JP2009028150A - Cuff member and cuff member unit - Google Patents

Abstract

In a cuff member having a flange portion that overlaps an outer surface of a living body, and a living body insertion tube is inserted through the flange portion, a force applied from the living body insertion tube to the flange portion is widely dispersed in the flange portion. A cuff member and a cuff member unit are provided.
A tube 6 is inserted through a flange portion 3 of a cuff member 2 constituting a cuff member unit 1. An annular body 5 made of a flexible synthetic resin material is provided at the corner between the base portion 3 b of the flange portion 3 and the tube 6.
[Selection] Figure 1

Description

  INDUSTRIAL APPLICABILITY The present invention is useful for living skin puncture sites such as blood circulation using an auxiliary artificial heart, which is a therapy for subcutaneous insertion of cannulas and catheters, peritoneal dialysis therapy, central parenteral nutrition, transcannula DDS, and transcatheter DDS. The present invention relates to a cuff member and a cuff member unit.

  The cannulas and catheters used in the recently developed therapies such as assisted ventricular assist and peritoneal dialysis are different from urethral catheters, transgastrointestinal nutrition methods, and airway management techniques that are inserted and placed in vessels open to the outside world. In addition, it is necessary to place the in vivo by inserting after inserting the subcutaneous tissue. When indwelling in a living body for a long period of time, a cuff member (also called a skin cuff or the like) is used in order to prevent bacteria from entering the living body and volatilization of body fluid moisture. Sealing of the insertion part is performed. Conventionally, in a blood circulation method using an auxiliary artificial heart, a fabric velour mainly made of polyester fiber is wound around a piercing cannula, the fabric velour and the subcutaneous tissue are fixed at the piercing portion, and the cannula is placed. Even in peritoneal dialysis therapy, a fabric velor made of polyester fiber is fixed as a cuff member at the skin insertion position of the catheter, and the catheter is placed by suturing the subcutaneous tissue so as to press the cuff member. . Some of these fabric velours have been impregnated with collagen to aim for stronger adhesion. There is also a method of fixing a cuff member made of a member excellent in biocompatibility to the subcutaneous tissue of the insertion portion.

  However, since the blood circulation method using the auxiliary artificial heart is a therapy for assisting blood circulation with a pulsation pump installed outside the patient's body, the vibration of the pulsation pump corresponding to about 1.5 Hz is transmitted to the cannula. That is, the insertion portion of the cannula is constantly subjected to a mechanical load due to vibration. Furthermore, stress that is intended to peel the subcutaneous tissue and the cuff member is also generated by the change of the patient's body position and the movement of the cannula during the sterilization operation of the insertion portion. Typical examples of troubles that are considered to be caused by a decrease in the adhesion between the cuff member and the subcutaneous tissue due to these stress loads include infections such as tunnel infections. The number of experiences has become very large. Considering the effects of bacterial infections on complications and heart failure, it can be said that the development of a cuff member that can prevent infection is urgently needed in this therapy.

  Similarly, a cuff member has a big problem also in peritoneal dialysis therapy in which a catheter is placed for a long time by performing subcutaneous insertion. That is, in this therapy, the catheter is placed in the abdominal cavity in order to inject and drain dialysate, but the action of the living body recognizing the catheter as a foreign substance works to eliminate the catheter, and the subcutaneous tissue adheres to the catheter. Without this, a downgrowth phenomenon occurs in which the epidermis enters the abdominal cavity along the catheter. This downgrowth pocket makes it difficult for the disinfectant to reach, causing epidermal inflammation and tunnel infection, and ultimately leading to peritonitis. Considering that there is a report that the incidence of SEP (sclerosing ulcerative peritonitis) is high in patients who frequently experienced Pseudomonas aeruginosa peritonitis, infection prevention by improving the cuff member is a major effect of peritoneal dialysis therapy. It can be said that it is a problem.

  For this reason, as described above, cuff members mainly composed of collagen have been developed. In the case of such cuff members, liquids such as physiological saline, alcohol, isodine, blood, and body fluids are absorbed. As a result, the volume is reduced, and it is difficult to grow the subcutaneous tissue at the catheter insertion portion, and as a result, the effect of suppressing the downgrowth is not obtained.

  WO 2005/084742 A1 includes a flange portion that overlaps the outer surface of a living body, and a cylindrical portion that is erected from the flange portion, and these have a porous three-dimensional network structure that is communicated. A cuff member is described.

In the cuff member of the same publication, cells easily invade and engraft from the living body subcutaneous tissue into the inside of this network structure, and a capillary vessel is constructed, so that the cuff member and the subcutaneous tissue are robust. Adhere. At this time, since the flange portion adheres to the subcutaneous tissue over a wide range around the cylindrical portion, the downgrowth action of the epidermis hardly reaches the cylindrical portion, and the downgrowth can be effectively suppressed.
WO 2005/084742 A1 publication

  The present invention has a flange portion that overlaps with the outer surface of a living body, and in a cuff member in which the living body insertion tube is inserted into the flange portion, the force applied from the living body insertion tube to the flange portion is widely dispersed in the flange portion. An object is to provide a configured cuff member and a cuff member unit.

  The cuff member according to claim 1 is a cuff member having a flange portion that overlaps an outer surface of a living body and an opening for inserting a living body insertion tube provided in the flange portion. An annular body fixed to the edge of the opening and having a living body insertion tube insertion hole coaxial with the opening is provided.

  A cuff member according to a second aspect is characterized in that, in the first aspect, the annular body has a shape in which the outer diameter decreases as the distance from the flange portion increases.

  The cuff member according to claim 3 is the cuff member according to claim 2, wherein the outer diameter of the bottom of the annular body is 10 to 100% of the average diameter of the flange portion, and the height of the annular body is 1 / of the average diameter of the bottom surface of the annular body. The ratio is 2 to 1/50 times.

  A cuff member according to a fourth aspect of the present invention is the cuff member according to any one of the first to third aspects, wherein the edge portion of the opening of the one plate surface of the flange portion is a trapezoidal portion projecting from the outer periphery. The annular body is fixed to the base portion.

  According to a fifth aspect of the present invention, the cuff member according to any one of the first to fourth aspects is characterized in that the flange portion is formed of a porous three-dimensional network structure having communication.

  A cuff member unit according to a sixth aspect comprises the cuff member according to any one of the first to fifth aspects, and a living body insertion tube inserted through the cuff member.

  The cuff member unit according to claim 7 is characterized in that, in claim 6, the annular body is fixed to the living body insertion tube.

  In the cuff member and the cuff member unit of the present invention, an annular body having a diameter larger than that of the living body insertion tube is provided at the corner portion of the flange portion and the living body insertion tube. The force applied to the living body through the unit is dispersed in a wide range.

  When the annular body is also fixed to the living body insertion tube, the connection strength between the living body insertion tube and the flange portion is improved. In addition, a gap is created between the annular body and the living body insertion tube, and it is prevented that dirt or the like accumulates and becomes a source of infection.

  In the case where the cuff member of the present invention has a porous three-dimensional network structure in which the flange portion overlapping the outer surface of the living body has the same communication as the cuff member of the above-mentioned WO 2005/084742 A1, this network structure The cells easily enter and engraft the body from the subcutaneous tissue of the living body, and the capillaries are constructed, so that the cuff member and the subcutaneous tissue are firmly adhered.

  Embodiments of the present invention will be described below with reference to the drawings.

  1A is a perspective view of a cuff member according to an embodiment, FIG. 1B is a longitudinal sectional view of the cuff member, FIG. 2 is a sectional view showing an example of use of the cuff member, and FIG. FIG. 4 is a sectional view showing a method for manufacturing a cuff member unit, FIG. 4 is a perspective view of a flange portion, and FIG. 5 is a sectional view of an annular body.

  As shown in FIG. 1, the cuff member unit 1 includes a cuff member 2, a tube 6 as a living body insertion tube inserted through the cuff member 2, and an annular body 5 surrounding the tube 6. The cuff member 2 includes a flange portion 3 and a table-like portion 3 b that is erected from one surface of the flange portion 3. A circular opening 3a having a diameter of about 5 to 100 mm is provided in the center of the flange portion 3 so as to penetrate the flange portion 3 in the thickness direction.

  The flange portion 3 is formed of a porous resin material that is excellent in adhesion to a living tissue to be described later.

  The flange portion 3 may have a plan view shape such as a circular shape, an elliptical shape, a lens shape, and a teardrop shape. Usually, when the skin is cut straight with a scalpel, it is exemplified in FIG. Since the living tissue is exposed in such an oval shape, it is preferable that the oval shape can efficiently cover the exposed portion.

  In addition to the physical strength of the flange portion 3, the thickness of the portion other than the base portion 3b of the flange portion 3 is not limited to the average pore diameter of the porous resin material, which will be described later, or the gradient thereof (these are to the depth of tissue infiltration and the degree of differentiation). Complex) and other complex factors are related, but usually 0.05 to 20 mm is preferable.

  When the flange part 3 is circular, the diameter is suitable about 10-200 mm. When the flange portion 3 is elliptical, lens-shaped, teardrop-shaped, or the like, the major axis is preferably 10 to 200 mm, and the minor axis is preferably about 5 to 80% of the major axis.

  The height of the trapezoidal portion 3b is preferably about 10 to 100%, particularly 10 to 90%, especially about 20 to 40% of the thickness of the flange portion 3 in the portion other than the trapezoidal portion 3b. The average diameter of the trapezoidal portion 3b is the average diameter of the flange portion 3 (the diameter when the flange portion 3 is circular, the average of the major axis and the minor axis when the flange portion 3 is elliptical or a shape similar thereto). 5 to 95%, especially about 20 to 60% is preferable.

  In this embodiment, the annular body 5 is made of a soft synthetic resin such as a silicone resin, a polyester elastomer, a polyurethane elastomer, a hydrogenated rubber, or a fluororesin. The annular body 5 has an insertion hole 5 a for the tube 6. The bottom surface of the annular body 5 is flat and is fixed to the base portion 3b. The annular body 5 has a shape whose diameter decreases as the distance from the flange portion 3 increases.

  In this embodiment, the size of the bottom surface of the annular body 5 is the same as that of the base portion 3b. However, the size of the bottom surface of the annular body 5 may be different from that of the base portion 3b. In this case, the average diameter D of the bottom surface of the annular body 5 is 5 to 80% of the average diameter of the flange portion 3, particularly 10 to 10%. It may be 50%.

  The bottom surface of the annular body 5 is preferably circular, but may be oval.

  The height H of the annular body 5 is preferably about 1/2 to 1/50 times, particularly about 1/10 to 1/30 times the average diameter D of the bottom surface of the annular body 5.

  When the cuff member unit 1 is manufactured, the tube 6 is inserted into the opening 3a and is watertightly bonded by high frequency fusion, thermal fusion, laser fusion, ultrasonic fusion, an adhesive, or the like.

  As shown in FIG. 3, a mold 9 is mounted so as to surround the tube 6 and the base portion 3b, and a self-hardening synthetic resin material is injected into the mold 9. As the liquid synthetic resin material having self-curing property, organosiloxane type, urethane type, acrylic type or epoxy type material, thermosetting type, humidity (water) curable type or radiation curable type is preferable. The viscosity of the liquid synthetic resin material having self-hardness may be about 0.01 Pa · s to 300 Pa · s. The liquid synthetic resin material having self-hardening is firmly attached to the cuff when a part of the liquid synthetic resin material penetrates into the porous cuff and cures. That is, even if the chemical affinity between the synthetic resin material and the cuff is low, the synthetic resin material is physically strongly bonded to the cuff.

  In addition, an upper portion of the mold 9 is provided with an injection port 9a for injection and an air hole 9b for allowing air to flow out from the inside. Even if 9b does not exist, if the flange portion 3 is porous, air freely flows out, but in order to perform more precise bonding, it is preferable to adjust the injection pressure, the injection amount, and the internal pressure by the air holes 9b.

  After the injected synthetic resin material is cured, the mold 9 is removed. Thereby, the bottom surface 5b is fixed to the base portion 3b, and the annular body 5 in which the inner peripheral surface of the insertion 5a is fixed to the tube 6 is formed. As the synthetic resin material, a material excellent in water resistance and chemical resistance can be used. Examples of the constituent material of the tube 6 include flexible materials such as polyurethane, soft polyvinyl chloride, polyamide, silicone rubber, ethylene-vinyl acetate copolymer, and fluorine elastomer. Is preferred. Moreover, it is also possible to mix a pigment with this synthetic resin material. If a color is appropriately selected according to the color of the skin of the patient wearing the cuff member, it will be excellent in aesthetics.

  In order to insert the tube 6 into the living body using the cuff member 2, the living tissue is exposed by incising the skin as shown in FIG. Further, the living tissue is incised, the tube 6 of the cuff member 2 is inserted into the living tissue, and the flange portion 3 is overlaid on the outer surface of the living tissue. The biological tissue incision around the tube 6 is sutured as necessary. In order to perform suturing for fixing the flange portion 3 to the patient body surface, if several holes are provided in the flange portion 3 in advance, it is not necessary to penetrate the flange portion 3 with a suturing needle, and the suturing can be performed easily. . Furthermore, by adhering an adhesive tape (not shown) having air permeability and water shielding so as to straddle the flange portion 3 of the cuff member unit and the surrounding skin, intrusion of water or the like may be prevented. Is possible.

  In this embodiment, the stress applied to the living body from the tube 6 is dispersed by the annular body 5 and the stimulation applied to the living tissue around the tube 6 is alleviated.

  In the cuff member 2, cells can easily enter and engraft from the subcutaneous tissue of the living body inside the network structure of the flange portion 3, and a capillary vessel is constructed, so that adhesion with the subcutaneous tissue can be obtained firmly.

  Moreover, in this cuff member 2, since the thickness of the flange portion 3 is small, blood vessels that penetrate the flange portion 3 from the subcutaneous tissue below the flange portion 3 to reach the epidermis are more densely configured. Thus, a high infection suppression effect is obtained.

  A plurality of tubes 6 can be passed through the cuff member of the present invention. For example, in the auxiliary artificial heart therapy, two tubes 6 (cannulas) for blood transmission and devascularization are inserted into a patient. In this case, two openings 3a are provided, and one cuff member unit 2 A tube of the book can be inserted, and the invasion to the patient may be reduced. Whether it is better to insert the blood-feeding vessel and the blood-removal vessel independently with two cuff members, or whether it is better to insert the blood-feeding vessel and the blood removal vessel simultaneously with one cuff member, clinical significance In consideration of the patient's condition and the degree of invasiveness, those skilled in the art may use them properly, or the blood-feeding blood vessel and the blood vessel-removing blood vessel are inserted into one tube thicker than these, and the one tube is inserted into the cuff member. Or it is also possible to insert a tube by what is called a double lumen type inserted into a living body through a cuff member unit. Of course, even in cases other than auxiliary artificial heart therapy, a plurality of linear structures such as power cords for artificial heart pumps, control cords, measurement cords, and thin tubes for DDS are contained in a single tube. It is also possible to insert through the cuff member or the cuff member unit collectively.

  Another embodiment will be described with reference to FIGS.

  In the above embodiment, the annular body 5 has a bullet shape with an outer peripheral surface bulging, but the outer peripheral surface may be conical like the annular body 5A in FIG. 6, and the annular body 5B in FIG. The outer peripheral surface may be concavely curved.

  In the above embodiment, the annular body 6 is cast-molded using the mold 9, but a tube 6C in which the annular body 5C is integrally formed in advance is inserted into the flange portion as shown in FIG. The bottom surface of the annular body 5 </ b> C may be bonded to the base portion 3 b of the flange portion 3.

  When the annular body and the tube are integrally formed in this way, a gap 6d that circulates the tube is formed on the small diameter side (the side far from the flange portion 3) of the annular body 5D, as in the tube 6D with the annular body 5D in FIG. It may be provided. The gap 6d preferably has a tapered cross-sectional shape in which the gap width increases toward the inlet side. Providing such a gap 6d makes it easier for the tube 6D to bend in the inclined direction as indicated by the arrow A.

  In the present invention, as shown in FIG. 10, a separate annular body 5E is formed in advance from both the tube and the flange portion, and this annular body 5E is fitted to the tube 6 and fixed by adhesion, welding or the like. May be.

  In the present invention, as shown in FIG. 11 and FIG. 12, the bending strength of the flange portion 3 is increased, and as a reinforcing member for preventing the flange portion 3 from being bent and deformed by a down-growth action or the like, Thus, you may extend the some linear body 10 radially toward the outer peripheral side from the inner peripheral side of this flange part 3. As shown in FIG.

  The linear body 10 may be made of any material as long as it can secure sufficient strength to prevent the flange portion 3 from being bent and deformed by a down-growth action or a movement of a living body. However, a resin such as segmented polyurethane, polypropylene, polytetrafluoroethylene, or a metal material such as titanium or stainless steel can be used. In addition, when the flange part 3 is comprised with the said porous resin material, a segmented polyurethane resin is especially preferable as a material of the linear body 10 from adhesiveness with it.

  The thickness of the linear body 10 is preferably about 0.1 to 10 mm, particularly about 0.5 to 2 mm. It is desirable that the tip of the linear body 10 reaches the vicinity of the periphery of the flange portion 3. The tip of the linear body 10 may be made spherical to prevent the linear body 10 from protruding.

  It is preferable that about 2 to 36 linear bodies 10 are provided at intervals in the circumferential direction of the flange portion 3. Note that the intervals between the linear bodies 10 may be equal or may not be equal.

  Thus, in addition to extending the linear body 10 radially from the inner peripheral side to the outer peripheral side of the flange portion 3, the linear body 10 is also extended in the circumferential direction of the flange portion 3 as a whole. The linear body 10 may be provided so as to have a spider web shape. You may provide the cyclic | annular linear body which connects the radial direction front-end | tips of each linear body 10. FIG. In this way, the tip of the linear body 10 can be prevented from protruding.

  Instead of embedding the linear body 10 in the flange portion 3, the linear body 10 may be superposed on the outer surface of the flange portion 3, and these may be joined by an adhesive or the like. However, the installation method to the flange part 3 of the linear body 10 is not limited to this.

  Next, a suitable material for the flange portion 3 of the cuff member will be described.

The flange portion 3 of the cuff member of the present invention is preferably made of a thermoplastic resin or a thermosetting resin, and preferably has a three-dimensional network structure having communication properties, and particularly has an average pore diameter of 50 to 1,000 μm and an apparent density of 0. It is preferable to have a porous three-dimensional network structure of 0.01 to 0.5 g / cm ³ . The average pore diameter and the apparent density may partially change, for example, so-called anisotropy in which the average pore diameter and the apparent density gradually change from one surface side to the other surface side. You may have. When using a cuff member whose average pore diameter is not the same in the thickness direction, it is preferable that the contact surface side with the living tissue is enlarged and the pore diameter is small in the deep part. The reason for this is that the tissue infiltrated from the contact surface with the living tissue normally reaches the depth of about 10 mm in the thickness direction, but even if the new blood vessels formed in the porous body are mature, Since cells have a risk of necrosis or insufficient differentiation, it is preferable to reduce the pore diameter at a portion deeper than about 10 mm to suppress tissue infiltration.

  In addition, a hole having a large pore size that greatly deviates from the average pore size may exist on the contact surface side with the living tissue. As such pores, pores of about 500 to 2,000 μm are preferable, and since these pores are present near the surface layer on the living tissue side, it becomes easy to uniformly impregnate an extracellular matrix such as collagen to a deep part, This is advantageous for the invasion of cells and the construction of capillaries. However, such a hole having a large pore diameter is not introduced into the concept of calculating the average pore diameter of the porous three-dimensional network structure in the present invention.

The average pore diameter of the porous body having a porous three-dimensional network structure is 50 to 1,000 μm and the apparent density in the dry state is 0.01 to 0.5 g / cm ³ , but the preferable average pore diameter is 200 to 600 μm. More preferably, it is 200-500 micrometers. When the apparent density is within the range of 0.01 to 0.5 g / cm ³ , cell engraftment is good, excellent physical strength is maintained, and when cells invade, engraft and organize. Although the elastic characteristic approximated to a subcutaneous tissue is obtained, it is preferably 0.05 to 0.3 g / cm ³ , more preferably 0.05 to 0.2 g / cm ³ .

  The average pore diameter and the apparent density are measured as follows.

[Measurement of average pore size]
Using a photograph of the plane (cut surface) of the sample cut with a double-blade razor taken with an electron microscope (Topcon, SM200), individual holes on the same plane were surrounded from the skeleton of the three-dimensional network structure. Image processing is performed as a graphic (the image processing apparatus uses a LUZEX AP manufactured by Nireco, and the image capturing CCD camera uses a LE N50 manufactured by Sony Corporation), and the area of each graphic is measured. This is defined as a perfect circle area, and the diameter of the corresponding circle is determined as the hole diameter. However, due to the effect of phase separation during the formation of the porous body, the micropores drilled in the skeleton portion of the porous body are ignored and only the communication holes on the same plane are measured.

[Measurement of apparent density]
A value obtained by cutting a porous structure into a rectangular parallelepiped of about 10 mm × 10 mm × 3 mm with a double-blade razor and obtaining a volume from the dimensions obtained by measurement with a projector (Nikon, V-12), and dividing the weight by the volume. The apparent density is obtained from

  Further, even if the average pore diameter is the same, the distribution of the pore diameter is preferably such that the contribution ratio of pores having a pore diameter of 150 to 400 μm, which is important for cell invasion, is high, and the contribution ratio of pores having a pore diameter of 150 to 400 μm is high. When it is 10% or more, preferably 20% or more, more preferably 30% or more, still more preferably 40% or more, and particularly preferably 50% or more, cells easily invade, and the invading cells adhere and grow. It is preferable because it is easy.

  The contribution ratio of pores having a pore diameter of 150 to 400 μm in the average pore diameter of the porous three-dimensional network structure refers to the ratio of the number of pores having a pore diameter of 150 to 400 μm to the total number of pores in the above-described average pore diameter measurement method. .

  With such a porous three-dimensional network structure having an average pore size, apparent density and pore size distribution, cells can easily penetrate into the pores, and the cells can easily adhere to and grow in the porous three-dimensional network structure. A blood vessel is constructed, and a good cuff member in which the adhesion between the subcutaneous tissue and the catheter or cannula is robust at the insertion portion can be obtained.

  Examples of the thermoplastic resin or thermosetting resin constituting such a porous three-dimensional network structure include polyurethane resin, polyamide resin, polylactic acid resin, polyolefin resin, polyester resin, fluorine resin, urea resin, phenol resin, epoxy resin. One or two or more of resins, polyimide resins, acrylic resins and methacrylic resins and derivatives thereof can be exemplified, but polyurethane resins are preferable, and segmented polyurethane resins are particularly preferable.

  The segmented polyurethane resin is synthesized from three components of a polyol, a diisocyanate and a chain extender, and has an elastomeric property due to a block polymer structure having a so-called hard segment portion and soft segment portion in the molecule. The elastic properties obtained when using a dampens the stress generated at the interface between the subcutaneous tissue and the cuff member when the patient, catheter or cannula moves, or when the skin around the insertion site is moved during disinfection. Can be expected.

  In the present invention, of the flange portion of the cuff member, the lower layer side (biological side) is a layer formed with the specific porous three-dimensional network structure as a first layer, and the first layer has a different structure. It is also possible to have a structure in which the second layer is laminated. As the second layer, a fiber aggregate, a flexible film, and a porous three-dimensional network layer having an average pore diameter and an apparent density different from the porous three-dimensional network structure of the first layer can be used. It is.

The porous property of the nonwoven fabric or woven fabric is preferably in the range of 100 to 5,000 cc / cm ² / min in view of flexibility, suture strength with subcutaneous tissue, and the like. This porosity is a value measured according to JIS L 1004 and may be referred to as air permeability or air flow rate.

  As the fiber aggregate, one or more kinds selected from the group consisting of polyurethane resin, polyamide resin, polylactic acid resin, polyolefin resin, polyester resin, fluororesin, acrylic resin and methacrylic resin and derivatives thereof are synthesized. It may be made of resin, and fibers made of natural products such as one or more selected from fibroin, chitin, chitosan and cellulose and derivatives thereof can also be used. A synthetic fiber and a fiber derived from a natural product may be used in combination.

  In addition, as the flexible film, a thermoplastic resin film, specifically, polyurethane resin, polyamide resin, polylactic acid resin, polyolefin resin, polyester resin, fluororesin, urea resin, phenol resin, epoxy resin, polyimide resin, Examples thereof include a film made of one or more selected from the group consisting of an acrylic resin and a methacrylic resin, and derivatives thereof, preferably a polyester resin, a fluororesin, a polyurethane resin, an acrylic resin, vinyl chloride, a fluororesin, and It is a film consisting of one or more selected from the group consisting of silicon resins.

  As the flexible film, not only a solid film but also a porous film or a foam can be used. When laminated with a solid flexible film, a cuff member having a large bacterial barrier property and advantageous for infection control can be obtained.

When a porous three-dimensional network structure having an average pore diameter and an apparent density different from the porous three-dimensional network structure of the first layer is used as the second layer, the average pore diameter of 0.1 is used as the porous three-dimensional network structure. A porous three-dimensional network structure having an apparent density of about 0.01 to 1.0 g / cm ^{3 at} about 200 μm can be used.

  As a method of laminating these second layers on the porous three-dimensional network layer, the second layer is an average of the fiber aggregate, the flexible film, and the porous three-dimensional network structure of the first layer. In the case of porous three-dimensional network layers having different pore diameters and apparent densities, a method of bonding using an adhesive, in particular, a hot melt nonwoven fabric is sandwiched between the first layer and the second layer and laminated. And a method of pressure bonding under heating. As such a hot melt nonwoven fabric, for example, a polyamide-type thermal adhesive sheet such as PA1001 manufactured by Nittobo Co., Ltd. can be used. In addition, a method of dissolving and bonding the surface layer portion of the contact surface using a solvent, a method of melting and bonding the surface layer portion with heat, a method of using ultrasonic waves and high frequencies, and the like can be exemplified. Moreover, at the time of manufacturing the first layer, the polymer dope, the fiber assembly, and the flexible film can be laminated and formed continuously.

  As the second layer, two or more fiber aggregates, a flexible film, and a porous three-dimensional network structure layer may be provided, and the first layer may be provided via the second layer. A three-layer structure in which porous three-dimensional network layers are laminated may be used.

  In the porous three-dimensional network structure part of the cuff member of the present invention, collagen type I, collagen type II, collagen type III, collagen type IV, atelocollagen, fibronectin, gelatin, hyaluronic acid, heparin, keratanic acid, chondroitin, Chondroitin sulfate, chondroitin sulfate B, elastin, heparan sulfate, laminin, thrombospondin, vitronectin, osteonectin, entactin, copolymer of hydroxyethyl methacrylate and dimethylaminoethyl methacrylate, copolymer of hydroxyethyl methacrylate and methacrylic acid, alginic acid One or more selected from the group consisting of polyacrylamide, polydimethylacrylamide and polyvinylpyrrolidone may be retained, and platelet-derived increased Growth factor, epidermal growth factor, transforming growth factor α, insulin-like growth factor, insulin-like growth factor binding protein, hepatocyte growth factor, vascular endothelial growth factor, angiopoietin, nerve growth factor, brain-derived neurotrophic factor, hair Cone body neurotrophic factor, transforming growth factor β, latent transforming growth factor β, activin, bone plasma protein, fibroblast growth factor, tumor growth factor β, diploid fibroblast growth factor, heparin-binding epithelium Growth factor-like growth factor, schwanoma-derived growth factor, amphiregulin, betacellulin, epigrelin, lymphotoxin, erythroepoetin, tumor necrosis factor α, interleukin-1β, interleukin-6, interleukin-8, interleukin-8 17, selected from the group consisting of interferons, antiviral agents, antibacterial agents and antibiotics One type or two or more types may be retained, and embryonic stem cells (which may be differentiated), vascular endothelial cells, mesoderm cells, smooth muscle cells, peripheral vascular cells, and mesothelial cells One type or two or more types of cells selected from the group consisting of may be adhered.

  The cuff member of the present invention can also be provided with fine pores in the skeleton itself made of a thermoplastic resin or a thermosetting resin that constructs the porous three-dimensional network structure layer. Such micropores make the skeletal surface not a smooth surface but a complex uneven surface, and are also effective in retaining collagen and cell growth factors, and as a result, it is possible to increase cell engraftment. is there. However, the micropores in this case are not introduced into the concept of calculating the average pore diameter of the porous three-dimensional network layer in the present invention.

  Below, an example of the manufacturing method of the porous three-dimensional network structure which consists of the thermoplastic polyurethane resin which comprises the cuff member of this invention is given, However, The manufacturing method of the cuff member of this invention is limited to the following methods at all. It is not a thing.

  In order to produce a porous three-dimensional network structure made of a thermoplastic polyurethane resin, first, a polyurethane resin, a water-soluble polymer compound described later as a pore-forming agent, and an organic solvent that is a good solvent for the polyurethane resin are used. Mix to produce polymer dope. Specifically, after a polyurethane resin is mixed with an organic solvent to form a uniform solution, a water-soluble polymer compound is mixed and dispersed in this solution. Examples of the organic solvent include N, N-dimethylformamide, N-methyl-2-pyrrolidinone, tetrahydrofuran and the like. However, the organic solvent is not limited to this as long as the thermoplastic polyurethane resin can be dissolved. It is also possible to melt the polyurethane resin by the action of heat without using it, and to mix the pore-forming agent therein.

  Examples of the water-soluble polymer compound as the pore-forming agent include polyethylene glycol, polypropylene glycol, polyvinyl alcohol, polyvinyl pyrrolidone, alginic acid, carboxymethyl cellulose, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, etc., but homogeneously dispersed with the thermoplastic resin If it forms a polymer dope, this does not apply. Depending on the type of thermoplastic resin, it is also possible to use not only water-soluble polymer compounds but also lipophilic compounds such as phthalates and paraffins and inorganic salts such as lithium chloride and calcium carbonate. It is also possible to promote the generation of secondary particles during solidification, that is, the formation of a skeleton of the porous body, using a crystal nucleating agent for a polymer.

  The polymer dope produced from a thermoplastic polyurethane resin, an organic solvent and a water-soluble polymer compound is then immersed in a coagulation bath containing a poor solvent for the thermoplastic polyurethane resin, and the organic solvent and the water-soluble polymer dope are added to the coagulation bath. Molecular compounds are extracted and removed. Thus, by removing a part or all of the organic solvent and the water-soluble polymer compound, a porous three-dimensional network material made of polyurethane resin can be obtained. Examples of the poor solvent used here include water, lower alcohols, and low-carbon ketones. The solidified polyurethane resin may be finally washed with water to remove the remaining organic solvent and pore forming agent.

Furthermore, it is preferable that the porous body is provided with fine pores in the skeleton base material itself that forms the porous structure. In particular, a polyurethane having an average pore size of 100 to 650 μm, an apparent density in a dry state of 0.10 g / cm ³ or less and a continuous three-dimensional network structure, and the porous three-dimensional network layer being constructed. It is preferable that the resin skeleton itself is a porous body having a porosity of 70% or more, and the surface layer of the skeleton itself is a dense layer interspersed with fine pores. Such micropores make the skeletal surface not a smooth surface but a complex uneven surface, and are also effective in retaining collagen and cell growth factors, and as a result, it is possible to increase cell engraftment. is there. However, the micropores in this case are not introduced into the concept of calculating the average pore diameter of the porous three-dimensional network structure referred to in the present invention.

  FIG. 13 is an SEM image of a cross section of a polyurethane porous body in which fine holes are also provided in the skeleton substrate itself as described above, and FIG. 14A is an SEM photograph of the surface layer of this polyurethane porous body, FIG. 14B is a partially enlarged image thereof. From FIGS. 13, 14A and 14B, it can be seen that fine pores are scattered in the skeleton portion forming the porous body.

  FIG. 15B shows a photograph taken under the same conditions as those obtained by observing the cross section of the portion surrounded by a large circle in FIG. 14B by cutting with a feather cutter. Although it was described that the enclosed part was cut, the field of view corresponding to the same condition was actually selected from the cutting planes present at random).

  From FIG. 15, although the inside of the skeleton of the polyurethane porous body is porous with a high porosity, the surface layer is covered with a dense layer, and the size is such that cells cannot infiltrate in a scattered manner. It can be seen that the outside of the skeleton is communicated through the fine holes (portions surrounded by small circles in FIG. 8).

  The structural characteristics of the polyurethane porous body, that is, “the skeleton constituting the three-dimensional network structure is porous with a high porosity, and the surface layer of the skeleton itself is covered with a dense layer. “Communicating with the outside world through fine holes to be drilled” exhibits the following effects. In other words, since the skeleton of the polyurethane porous body itself is porous, it is infiltrated with extracellular matrix such as collagen, albumin, oxygen, waste products, water, electrolytes, etc., and diffuses and exchanges with living tissues. Is done. On the other hand, cell components do not exist inside the skeleton, that is, cell infiltration is blocked by a dense layer on the skeleton surface layer. In this way, since the skeleton part of the porous body is also porous and cells (formable components) cannot infiltrate, the inside of the skeleton is not clogged and oxygen, nutrients are introduced into the entire porous body. As a result, functions useful as a bio-implanting material such as good tissue infiltration, engraftment, maturation, and angiogenesis are expressed.

In order to obtain the porosity of the skeleton portion of the polyurethane porous body, first, the average pore diameter is measured as described above. That is, the area of the white part and the area of the black part are calculated by an image processing method with the resin part of the porous body photograph being white and the void (air part) being black. A calculated apparent density is obtained from the total area of the measurement visual field obtained by the image processing, the total area of the gap portion, and the specific gravity of the polyurethane resin according to JIS K7311. This apparent density is generally about 10 times or more larger than the actually measured value. This is a result of assuming that the skeleton portion has a solid structure made of a polyurethane resin. Therefore, the porosity of the skeleton itself of the porous body is obtained by substituting the calculated apparent density A and the actually measured apparent density B into the calculation formula (AB) / A × 100 (%). It becomes possible. When the apparent density in calculation is 0.91 g / cm ³ and the apparent density of the actually measured value is 0.077 g / cm ³ , the porosity is calculated to be 91.5%.

  In this polyurethane porous body, there are micropores on the surface of the skeleton, but this is not the size that cells can infiltrate, but it is only about irregularities that help cell survival as described above. It is. Although the pores of this skeleton have the meaning of unevenness for the purpose of assisting engraftment as a result, the entire porous body is essentially in a so-called “clogged state” after cell infiltration. After becoming a high-porosity porous body, the skeleton functions as an entrance / exit to maximize the contribution to diffusion / exchange of nutrients, oxygen, and water.

  The above embodiment is an example of the present invention, and the present invention is not limited to the above embodiment. In the present invention, the flange portion 3 may be provided with a cylindrical portion extending to the side opposite to the base portion 3b. The inner hole of this cylindrical part is coaxial and has the same diameter as the opening 3a, and the tube 6 is inserted therethrough.

It is a block diagram of the cuff member concerning an embodiment. It is sectional drawing which shows the usage example of the cuff member of FIG. It is sectional drawing which shows the manufacturing method of a cuff member. It is a perspective view of a flange part. It is sectional drawing of an annular body. It is sectional drawing of an annular body. It is sectional drawing of an annular body. It is sectional drawing of a tube with an annular body. It is sectional drawing of a tube with an annular body. It is a perspective view of an annular body and a tube. It is a perspective view of the cuff member unit concerning another embodiment. It is sectional drawing of the cuff member unit of FIG. It is a SEM photograph of the section of a polyurethane porous body. It is a SEM photograph of the surface layer of a polyurethane porous body. It is a SEM photograph of the section of a polyurethane porous body.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Cuff member unit 2 Cuff member 3 Flange part 4 Cylindrical part 5, 5A, 5B, 5C, 5D, 5E Annular body 6, 6C, 6D Tube 9 Formwork 10 Linear body

Claims (7)

A flange that overlaps the outer surface of the living body,
In the cuff member having an opening for inserting the biopsy tube provided in the flange portion,
A cuff member comprising an annular body fixed to an edge of the opening of one plate surface of the flange portion and having a living body insertion tube insertion hole coaxial with the opening.   The cuff member according to claim 1, wherein the annular body has a shape in which an outer diameter decreases as the distance from the flange portion increases.   3. The outer diameter of the bottom of the annular body is 10 to 100% of the average diameter of the flange portion, and the height of the annular body is 1/2 to 1/50 times the average diameter of the bottom surface of the annular body. A cuff member characterized by that.   4. The rim according to claim 1, wherein an edge of the opening of the one plate surface of the flange portion is a pedestal portion protruding from an outer periphery thereof, and the annular body is the pedestal. A cuff member characterized by being fixed to a shape portion.   The cuff member according to any one of claims 1 to 4, wherein the flange portion is formed of a porous three-dimensional network structure having communication properties.   A cuff member unit comprising the cuff member according to any one of claims 1 to 5 and a living body insertion tube inserted through the cuff member.   The cuff member unit according to claim 6, wherein the annular body is fixed to the living body insertion tube.

Images