 70%, and 80% to form a film with a thickness of 0.2 μm. In order to improve the adhesion strength of the DLC film, silicon (Si) was coated as an intermediate layer on the surface of the stainless steel foil by sputtering before the DLC film was formed. The DLC film was analyzed by X-ray photoelectron spectroscopy (XPS) measurement. Separately, in order to grasp the film formation state of the DLC film, a DLC thin film was deposited on a silicon (Si) substrate, and measurement was performed with a laser Raman spectrophotometer. The Si substrate was immersed in acetone in advance and subjected to ultrasonic cleaning for 10 minutes, and DLC film formation was performed under the same conditions as in the case of stainless steel foil. Table 3 shows the coating conditions for the DLC film.

FIG. 6 shows the dependency of the Raman spectrum on the CF ₄ flow rate. The Figure 6, the D band near 1350 cm ^-1, 1550 cm G band near ^-1 _CF 4 _60% to _(CH 4 40%) is confirmed, it was found that DLC is deposited. However, since no peak could be confirmed with CF ₄ 80% (CH ₄ 20%), it was found that the film was not a DLC film.

FIG. 7 shows the XPS result of the C—C bond peak of C1s, and FIG. 8 shows the XPS analysis result of the C—F bond peak of F1s. FIG. 7 shows that the C—C bond decreases as the proportion of CF ₄ is increased. Further, FIG. 8 indicates that the C—F bond increases as the proportion of CF ₄ increases.

From the results of Raman spectroscopic analysis shown in FIG. 6, it was confirmed that the samples up to 60% CF ₄ (CH ₄ 40%) were DLC, but the peak of DLC was confirmed at 80% CF ₄ (CH ₄ 20%). There wasn't.

Here, looking at the result of the XPS C1s peak, the C—C bond decreases as the proportion of CF ₄ increases. Looking at the F1s peak, it was confirmed that the CF bond was increased by increasing the proportion of CF ₄ . The C—F bond is considered to be mainly composed of CF ₂ and CF ₃ , and when many of these bonds exist, the hydrophobicity of the surface of the DLC film becomes high.

As described above, when CF ₄ is 60% or less, it is confirmed that it is diamond-like carbon, and when CF ₄ is 80% or more, it is no longer strictly diamond-like carbon. Was confirmed. However, in the following, for convenience, the material obtained when CF ₄ is 0% is DLC, and the material obtained when CF ₄ is included (including the case where CF ₄ is 80% or more) is referred to as F-DLC. Call it.

  The stainless steel foil tape having the DLC film and F-DLC film produced as described above had a surface roughness (Ra) in the range of 0.05 to 0.09 μm. Since the coating film is very thin, it can be formed with almost no difference from the surface roughness (Ra) of the stainless steel foil tape before it is formed.

Next, a method for producing a coating film using titanium dioxide (TiO ₂ ) will be described. Same size as above (20mm × 8mm), subjected to ultrasonic cleaning in thickness (30 [mu] m) and surface roughness (Ra) of stainless steel having a 0.07μ m (SUS316) 10 min substrate with acetone, TiO ₂ Film formation was performed to apply the coating. A high frequency magnetron sputtering apparatus was used for film formation, and the sputtering gas was argon (Ar). Table 4 shows the conditions.

The stainless steel foil tape on which the TiO ₂ coating film was formed under the conditions shown in Table 4 had a surface roughness (Ra) of 0.08 μm.

The stainless steel foil tape having the DLC film, F-DLC film and TiO ₂ film obtained as described above was adhered to the blood vessel by the same method as in Examples 1-5. Adhesion with the blood vessel was performed at a heater preheating temperature of 125 ° C. and a vibration preheating temperature of 50 ° C., an adhesion temperature of 120 ° C., a pressure of 125 MPa, a vibration frequency of 11.84 kHz, a vibration amplitude of 5 μm, and an adhesion time of 120 seconds. The adhesive strength between the stainless steel foil tape having these coating films and the blood vessels was measured by the same method as in Examples 1 to 4. The number of samples was 5 or more under each condition. The measurement result of adhesive strength is shown in FIG. FIG. 9 also shows the adhesive strength of a sample that is bonded to a blood vessel under the same bonding conditions using a stainless steel foil tape on which a coating film is not formed.

As shown in FIG. 9, when CF ₄ is 60%, it has almost the same adhesive strength as the uncoated stainless steel foil tape, and when CF ₄ is 70% or more, the adhesive strength is improved. Furthermore, it was found that the stainless steel foil tape having the TiO ₂ film has higher adhesive strength than the F-DLC film.

In this example, the stainless steel foil tape on which the coating film was formed and the blood vessel were bonded and peeled, and then the blood vessel remaining on the coated stainless steel was observed with a scanning electrophotographic microscope (SEM). Measurement conditions are a magnification of 1000 times and an acceleration voltage of 1 kV. FIG. 10 shows an SEM image photograph observed on a stainless steel foil tape having an F-DLC film formed using a source gas of CF ₄ 80% (CH ₄ 20%) or more. In the SEM image photograph shown in FIG. 10, tissue that appears to be blood vessels remains on the surface of the stainless steel foil tape on which the F-DLC coating film is formed, and the boundary between the remaining tissue and the remaining surface of the tissue The surface is observed.

In FIG. 10, the vascular tissue 15 and the stainless steel foil tape 16 are observed, showing that the vascular tissue 15 is a mesh, and it can be seen that the fibers are about 1 μm thick. Further, the surface where the adhesive surface between the stainless steel foil tape and the blood vessel was forcibly peeled was cohesive failure, and an F-DLC film was formed using a raw material gas of CF ₄ 80% (CH ₄ 20%) or more. It was confirmed that the stainless steel foil tape has high adhesiveness.

  From this result, the metal foil tape formed with this coating can be adhered to the blood vessel and is stronger than the adhesive strength between the blood vessels. For example, the metal foil tape is adhered to the blood vessel, It is possible to prevent the tape from shifting.

From the result of FIG. 10, F-DLC or TiO ₂ using a source gas with CF ₄ of 70% or more (CH ₄ 30% or less) is used as the material of the first coating film 7a shown in FIG. It is clear that very strong adhesion can be realized by using. In addition, these coating films have antithrombogenic characteristics and do not have an adverse effect on living tissue, so that they are very useful as a flexible tape for bonding to living tissue.

On the other hand, the DLC film shown in FIG. 9 and the F-DLC film using the raw material gas with CF ₄ of 60% or less (CH ₄ 40% or more) have the same or slightly lower adhesive strength than the uncoated stainless steel foil tape. There is a tendency. However, since the metal foil tape having these coating films also has anti-thrombogenic properties, it can be used as a flexible tape for adhesion to living tissue. The metal foil tape having these coating films may be applied as a temporary adhesive tape used for the purpose of facilitating peeling after being used for a predetermined period after being bonded.

[Example 15]
Stainless steel foil tape in which a cut is made in the aorta of a living pig and an F-DLC film containing fluorine (F) is formed on the surface using a raw material gas of CF ₄ 80% (CH ₄ 20%) or more Was glued into the blood vessels of the pig. This stainless steel foil tape has a thickness of 30 μm, a surface roughness (Ra) of 0.4 μm, and is cut into a strip shape of 8 mm × 20 mm. The bonding conditions were a temperature of 120 ° C., a pressure of 125 MPa, a vibration frequency of 12 kHz, a vibration amplitude of 5 μ, and a bonding time of 50 sec. Adhesion includes (1) a step of cutting and cooling a blood vessel of a porcine aorta in half, (2) a step of inserting a stainless steel foil tape having an F-DLC film into the blood vessel, and matching the shape of the blood vessel, And a step of bonding the stainless steel foil tape having the F-DLC film using the bonding apparatus A shown in FIGS. 1 and 2, and (4) cooling the stainless steel foil tape having the bonded blood vessel and the F-DLC film. The process of suppressing tissue damage was performed. As a result, it was possible to attach the stainless steel foil tape having the F-DLC film to the blood vessel without damaging the blood vessel by using the bonding apparatus 1 shown in FIGS. Moreover, it confirmed that the stainless steel foil tape and the blood vessel which have the F-DLC film | membrane adhered under the pulsation of about 1 hour did not peel off.

In Examples 14-15, it forms on the metal foil tape 7 which has the 1st coating film 7a previously with the other apparatus (means) which is not mounted | worn with the bonding apparatus 1. FIG. The coated metal foil tape 7 is attached to the supporting means in the bonding apparatus 1. However, a coating means for forming these coating films can also be provided in the bonding apparatus. In that case, a high-frequency plasma CVD apparatus or the like (in the case of DLC or F-DLC) or a high-frequency magnetron sputtering apparatus or the like (in the case of TiO ₂ ) at a location away from the vibrator 3 or the ceramic heater 4 shown in FIGS. A similar mechanism is provided. Thus, after the first coating film 7a is formed on the surface of the metal foil tape 7, the living tissue 5 and the coated metal foil tape 7 may be bonded with the configuration shown in FIG.

  Further, as the applying means for applying pressure, the applying means for applying vibration, and the applying means for applying heat, various configurations other than the above-described configurations can be applied. It is clear that the same effect can be obtained by that. At that time, at least any one of heat, vibration, and pressure is applied, whereby the metal foil tape 7 and the living tissue (for example, blood vessel or the like) 6 can be bonded.

In Examples 14-15, the coating which consists of one type of material was formed in 1 surface of the flexible metal foil tape for adhesion | attachment for biological tissues. In the present invention, it is possible to use two or more types. For example, a first coating film made of F-DLC having a high F concentration (F-DLC with CF ₄ of 70% or more) is formed in a limited region including a diseased part or a damaged part of a living tissue, and the peripheral region thereof is formed. Is a metal foil tape on which a second coating film made of F-DLC or DLC (F-DLC or DLC with CF ₄ of 40% or less) having a low F concentration is formed. By using the metal foil tape having such a configuration, only a limited region including a diseased part or damaged part of a living tissue can be firmly bonded, whereas the periphery other than that part reinforces the bonded part. It is sufficient that there is only an adhesive force, and it has the effect of suppressing excessive deformation and adverse effects of the living tissue due to adhesion. Such a metal foil tape uses DLC or F-DLC as a coating material, and by simply adjusting the component (CF ₄ / CH ₄ ) of the raw material gas, Since the coating film is formed, it can be easily produced.

[Example 16]
As shown in FIG. 4, the biological tissue bonding metal foil tape 25 provided with a plurality of holes 26 was bonded into the blood vessels of the living porcine aorta using the same method and bonding conditions as in Example 13. This metal foil tape is made of uncoated stainless steel, has a thickness of 30 μm, a surface roughness (Ra) of 0.4 μm, and is cut into a strip shape of 8 mm × 20 mm. A plurality of pores, except for a portion that directly adheres to a diseased or damaged portion of a biological tissue of a blood vessel (portion indicated by hatching in FIG. 4), a pore having a diameter of 0.1 mm on both sides, A plurality of films are formed by etching through a mask. In this example, the ratio of all of the plurality of holes to the uncoated stainless steel foil tape was about 25%.

  The sample after the bonding operation was able to attach the uncoated stainless steel foil tape provided with a plurality of holes to the blood vessel without damaging the blood vessel. The initial bond strength was about 10% higher than that obtained in Example 13, which is because some of the vascular tissue deformed during bonding penetrates into a plurality of pores, resulting in bond strength. This is thought to be due to the effect of increasing It was also confirmed that the uncoated stainless steel foil tape adhered under the pulsation of about 1 hour did not peel from the blood vessel.

[Example 17]
As shown in FIG. 5 (a), using a flexible metal foil tape 28 for bonding biological tissue of a cylindrical strip, two blood vessels 29 are inserted from both ends of the metal foil tape and abutted to each other. The vessel was sutured. The flexible metal foil tape for cylindrical tissue bonding used in this example is made of uncoated stainless steel foil, has a thickness of 30 μm, an outer diameter of 0.2 mm, and a length of 4 mm. Met. This stainless steel foil cylindrical tape is obtained by forming an extruded tube of a cylindrical strip into an outer diameter of 0.2 mm by a method such as ironing. The inner surface corresponding to the adhesion surface with the blood vessel was adjusted so that the surface roughness (Ra) was 1.0 μm. As shown in (a) of FIG. 5, as the bonding jig 30, a semi-circular processed jaw was used in accordance with the shape of the cylindrical metal foil tape. The bonding conditions were a temperature of 200 ° C., a pressure of 10 MPa, a bonding time of 200 sec, and application by ultrasonic vibration was not used in combination.

  After the bonding operation, the two blood vessels cooled to room temperature were firmly bonded and sutured. Furthermore, even if both ends of the two blood vessels after suturing were grasped and pulled in the reverse method, they were not separated from the bonded and sutured portions of the two blood vessels, but were cut and separated at different locations. Thus, it was confirmed that the flexible metal foil tape for bonding biological tissue of a cylindrical strip according to the invention is an effective adhesive base material for blood vessel adhesion and suturing.

  As described above, the flexible metal foil tape for bonding biological tissue of the present invention can specifically adhere to blood vessels as human tissue. Since the present invention can be applied not only to blood vessels but also to other human tissues by optimizing the bonding apparatus and bonding conditions, its application range is wide. In addition, the present invention has high flexibility so that it can be freely and easily adapted to the shape of the human body tissue, and can also be processed into a free shape of a cylindrical strip or a bag strip. Is significantly improved in that it can be applied to various purposes.

DESCRIPTION OF SYMBOLS 1 ... Bonding apparatus of biological metal tissue and flexible metal foil tape for biological tissue adhesion, 1a ... mounting body, 1b ... mounting body, 2 ... load cell (load converter), ... -Vibrator (piezo actuator), 4 ... ceramic heater, 5 ... sample contact part, 6, 21, 27, 29 ... biological tissue (blood vessel), 7, 22, 25 ... biological tissue adhesion Flexible metal foil tape, 7a, 22a ... coating film, 8 ... ceramic heater controller, 9 ... piezo actuator (vibrator) driver, 10 ... capacitance displacement meter (capacitance) Mold gap detector), 11 ... oscilloscope, 12 ... thermography, 13 ... AD converter, 14 ... personal computer, 15 ... vascular tissue, 16 ... stainless steel foil, 23 ... ..Kanko, 2・ ・ ・ Disease part or damaged part of biological tissue, 26 .. Hole, 28 .. Flexible metal foil tape for cylindrical biological tissue adhesion, 30... Adhesive jig, 31. Flexible metal foil tape for living tissue adhesion.

Claims (8)

It is used for adhering to a living tissue by applying at least one of heat, vibration, and pressure, and has a thickness of 5 to 300 μm, and the surface roughness of the adhesive surface with the living tissue is arithmetic A flexible metal foil tape comprising a metal foil having an average roughness (Ra) of 0.05 to 5.0 μm,
In the flexible metal foil tape, a plurality of holes are provided to avoid a portion that directly contacts a diseased or damaged part of the living tissue, and all of the plurality of holes are the flexible metal. The area ratio to the foil tape is 50% or less.
A flexible metal foil tape for bonding biological tissue.   The flexible metal foil tape for biological tissue bonding according to claim 1, wherein the thickness is 10 to 100 μm, and the surface roughness of the adhesive surface with the biological tissue is 0.07 μm or more in terms of arithmetic average roughness (Ra) 2. A flexible metal foil tape for bonding a living tissue, characterized by comprising a metal foil of less than 0.0 μm.   3. The flexible metal foil tape for biological tissue adhesion according to claim 1 or 2, wherein the metal foil is a stainless steel foil or a NiTi alloy foil.   The flexible metal foil tape for biological tissue adhesion in any one of Claims 1-3 WHEREIN: An antithrombogenic and / or highly adhesive film is surface-treated by the surface of the metal foil with the biological tissue. A flexible metal foil tape for bonding a living tissue, characterized by being formed.   The flexible metal foil tape for bonding to living tissue according to claim 4, wherein the coating is a diamond-like carbon film or a titanium oxide film.   6. The flexible metal foil tape for bonding biological tissue according to claim 5, wherein the diamond-like carbon film is formed by a high-frequency plasma CVD method using a mixed gas of CH4 and CF4 in which the composition ratio of CF4 is 70% or more. A flexible metal foil tape for adhesion to biological tissue, characterized in that it is a fluorine-containing diamond-like carbon (F-DLC). The flexible metal foil tape for bonding biological tissue according to any one of claims 4 to 6, wherein any one of Si, W, Ti, Cr and a carbonized compound thereof is provided between the metal foil and the coating. A flexible metal foil tape for bonding a living tissue, characterized in that an intermediate layer composed of two layers is formed.   The flexible metal foil tape for biological tissue adhesion according to any one of claims 1 to 7, wherein the flexible metal foil tape has a cylindrical shape or at least one opening so as to enclose the biological tissue. A flexible metal foil tape for bonding a living tissue, which is processed into a shape.

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