JP2018027155A - Stent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an inexpensive stent having both self-extensibility and removability, and not fragmenting in an organism.SOLUTION: There is provided a tubular stent using as a base material, a material containing a bridged hydrophilic polymer whose principal chain is a carbon-carbon covalent bond, which is a self-expandable stent swelled by absorbing a body fluid to thereby expand an outer diameter and an inner diameter. The hydrophilic polymer is preferably a radiation-crosslinked polyvinyl alcohol (PVA).SELECTED DRAWING: None

Description

  The present invention relates to a stent. More particularly, the present invention relates to a stent for insertion into a hollow or tubular part of a body organ, such as a blood vessel, bladder, trachea, bronchi or biliary tract, pancreatic duct, etc. to maintain an open state or prevent stenosis.

  A tubular organ existing in the body is narrowed or occluded due to various causes. A medical device that expands this from the inside of the lumen and maintains the patency state is called a stent. It is roughly divided into metal stents and plastic stents.

  A metal stent is a cylindrical structure having a network structure, and a method of expanding and indwelling in an affected area with the aid of a balloon catheter is generally used. Self-expanding metal stents (SEMS) using shape memory alloys Nitinol and stainless steel that self-expand without the aid of a balloon catheter are also popular. Since SEMS has a network structure and may have a restenosis due to proliferation and infiltration of surrounding tissues and mucous membranes, covered SEMS in which the entire stent is covered with a resin film has been put into practical use.

  The advantage of SEMS is that the tubular organ can be reliably expanded because of its strong radial force. However, when restenosis occurs, the problem is that removal is difficult because the mucous membranes that have proliferated are damaged. Although it is possible to prevent restenosis to some extent by the above-mentioned covering, or by imparting sustained drug release to the stent, the problem that removal is difficult has not been solved essentially.

  On the other hand, plastic stents frequently used in the biliary tract and pancreatic duct are smooth cylindrical structures and do not have expandability. For this reason, the patent diameter that can be secured depends on the diameter of the catheter that can be inserted, and it is a weak point that it tends to lead to restenosis earlier than a metal stent, but there is an advantage that extraction / reposition is easy. It is frequently used for the purpose of increasing QOL of patients with a relatively short prognosis, particularly in the area of the bile pancreas.

  In order to overcome the problems of the stent described above, a stent (SMPS) using a shape memory polymer (SMP) having biodegradability is known. For example, Japanese Patent No. 4034036 discloses a biodegradable / self-expandable stent using a polymer composed of a segment having a high melting point or glass transition point (hard segment) and a segment having a low melting point (soft segment). Japanese Patent No. 4881728 discloses an SMPS that has a heat responsiveness or a photosensitive shape recovery property and stores a plurality of shapes.

  Biodegradable / self-expanding SMPS has the self-expandability similar to SEMS, and further has the advantage of decomposing and disappearing in the long term without removal. However, it has been pointed out that it cannot be applied to cases where urgent removal is assumed, and the risk that stent fragments will flow out due to biodegradability.

  As described above, a stent that has self-expandability, does not fragment in vivo, and has excellent extraction properties is desired, but has not yet been developed.

Patent No. 4034036 Japanese Patent No. 4881728

  An object of the present invention is to provide a stent that has both self-expandability and extraction property and does not fragment in vivo.

The present invention has the following configuration.
[1] A tubular stent whose base material is a material containing a crosslinked hydrophilic polymer whose main chain is a carbon-carbon covalent bond, and which swells by absorbing body fluid and expands its outer diameter and inner diameter. A self-expanding stent characterized by that.
[2] The self-expanding stent according to [1], wherein the hydrophilic polymer is radiation-crosslinked polyvinyl alcohol (PVA).
[3] The self-expanding stent according to the above 1 or 2, wherein the internal diameter expands by 1.5 to 3.0 times by absorbing body fluid.

The stent of the present invention uses a material containing a crosslinked hydrophilic polymer whose main chain is a carbon-carbon covalent bond as a base material, so that the water absorption / swellability of the polymer can be used as the expansion force of the stent. By using the lubricity in the case of becoming a pull-out property, a self-expandable stent having an excellent pull-out property can be obtained.
The hydrophilic polymer hydrogel is not easily decomposed in vivo, has a low risk of fragmentation, and has a low protein adsorptivity, so that it is difficult for the stent to be clogged due to adsorption / deposition of in vivo substances. Has the advantage of Furthermore, since a network structure for exhibiting extensibility is unnecessary, tissue infiltration from surrounding tissues does not occur, and the risk of restenosis is low.

The front photograph (a) and side photograph (b) of the PVA tube manufactured in the Example. The front photograph (a) and the side photograph (b) of what swollen the PVA tube manufactured in the Example.

The self-expanding stent of the present invention is based on a material containing a crosslinked hydrophilic polymer whose main chain is a carbon-carbon covalent bond. Since it has a carbon-carbon covalent bond as the main chain, it is stable and resistant to enzymatic degradation and hydrolysis in vivo. There is an advantage that embolism is low.
Examples of such a hydrophilic polymer include polyvinyl alcohol (PVA), polyvinyl pyrrolidone, polyacrylic acid and the like, but PVA which is inexpensive and has demonstrated biocompatibility is preferable.

The molecular structure of PVA is generally defined by saponification degree and molecular weight, each of which affects the properties of the gel. When the degree of saponification is low, the gel swellability tends to increase, and when the molecular weight is large, the gel strength tends to increase.
The physical properties of the self-expanding stent of the present invention are further modified by the crosslinking method and polymer concentration, so the molecular structure of PVA is not limited, but if the gel swellability is too high, the strength after swelling Is preferably in the range of 80% to 100% (where 100% means a state in which the residual vinyl acetate monomer in the PVA chain is less than the measurement error). If the molecular weight is too low, the strength may be insufficient. If the molecular weight is too high, the viscosity of the PVA aqueous solution as a raw material may become too high and uniform mixing may be difficult. Ten thousand.
The crosslinking method, the degree thereof, the polymer concentration and the like are not particularly limited, but are selected within a range that satisfies the utility as a self-expandable stent.

  Other hydrophilic polymers can be added to the matrix of the self-expanding stent of the present invention for the purpose of changing the mechanical properties of the stent. For example, chitin, cellulose and the like have biocompatibility and excellent mechanical properties, and thus can be suitably used as a reinforcing material for the base material gel. Further, a plurality of types of the hydrophilic polymers listed above can be mixed and used.

  The hydrophilic polymer used in the present invention needs to be crosslinked. It exhibits excellent gel elastic modulus even after water absorption and swelling due to crosslinking, and can exhibit self-expandability. There are various crosslinking methods, and radiation crosslinking such as electron beams and gamma rays, aldehyde-based crosslinking agents such as glutaraldehyde, and boric acid compounds are used. Radiation cross-linking is preferred for medical stents because no foreign compound is introduced.

  The self-expanding stent of the present invention swells by absorbing body fluid and expands its outer diameter and inner diameter. The inner diameter is preferably expanded to 1.5 to 3.0 times. The outer diameter is preferably expanded to 1.5 times to 5.0 times. If the expandability of the inner diameter is less than 1.5 times, the tubular organ cannot be sufficiently expanded after passing through a thin catheter. On the other hand, when the expandability of the inner diameter exceeds 3.0 times, the gel strength is significantly lowered, and it may not be able to withstand the tensile load at the time of extraction, which is not preferable.

  The surface of the hydrophilic polymer hydrogel is extremely lubricious and can be easily removed using a catheter after being placed in a tubular organ by self-expansion. Further, this surface is a low protein adsorption surface, and there is an advantage that clogging hardly occurs due to the adsorption of a biological substance (protein etc.) in the body fluid.

  In the self-expanding stent of the present invention, a hydrophilic polymer having a carbon-carbon covalent bond as a main chain is dissolved in a solvent, poured into a stent mold, irradiated with radiation, crosslinked, and then dried (solvent is removed). To be removed). In the case of using a crosslinking agent, the hydrophilic polymer and the crosslinking agent can be dissolved in a solvent, poured into a mold, crosslinked by heating or the like, and dried. Any mold may be used according to the size and shape of the stent to be manufactured.

  The self-expandable stent of the present invention utilizes the expandability due to water absorption and swelling of a hydrophilic polymer molded into a tubular shape, and eliminates the need for a network structure for exhibiting expandability used in SEMS and SMPS. Become. For this reason, the stent of this invention is comprised from the dense gel wall, the tissue infiltration from the surrounding tissue does not occur, and the risk of restenosis is low.

  The present invention will be described in more detail below with typical examples.

Preparation of PVA tube PVA (manufactured by ALDRICH) having a saponification degree of 99% or more and a molecular weight of 89,000 to 98,000 was added to pure water so as to have a concentration of 20% and completely dissolved while heating. This solution was poured into a cylindrical plastic container having an inner diameter of 10 mm and a length of 20 mm, and a cylindrical plastic rod having a diameter of 4 mm was inserted into the center. After sealing with a wrap so as not to leak, a 50 kGy electron beam was irradiated to gel the aqueous PVA solution. The obtained PVA gel was passed through a wire and dried at room temperature to obtain a PVA tube. The size of the PVA tube was an inner diameter of 2.0 mm, an outer diameter of 4.7 mm, and a total length of 18 mm at the center of the tube (FIG. 1).

PVA tube swelling test The PVA tube was placed in a cup containing pure water and allowed to stand at room temperature. When the size was measured after taking out after 24 hours, the inner diameter was 3.6 mm, the outer diameter was 9.0 mm, and the total length was 26 mm at the center of the tube (FIG. 2).
When the swollen PVA tube was crushed with a finger, it exhibited resistance and exhibited a shape recovery property like rubber. The elastic modulus of the human artery is 16 kPa (160 gf / cm ² ), and if the resistance force is 1/10 of this value, it can be estimated that the artery inner diameter is expanded by 10%. A 50 g weight was placed on the swollen PVA tube piece, and the elastic modulus was estimated from the change in thickness due to the load and the area of the piece, and it was 90 gf / cm ^2. Estimated to have. Thus, it can be seen that when placed in a tubular organ in a dry state, it absorbs bodily fluid and exhibits expandability, and can maintain a hollow state.

  The self-expanding stent of the present invention can be used by being inserted into a hollow part or a tubular part of a body organ, and after insertion, absorbs a bodily fluid to swell and self-expand. Absent. Since it can be manufactured at a lower cost than a self-expanding metal stent (SEMS) having a complicated structure, it also helps to reduce medical costs.

Claims (3)

  A tubular stent based on a material containing a cross-linked hydrophilic polymer whose main chain is a carbon-carbon covalent bond, characterized in that it swells by absorbing body fluid and expands its outer diameter and inner diameter And self-expanding stent.   The self-expanding stent according to claim 1, wherein the hydrophilic polymer is radiation-crosslinked polyvinyl alcohol (PVA).   The self-expanding stent according to claim 1 or 2, wherein the internal diameter expands by 1.5 to 3.0 times by absorbing body fluid.