JP2010240163A - Medical structure - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide medical structure which maintains advantages of a structure precursor showing superelasticity as they are even if the medical structure is coated by polymer, and which is obtained by coating the structure precursor or the like with the polymer having biocompatibility. <P>SOLUTION: The medical structure has: the structure precursor; and the polymer to be formed on the surface of the structure precursor, wherein the polymer has polyrotaxane, and polyrotaxane is formed by arranging a blocking groups at both ends of pseudopolyrotaxane so that circular molecules are not detached from the pseudopolyrotaxane constituted by including openings of the circular molecules like a skewer by linear molecules. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

The present invention relates to a medical structure having a structural precursor; and a polymer having biocompatibility, the medical structure having a polymer coated on the structural precursor.
In particular, the present invention uses an elastic material, particularly a superelastic material, as a material for a structural precursor, and a polyrotaxane having a property that follows the elasticity of the structural precursor, in particular superelasticity, and having biocompatibility as a polymer. The present invention relates to the medical structure used.

A minimally invasive treatment method that has made great progress in recent years, that is, without damaging the body too much, with the aid of an endoscope or X-ray, approaching the affected area directly from outside the body with a catheter etc., placing medical materials such as stents in place and treating In this method, a medical material is folded small outside the body, inserted into the body, and then used in a widened manner, and a medical material suitable for this method is required.
For example, Patent Document 1 discloses a stent and a stent graft obtained by coating a metal wire surface with a polymer.

JP2003-325655A.

  However, when a normal polymer such as the polymer disclosed in Patent Document 1 is used, even if a metal wire or the like exhibits superelastic characteristics, the polymer cannot follow the characteristics, particularly deformation of the superelastic material. There is a problem. Specifically, a stent or the like is folded before insertion into the body, but if a normal polymer is used, it has a problem that it cannot be folded sufficiently or folds are generated and becomes difficult to handle. Further, after insertion into the body, the stent or the like is required to take a desired form at a desired position, but even if the superelastic material can take the form, the polymer cannot follow the deformation, There is a problem that a desired form cannot be adopted.

Then, the objective of this invention is providing the medical structure which can solve the said subject.
Specifically, an object of the present invention is a medical structure having the advantage of a structural precursor exhibiting elasticity, particularly superelasticity, that is, even if the structural precursor is coated with a polymer, for example, elasticity, particularly superelasticity. An object of the present invention is to provide a medical structure in which the surface of the structure exhibits biocompatibility by using a polymer having biocompatibility.
Moreover, the objective of this invention is providing the novel medical structure which has characteristics, such as a superelasticity, in addition to the said objective or in addition to the said objective.

The inventors have found the following invention.
<1> a structural precursor; and a polymer formed on the surface of the structural precursor;
The polymer has a polyrotaxane, and the polyrotaxane has blocking groups arranged at both ends of the pseudopolyrotaxane in which the opening of the cyclic molecule is skewered by a linear molecule so that the cyclic molecule is not detached. And
The medical structure, wherein the polymer forms an outer surface of the medical structure.

<2> In the above item <1>, the structure may have a deformation rate of 300% or more, preferably 500% or more, and more preferably 800% or more.
<3> In the above <1> or <2>, the material constituting the structural precursor may have a proportional elastic region of 2% or more, preferably 4% or more, more preferably 6% or more.
<4> In any one of the above items <1> to <3>, the proportional elastic region of the structural precursor itself may be 2% or more, preferably 4% or more, more preferably 6% or more.
<5> In any one of the above items <1> to <4>, the proportional elastic region of the structure itself may be 2% or more, preferably 4% or more, more preferably 6% or more.

  <6> In any one of the above items <1> to <5>, the structural precursor is: i) superelastic alloy; ii) amorphous alloy; iii) rubber metal, iv) shape memory alloy; v) nylon fiber; It is preferable to have at least one material selected from the group A consisting of carbon fiber; vii) boron fiber; viii) polyimide fiber; and ix) polyetherimide fiber. The terms “superelastic alloy”, “amorphous alloy” and “rubber metal” will be described in detail later.

<7> In the above item <6>, the structural precursor may be composed of at least one material selected from Group A.
<8> In any one of the above items <1> to <7>, the structural precursor is a braided body made of a thin wire; a stranded wire made of a thin wire; a coil body; a thin plate cutout body; It is good to have at least 1 sort (s) of structure chosen from B group which consists of; In addition, these are good to be formed from the above-mentioned material.

<9> In any one of the above items <1> to <8>, the structure may be a hollow body.
<10> In any one of the above items <1> to <9>, the structure is a first selected from the group consisting of a linear body; a cylindrical body; a bag-like body; a cage-like body; and a desired form. The shape may be variable from a linear body; a cylindrical body; a bag-like body; a cage-like body; and a desired form to a second form different from the first form. In particular, when a medical structure is used, the structure can have the first form before being introduced into the living body, and can have the second form in the living body.

<11> In the above <1> to <10>, the polymer has a general polymer other than the polyrotaxane in addition to the polyrotaxane, and the general polymer and the polyrotaxane have a covalent bond and / or an ionic bond. It is good to combine through.
<12> In the above <1> to <11>, the polyrotaxane is preferably formed by chemical crosslinking of at least two molecules via the above-described cyclic molecule.
<13> In the above items <1> to <12>, the polymer may be composed of only the above-described polyrotaxane, and at least two molecules of the polyrotaxane may be chemically crosslinked via the above-described cyclic molecule.
<14> In any one of the above items <1> to <13>, the cyclic molecule may be selected from the group consisting of α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin.

  <15> In any one of the above items <1> to <14>, the linear molecule is polyvinyl alcohol, polyvinyl pyrrolidone, poly (meth) acrylic acid, cellulose resin (carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, etc.) , Polyacrylamide, polyethylene oxide, polyethylene glycol, polypropylene glycol, polyvinyl acetal resin, polyvinyl methyl ether, polyamine, polyethyleneimine, casein, gelatin, starch, and / or copolymers thereof, polyethylene, polypropylene, and other olefins Polyolefin resins such as copolymer resins with monomers, polyester resins, polyvinyl chloride resins, polystyrene and acrylonitrile-styrene copolymers Polystyrene resins such as fat, acrylic resins such as polymethyl methacrylate and (meth) acrylic acid ester copolymers, acrylonitrile-methyl acrylate copolymer resins, polycarbonate resins, polyurethane resins, vinyl chloride-vinyl acetate copolymer resins, polyvinyl Butyral resin, etc .; and derivatives or modified products thereof, polyisobutylene, polytetrahydrofuran, polyaniline, acrylonitrile-butadiene-styrene copolymer (ABS resin), polyamides such as nylon, polydienes such as polyimides, polyisoprene, and polybutadiene , Polysiloxanes such as polydimethylsiloxane, polysulfones, polyimines, polyacetic anhydrides, polyureas, polysulfides, polyphosphazenes, polyketones, polyphenyle , Polyhaloolefins, and derivatives thereof, such as polyethylene glycol, polyisoprene, polyisobutylene, polybutadiene, polypropylene glycol, polytetrahydrofuran, polydimethylsiloxane, polyethylene, polypropylene, polyvinyl alcohol and It is preferably selected from the group consisting of polyvinyl methyl ether, and more specifically, selected from the group consisting of polyethylene glycol, polypropylene glycol, polytetrahydrofuran, polydimethylsiloxane, polyethylene, and polypropylene, particularly polyethylene glycol. It is good.

<16> In any one of the above items <1> to <15>, the linear molecule may have a molecular weight of 3,000 or more, preferably 20,000 or more, more preferably 35,000 or more.
<17> In any one of the above items <1> to <16>, the blocking group is a dinitrophenyl group, a cyclodextrin, an adamantane group, a trityl group, a fluorescein, a pyrene, a substituted benzene (as a substituent) , Alkyl, alkyloxy, hydroxy, halogen, cyano, sulfonyl, carboxyl, amino, phenyl, etc., but are not limited to them. Selected from the group consisting of polynuclear aromatics (substituents may include, but are not limited to, the same as those described above. One or more substituents may be present) and steroids It is good. In addition, it is preferably selected from the group consisting of dinitrophenyl groups, cyclodextrins, adamantane groups, trityl groups, fluoresceins, and pyrenes, more preferably an adamantane group or a trityl group. .

<18> In any one of the above items <1> to <17>, the cyclic molecule may be derived from α-cyclodextrin, and the linear molecule may be polyethylene glycol.
<19> In any one of the above items <1> to <18>, when the amount of cyclic molecules included to the maximum when the cyclic molecules are included in a skewered manner by linear molecules is 1, Cyclic molecules should be skewered into linear molecules in an amount of 0.001-0.6, preferably 0.01-0.5, more preferably 0.05-0.4.

<20> In any one of the above items <1> to <19>, the medical structure may be a medical structure having a medical flange.
<21> In any one of the above items <1> to <19>, the medical structure may be a medical structure including only a medical flange.

  <22> In any one of the above items <1> to <19>, the medical structure is a catheter for treating an atrial septal defect, and the structure has a smaller diameter than the diameter of the atrial septal defect when the catheter is inserted. The first and second flange portions having a first form which is a certain cylindrical body and having a diameter larger than the diameter of the atrial septal defect when the catheter is added, and the first and second flange portions are connected to each other It is preferable to have a second form having an association portion of a desired length communicating with the atrial septal defect.

<23> An associated portion having a desired length communicating with the atrial septal defect; an atrial septum having first and second flange portions disposed at both ends of the associated portion and having a diameter larger than the diameter of the atrial septal defect A method for laying a catheter for defect treatment,
The atrial septal defect treatment catheter is a medical structure according to any one of the above <1> to <18>,
xi) storing the atrial septal defect treatment catheter in a cylindrical insertion tube;
xii) communicating the tubular insertion tube to the atrial septal defect;
xiii) a step of extruding the first pushing portion of the catheter for treating atrial septal defect from the cylindrical insertion tube on the communication distal side, and using the first pushing portion as the first flange portion;
xiv) Further, the second push-out portion of the atrial septal defect treatment catheter is pushed out from the cylindrical insertion tube on the communication proximal side, and the second push-out portion is connected to the linkage portion and the second flange portion. The step of:
The above method.

<24> The tubular prosthesis selected from the group consisting of a stent graft, an artificial blood vessel, an artificial esophagus, an artificial trachea, an artificial bile duct, an artificial ureter, and an artificial urethra in any one of the above items <1> to <19> Good material.
<25> In any one of the above items <1> to <19>, the medical structure may be a flexible catheter.
<26> In any one of the above items <1> to <19>, the medical structure may be selected from the group consisting of a reservoir, a drainage bag, and an artificial bladder.

According to the present invention, even if a structural precursor is coated with a polymer, etc., it is a medicinal structure having elasticity, particularly superelasticity, that is, a medical structure having elasticity, particularly superelasticity, and has biocompatibility. By using the polymer, it is possible to provide a medical structure in which the surface of the structure exhibits biocompatibility.
In addition to the above effects, or in addition to the above effects, the present invention can provide a novel medical structure having characteristics such as superelasticity.

It is the figure which showed notionally the structure of the structure precursor. It is the schematic of the bendable catheter 1 using the structure of this invention. It is the schematic of the tubular medical device 11 which has the 1st flange part 14 using the tubular body 12 and the structure of this invention. It is the schematic which illustrates the catheter 31 for atrial septal defect treatment, and its laying method. 1 is a diagram showing the structure of a structural precursor used in Example 1. FIG. It is a figure which shows the structure of the simulation circuit used in Example 2 and 3 and Comparative example 2 and 3. FIG.

Hereinafter, the present invention will be described in detail.
The present invention relates to a medical structure having a structural precursor; and a polymer formed on the surface of the structural precursor, the polymer having a polyrotaxane, and the polymer covering the outer surface of the medical structure. A medical structure to be formed is provided.

<Structure precursor>
In the present invention, the structural precursor means a precursor of a medical structure, as the term implies. In other words, the structural precursor forms the skeleton of the medical structure.
The material constituting the structural precursor may have a proportional elastic region of 2% or more, preferably 4% or more, more preferably 6% or more.
Also, the proportional elastic region of the structural precursor itself should be 2% or more, preferably 4% or more, more preferably 6% or more.
Further, the proportional elastic region of the structure itself should be 2% or more, preferably 4% or more, more preferably 6% or more.

  Here, the proportional elastic region refers to a region where stress and strain are proportional when a stress-strain curve of a certain substance is measured. In general, when this region is exceeded, the region changes from an elastic property to a region in which plastic deformation is not restored.

  The structural precursors are: i) superelastic alloy; ii) amorphous alloy; iii) rubber metal, iv) shape memory alloy; v) nylon fiber; vi) carbon fiber; vii) boron fiber; viii) polyimide fiber; It is preferable to have at least one material selected from the group A consisting of polyetherimide fibers.

  Here, as a “superelastic alloy”, a Ni—Ti (50:50 atom%) alloy and an alloy containing a small amount of Cu in the alloy, Ti—Pd alloy, platinum alloy, Fe—Mn—Si alloy, Ag—Cd alloy (44/49 atom% Cd), Au—Cd alloy (46.5 / 50 atom% Cd), Cu—Al—Ni alloy (14 / 14.5 wt% Aland 3 / 4.5 wt% Ni), Cu—Sn alloy (About 15 atom% Sn), Cu-Zn alloy (38.5 / 41.5 wt% Zn), Cu-Zn-X alloy (X = Si, Al, Sn), Fe-Pt alloy (about 25 atom% Pt), Examples thereof include, but are not limited to, a Co—Ni—Al alloy, a Co—Ni—Ga alloy, and a Ni—Fe—Ga alloy. Ni-Ti (50:50 atom%) alloy and an alloy containing a small amount of Cu in the alloy, Ti-Pd alloy, platinum alloy, and Fe-Mn-Si alloy are preferable, and Ni-Ti is more preferable. A (50:50 atom%) alloy and an alloy containing a small amount of Cu in the alloy are preferable.

The “amorphous alloy” refers to a substantially amorphous alloy including an amorphous phase having a volume ratio of at least 50%, and M1 _a M2 _b M3 _c M4 _d M5 _e (M1 is Zr, Hf and One, two or three elements selected from Ti, M2 is at least one element selected from the group consisting of Cu, Fe, Co, Mn, Nb, V, Cr, Zn, Al, Sn and Ga , M3 is at least one element selected from the group consisting of B, C, N, P, Si and O, M4 is at least one element selected from the group consisting of Ta, W and Mo, M5 is Au, Pt , Pd and Ag, at least one element selected from the group consisting of a, b, c, d and e, each in atomic percent, 25 ≦ a ≦ 85, 15 ≦ b ≦ 75, 0 ≦ c ≦ 30 0 ≦ d ≦ 15 and 0 ≦ e ≦ 15) Alloy. The amorphous alloy is preferably composed mainly of a ternary alloy composed of Zr, Al and Cu, and Zr is 40 atomic% to 55 atomic% and Al is 5 atomic% to 15 atomic% in the main component. Cu is preferably contained in an amount of 30 atomic% to 50 atomic%, and a part of Zr, Al, and Cu constituting the alloy may be replaced with any one of Hf, Ti, Fe, and Co. The contents relating to the amorphous alloy in the open 2005-27840 are included in the present application as a reference).

  Furthermore, “rubber metal” refers to Ti-15 to 30 (V, Nb, Ta) -0.3 (Zr, Hf) -1.8 to 6.5 O (wherein the numerical value is Ti as the main component). Yes, it is atom% when the total number of atoms is 100 atom% (Note that atom% for Ti is omitted) (content of rubber metal in WO2002-077305) Included as a reference).

  Although the structural precursor depends on how the medical structure is used, the structural precursor may have another material of the group A material. Moreover, although a structural precursor also depends on how to use a medical structure, etc., it may be composed of only one or a plurality of types of materials in the group A. Of course, the structural precursor may be made of only one material of the group A, although it depends on how the medical structure is used.

The structural precursor may have various structures in order to show the value of the above-described proportional elastic region and / or to show the value of the deformation rate of the structure described below. These structures have at least one structure selected from the group B consisting of a braided body made of a thin wire; a twisted wire body made of a thin wire; a coil body; a thin plate cutout body; and a cylindrical cutout body. Is good. In addition, these fine diameter wires etc. are good to be formed from the above-mentioned material.
FIG. 1 is a diagram conceptually showing the structure of the structural precursor. In FIG. 1, (a) is a conceptual diagram of a braided hollow body made of a thin wire, (b) is a conceptual diagram of a stranded wire hollow body (a bag-like body closed at both ends), and (c) is (a) ) Is a conceptual diagram of a braided hollow body (a bag-like body closed at both ends) made of a thin wire different from (b), and (d) is a stranded hollow body (a bag-like body closed at both ends) made of a thin wire different from (b) ), And (e) shows a conceptual view of a cylindrical notch. In addition, these figures are illustrations, Comprising: The structural precursor of this invention is not limited to these.
Since the structural precursor has these structures, the structural precursor can achieve the above-described proportional elastic region in combination with the proportional elastic region of the material constituting the structural precursor, thereby achieving the object of the present invention. can do.

<Polymer>
In the medical structure of the present invention, the polymer is formed on the surface of the structural precursor described above and forms the outer surface of the structure. In particular, the medical structure of the present invention is preferably a hollow body, as will be described later, in which case the polymer forms the outer surface of the hollow body.
Schematically speaking, the structural precursor is the framework of the structure, and the polymer is the part of the structure precursor (framework) that is fleshed out. For example, when the structural precursor is a coil body and the structure body is a hollow body, a polymer is attached to the coil body that is a framework to form a hollow body.
In addition, when forming the outer surface of the structure by forming the polymer on the surface of the structural precursor and forming the outer surface of the structure, a plurality of layers may be formed using a plurality of types of polymers. That is, in the vicinity of the surface of the structural precursor, a polymer having a high affinity with the material constituting the structural precursor is disposed, while a biocompatible polymer is disposed on the surface of the structural body. May be formed.

In the present invention, the polymer has a polyrotaxane.
The polyrotaxane has a structure in which a blocking group is arranged at both ends of a pseudopolyrotaxane in which an opening of a cyclic molecule is skewered by a linear molecule so that the cyclic molecule is not detached. Each component of the polyrotaxane will be described later.
In the present invention, the polymer may have a general polymer other than polyrotaxane, or may be composed only of polyrotaxane. The polyrotaxane is preferably formed by chemically crosslinking at least two molecules of the polyrotaxane via a cyclic molecule. In addition, although it does not specifically limit as a general polymer, It is preferable that it has biocompatibility.
Since the polymer of the present invention has a polyrotaxane, and particularly has the above-mentioned chemical crosslinking structure, the polymer of the present invention can retain properties such as elasticity, particularly superelasticity, and thereby the structural precursor. A medical structure that follows the deformation can be provided.

Hereinafter, each structure of the polyrotaxane contained in the polymer of the structure of the present invention will be described.
<< Cyclic molecule >>
The cyclic molecule is not particularly limited as long as it is a molecule in which a linear molecule is included in a skewered manner in the opening.
The cyclic molecule may be a cyclic molecule having a hydroxyl group, and may be selected from the group consisting of α-cyclodextrin, β-cyclodextrin and γ-cyclodextrin, for example. When the cyclic molecule has a hydroxyl group, a part of the hydroxyl group may be substituted with another group. Examples of other groups include a hydrophilizing group that hydrophilizes the polyrotaxane of the present invention, a hydrophobizing group that hydrophobizes the polyrotaxane of the present invention, and a photoreactive group. Not.

<< Linear molecule >>
The linear molecule of the polyrotaxane of the present invention is not particularly limited as long as it can be clasped into the opening of the cyclic molecule.
For example, as linear molecules, polyvinyl alcohol, polyvinyl pyrrolidone, poly (meth) acrylic acid, cellulosic resins (carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, etc.), polyacrylamide, polyethylene oxide, polyethylene glycol, polypropylene glycol, polyvinyl Polyolefin resins such as acetal resins, polyvinyl methyl ether, polyamines, polyethyleneimine, casein, gelatin, starch, and / or copolymers thereof, polyethylene, polypropylene, and copolymers of other olefin monomers; Polyester resins, polyvinyl chloride resins, polystyrene resins such as polystyrene and acrylonitrile-styrene copolymer resins, polymethyl Acrylic resins such as tacrylate, (meth) acrylic acid ester copolymer, acrylonitrile-methyl acrylate copolymer resin, polycarbonate resin, polyurethane resin, vinyl chloride-vinyl acetate copolymer resin, polyvinyl butyral resin, etc .; and their derivatives or Modified products, polyisobutylene, polytetrahydrofuran, polyaniline, acrylonitrile-butadiene-styrene copolymer (ABS resin), polyamides such as nylon, polyimides, polydienes such as polyisoprene and polybutadiene, polysiloxanes such as polydimethylsiloxane , Polysulfones, polyimines, polyacetic anhydrides, polyureas, polysulfides, polyphosphazenes, polyketones, polyphenylenes, polyhaloolefins, and the like Preferably selected from the group consisting of these derivatives. For example, it may be selected from the group consisting of polyethylene glycol, polyisoprene, polyisobutylene, polybutadiene, polypropylene glycol, polytetrahydrofuran, polydimethylsiloxane, polyethylene, polypropylene, polyvinyl alcohol and polyvinyl methyl ether. More specifically, it may be selected from the group consisting of polyethylene glycol, polypropylene glycol, polytetrahydrofuran, polydimethylsiloxane, polyethylene, and polypropylene, particularly polyethylene glycol.

The linear molecule should have a molecular weight of 3,000 or more, preferably 20,000 or more, more preferably 35,000 or more.
In the polyrotaxane of the present invention, the cyclic molecule may be derived from α-cyclodextrin, and the linear molecule may be polyethylene glycol.

When the amount of cyclic molecules to be included at the maximum when the cyclic molecules are included in a skewered manner by linear molecules is 1, the cyclic molecules are 0.001 to 0.6, preferably 0.00. It is preferable to be included in a skewered manner in a linear molecule in an amount of 01 to 0.5, more preferably 0.05 to 0.4.
The maximum inclusion amount of the cyclic molecule can be determined by the length of the linear molecule and the thickness of the cyclic molecule. For example, when the linear molecule is polyethylene glycol and the cyclic molecule is an α-cyclodextrin molecule, the maximum inclusion amount is experimentally determined (see Macromolecules 1993, 26, 5698-5703). The contents of this document are all incorporated herein.

<< Blocking group >>
The blocking group of the polyrotaxane of the present invention is not particularly limited as long as it is a group that is arranged at both ends of the pseudopolyrotaxane and acts so that the cyclic molecule is not eliminated.
For example, as a blocking group, dinitrophenyl groups, cyclodextrins, adamantane groups, trityl groups, fluoresceins, pyrenes, substituted benzenes (substituents are alkyl, alkyloxy, hydroxy, halogen, cyano, sulfonyl, Examples include, but are not limited to, carboxyl, amino, phenyl, etc. One or more substituents may be present, and polynuclear aromatics that may be substituted (the same as the above as the substituent). The substituent may be one or more, and may be selected from the group consisting of steroids. In addition, it is preferably selected from the group consisting of dinitrophenyl groups, cyclodextrins, adamantane groups, trityl groups, fluoresceins, and pyrenes, more preferably an adamantane group or a trityl group. .

<Medical structure>
In the present invention, the medical structure comprises a structural precursor and a polymer, and has a structure as described in the section <Polymer>. In particular, the medical structure of the present invention may be a medical hollow structure.
The structure body may have a deformation rate of 300% or more, preferably 500% or more, and more preferably 800% or more.
By using a polymer that can follow the characteristics of the structural precursor, particularly a polyrotaxane, the deformation rate can be achieved, and it can be used as various medical structures.
The structure includes a linear body; a cylindrical body; a bag-like body; a cage-like body; and a desired form; a first form selected from the group consisting of: a linear body; a cylindrical body; a bag-like body; And a second form selected from the group consisting of a desired form and different from the first form. In particular, when a medical structure is used, the structure can have the first form before being guided to a desired place in the living body, and can have the second form at the desired place in the living body.

<Application of medical structures>
The above-described medical structure can be used as various medical materials. Hereinafter, examples will be described, but the application fields are not limited thereto.

The medical structure of the present invention can be applied as a tubular prosthesis material selected from the group consisting of a stent graft, an artificial blood vessel, an artificial esophagus, an artificial trachea, an artificial bile duct, an artificial ureter, and an artificial urethra. In addition, as a tubular prosthesis material, it is not limited only to the above.
In the tubular prosthesis, depending on the usage, the dimensions of the structure and the components of the structure (that is, the structural precursor and the polymer) can be appropriately changed.
For example, when used as a stent graft, the stent graft which is the structure of the present invention can be provided at a desired location in the patient's body by the following operation. First, the stent graft which is the structure of the present invention is folded and provided at the distal end portion of the delivery catheter. After the distal end of the delivery catheter is brought close to a desired location in the patient's body, the stent graft folded by the pushing member provided in the delivery catheter is pushed out to the desired location in the patient's body. In the stent graft that is the structure of the present invention, since the structural precursor is made of a superelastic metal and / or shape memory alloy, the extruded stent graft changes to a structure before folding, and the polymer follows the desired structure. A desired structure can be taken at a location.
In addition, there are stent grafts that are expanded at the affected part by a balloon catheter or the like, and those that are self-expanded when placed in the affected part. Even in these cases, the stent graft that is the structure of the present invention is desired. The structure can be taken.

The medical structure of the present invention can be used as a flexible catheter.
As described above, the medical structure of the present invention has a deformation rate of 300% or more, preferably 500% or more, more preferably 800% or more. The material constituting the structure precursor, the structure precursor itself, And / or the structure itself has a proportional elastic region of 2% or more, preferably 4% or more, more preferably 6% or more. Therefore, when the medical structure of the present invention is used as a catheter, a bendable catheter that can adapt to the bending of a body cavity can be obtained.
FIG. 2 is a schematic view of the bendable catheter 1. The bendable catheter 1 in FIG. 2 (a) has a structure part 3 and a hand operating part 5 of the present invention. The structure body 3 includes a structure precursor that is a substantially linear hollow body (not shown) and a polymer on the outer surface of the structure precursor.
FIG. 2B is a schematic view in which the structure 3 of the bendable catheter 1 is inserted into the bent body cavity 7. The structure part 3 can be bent in accordance with the bent part of the body cavity 7 of the patient 9.

  The medical structure of the present invention is preferably used for an application selected from the group consisting of a reservoir, a drainage bag, and an artificial bladder.

The medical structure of the present invention can be used for a tubular medical device having a medical flange, for example, a drainage tube, a catheter, a cannula, etc. having a medical flange.
After surgery, such as laparotomy or thoracotomy, where the incision is made and the organ is treated, a drainage tube is inserted for bleeding and exudate discharge after the operation, and the affected area recovers. When the liquid stops, remove these intubations. However, these intubations are troublesome if they come off during use, so a structure that does not come off is necessary, and protrusions for preventing the removal are made, but this is not sufficient. In addition, if a large protrusion is made, it is difficult to intubate except during surgery. For this reason, it is preferable that it has a diameter close to that of the tube at the time of insertion (referred to as a non-profile), greatly expands in the body, and preferably expands in a bowl shape. In addition, a bowl-shaped body or a board-shaped body is called a flange here.
In addition, if something outside the body of the tube is pushed into the body, there is a possibility that bacteria will enter the body. For this reason, not only the flange in the body but also a tube having a rod-like body outside the body, that is, a tube having a plurality of flanges is preferable so that the tube is not pushed.
Furthermore, in the cardiovascular treatment, a cannula is used for blood removal and blood transmission from the atria and ventricles, but these also have a flange to prevent the removal, like the drainage tube, to prevent infection. Similarly, a cannula having a plurality of flanges is preferable.

In other words, the tubular medical device having the medical flange has the following configuration.
That is, the medical structure is a tubular medical device having a tubular body and a first flange portion, and the tubular medical device has a tubular shape whose diameter is substantially the same as the diameter of the tubular body when the tubular body is inserted. The first flange portion has a second shape that becomes a first rod-like body having a diameter larger than the diameter of the tubular body insertion port when the tubular medical device is added. The first flange is disposed in the vicinity of the insertion slot and disposed in the insertion slot.
If desired, the tubular medical device has a second flange portion on the distal side of the insertion port, and when the tubular medical device is added, the second flange portion has a diameter larger than the diameter of the tubular body insertion port. It has the 2nd form used as the 2nd bowl-like body, and this 2nd flange is arranged near the insertion slot, and is arranged outside the insertion slot.
Note that the tubular body is preferably arranged on the far side of the second flange from the insertion port. Further, if desired, the tubular body may be disposed further ahead of the first flange.

FIG. 3 is a schematic view of the tubular medical device 11 having the tubular body 12 and the first flange portion 14.
The tubular body 12 includes a distal end portion 15 and a proximal portion 16, and a groove portion 17 between the distal end portion 15 and the proximal portion 16. The tubular body 12 is provided in a tubular interior 18 of a tubular fixing portion 13 having a portion 19 that becomes the first flange portion 14. The first flange portion is tubular before the tubular medical device is inserted into the patient body cavity, and the distal end of the first flange portion 14 is fixed to the distal end portion 20 and the proximal side is fixed to the tubular fixing portion proximal portion 18. The tubular fixing portion 13 includes a maintenance member 21 that maintains the flange state of the flange portion 14.
The tubular medical device 11 is inserted into the patient body cavity through the holes 23a and 24a of the body cavity fastener 23 and the body cavity fastener 24 provided in the patient body cavity, as shown in FIG.
Next, as shown in (B), the tubular medical device 11 has a protrusion (not shown) provided on the distal end portion 15 of the tubular body by pulling the tubular body 12 in the proximal side, that is, in the X direction. The locking portion 13 is engaged with a groove portion (not shown) provided at the distal end portion 20. Further, by fixing the tubular fixing portion proximal portion 18 in the vicinity of the holes 23a and 24a, the flange portion 14 gradually changes from a substantially ball shape as shown in FIG. To change.
Further, by pulling the tubular body 12 in the X direction, the flange portion 14 becomes a flange shape as shown in FIG. Further, in order to maintain the flange shape, the button 25 of the maintaining member 21 is pushed to lock the button lower portion 26 with the groove portion 17 provided in the tubular body 12.
On the other hand, although not shown, when the tubular medical device 11 is detached from the patient's body cavity, the button 25 is pressed in (C) to release the locking between the button lower portion 26 and the groove portion 17 and the tubular body 12 is moved in the X direction. By reversing, since the flange portion 14 is deformed from a flange shape to a tubular shape, the tubular medical device 11 can be easily detached from the patient's body cavity.
In FIG. 3, the flange portion is illustrated as being composed only of the structural precursor of the braided body, but this is merely for the sake of understanding, and in fact, the flange portion is a polymer in the structural precursor (skeleton). Is a structure according to the present invention.

The medical structure of the present invention can be used for a structure substantially consisting only of a medical flange, such as a catheter for treating an atrial septal defect.
In this case, the catheter for treating an atrial septal defect has a first form which is a cylindrical body having a diameter smaller than the diameter of the atrial septal defect when the catheter is inserted, and the diameter of the atrial septal defect is increased when the catheter is added. Having a first diameter and a second flange portion having a large diameter, and a link portion having a desired length connecting the first flange portion and the second flange portion to communicate with the atrial septal defect. Is good.

The catheter for treating an atrial septal defect can be laid by the following method.
That is, an atrial septal defect having a desired length communicating with the atrial septal defect; first and second flange portions arranged at both ends of the associated part and having a diameter larger than the diameter of the atrial septal defect A method of laying a therapeutic catheter,
xi) storing the atrial septal defect treatment catheter in a cylindrical insertion tube;
xii) communicating the tubular insertion tube to the atrial septal defect;
xiii) a step of extruding the first pushing portion of the catheter for treating atrial septal defect from the cylindrical insertion tube on the communication distal side, and using the first pushing portion as the first flange portion;
xiv) Further, the second push-out portion of the atrial septal defect treatment catheter is pushed out from the cylindrical insertion tube on the communication proximal side, and the second push-out portion is connected to the linkage portion and the second flange portion. The step of:
It can be laid by a method having

FIG. 4 is a schematic view illustrating an atrial septal defect treatment catheter 31 and a method for laying it.
The atrial septal defect treatment catheter 31 includes a distal end portion 33, a first flange portion 34, an association portion 35, a second flange portion 36, and a proximal portion 37. The structural precursors of the first flange portion 34 and the second flange portion are made of a shape memory alloy in the example.
The atrial septal defect treatment catheter 31 is disposed on the distal end side of the cylindrical insertion tube 41, and the pushing portion 43 is disposed on the proximal side of the cylindrical insertion tube 41.
4A to 4E illustrate a method of laying the catheter 31 for treating the atrial septal defect.
First, as shown in FIG. 4 (A), the distal end of the cylindrical insertion tube 41 in which the catheter 31 for atrial septal defect treatment and the push-out portion 43 are arranged is pushed onto a fastener 51 provided in the atrial septal defect. The pushing portion 43 is pushed out in the X direction, and the distal end portion 33 and the first flange portion 34 are provided in the patient body cavity.
Thereafter, since the structural precursor of the first flange portion 34 is made of a shape memory alloy as described above, the first flange portion 34 has a ball-like shape (((B) and (C)). B)) to a flange shape ((C)).
Next, as shown in FIG. 4D, the cylindrical insertion tube 41 is pulled in the Y direction so that the linkage part 35 is disposed in the fastener 51, and the push-out part 43 is moved in the X direction as necessary. Extrude. As a result, the second flange portion 36 is exposed from the cylindrical insertion tube 41, and the structural precursor of the second flange portion 36 is made of the shape memory alloy as described above. As shown in 4 (D), it changes into a ball shape.
Furthermore, by exposing the second flange portion 36 and the hand portion 37 from the cylindrical insertion tube 41, the second flange portion 36 changes to a flange shape as shown in FIG.
Thereby, the catheter which closes an atrial septal defect | deletion part can be provided.
In FIG. 4, the fastener 51 is used, but this may or may not be used as desired. Further, in FIG. 4, the flange portion is illustrated as being composed of only the structural precursor of the braided body, but this is merely for the sake of understanding. In fact, the flange portion is made of polymer on the structural precursor (skeleton). Is a structure according to the present invention.

<Method for producing medical structure>
The medical structure described above can be manufactured by the following method.
That is, first, a structural precursor that is a framework is prepared.
Next, a polymer is thickened on the surface of the structural precursor to form a medical structure. In general, for example, a structural precursor is put into a tubular body, a polymer precursor such as a monomer or oligomer solution is injected into the tubular body, and then the polymer precursor is polymerized while rotating the tubular body. Thus, a polymer structure can be formed on the surface of the structural precursor to form a medical structure. The tubular body into which the structural precursor is put can be made of a desired polymer, and the structural body can be integrally formed.
EXAMPLES Hereinafter, although this invention is demonstrated further in detail based on an Example, this invention is not limited to a present Example.

An SUS316 tube (outer diameter 4 mm, wall thickness 0.3 mm, length 120 mm) was used as a material for the structural precursor, and this was cut into a pattern as shown in FIG. 5 by a YAG laser and chemically polished.
The stent skeleton wraps the outer periphery of the stent with 8 folds of the stent struts (zigzag folds) and 8 folds. The connecting element between the struts was 7 mm long, and the strut width was 0.5 mm. One stent skeleton has nine struts and six strut connecting elements that are offset by 60 ° between the struts, and the adjacent strut connecting elements are arranged so as to be offset from each other by approximately 30 °. The number of elements was 48.

Next, a polyrotaxane sleeve having an outer diameter of 4.0 mm and a wall thickness of 0.5 mm was produced.
The polyrotaxane sleeve uses α-cyclodextrin as a cyclic molecule, polyethylene glycol (molecular weight: 35,000) as a linear molecule, adamantaneamine as a blocking group, and 1,4-butanediol diglycidyl ether (BDGE) as a crosslinking agent. Was prepared by substantially the same method as described in WO2001-083566 and WO2005-080469 (the contents of this document are all incorporated herein by reference).
A polyrotaxane sleeve was placed outside the previously obtained stent skeleton, and a polyrotaxane solution (same as the one prepared from the polyrotaxane sleeve) was applied also from the inside, and integrated with the stent skeleton to obtain a stent SA-1.

  Stent SA-2 was obtained in substantially the same manner as in Example 1, except that a Zr—Al—Cu amorphous alloy was used as the material for the structural precursor.

(Comparative Examples 1 and 2)
In Examples 1 and 2, polyurethane of the same size (Pelecene 80A) was used instead of the polyrotaxane sleeve having an outer diameter of 4.0 mm and a wall thickness of 0.5 mm, and polyurethane (Pelecene 80A) was used instead of the inner polyrotaxane. Except that, stents SC-1 and SC-2 were obtained in the same manner as in Example 1.

(Stent evaluation)
Regarding the stents SA-1, SA-2, SC-1 and SC-2 of Examples 1 and 2 and Comparative Examples 1 and 2, the properties required for the stent, <passability> and <expandability> were examined. It was.
<Passability>
The simulation circuit shown in FIG. 6 was used. That is, two semicircular circles with R = 25 were connected, and the passability of an S-shaped 10φ simulated circuit (in water) was evaluated.
The sample stent was delivered with a balloon catheter with an expansion diameter of 35 mm (outer diameter before expansion) and a PTA balloon with 10 F (3.3 mmφ). The results are shown in Table 1.
In Table 1, “A”: easy delivery and no deformation (“AA” is particularly good); “B”: delivery is possible but resistance is large or deformation; “C”: cannot pass; Indicates.

<Extensibility>
The expandability with the dilatation catheter was evaluated. The results are shown in Table 1.
In Table 1, “A”: expanded to a predetermined diameter; “B”: expanded only partially; “C”: failed to expand;

  From Table 1, it can be seen that the stents of Examples 1 and 2 show good results in both <passability> and <expandability> and have the characteristics required for the stent. On the other hand, it can be seen that the stents of Comparative Examples 1 and 2 have no problem in <passability> but do not have the characteristics required for the stent in <expandability>.

A polyrotaxane (wall thickness: 0.2 mm, length: 150 cm) was molded using a rod having an outer diameter of 3 mm as a core (mandrel). Here, the polyrotaxane was molded from a polyrotaxane solution prepared in the same manner as in Example 1.
On the obtained polyrotaxane molded body, a braided body (length: 150 cm) was formed at a braid density of 13 using a 100 μm superelastic wire (Ni / Ti = 55.9 / 44.01 (wt%)).
A polyrotaxane was further formed on the braided body so as to have a thickness of 0.2 mm, to obtain a superelastic body / polyrotaxane composite tube TA-1. The core of this tube was removed. In addition, the polyrotaxane used the same preparation as the above.
Further, a flexible adhesive resin was applied to the tip of the tube, and the tip was rounded.
A catheter base having a luer lock structure was injection-molded with a resin such as nylon 12, and the proximal portion of the tube TA-1 was inserted and bonded and fixed to obtain a catheter CA-3.

(Comparative Example 3)
In Example 3, catheter CC-3 was obtained in the same manner as in Example 3 except that urethane (peresen hardness 65D) was used instead of polyrotaxane.

The insertion properties of the catheters CA-3 and CC-3 obtained in Example 3 and Comparative Example 3 were evaluated.
Evaluation is made about whether or not the circuit as shown in FIG. 6 is made of polycarbonate (transparent), put into a water tank, and the catheter CA-3 or CC-3 is inserted from the entrance (1) and can pass through this circuit. Tested.
As a result, the catheter CA-3 (Example 3) was able to pass without problems, whereas the catheter CC-3 (Comparative Example 3) was struck by the second curve and could not pass.
From this result, it is considered that the catheter of the present invention (catheter CA-3 (Example 3)) can easily pass through tubular tissues (such as blood vessels and gastrointestinal tracts) that are subject to large deformations that cannot be considered in the past. It is done.

A super elastic nitinol wire (NiTi = 55.99 / 44.01 (wt%)) with a wire diameter of 50 μm and an AF point of 5 ° C. was used, and a hollow body was formed by braiding a 2 mm core into a braid. A platinum ring and a platinum cap were used for the entrance and exit of this hollow body, and laser welding and fixing were performed.
The hollow body was crushed from both sides with the core body inserted, deformed into two continuous and overlapping discs whose diameter was increased to 20 mm (10 mm to 30 mm), and the shape was fixed with a fixing jig. . This was heat-treated at 450 ° C. for 30 minutes to memorize this shape.
After removing the core and storing the shape, the hollow body was dipped in polyrotaxane and the wire was coated. The polyrotaxane used was a polyrotaxane solution prepared with the same composition as in Example 1.

The hollow body was returned to a shape close to the original cylindrical shape by using a spacer jig to separate the two disks, and in this state, a polyrotaxane tube was fitted.
Both ends of the polyrotaxane tube were tied and fixed to a platinum ring or platinum cap with a platinum fine wire (10 μm).
The polyrotaxane coated on the wire and the polyrotaxane fitted on the sleeve were partially compatible with each other, and the sleeve was stably fixed to the wire hollow body.
This wire passes through the polyrotaxane composite hollow body, pushes the cap on the distal side from the inside, keeps the proximal side, keeps the distance between both ends, and mounts it on the indwelling jig to make it nearly cylindrical And placed in a delivery catheter. This was double aseptic packaged and sterilized to obtain Product A-4.

The atrial septal defect treatment catheter of this example was used as a model in the same manner as in FIG. In other words, during use, the catheter is approached to the heart model minimally invasively via the blood vessel, the distal half of the product is passed through the atrial septal wall, pushed out of the delivery catheter, and the hollow body indwelling jig is loosened, Recover the memorized disk shape and fix it to the left ventricular side of the atrial septal defect (eggular foramen), then push it out to the proximal side of the hollow body, loosen the jig, and distance between both ends of the hollow body The two discs were restored.
Since the polyrotaxane was flexible, it was able to restore the shape close to the original shape of the wire braid and close the foramen.

(Comparative Example 4)
A delivery catheter product C-4 was obtained in the same manner as in Example 5, except that polyurethane (Tecoflex, hardness 80A) was used instead of the polyrotaxane of Example 4.
However, when the product C-4 was used, the original shape could not be sufficiently recovered even when the indwelling jig was opened. Therefore, the oval hole could not be sufficiently sealed.

Claims (10)

A medical structure comprising: a structural precursor; and a polymer formed on a surface of the structural precursor,
The polymer has a polyrotaxane, and the polyrotaxane has blocking groups arranged at both ends of the pseudopolyrotaxane in which the opening of the cyclic molecule is skewered by a linear molecule so that the cyclic molecule is not detached. And
The medical structure, wherein the polymer forms an outer surface of the medical structure.   The structure according to claim 1, wherein the deformation rate of the structure is 300% or more.   The structure according to claim 1 or 2, wherein the material constituting the structural precursor has a proportional elastic region of 2% or more.   The structure according to any one of claims 1 to 3, wherein a proportional elastic region of the structural precursor itself is 2% or more.   The structure according to any one of claims 1 to 3, wherein a proportional elastic region of the structure itself is 2% or more.   The structural precursors are: i) superelastic alloy; ii) amorphous alloy; iii) rubber metal, iv) shape memory alloy; v) nylon fiber; vi) carbon fiber; vii) boron fiber; viii) polyimide fiber; The structure according to any one of claims 1 to 5, which comprises at least one material selected from Group A consisting of :)) polyetherimide fiber.   The structure according to claim 6, wherein the structural precursor is made of at least one material selected from the group A.   The structural precursor has at least one structure selected from the group B consisting of a braided body made of a thin wire; a stranded wire made of a thin wire; a coil body; a thin plate cutout body; and a cylindrical cutout body. The structure according to any one of claims 1 to 7.   The structure according to claim 1, wherein the structure is a hollow body.   The structure is a linear body; a cylindrical body; a bag-like body; a cage-like body; and a desired form; a first form selected from the group consisting of: a linear body; a cylindrical body; a bag-like body; The structure according to any one of claims 1 to 9, wherein the structure is variable to a second form selected from the group consisting of a cage; and a desired form and different from the first form.

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