1
5 fOOOlj
The present invention belongs to the field of medical instruments, and relates
to, in particular, an endovascular treatment aiding device for capturing free thrombi
or the like during percutaneous treatment for a blood vessel.
BACKGROUND ART
10 [0002]
In recent years, the number of patients with cardiac infarction., cerebral
infarction, or the like is increasing. These infarctions are caused by interruption of
blood flow due to obstruction or stenosis of a blood vessel, which occurs by
deposition of thrombi, plaques, or the like on the vascular wall. In general, for
15 treatment of a site of obstruction or stenosis in a blood vessel, percutaneous treatment
by balloon angioplasty or stenting using a balloon catheter or a stent is carried out. [0003J
In treatment by balloon angioplasty, an inflatable balloon at the distal end
portion of a balloon catheter is expanded at a site of obstruction or stenosis in a blood
2 0 vessel to secure the intravascular lumen and to thereby maintain the blood flow.
However, when a blood vessel is expanded by the balloon, thrombi or plaques
deposited on the vascular wall might be unexpectedly released, and such a substance
might then be carried away by blood flow to cause obstruction of a peripheral thin
blood vessel, resulting in infarction.
2 5 [0004]
In treatment by stenting, a stent composed of a material such as nitinol or cobalt alloy having the shape of an almost cylindrical tube or mesh sleeve is

9
pemianently or temporarily introduced to a site of stenosis in a blood vessel to secure
the intravascular lumen and to thereby maintain the blood flow. However, similarly
to the case of balloon angioplasty, when the stent is placed in a blood vessel, thrombi
or plaques deposited on the vascular wall might be unexpectedly released, causing
5 infarction.
[0005]
In order to avoid such a risk, an endovascular treatment aiding device to be used in combination with a treatment device such as a balloon catheter or a stent has been developed. The endovascular treatment aiding device is percutaneousiy placed
10 in a site which is more peripheral than the lesion where the balloon catheter or the
stent is to be placed, and used for capturing thrombi or plaques released from the vascular wall. [0006]
As such an endovascular treatment aiding device, one having a structure
15 containing: a shaft with an outer diameter which allows the shaft to pass through the
guide wire lumen of a treatment device such as a balloon catheter; and a filter fixed in the distal side of the shaft; has been reported. The filter has a mesh-shaped or sheet-shaped membrane composed of a poiymer material on which a plurality of openings are formed, and has a shape in which the peripheral vessel side, that is, the
2 0 distal side, is closed, and the central vessel side, that is, the proximal side, is open
(Patent Document 1). [0007]
By this, during treatment using a treatment device such as a balloon catheter, thrombi or plaques released and carried away from the vascular wall can be captured
2 5 by the filter constituting a part of the endovascular treatment aiding device placed in
the peripheral side, without blocking the blood flow. [0008]

3
When such an endovascular treatment aiding device is used, the endovascular
treatment aiding device, with its filter closed, is contained in a delivery sheath, and
delivered to the site where the device is to be placed, which is located more
peripheral than the lesion. After the delivery, the filter is released by removal of the
5 delivery sheath to the outside of the body. This causes self-expansion of the
opening section of the filter, thereby allowing close contact of the opening section to the vascular wall. When the endovascular treatment aiding device is to be retrieved, a retrieval sheath is delivered along the endovascular treatment aiding device, and the filter containing thrombi or plaques is stored inside the retrieval sheath, followed by
10 its removal to the outside of the body.
[0009]
As an endovascular treatment aiding device that enables reduction of leakage of thrombi, plaques, or the like by increasing adhesion to the vascular wall, an endovascular treatment aiding device comprising a ring-shaped member formed with
15 a superelastic metal provided in the opening section of the filter, wherein, by folding
the ring-shaped member by bundling of a supporting member that acts as a support between the shaft and the ring-shaped member, the filter can be folded into a bag shape, has been reported (Patent Document 2). [0010]
20 When such an endovascular treatment aiding device is placed in a blood
vessel, the living body recognizes it as a foreign substance, and blood coagulation reaction proceeds to cause formation of a thrombus. Therefore, antithrombogcnicity is required for the device. In view of this, endovascular treatment aiding devices to which antithrombogenic compounds are given have been reported (Patent Documents
2 5 3 to 5).
PRIOR ART DOCUMENTS [Patent Documents]

4
L0011]
[Patent Document 1] JP 2008-35923 A
[Patent Document 2] JP 4073869 B
[Patent Document 3] WO 2003/084437
5 [Patent Document 4] WO 2008/005898
[Patent Document 5] WO 2013/059069
SUMMARY OF THE INVENTION
PROBLEMS TO BE SOLVED BY THE INVENTION
[0012]
10 However, in the endovascular treatment aiding device described in Patent
Document 1, contacting with the stent may occur during delivery of a retrieval sheath
because of the thick diameter of the distal end of the retrieval sheath, so that there is
a possibility that the retrieval sheath cannot be delivered to the filter. Moreover,
since the opening section of the filter does not have a ring shape, its adhesion to the
15 vascular wall is insufficient, so that there is a possibility of leakage of thrombi,
plaques, or the like during, treatment using a balloon catheter or the like.
[0013]
In the endovascular treatment aiding device described in Patent Document 2,
a sudden diameter transition like step is generated between the opening section of the
2 0 filter and the shaft when the filter is in the closed state. Therefore, when the
endovascular treatment aiding device is used at the same time as a treatment device
such as a balloon catheter or a stent, there is a possibility that the end portion of the
stent or the distal end portion of the guiding catheter is caught in the step generated
between the opening section of the filter and the shaft, and a part of the filler is
2 5 turned up, leading to leakage of the thrombi or the plaques captured.
[0014]
Although Patent Documents 3 to 5 describe giving of antithrombogenic

5
compounds to endovascular treatment aiding devices, there is no description on the
optimal types and combinations of the antithrombogenic compounds.
[0015]
That is, conventionally, there is no known endovascular treatment aiding
5 device which solves both of the two problems, that is, there is no known
endovascular treatment aiding device which, during its retrieval, securely allows
delivery of a retrieval sheath to the filter, and which can prevent the filter with
captured thrombi or plaques from being caught in a device such as a stent or a
guiding catheter.
10 [0016]
In view of this, the present invention aims to provide an endovascular
treatment aiding device which, during its retrieval, securely allows delivery of a
retrieval sheath to the filter, and which can prevent the filter with captured plaques or
the like from being caught in a treatment device such as a stent or a guiding catheter.
15 MEANS FOR SOLVING THE PROBLEMS
[0017]
Jn order to solve the problems described above, the present inventors
intensively studied to discover the following inventions (1) to (13).
[0018]
20 (1) An endovascular treatment aiding device comprising:
a flexible shaft;
a filter fixed to the shaft such that a closed-end section is formed in the distal
side in the longitudinal direction of the shaft, and an opening section is formed in the
proximal side in the longitudinal direction, which filter can be opened and closed in
2 5 an umbrella-like manner;
a supporting member composed of linear members each of which is fixed to the end portion in the opening-section side of the filter and a part of the shaft such

6
that these are connected to each other, which Hnear members enable to close the filter by tension caused by application of an external force to the proximal side in the longitudinal direction; and
an elastomer member which is a member composed of an elastomer in which
5 a penetrating hole (A) is formed, the elastomer member being arranged in the
proximal side in the longitudinal direction relative to the opening section of the filter such that the shaft penetrates the penetrating hole (A), wherein the outer diameter of the end face in which the penetrating hole (A) is formed is larger than the outer diameter of the opening-section side of the filter when the filter is closed;
10 and comprising:
an outer tube in which a penetrating hole (B) is formed, the outer tube being arranged in the proximal side in the longitudinal direction relative to the opening section of the filter such that the shaft penetrates the penetrating hole (B) in a state which allows movement of the shaft in the longitudinal direction;
15 wherein the elastomer member is fixed in the distal side in the longitudinal direction
of the outer tube. [0019]
(2) The endovascular treatment aiding device according to (1), further comprising
an annular member in which a penetrating hole (C) is formed, the annular member
20 being arranged in the proximal side in the longitudinal direction relative to the
opening section of the filter such that the shaft penetrates the penetrating hole (C) in a state which allows movement of the shaft in the longitudinal direction, the annular member having a thick section whose outer diameter is smaller than the outer diameter of the opening-section side of the filter when the filter is closed, and whose
2 5 outer diameter is larger than the inner diameter of the elastomer member.
[0020]
(3) The endovascular treatment aiding device according to (1) or (2), wherein,

7
when the outer tube is slid toward the distal side in the longitudinal direction, the
filter is closed by bundling of the supporting member.
[0021]
(4) The endovascular treatment aiding device according to any one of (1) to (3),
5 wherein, when the outer tube is slid toward the distal side in the longitudinal
direction to close the filter, the endovascular treatment aiding device can have a
shape in which the elastomer member covers the thick section, and the thick section
is pressed into the penetrating hole (A).
[0022]
10 (5) The endovascular treatment aiding device according to any one of (1) to (4),
which can be contained in a sheath when the filter is in a closed state.
[0023]
(6) The endovascular treatment aiding device according to any one of (1) to (5),
wherein a cationic polymer containing, as constituent monomers, at least one
15 compound selected from the group consisting of alkyleneimine, vinylamine,
allylamine, lysine, protamine, and diallyldimethylammonium chloride is covalently
bound to the filter, and an anionic sulfur compound having anticoagulant activity is
bound to the filter and/or the cationic polymer.
[0024]
20 (7) The endovascular treatment aiding device according to any one of (1) to (6),
wherein the ratio of the abundance of nitrogen atoms to the abundance of total atoms
on the surface of the filter as measured by X-ray photoelectron spectroscopy (XPS) is
7.0 to 12,0 atomic percent.
[0025]
2 5 (8) The endovascular treatment aiding device according to any one of (1) to (7),
wherein the ratio of the abundance of sulfur atoms to the abundance of total atoms on
the surface of the filter as measured by X-ray photoelectron spectroscopy (XPS) is

8
3.0 to 6.0 atomic percent. [0026J
(9) The endovascular treatment aiding device according to any one of (1) to (8),
wherein the anionic sulfur compound having anticoagulant activity is at least one
5 selected from the group consisting of heparin and heparin derivatives.
[0027]
(10) The endovascular treatment aiding device according to any one of (1) to (9),
wherein the surface amount of the anionic sulfur compound having anticoagulant
activity on the filter after soaking in physiological saline at 37°C for 30 minutes as
10 measured based on the anti-factor Xa activity is not less than 30 mlU/cm .
[0028]
(11) The endovascular treatment aiding device according to any one of (1) to (10),
wherein the cationic polymer and the anionic sulfur compound having anticoagulant
activity form an antithrombogenie compound layer with a thickness of 1 to 600 nm
15 on the surface of the filter.
[0029]
(12) The endovascular treatment aiding device according to any one of (1) to (11),
wherein the filter is formed with polyester.
EFFECT OF THE INVENTION
2 0 [0030]
The present invention can provide an endovascular treatment aiding device wherein, since the outer diameter of the distal side in the longitudinal direction of the elastomer member is larger than the outer diameter of the opening section of the filter when the filter is closed, the step present between the opening section of the filter
25 and the shaft can be covered, so that the endovascular treatment aiding device can be
prevented from being caught in a device such as a stent or a guiding catheter during its retrieval.

9
BRIEF DESCRIPTION OF THE DRAWINGS [0031]
Fig. 1 is a schematic view showing a side view, in the longitudinal direction,
of the endovascular treatment aiding device according to an embodiment of the
5 present invention.
Fig. 2 is a schematic view showing a front view, in the longitudinal direction,
of the endovascular treatment aiding device according to an embodiment of the
present invention, wherein the positional relationships among the filter, the ring, and
the supporting member in the filter section are illustrated.
10 Fig. 3 is a schematic view showing a side view, in the longitudinal direction,
of the endovascular treatment aiding device according to an embodiment of the present invention, wherein the opening section of the filter section is closed.
Fig. 4 is a schematic view showing a side view, in the longitudinal direction,
of the endovascular treatment aiding device according to Comparative Example 1 in
15 the present invention.
MODE FOR CARRYING OUT THE INVENTION [0032]
The endovascular treatment aiding device of the present invention comprises:
a flexible shaft;
2 0 a filter fixed to the shaft such that a closed-end section is formed in the distal
side in the longitudinal direction of the shaft, and an opening section is formed in the proximal side in the longitudinal direction, which filter can be opened and closed in an umbrella-like manner;
a supporting member composed of linear members each of which is fixed to
2 5 the end portion in the opening-section side of the filter and a part of the shaft such
that these are connected to each other, which linear members enable to close the filter by tension caused by application of an external force to the proximal side in the

10
longitudinal direction; and
an elastomer member which is a member composed of an elastomer in which
a penetrating hole (A) is formed, the elastomer member being arranged in the
proximal side in the longitudinal direction relative to the opening section of the filter
5 such that the shaft penetrates the penetrating hole (A), wherein the outer diameter of
the end face in which the penetrating hole (A) is formed is larger than the outer diameter of the opening-section side of the filter when the filter is closed; and comprises:
an outer tube in which a penetrating hole (B) is formed, the outer tube being
10 arranged in the proximal side in the longitudinal direction relative to the opening
section of the filter such that the shaft penetrates the penetrating hole (B) in a state which allows movement of the shaft in the longitudinal direction; wherein the elastomer member is fixed in the distal side in the longitudinal direction of the outer tube.
15 [0033]
Specific embodiments of the present invention are described below with reference to drawings. However, the present invention is not limited to these embodiments. Each identical element is represented using an identical symbol, and redundant explanations are omitted. The ratios used in the drawings are not
20 necessarily the same as those in the description. The following terms used in the
present description are defined as described below unless otherwise specified. [0034]
Fig. 1 is a schematic view showing a side view, in the longitudinal direction, of the endovascular treatment aiding device 1 according to an embodiment of the
2 5 present invention. The endovascular treatment aiding device 1 shown in Fig. 1 can
pass through the inside of a guide wire lumen of a treatment device such as a balloon catheter, and comprises: a linear shaft 2 having flexibility; a filter section 3 which

11
can capture thrombi, plaques, or the like; an annular member 4 having a thick
section; an outer tube 5 arranged in the proximal side in the longitudinal direction
relative to the annular member 4; and an elastomer member 6.
[0035]
5 The shaft 2 preferably has flexibility to achieve secure delivery to the
peripheral side relative to the lesion where the treatment device is lo be placed. The term "having flexibility" herein means that the original shape of the shaft can be recovered after bending the shaft at an angle of 180° such that the radius of curvature is 100D, wherein D represents the diameter of the shall.
10 [0036]
The filter section 3 comprises: a filter 7 in which a plurality of openings are formed, which filter 7 is arranged in the distal side in the longitudinal direction of the shaft 2, and can be opened and closed in an umbrella-like manner; a ring 8 having a circular shape which is provided in the proximal side in the longitudinal direction of
15 the filter 7, that is, the opening-section side of the filter 7, which ring 8 is composed
of a flexible wire having elastic restoring force; and a supporting member 9 composed of linear members arranged between the shaft 2, and the filter 7 and the ring 8, such that the filter 7 can be closed by tension caused by application of an external force to the proximal side in the longitudinal direction. The distance
2 0 between the distal side in the longitudinal direction of the filter 7 and the distal side
of the shaft 2 is preferably 5 lo 20 mm, more preferably 10 to 15 mm. The distance between the distal side in the longitudinal direction of the balloon portion of the balloon catheter and the proximal side in the longitudinal direction of the filter 7 is preferably not more than 10 mm.
2 5 [0037]
Here, the distal side in the longitudinal direction means the peripheral side of the blood vessel, and the proximal side in the longitudinal direction means the central

12
side of the blood vessel. [0038]
The annular member 4, in which a thick section and a penetrating hole (C) are
formed, is movably arranged on the shaft 2 so that it can be arranged at a position
5 where it contacts the proximal side in the longitudinal direction of the filter section 3
when the filter section3 is closed. The annular member 4 can therefore be slid on the shaft 2. [0039]
Here, the thick section is a portion on the annular member 4 where the
10 diameter in the direction vertical to the longitudinal direction is locally increased.
The thick section is preferably a portion where the outer diameter is smaller than the outer diameter of the opening-section side of the filter section 3 when the filter section 3 is closed, and where the outer diameter is larger than the inner diameter of the elastomer member 6.
15 [0040]
The outer tube 5, in which a penetrating hole (B) is formed, is movably arranged on the shaft 2. It can therefore slide on the shaft 2. For improving the kink resistance of the shaft 2, and securing the rigidity required for closing the filter section 3, a braided layer using a metal wire such as a stainless steel wire or using a
2 0 resin such as a polyamide may be incorporated in the outer tube 5.
[0041]
The elastomer member 6, in which a penetrating hole (A) is formed, is movably arranged on the shaft 2 in the proximal side in the longitudinal direction relative to the opening section of the filter section 3. The elastomer member 6 can
2 5 therefore slide on the shaft 2. During the operation, for adjusting the position of
placement of the endovascular treatment aiding device 1 in the blood vessel, the outer tube 5 in the operator side, where the operator manipulates the device, may be

13
slid toward the distal side or the proximal side in the longitudinal direction. Thus,
the proximal end portion in the longitudinal direction of the elastomer member 6 is
preferably fixed to the distal end portion in the longitudinal direction of the outer
tube 5 since, without the fixation, the elastomer member 6 may not follow the sliding
5 of the outer tube 5, and therefore adjustment of the relative positions of the elastomer
member 6 and the filter section 3 may be impossible. [0042]
The filter 7 is fixed to the shaft 2 such that the distal side in the longitudinal direction of the filter 7 is closed. This portion of fixation is provided as the closed-
10 end section. The proximal side in the longitudinal direction of the filter 7 is open.
This portion of opening is provided as the opening section. For increasing adhesion to the vascular wall, the opening section of the filter 7 is preferably fixed to the entire circumference of the ring 8 having a circular shape so that the filter 7 can be opened and closed by movement of the ring 8.
15 [0043]
The supporting member 9 is constituted by a plurality of linear members. In the end portion of the opening-section side of the filter 7, each linear member is fixed to the filter 7 and the ring 8, and, on the shaft 2, the linear members are fixed together to the same position, thereby connecting the filter 7 and the ring 8 to the part of the
2 0 shaft 2. In the embodiment shown in Fig. 1, the supporting member 9 is constituted
by a plurality of linear members. The number of the linear members in the supporting member 9, and the positions in the filter 7 and the ring 8 to which the linear members are fixed, are not limited. The linear members may be in a number with which the filter 7 and the ring 8 can be closed by the supporting member 9.
2 5 The position where the supporting member 9 is fixed on the shaft 2 is also not
limited. The position is preferably in the proximal side in the longitudinal direction relative to the opening section of the filter section 3.

14
[0044]
In the present invention, in order to cover the step formed between the
opening section of the filter section 3 and the shaft 2, and to thereby prevent the
endovascular treatment aiding device 1 from being caught in a device such as a stent
5 or a guiding catheter during retrieval, the end face in the distal side in the
longitudinal direction of the penetrating hole (A) formed in the elastomer member 6 is designed such that its outer diameter can become larger than the outer diameter of the opening-section side of the filter section 3 when its opening section is closed. If the elastomer member 6 after the change in the outer diameter (expansion) has over-
10 covered the filter section 3 in the closed state, the outer diameter of the endovascular
treatment aiding device 1 becomes large, leading to difficulty in the retrieval using a retrieval sheath. Thus, the inner diameter of the end face in the distal side in the longitudinal direction of the penetrating hole (A) formed in the elastomer member 6, after the change in the outer diameter, is preferably smaller than the outer diameter of
15 the opening-section side of the filter section 3 when its opening section is closed.
The elastomer member 6 after the change in the outer diameter (expansion) preferably contains a taper section in which the outer diameter decreases toward the proximal side in the longitudinal direction of the shaft 2, from the viewpoint of preventing the member from being caught in a treatment device.
2 0 [0045]
Fig. 2 is a schematic view showing a front view, in the longitudinal direction, of the endovascular treatment aiding device 1 according to an embodiment of the present invention, wherein the positional relationships among the ring 8 and the supporting member 9 in the filter section 3, and the shaft 2, are illustrated. In this
2 5 embodiment, as shown in Fig. 2, the supporting member 9 is fixed to the ring 8 such
that the circumference of the ring 8 is equally divided at four points. By making the supporting member 9 have a uniform length, the shaft 2 is in a state where it is

15
positioned on the central axis of the ring 8. [0046]
Fig. 3 is a schematic view showing a side view, in the longitudinal direction,
of the endovascular treatment aiding device 1 according to an embodiment of the
5 present invention, wherein the opening-section of filter section 3 is closed. The
inner diameter of the distal side in the longitudinal direction of the penetrating hole (A) formed in the ring-shaped elastomer member 6 is smaller than the outer diameter of the thick section present in the proximal side in the longitudinal direction of the penetrating hole (C) formed in the annular member 4. Therefore, by sliding the
10 elastomer member 6, or the outer tube 5 to which the elastomer member 6 is fixed,
toward the distal side in the longitudinal direction on the shaft 2, the annular member 4 can be slid toward the distal side in the longitudinal direction on the shaft 2. The penetrating hole (B) formed in the outer tube 5, and the penetrating hole (C) formed in the annular member 4, have inner diameters which allow the linear supporting
15 member 9 to pass therethrough. Therefore, when an external force is applied to the
proximal side in the longitudinal direction of the supporting member 9 to cause tension, the supporting member 9 is drawn, while being bundled, into the gap between each penetrating hole and the shaft 2, as the supporting member 9 slides on the shaft 2. When the distal end portion in the longitudinal direction of the annular
2 0 member 4 reaches the position where the drawing of the supporting member 9 has
proceeded to the end portion in the opening-section side of the filter section 3, that is, when the annular member 4 finishes bundling of the supporting member 9, the opening section of the filter section 3 becomes a closed state. At this time, the filter section 3 is not in close contact with the shaft 2, so that a step is formed between the
2 5 opening section of the filter section 3 and the shaft 2.
[0047]
In this state, when the operator further attempts to slide the elastomer member

16
6, or the outer tube 5 to which the elastomer member 6 is fixed, toward the distal side
in the longitudinal direction on the shaft 2, the annular member 4 is prevented from
further sliding toward the distal side by the presence of the filter section 3 containing
the completely bundled supporting member 9, and, as a result, the distal end portion
5 in the longitudinal direction of the flexible elastomer member 6 covers the thick
section present in the proximal side in the longitudinal direction of the annular member 4, so that the thick section is pressed into the penetrating hole (A) formed in the elastomer member 6. As in the present invention, when the elastomer member covers the thick section, the outer diameter of the end face of the penetrating hole (A)
10 formed in the elastomer member 6 becomes larger than the outer diameter of the
opening section of the filter section 3 when its opening section is closed. Since, by this, the step formed between the opening section of the filter section 3 and the shaft 2 can be covered, the cndovascular treatment aiding device 1 can be prevented from being caught in a treatment device such as a stent or a guiding catheter during
15 retrieval. The inner diameter of the end face in the distal side in the longitudinal
direction of the penetrating hole (A) formed in the elastomer member 6 that is covering the thick section is preferably smaller than the outer diameter of the opening section of the filter section 3 when its opening section is closed. In this case, the step formed between the opening section of the filter section 3 and the shaft 2 can be
20 more securely covered.
[0048]
The material of the shaft 2, which acts as the core member of the endovascular treatment aiding device 1, is preferably a metal commonly used for guide wires, such as a stainless steel, tungsten, or cobalt alloy.
2 5 [0049]
Examples of the material of the annular member 4 include metals such as stainless steels, platinum alloys, and palladium alloys. From the viewpoint of

17
simplicity in production, the material of the annular member 4 is more preferably a
resin such as a polycarbonate, polypropylene, or polyethylene that can be molded
using a mold or the like.
[0050]
5 The material of the outer tube 5 is not limited as long as it can achieve both
the rigidity required for closing the filter section 3 by tension caused by bundling of the supporting member 9 by the annular member 4, and the flexibility required for securing the blood vessel tracking ability. Examples of the material of the outer tube 5 include metals such as nickel alloys and stainless steels. The material of the
10 outer tube 5 is more preferably a resin such as a polyimide or polyamide.
[0051]
In cases where the material of the outer tube 5 is a resin such as a polyimide or polyamide, an easily slidable resin such as a polyimide, polyamide, or polyethylene blended with a polytetrafluoroethylene, tetrafluoroethylene copolymer,
15 and/or lubricant may be incorporated into an inner layer for increasing the slidability
of the outer tube 5 on the shaft 2. For securing the rigidity required for closing the filter section 3, a braided layer prepared using a metal wire such as a stainless steel wire or using a resin such as a polyamide may also be incorporated. [0052]
2 0 The outer tube 5 may also have a function as a sheath. When the outer
diameter of the outer tube 5 is one with which the whole outer tube 5 can be contained in a treatment device such as a balloon catheter, and the inner diameter of the penetrating hole (B) is one with which the whole filter section 3 with its opening section closed can be contained in the penetrating hole (B), the endovascular
2 5 treatment aiding device 1 can have a constitution that does not require a sheath.
[0053]
The material of the elastomer member 6 is not limited as long as the

18
elastomer member 6 can have flexibility which allows changing of its outer diameter.
The Shore hardness (Shore D) of the material according to ISO868:2003 is preferably
20 to 65 D. The material is preferably, but not limited to, a resin such as a
polyurethane, silicone, or polyamide elastomer.
5 [0054]
Examples of the material constituting the filter 7 include polymers such as polyester, polyurethane, polyether urethane, polyamide, polyvinyl chloride, polycarbonate, polystyrene, polyethylene, polypropylene, polymethylpentene, polymethyl methacrylate, and polytetrafluoroethylene; and superelastic metals such
10 as nickel alloys. The filter 7 is especially preferably constituted using polyester.
In terms of the shape of the filter 7, the filter can be provided by preparing a polymer sheet, and forming a plurality of openings thereon. For increasing the opening ratio of the filter to secure a sufficient blood passing rate, the filter 7 is more preferably prepared as a mesh using a polymer or a metal processed into a fiber. Examples of
15 the polyester include polyethylene terephthalate (hereinafter referred to as "PET"),
polytrimethylene terephthalate, polybutylene terephthalate, polyethylene naphthalate, and polybutylene naphthalate. Among these, PET is more preferred as the base material of the antithrombogenic material because of its versatility. [0055] '
2 0 The pore size is not limited as long as capturing of thrombi or plaques is
possible while the blood flow can be secured. In cases where the filter 7 is formed as a sheet, the pore size is preferably 30 to 100 um. In cases where the filter 7 is formed as a mesh, each opening is preferably 30 to 100 \xm on a side. Since the pore size is small, not only capturing of thrombi or plaques released from the
2 5 vascular wall, but also formation of thrombi due to the filter 7, which is a foreign
substance in the human body, may occur. Therefore, an antithrombogenic compound is preferably bound to the surface of the filter 7.

19
[0056]
The material of the ring 8 is not limited as long as it is a flexible wire having
elastic restoring force that allows free bending of the ring 8. The material is
preferably a superelastic metal whose shape can be changed into various shapes, but
5 can be restored to the original ring shape. The ring 8 can therefore be constituted by
a shape-memory polymer. The ring 8 is more preferably constituted by a metal such as a nickel alloy. [0057]
The material of the supporting member 9 is not limited as long as the
10 restoring force of the ring 8 is not inhibited, and the supporting member 9 is not
broken by the bundling into the annular member 4. Examples of the material of the supporting member 9 include thin metal wires. The material of the supporting member 9 is more preferably a high-strength resin fiber such as an aramid fiber, polyarylate fiber, or polyester fiber.
15 [0058]
In the filter section 3 of the present embodiment, the filler 7 and the supporting member 9 are fixed to each other through the ring 8. Alternatively, the supporting member 9 may be fixed directly, not through the ring 8, to the filter 7. In such a case, the supporting member 9 is preferably formed with a superelastic metal
2 0 such as a nickel alloy.
[0059]
The endovascular treatment aiding device is preferably one that suppresses thrombus formation caused thereby, and exerts high antithrombogenicity continuously for a long period. The antithrombogenicity herein means a property
2 5 with which blood coagulation does not occur on the surface in contact with blood.
For example, the antithrombogenicity means a property that inhibits blood coagulation which proceeds due to platelet aggregation, activation of blood

20
coagulation factors represented by thrombin, and/or the like.
[0060]
The antithrombogenic compound herein means a compound having
antithrombogenicity. In particular, an antithrombogenic compound needs to be
5 bound to the surface of the filter 7, which has a large contacting area with blood and
is prone to formation of thrombi.
[0061]
Specific examples of the antithrombogenic compound include cationic
polymers containing, as constituent monomers A, at least one compound selected
10 from the group consisting of alkyleneimine, vinylamine, allylamine, lysine,
protamine, and diallyldimethylammonium chloride; and anionic sulfur compounds
having anticoagulant activity.
[0062]
The endovascular treatment aiding device of the present invention is in a state
15 where antithrombogenicity is given by covalent bonding of a cationic polymer to the
surface of the filter 7, and binding of an anionic sulfur compound having
anticoagulant activity to the filter 7 and/or the cationic polymer.
[0063]
Here, since the constituent monomer A, which is a monomer constituting the
2 0 cationic polymer, has a cationic nitrogen atom, the polymer is cationic. On the
other hand, the compound having anticoagulant activity and containing a sulfur atom
is anionic. Therefore, the polymer and the compound can be ionically bound to
each other. Examples of the anionic sulfur compound having anticoagulant activity
include heparin and heparin derivatives, dextran sulfate, polyvinyl sulfonate, and
2 5 polystyrene sulfonate. Heparin and heparin derivatives are more preferred. The
heparin and heparin derivatives may be either purified or unpurified, and are not
limited as long as they can inhibit blood coagulation reaction. Examples of the

21
heparin and heparin derivatives include heparins which arc clinically generally and
widely used, unfractionatcd heparins, and low-molecular-weight heparins, as well as
heparins having high affinity to antithrombin III. Specific examples of the heparin
include "heparin sodium" (manufactured by Organon API Inc.). Examples of the
5 heparin derivatives include Fragmin, Crexane, Orgaran, and Arixtra.
[0064]
Since cationic polymers have cationic properties, they may exhibit hemolytic toxicity and/or the like, so that their elution into blood is not preferred. The cationic polymer is therefore preferably covalently bound to the surface of the filter 7. The
10 covalent bonding of the cationic polymer to the surface of the filter 7 can be earned
out by covalently binding a functional group of the cationic polymer to a functional group on the surface of the filter 7 by a well-known method. For example, the covalent bonding can be earned out by binding an amino group of the cationic polymer to a carboxyl group of a polyester constituting the filter 7, using a
15 condensing agent such as 4-(4,6-dimethoxy-l,3,5-triazin-2~yl)-4-
methylmorpholinium chloride n-hydrate ("DMT-MM"). As an alternative method, a method in which the cationic polymer is brought into contact with the filter 7 under heat to allow covalent bonding by amino lysis reaction may be used. Alternatively, radiation irradiation may be carried out to cause generation of radicals on the surface
2 0 of the filter 7 and the cationic polymer, and covalent bonding between the surface of
the filter 7 and the polymer may be achieved by recombination reaction of the radicals. [0065]
The covalent bond herein means a chemical bond formed by sharing of an
2 5 electron(s) between atoms. In the present invention, the covalent bond is a covalent
bond between atoms such as a carbon atom(s), nitrogen atom(s), oxygen atom(s), and/or sulfur atom(s) present in the cationic polymer and on the surface of the filter 7

22
The covalent bond may be either a single bond or a multiple bond. Examples of the
type of the covalent bond include, but are not limited to, an amine bond, azidc bond,
amide bond, and imine bond. Among these, from the viewpoint of ease of
formation of the covalent bond, stability after bonding, and the like, an amide bond is
5 more preferred. As a result of intensive study, the present inventors discovered that,
in cases where amide bonds are formed between the cationic polymer and the surface of the filter 7, the configuration of the cationic polymer on the surface of the filter 7 optimizes the state of ionic bonding to the anionic sulfur compound having anticoagulant activity. Confirmation of the covalent bonds is possible by
10 observation of the fact that clution does not occur by washing with a solvent that
dissolves the polymer. [0066]
The cationic polymer may be either a homopolymer or a copolymer. In cases where the cationic polymer is a copolymer, the copolymer may be any of a
15 random copolymer, block copolymer, graft copolymer, and alternating copolymer.
The cationic polymer is more preferably a block copolymer since, in cases where the block copolymer has a block containing consecutive repeat units containing nitrogen atoms, the block portion interacts with the anionic sulfur compound having anticoagulant activity, to form strong ionic bonds.
2 0 [0067]
The homopolymer herein means a macromolecular compound obtained by polymerization of a single kind of constituent monomers. The copolymer herein means a macromolecular compound obtained by copolymerization of two or more kinds of monomers. The block copolymer means a copolymer having a molecular
2 5 structure in which at least two kinds of polymers having different repeat units are
covaiently bound to each other to form a longer chain. The block means each of the at least two kinds of polymers having different repeat units constituting the block

23
copolymer. [0068]
In the present invention, the structure of the cationic polymer may be either
linear or branched. In the present invention, the polymer is preferably branched
5 since a branched polymer can form more stable ionic bonds at multiple positions with
the anionic sulfur compound having anticoagulant activity, [0069]
In the present invention, the cationic polymer has at least one functional group selected from primary to tertiary amino groups and a quaternary ammonium
10 group. In particular, the cationic polymer more preferably has a quaternary
ammonium group rather than primary to tertiary amino groups since a quaternary ammonium group has stronger ionic interaction with the anionic sulfur compound having anticoagulant activity, and hence allows easier control of the elution rate of the anionic sulfur compound having anticoagulant activity.
15 [0070]
In the present invention, the carbon numbers of the three alkyl groups constituting the quaternary ammonium group are not limited. However, in cases where the carbon numbers are too large, hydrophobicity is high, and steric hindrance is enhanced, so that the anionic sulfur compound having anticoagulant activity cannot
2 0 effectively bind to the quaternary ammonium group by ionic bonding. In cases
where the carbon number is too large, the polymer is more likely to show hemolytic toxicity, so that the carbon number per alkyl group bound to the nitrogen atom constituting the quaternary ammonium group is preferably 1 to 12, more preferably 2 to 6. The carbon numbers of the three alkyl groups bound to the nitrogen atom
2 5 constituting the quaternary ammonium group may be the same as or different from
each other. [0071]

24
In the present invention, a polyalkyleneimine is preferably used as the cationic
polymer since the amount of the anionic sulfur compound having anticoagulant
activity adsorbed thereto by ionic interaction can be large. Examples of the
polyalkyleneimine include polyethyleneimines (hereinafter referred to as "PEIs"),
5 polypropyleneimines, and poiybutyleneimines, as well as alkoxylated
polyalkyleneimines. Among these, PEIs are more preferred. [0072]
Specific examples of the PEIs include "LUPASOL" (registered trademark) (manufactured by BASF) and "EPOMIN" (registered trademark) (manufactured by
10 Nippon Shokubai Co., Ltd.). The PEI may be a copolymer with other monomers, or
may be a modified body, as long as the effect of the present invention is not deteriorated. The modified body herein means a cationic polymer which has the same monomer repeat units constituting it, but has partially undergone, for example, radical decomposition or recombination due to radiation irradiation.
15 [0073]
The cationic polymer of the present invention may be composed only of at least one kind of constituent monomers selected from the group consisting of alkyleneimine, vinylamine, allylamine, lysine, protamine, and dialiyldimethylammonium chloride. Alternatively, the cationic polymer of the
2 0 present invention may form a copolymer with one or more kinds of other monomers
that do not adversely affect the antithrombogenicity. The other constituent monomers forming the copolymer are not limited, and examples of such monomers include constituent monomers B such as ethylene glycol, propylene glycol, vinylpyrrolidone, vinyl alcohol, vinylcaprolactam, vinyl acetate, styrenc, methyl
2 5 mcthacrylate, hydroxyethyl methacrylate, and siloxane. In cases where the weight
of the constituent monomers B is too high, the ionic bonding between the cationic polymer and the anionic sulfur compound having anticoagulant activity is weak.

25
Therefore, the weight of the constituent monomers B with respect to the total weight
of the cationic polymer is preferably not more than 10 wt%.
[0074]
In the present invention, in cases where the weight average molecular weight
5 of the cationic polymer is too low, and lower than the molecular weight of the
anionic sulfur compound having anticoagulant activity, stable ionic bonds cannot be formed, so that the antithrombogenicity of interest is less likely to be obtained. On the other hand, in cases where the weight average molecular weight of the cationic polymer is too high, the anionic sulfur compound having anticoagulant activity is
10 included and embedded inside the cationic polymer. Thus, the weight average
molecular weight of the cationic polymer is preferably 600 to 2,000,000, more preferably 1000 to 1,500,000, still more preferably 10,000 to 1,000,000. The weight average molecular weight of the cationic polymer can be measured by, for example, gel permeation chromatography or the light scattering method.
15 [0075]
As a result of intensive study, the present inventors discovered that, from the viewpoint of suppressing thrombus formation caused by the endovascular treatment aiding device, and allowing exertion of high antithrombogenicity continuously for a long period in the present invention, there is a preferred value of the abundance ratio
20 of sulfur atoms to the abundance of total atoms on the surface of the filter 7 as
measured by X-ray photoelectron spectroscopy (hereinafter referred to as "XPS"). The abundance ratio of atoms is expressed as "atomic percent". The atomic percent means the abundance ratio of a particular kind of atoms to the abundance of total atoms, which is taken as 100. in terms of the number of atoms.
2 5 [0076]
That is, in the present invention, the abundance ratio of sulfur atoms to the abundance of total atoms on the surface of the filter 7 as measured by XPS is

26
preferably 3.0 to 6.0 atomic percent, more preferably 3.2 to 5.5 atomic percent, still
more preferably 3.5 to 5.0 atomic percent. In cases where the abundance ratio of
sulfur atoms to the abundance of total atoms is less than 3.0 atomic percent, the
binding amount of the anionic sulfur compound having anticoagulant activity is small,
5 and therefore the anlilhrombogenicity of interest required for suppressing the
thrombus formation due to the endovascular treatment aiding device is less likely to
be obtained. On the other hand, in cases where the abundance ratio of sulfur atoms
to the abundance of total atoms is higher than 6.0 atomic percent, the binding amount
of the anionic sulfur compound having anticoagulant activity is sufficient, and the
10 amithrombogenicity of interest can therefore be obtained, but the amount of the
cationic polymer covaiently bound to the filter 7 for allowing the ionic bonding needs
to be large. Moreover, as elution of the anionic sulfur compound having
anticoagulant activity proceeds, the exposed cationic polymer may exhibit hemolytic
toxicity and/or the like, which is not preferred.
15 [0077]
More specifically, the abundance ratio of sulfur atoms to the abundance of
total atoms on the surface of the filter 7 as measured by XPS can be determined by
XPS.
[~0078]
2 0 [Measurement Conditions]
Apparatus: ESCALAB 220iXL (manufactured by VG Scientific)
Excitation X-ray: monochromatic A1K al, 2 ray (1486.6 eV)
X-ray diameter: 1 mm
X-electron escape angle: 90° (the angle of the detector with respect to the
2 5 surface of the filter 7)
[0079]
The surface of the filter 7 as measured by XPS herein means the portion from

27
the measurement surface to a depth of 10 nm as detected under the measurement
conditions in XPS wherein the X-electron escape angle, that is, the angle of the
detector with respect to the surface constituted by the antithrombogenic compound
and the filter 7, is 90°. In the present invention, the filter 7 may or may not contain
5 sulfur atoms.
[0080]
By radiating X-ray to the surface of the filter 7, and measuring the energy of pholoelectrons generated therefrom, the binding energy values of bound electrons in the substance can be obtained. From the binding energy values, information on the
10 atoms on the surface of the filter 7 as measured by XPS can be obtained, and, from
the energy shift of the peak at each binding energy value, information on the valence and the binding slate can be obtained. In addition, by using the area ratio of each peak, quantification, that is, calculation of the abundance ratios of various atoms, valences, and binding states, is possible.
15 [0081]
More specifically, the S2p peak, which indicates the presence of sulfur atoms, appears near a binding energy value of 161 eV to 170 eV. In the present invention, it was discovered that the area ratio of the S2p peak in the whole peak area is preferably 3.0 to 6.0 atomic percent. In the calculation of the abundance ratio of
2 0 sulfur atoms to the abundance of total atoms, the obtained value is rounded to one
decimal place. [0082]
Similarly, it was discovered that there is a preferred value of the abundance ratio of nitrogen atoms to the abundance of total atoms on the surface of the filter 7
25 as measured by XPS. That is, the abundance ratio of nitrogen atoms to the
abundance of total atoms on the surface of the filter 7 as measured by XPS is preferably 7.0 to 12.0 atomic percent, more preferably 7.5 to 11.0 atomic percent,

28
still more preferably 8.0 to 10.0 atomic percent. In cases where the abundance ratio
of sulfur atoms to the abundance of total atoms is less than 7.0 atomic percent, the
amount of the cationic polymer bound to the filter 7 is small, so that the
antithrombogenicity of interest required for suppressing the thrombus formation due
5 to the endovascular treatment aiding device is less likely to be obtained. On the
other hand, in cases where the abundance ratio of nitrogen atoms to the abundance of total atoms is higher than 12.0 atomic percent, the amount of the cationic polymer bound to the filter 7 is large, so that the anionic sulfur compound having anticoagulant activity bound to the cationic polymer by ionic bonding is present in a
10 sufficient amount. However, it was found that, as elution of the anionic sulfur
compound having anticoagulant activity proceeds, a large amount of the cationic polymer is exposed to show hemolytic toxicity. More specifically, the Nls peak, which indicates the presence of nitrogen atoms, appears near a binding energy value of 396 eV to 403 eV. In the present invention, it was discovered that the area ratio
15 of the Nls peak in the whole peak area is preferably 7.0 to 12.0 atomic percent. The
Nls peak can be split mainly into the nl component (near 399 eV), which is attributed to carbon-nitrogen (hereinafter referred to as "C-N") bonds; and the n2 component (near 401 to 402 eV), which is attributed to ammonium salt, C-N (structure different from nl), and/or nitrogen oxide (hereinafter referred to as "NO").
2 0 The abundance ratio of each split peak component can be calculated according to the
Equation 1 below. In this calculation, the abundance ratio of nitrogen atoms to the abundance of total atoms, and the abundance ratio of each split peak component, are rounded to one decimal place. [0083]
2 5 SpliW = Nlsraii0 x (Splitpermit/lOO) ... Equation 1
Sp!itril|K>: abundance ratio of each split peak component (%) Nlsliltj0: abundance ratio of nitrogen atoms to the abundance of total

29
atoms (%)
Splitpcrcem- abundance ratio of each split peak component in the Nls
peak (%)
[0084]
5 The n2 component, which is attributed to NO, obtained by splitting the Nls
peak indicates the presence of quaternary ammonium groups in the present invention. It was discovered that the abundance ratio of the n2 component in the total component of the Nls peak, that is, Splitpercent (n2), is preferably 20 to 70 atomic percent, more preferably 25 to 65 atomic percent, still more preferably 30 to 60
10 atomic percent. In cases where Splitpcrcem (n2) is less than 20 atomic percent, the
abundance of quaternary ammonium groups is low. Therefore, the ionic interaction with the anionic sulfur compound having anticoagulant activity is weak, and the elution rate is therefore high, so that the antithrombogenicity of interest required for suppressing the thrombus formation due to the endovascular treatment aiding device
15 is less likely to be obtained. On the other hand, in cases where Splitpercent (n2) is
higher than 70 atomic percent, the ionic interaction with the anionic sulfur compound having anticoagulant activity is too strong. In such cases, because of a decrease in the degree of freedom due to formation of ionic complexes, it is impossible to maintain a high anticoagulant activity for a long period, and the elution rate tends be
20 low. Because of the above reasons, the abundance ratio of the n2 component, that is.
Sphtraiio (n2), which is calculated according to Equation 1, is preferably 1.4 to 8.4 atomic percent, more preferably 1.8 to 7.2 atomic percent, still more preferably 2.4 to 6.0 atomic percent. [0085]
2 5 The Cls peak, which indicates the presence of carbon atoms, appears near a
binding energy value of 282 to 292 eV. The Cls peak can be split mainly into the cl component (near 285 eV), which is attributed to carbon-hydrogen (hereinafter

30
referred to as "CHx") bonds suggesting the presence of a saturated hydrocarbon(s)
and/or the like, to carbon-carbon (hereinafter referred to as "C-C") bonds, and/or to
carbon=carbon (hereinafter referred to as "C=C") bonds; the c2 component (near 286
eV), which is attributed to carbon-oxygen (hereinafter referred to as "C-O") bonds
5 suggesting the presence of an ether(s) and/or hydroxy! groups, and/or to carbon-
nitrogen (hereinafter referred to as "C-N") bonds; the c3 component (near 287 to 288 eV), which is attributed to carbon-oxygen (hereinafter referred to as "C=0") bonds suggesting the presence of carbonyl groups; the c4 component (near 288 to 289 eV), which is attributed to oxygen=carbon-oxygen (hereinafter referred to as "0=C-0")
10 bonds suggesting the presence of ester groups and/or carboxyl groups; and the c5
component (near 290 to 292 eV), which is attributed to TZ-TZ* satellite peak (hereinafter referred to as "JWI") bonds suggesting the presence of a conjugated system(s) such as benzene rings. The abundance ratio of each split peak component can be calculated according to the following Equation 2. In this calculation, the
15 abundance ratio of carbon atoms to the abundance of total atoms, and the abundance
ratio of each split peak component, are rounded to one decimal place. [0086]
Splitratio = C1 sralj0 x (Splitpereent /100) ... Equation 2
Splitraii0: abundance ratio of each split peak component (%)
20 Clsraiioi abundance ratio of carbon atoms to the abundance of total
atoms (%)
Splitpercent: abundance ratio of each split peak component in the CIs peak (%) [0087]
2 5 The c3 component, which is attributed to C=0 bonds, obtained by splitting
the CIs peak indicates the presence of amide groups in the present invention. It was discovered that the abundance ratio of the c3 component in the total component of

31
the CI s peak in the present invention, that is, the abundance ratio of amide groups in
the present invention, is preferably not less than 2.0 atomic percent, more preferably
not less than 3.0 atomic percent. In cases where the abundance ratio of the amide
groups is less than 2.0 atomic percent, the number of covalent bonds due to amide
5 bonds between the cationic polymer and the filter 7 is small, and therefore the
binding amount of the cationic polymer is small. Moreover, since the state of ionic
bonding between the cationic polymer and the anionic sulfur compound having
anticoagulant activity is poor, the antithrombogenicity of interest is less likely to be
obtained.
10 [0088]
In addition, as another/other antithrombogenic materiai(s),
an anionic polymer(s) containing, as constituent monomers, at least one
compound selected from the group consisting of acrylic acid, methacrylic acid, a-
glutamic acid, -/-glutamic acid, and aspartic acid; and/or
15 at least one anionic compound selected from the group consisting of
dicarboxylic acids such as oxalic acid, malonic acid, succinic acid, fumaric acid,
glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, malic
acid, tartaric acid, and dodecanedioie acid, and citric acid;
is/are preferably bound to the filter 7 and/or the cationic polymer. The anionic
2 0 polymer(s) and/or anionic compound(s) can be bound to the cationic polymer by
ionic bonding. [0089]
The anionic polymer is preferably, but does not necessarily need to be, a
polyaerylic acid (hereinafter referred to as "PAA"), polymethacrylic acid, poly(a-
2 5 glutamic acid), poly(7-glutamic acid), or polyaspartic acid since, in cases where the
weight ratio of anionic functional groups is high, the amount of the anionic polymer bound to the filter 7 can be large. The anionic polymer is more preferably a PAA.

32
[00901
Specific examples of the PAA include "polyacrylic acid" (manufactured by
Wako Pure Chemical Industries, Ltd.). The PAA may be a copolymer with other
monomers, or may be a modified body as long as the effect of the present invention is
5 not deteriorated.
[0091]
From the viewpoint of safety and the like, elution of the anionic polymer into
blood is not preferred. Thus, the anionic polymer is preferably bound, more
preferably covalently bound, to the surface of the filter 7.
10 [0092]
The anionic polymer may be either a homopolymer or a copolymer. In cases
where the anionic polymer is a copolymer, the copolymer may be any of a random
copolymer, block copolymer, graft copolymer, and alternating copolymer.
[0093]
15 The anionic polymer may be constituted only by the constituent monomers
described above, or may form a copolymer with constituting monomers other than
those described above as long as the antithrombogenicity is not adversely affected.
The constituent monomers other than acrylic acid, methacrylic acid, a-glutamic acid,
y-glutamic acid, and aspartic acid to be used for forming the copolymer are not
2 0 limited, and examples of such monomers include constituent monomers B such as
ethylene glycol, propylene glycol, vinylpyrrolidone, vinyl alcohol, vinylcaprolactam,
vinyl acetate, styrene, methyl methacrylate, hydroxyethyl methacrylate, and siloxane.
In cases where the weight of the constituent monomers B is too high, the number of
reaction sites for binding to the filler 7 or to the other antithrombogenic compound(s)
25 is small. Accordingly, the weight of the constituent monomers B with respect to the
total weight of the anionic polymer is preferably not more than 10 wt%.
[0094]

1 1
The anionic compound is preferably, but does not necessarily need to be, at
least one selected from the group consisting of oxalic acid, malonic acid, succinic
acid, fumaric acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid,
sebacic acid, malic acid, tartaric acid, and citric acid since, in cases where the weight
5 ratio of anionic functional groups is high, a larger amount of the anionic compound
can be bound to the filter 7 or the other antithrombogenic compound(s). The anionic compound is more preferably succinic aeid. [0095]
In cases where the weight average molecular weight of the anionic polymer is
10 too small, the amount of the polymer bound to the filter 7 or to the other
antithrombogenic compound(s) is small. It is therefore difficult to obtain a high and long-lasting antithrombogenicity. On the other hand, in cases where the weight average molecular weight of the anionic polymer is too high, the antithrombogenic compound is included in the inside. Therefore, the weight average molecular
15 weight of the anionic polymer is preferably 600 to 2,000,000, more preferably 10,000
to 1,000,000. [0096]
In the present invention, the surface amount of the anionic sulfur compound having anticoagulant activity on the filter 7 after soaking in physiological saline at
2 0 37°C for 30 minutes was measured based on the anti-factor Xa activity. The anli-
factor Xa activity herein is an index indicating the degree of inhibition of the activity of factor Xa, which promotes conversion of prothrombin to thrombin. By this, the surface amount of the compound can be known in terms of the unit of activity. For the measurement, "Test Team (registered trademark) Heparin S" (manufactured by
2 5 Sekisui Medical Co., Ltd.) (hereinafter referred to as Test Team Heparin) was used.
In cases where the anti-factor Xa activity is too low, the surface amount of the anionic sulfur compound having anticoagulant activity on the filter 7 is small, so that

34
the antithrombogenicity of interest is less likely to be obtained. That is, the anti-
tactor Xa activity is preferably 30 mlU/cm , more preferably 50 mlU/cm . More
specifically, the surface amount was measured as follows. The filter 7 to which the
anionic sulfur compound having anticoagulant activity is bound was cut into a test
5 piece having an effective surface area of about 0.26 cm2, and the test piece was then
soaked in 0.5 mL of physiological saline at 37°C for 30 minutes. To the filter 7 after the soaking, 0.02 mL of human blood plasma, 0.02 mL of the antithrombin III liquid in Test Team Heparin, and 0.16 mL of a buffer were added to provide a sample, and the sample was then allowed to react according to the operation procedure for
10 Test Team Heparin (end-point method). The absorbancc at 405 nm was measured
using a microplate reader (MTP-300, manufactured by Corona Electric Co., Ltd.). Using a calibration curve separately prepared using Heparin Sodium Injection (manufactured by Ajinomolo Pharmaceuticals Co., Ltd.), the surface amount was calculated. The heating time of the sample in the end-point method was 6 minutes.
15 [0097]
The endovascular treatment aiding device of the present invention is characterized in that, irrespective of the fact that the total binding amount of the anionic sulfur compound having anticoagulant activity on the filter 7 as measured based on the anti-factor Xa activity is small, the surface amount after soaking in
2 0 physiological saline at 37°C for 30 minutes is large. The total binding amount
herein is the sum of the amount of the anionic sulfur compound having anticoagulant activity eluted in human blood plasma (product number, 12271210; manufactured by COSMO BIO Co., Ltd.) after 24 hours of soaking in the human blood plasma at 37°C, as calculated based on the anti-factor Xa activity, and the surface amount of the
2 5 anionic sulfur compound having anticoagulant activity on the filter 7 after the 24
hours of soaking, as calculated based on the anti-factor Xa activity. More specifically, the amount of the anionic sulfur compound having anticoagulant activity

35
eluted as calculated based on the anti-factor Xa activity was evaluated as follows.
The filter 7 to which the anionic sulfur compound having anticoagulant activity is
bound was cut into a test piece having an effective surface area of about 4.24 cm ,
and the test piece was then soaked in 1.5 mL of human blood plasma at 37°C for 24
5 hours. To 0.04 mL of the resulting human blood plasma, 0.04 mL of the
antithrombin III liquid in Test Team Heparin and 0.32 mL of a buffer were added to provide a sample, and the sample was then allowed to react according to the operation procedure for Test Team Heparin (end-point method). The absorbance at 405 nm was measured using a microplate reader. Using a calibration curve
10 separately prepared using Heparin Sodium Injection, the amount of the anionic sulfur
compound having anticoagulant activity eluted was calculated. The heating time of the sample in the end-point method was 5 minutes. The surface amount of the anionic sulfur compound having anticoagulant activity on the filter 7 after the 24 hours of soaking, as calculated based on the anti-factor Xa activity, was determined
15 in the same manner as the surface amount of the anionic sulfur compound having
anticoagulant activity on the filter 7 after soaking in physiological saline at 37°C for 30 minutes as calculated based on the anti-factor Xa activity, except that the filter 7 after the 24 hours of soaking was used. [0098]
20 In cases where the total binding amount is too large, the microstructure on the
surface of the filter 7 is destroyed, while in cases where the total binding amount is too small, the antithrombogenicity of interest is less likely to be obtained. That is, preferably, the total binding amount of the anionic sulfur compound having anticoagulant activity on the filter 7 as measured based on the anti-factor Xa activity
2 5 is not more than 10:000 mIU/cm2, and the surface amount of the anionic sulfur
compound having anticoagulant activity on the filter 7 after soaking in physiological saline at 37°C for 30 minutes as calculated based on the anti-factor Xa activity is not

36
less than 30 mlU/cm . More preferably, the total binding amount is not more than
5000 mlU/cm2, and the surface amount is not less than 50 mlU/cm .
[0099]
The endovascular treatment aiding device of the present invention is
5 characterized in the elution behavior of the anionic sulfur compound having
anticoagulant activity on the filter 7. That is, elution of the anionic sulfur compound having anticoagulant activity hardly occurs when the filter 7 is soaked in physiological saline at 37°C, while the elution rapidly occurs when the filter 7 is soaked in human blood plasma (product number, 12271210; manufactured by
10 COSMO BIO Co., Ltd.) at 37°C. More specifically, during 1 hour of soaking in
human blood plasma at 37°C, elution of not less than 50%, more preferably not less than 70%o, still more preferably not less than 80%>, of the total binding amount occurs. Similarly, during 15 minutes of soaking, elution of not less than 50%, more preferably not less than 70%, still more preferably not less than 80%, of the total
15 binding amount occurs.
[0100]
In terms of the range of the thickness of the antithrombogenic compound layer, in cases where the layer is too thick, the microstructure on the surface of the filter 7 is destroyed, and, moreover, thrombus formation may occur due to the change
2 0 in the pore size and the change in the outer diameter of the opening-section side in
the state where the filter section 3 is closed. That is, the thickness is preferably 1 to
600 nm.
[0101]
The thickness of the antithrombogenic compound layer herein can be
2 5 determined by, for example, combination of a scanning transmission electron
microscope (hereinafter referred to as "STEM"), XPS, and/or the like. More specifically, when observation of the atomic distribution in the vertical direction

37
from the interface of the filter 7 toward the inside is earned out, the thickness of the
antithrombogenic compound layer means the distance from the start point to the end
point of the range in which atoms derived from the antithrombogenic material layer
are found. The thickness is measured as the mean of thickness values observed at at
5 least three points.
[0102]
The interface of the filter 7 as measured by STEM herein means the boundary
between the acrylic resin or the like used for embedding the filter 7 in the sample
preparation before the measurement by STEM, and the surface of the layer composed
10 of the filter 7 and the antithrombogenic compound.
[0103]
More specifically, STEM has detectors such as an energy dispersive X-ray
spectrometer (hereinafter referred to as "EDX") and an electron energy-loss
spectrometer (hereinafter referred to as "EELS")- Measurement conditions for the
15 STEM are as follows.
[0104] [Measurement Conditions]
Apparatus: field emission transmission electron microscope JEM-2100F
(manufactured by JEOL Ltd.)
2 0 EELS detector: GIF Tridiem (manufactured by GATAN, Inc.)
EDX detector: JED-2300T (manufactured by JEOL Ltd.)
Image acquisition: Digital Micrograph (manufactured by GATAN, Inc.)
Sample preparation: ultrathin sectioning (suspension using a copper
microgrid; use of an acrylic resin as an embedding resin)
2 5 Acceleration voltage: 200 kV
Beam diameter: 0.7-nm diameter
Energy resolution: about 1.0 eV FWHM

38
[0105]
Here, the presence of each kind of atoms is judged based on whether a peak
intensity derived from the atoms can be found in a spectrum obtained by STEM
measurement after subtraction of the background.
5 EXAMPLES
[0106]
Examples of the endovascular treatment aiding device 1 of the present
invention are concretely described below with reference to figures. The present
invention is described below in detail by way of Examples and Comparative
10 Examples. However, the present invention is not limited thereto.
[0107]
Example 1
An endovascular treatment aiding device 1 according to the embodiment of
the present invention shown in Fig. 1 was prepared. More specifically, the filter 7
15 was constituted by a mesh using monofilament polyester (PET) fibers having a fiber
diameter of 28 um such that the pore size was 100 urn on a side. This mesh was
prepared such that the length in the longitudinal direction was about 8 mm, and the
circular diameter of the opening section of the filter section 3 was 4 mm.
[0108]
2 0 The ring 8 was prepared using a NiTi alloy wire having a wire diameter of 42
um by triple winding such that the inner diameter was 4 mm. The inner-diameter
portion of the ring 8 was fixed to the outer diameter of the opening section of the
filter 7.
[0109]
2 5 For the supporting member 9, aramid fibers having a fiber diameter of about
60 um were used. The filter section 3 was prepared by binding each fiber to both
the ring 8 and the filter 7 such that the fibers were fixed in the positional relationship

39
shown in Fig. 2, wherein the circumference of the ring 8 was equally divided into
four segments.
[0110]
For the shaft 2, a stainless-steel wire having an outer diameter of 0.2 mm and
5 a length in the longitudinal direction of 1800 mm was used. A taper shape was
given to the wire such that the outer diameter of the portion from the distal end a position about 20 mm distant therefrom in the longitudinal direction was 0.06 mm to 0.15 mm; the outer diameter of the shaft 2 in the next portion having a length of about 30 mm was 0.15 mm; and the outer diameter in the further next portion having
10 a length of 20 mm was 0.15 mm to 0.2 mm, to prepare the shaft 2.
[0111]
The shaft 2 was arranged such that it coaxially passed through the closed-end section and the opening section of the filter section 3 and the polyimide tube bundling the supporting member, and such that the entire supporting member 9 had a
15 uniform length, that is. such that the shaft 2 was positioned on the centra! axis of the
ring 8. On the portion of the shaft 2 having an outer diameter of 0.15 mm, the supporting member 9 was fixed to the shaft 2 using a polyimide tube having an inner diameter of 0.25 mm, an outer diameter of 0.29 mm, and a length of 1.5 mm, with an adhesive.
20 [0112]
The annular member 4 was prepared by molding using a polypropylene such that it had a total length was 2.5 mm and an inner diameter of 0.4 mm; the outer diameter of the portion other than the thick section was 0.5 mm; the thick section was arranged in the area from the position 0.7 mm distant from the proximal side of the
2 5 annular member 4, along a width of 0.2 mm from the distal side; and the outer
diameter of the thick section was 0.75 mm. The annular member 4 was arranged on the shaft 2 as shown in Fig. 1 such that the thick section was positioned closer to the

40
proximal side of the annular member 4. [0U3]
The outer tube 5 was prepared such that it had a three-layer structure
composed of a polytetrafluoroethylene inner layer, a braided layer of stainless-steel
5 flat rectangular wires as an intermediate layer, and a polyimide outer layer, and had
an inner diameter of 0.23 mm, an outer diameter of 0.36 mm, and a length of 1500 mm. To the distal end of the outer tube 5, a polyimide tube having an inner diameter of 0.4 mm, an outer diameter of 0.52 mm, and a length of 0.5 mm was fixed using an adhesive such that the end portions of the outer tube 5 and the polyimide
10 tube joined together.
[0114]
The elastomer member 6 was prepared using a polyamide elastomer having a Shore hardness of about 55 D, such that it had an inner diameter of 0.55 mm, an outer diameter of 0.7 mm, and a total length of 1.5 mm. To the polyimide tube
15 adhered to the distal end of the outer tube 5, a portion with a length of 0.5 mm in the
elastomer member 6 was adhered using an adhesive such that the remaining portion of the elastomer member 6 with a length of 1 mm protruded from the outer tube 5. [0115]
The member composed of the combination of the outer tube 5 and the
2 0 elastomer member 6 was arranged on the shaft 2 such that the elastomer member 6
was positioned in the distal side in the longitudinal direction, to prepare the endovascuiar treatment aiding device 1. The outer diameter, in the direction vertical to the longitudinal direction, of the opening section of the filter section 3 in the state where the filter section 3 of the endovascuiar treatment aiding device 1 was closed
2 5 was about 0.8 mm, and the outer diameter, in the direction vertical to the longitudinal
direction, of the end face of the elastomer member 6 in the state where the elastomer member 6 covered the thick section of the annular member 4 was about 1 mm.

41
[0116]
Comparative Example 1
As Comparative Example 1, an endovascular treatment aiding device 10
having no thick section in the annular member was prepared as shown in Fig. 4.
5 More specifically, the same endovascular treatment aiding device as in the Example
was prepared except that an annular member 11 using a polyimide tube having an inner diameter of 0.4 mm, an outer diameter of 0.52 mm, and a length of 3.5 mm was used instead of the annular member 4, and that the elastomer member was not used. The preparation of the endovascular treatment aiding device 10 was carried out in
10 exactly the same manner as in the Example except that the annular member 11 was
adhered to the outer tube 5 such that a 3-mm portion protruded therefrom, and that the resultant was arranged on the shaft 2 such that the side with the annular member 11 was positioned in the distal side. In the endovascular treatment aiding device 10 of Comparative Example 1, the outer diameter, in the direction vertical to the
15 longitudinal direction, of the opening section of the filter section 3 in the state where
the filter section 3 was closed was about 0.8 mm, similarly to the Example. [0117] Comparative Example 2
Filtrap (registered trademark) FTS-35-18S, which is a thrombus capturing
20 catheter manufactured by NIPRO, in which a plurality of supporting members are
spirally intersecting each other on a shaft; the supporting members are bundled at their tips and their proximal ends; the intermediate portion of the supporting members has an expanded spindle shape; and the end-portion side corresponding to the half of the spindle shape in the distal end portion is covered with a filter fixed
2 5 thereto, to constitute a parachute-like filter section; was provided as Comparative
Example 2. Comparative Example 2 was an endovascular treatment aiding device having a maximum filter expansion diameter of 3.5 mm, a shaft length of 1800 mm,

42
and a shaft diameter of 0.36 mm, which is retrieved using a retrieval sheath. The
outer diameter of the portion in the retrieval sheath where the filter section is to be
contained was 1.1 mm, and the outer diameter of the opening section of the filter
section in the closed state was slightly larger than 1.1 mm.
5 [0118]
Comparative Experiments on Catching of Endovascular Treatment Aiding Device during Retrieval
To cany out comparative experiments, a guiding catheter for 6Fr was inserted
from Femoral approach (whose description is available in the product) using a PCI
10 TRAINER for BEGINNERS (commercially available from Medialpha), which is a
two-dimensional blood vessel model, and the distal end of the guiding catheter was
placed at the inlet of the portion corresponding to the coronary artery in the two-
dimensional blood vessel. In the middle of the coronary artery model, a stent was
placed, and the endovascular treatment aiding device ofExample or Comparative
15 Example 1 or 2 was allowed to pass through the inside of the guiding catheter and the
stent, to place the filter section in the distal side relative to the stent. [0H9]
In this state, comparative experiments were earned out in 10 replicates for
each experiment in order to investigate whether or not the endovascular treatment
2 0 aiding devices ofExample and Comparative Examples 1 and 2 are caught in the stent
or the guiding catheter during retrieval of the devices. [0120]
As a result, in Example, catching in the stent or the guiding catheter did not
occur at all in the 10 replicates of the experiment. On the other hand, in
2 5 Comparative Example 1, catching in the stent occurred once in the 10 replicates of
the experiment, and catching in the distal end of the guiding catheter occurred three times in the 10 replicates of the experiment. In Comparative Example 2, the

43
retrieval sheath could not pass through the vascular bifurcation before the coronary
artery model in which the stent is placed, in all of the 10 replicates of the experiment.
Thus, the retrieval sheath could not reach the filter section.
[0121]
5 Example 2
Endovascular treatment aiding devices 1 according to the embodiment of the present invention shown in Fig. 1 were prepared. More specifically, a mesh was prepared with monofilament polyester (PET) fibers having a fiber diameter of 28 urn such that the pore size was 100 urn on a side.
10 [0122]
Subsequently, the mesh was soaked in an aqueous solution of 5.0 wt% potassium permanganate (manufactured by Wako Pure Chemical Industries, Ltd.) and 0.6 mol/L sulfuric acid (manufactured by Wako Pure Chemical Industries, Ltd.), and the reaction was allowed to proceed at 60°C for 3 hours, thereby hydrolyzing and
15 oxidizing the mesh (step of hydrolysis and oxidation). The aqueous solution after
the reaction was removed, and the mesh was washed with hydrochloric acid (manufactured by Wako Pure Chemical Industries, Ltd.) and distilled water. [0123]
Subsequently, the mesh was soaked in an aqueous solution of 0.5 wt% 4-(4,6-
2 0 dimethoxy-l,3,54riazin~2~yl)~4-methylmorpholinium chloride n-hydrate (hereinafter
referred to as "DMT-MM") (condensing agent) (manufactured by Wako Pure Chemical Industries, Ltd.) and 5.0 wt% PEI (LUPASOL (registered trade mark) P, manufactured by BASF), followed by allowing the reaction to proceed at 30°C for 2 hours, thereby covalently binding PEI to the mesh by condensation reaction (first
2 5 coating step). The aqueous solution after the reaction was removed, and the mesh
was washed with distilled water. [0124]

44
The mesh was further soaked in 1 wt% aqueous methanol solution of ethyl
bromide (manufactured by Wako Pure Chemical Industries, Ltd.) orpentyl bromide
(manufactured by Wako Pure Chemical Industries, Ltd.), and the reaction was
allowed to proceed at 35°C for 1 hour, and then at 50°C for 4 hours, thereby allowing
5 modification of PEI covalently bound to the surface of the mesh with quaternary
ammonium (quaternary ammonium modification step). The aqueous solution after the reaction was removed, and the mesh was washed with methanol and distilled water. [0125]
10 Finally, the mesh was soaked in an aqueous solution (pH=4) of 0.75 wt%
heparin sodium (manufactured by Organon API Inc.) and 0.1 mol/L sodium chloride, and the reaction was allowed to proceed at 70°C for 6 hours, thereby allowing ionic bonding with PEI (second coating step). The aqueous solution after the reaction was removed, and the mesh was washed with distilled water.
15 [0126]
Here, a mesh treated with PEI (average molecular weight, about 600; manufactured by Wako Pure Chemical Industries, Ltd.) and ethyl bromide was provided as Mesh A; a mesh treated with PEI (LUPASOL (registered trade mark) P, manufactured by BASF), but not subjected to the quaternary ammonium modification
2 0 step was provided as Mesh B; a mesh treated with PEI (LUPASOL (registered trade
mark) P, manufactured by BASF) and ethyl bromide was provided as Mesh C; and a mesh treated with PEI (LUPASOL (registered trade mark) P, manufactured by BASF) and pentyl bromide was provided as Mesh D. [0127]
2 5 Using Meshes A to D, filters 7 having a length in the longitudinal direction of
about 8 mm and a circular diameter of the opening-section side of 4 mm were prepared to provide Sample A, Sample B, Sample C, and Sample D, respectively.

45
In Example 1, Samples A to D were used as filters 7.
[0128]
The ring 8 was prepared using a nickel-titanium alloy wire having a wire
diameter of 42 um by triple winding such that the inner diameter was 4 mm. The
5 inner-diameter portion of the ring 8 was fixed to the outer diameter of the opening
section of the filter 7 using polyurethane.
[0129]
For the supporting member 9, four polyacrylate fibers having a fiber diameter
of about 60 urn were used. The filter section 3 was prepared by binding each fiber
10 to both the ring 8 and the filter 7 such that the fibers were fixed in the positional
relationship shown in Fig. 2, wherein the circumference of the ring 8 was equally
divided into four segments.
[0130]
For the shaft 2, a stainless-steel wire having an outer diameter of 0.2 mm and
15 a length in the longitudinal direction of 1800 mm was used. A taper shape was
given to the portion from the dislal end to a position about 20 mm distant therefrom
in the longitudinal direction; the outer diameter of the next portion in the shaft 2
having a length of about 30 mm was adjusted to 0.15 mm; and a taper shape was
given to the further next portion having a length of 20 mm.
20 [0131]
The shaft 2 was arranged such that it penetrated the closed-end section and
the opening section of the filter section 3 and the polyimide tube bundling the
supporting member 9, and such that the entire supporting member 9 had a uniform
length, that is, such that the shaft 2 was positioned on the central axis of the ring 8.
2 5 On the portion of the shaft 2 having an outer diameter of 0.15 mm, the supporting
member 9 was fixed to the shaft 2 using a polyimide tube having an inner diameter of
0.25 mm, an outer diameter of 0.29 mm, and a length of 1.5 mm, using an adhesive.

46
[0132]
The annular member 4 was prepared by molding using a polypropylene such
that it had a total length of 2.5 mm and an inner diameter of 0.4 mm; the outer
diameter of the portion other than the thick section was 0.5 mm; the thick section was
5 arranged in the area from the position 0.7 mm distant from the proximal side in the
longitudinal direction of the annular member 4, along a width of 0.2 mm from the
distal side in the longitudinal direction; and the outer diameter of the thick section
was 0.75 mm. The annular member 4 was arranged on the shaft 2 as shown in Fig.
1 such that the thick section was positioned closer to the proximal side of the annular
10 member 4.
[0133]
The outer tube 5 was prepared such that it had a three-layer structure
composed of a polytetrafluoroethylene inner layer, a braided layer of stainless-steel
flat rectangular wires as an intermediate layer, and a polyimide outer layer, and had
15 an inner diameter of 0.23 mm, an outer diameter of 0.36 mm, and a length of 1500
mm. To the distal end of the outer tube 5, a polyimide tube having an inner
diameter of 0.4 mm, an outer diameter of 0.52 mm, and a length of 0.5 mm was fixed
using an adhesive such that the end portions of the outer tube 5 and the polyimide
tube joined together.
2 0 [0134]
The elastomer member 6 was prepared using a polyamide elastomer having a
Shore hardness of about 55 D, such that it had an inner diameter of 0.55 mm, an
outer diameter of 0.7 mm, and a total length of 1.5 mm. To the polyimide tube
adhered to the distal end of the outer tube 5, a portion with a length of 0.5 mm in the
2 5 elastomer member 6 was adhered using an adhesive such that the remaining portion
of the elastomer member 6 with a length of 1 mm protruded from the outer tube 5. [0135]

47
The member composed of the combination of the outer tube 5 and the
elastomer member 6 was arranged on the shaft 2 such that the elastomer member 6
was positioned in the distal side in the longitudinal direction, to prepare the
endovascular treatment aiding device 1. The outer diameter, in the direction vertical
5 to the longitudinal direction, of the opening section of the filter section 3 in the state
where the filter section 3 of the endovascular treatment aiding device 1 was closed was about 0.8 mm, and the outer diameter, in the direction vertical to the longitudinal direction, of the end face in the distal side in the longitudinal direction of the elastomer member 6 in the state where the elastomer member 6 covered the thick
10 section of the annular member 4 was about 1 mm.
[0136]
For the endovascular treatment aiding device 1 using Sample A as the filter 7, a comparative experiment on catching of the endovascular treatment aiding device during its retrieval was carried out. The results are shown in Table 1. As shown in
15 Table 1, catching in the stent or the guiding catheter did not occur at all in 10
replicates of the experiment. [0137]
Samples A to D used for endovascular treatment aiding devices 1 were subjected to evaluation by the human whole blood test. The results are shown in
2 0 Table 2. As shown in Table 2, no thrombus adhesion (-) was found for Sample A,
and no thrombus adhesion (—) was found for Samples B to D, in the evaluation by the human whole blood test. [0138] Example 3
2 5 The first coating step was carried out by the same operation as in the case of
Mesh B in Example 2, and the mesh was then soaked in a solution of 0.5 wt% DMT-MM and 40 wt% succinic anhydride (manufactured by Wako Pure Chemical

48
Industries. Ltd.) in dimethylacetamide, followed by allowing the reaction to proceed
at 50°C for 17 hours (first additional step). The solution after the reaction was
removed, and the mesh was washed with methanol and distilled water.
[0139]
5 The mesh was further immersed in an aqueous solution of 0.5 wt% DMT-
MM and 5.0 wt% PEI, and the reaction was allowed to proceed at 30°C for 2 hours
(second additional step). The aqueous solution after the reaction was removed, and
the mesh was washed with distilled water. The quaternary ammonium modification
step using ethyl bromide was carried out by the same operation as in the case of
10 Mesh C in Example 2, and the second coating step was then carried out. The same
reagents as in Example 2 were used except for the antithrombogenie compound.
[0140]
Here, a filter 7 prepared with a mesh subjected to the second additional step
using PEI (LUPASOL (registered trade mark) P, manufactured by BASF) was
15 provided as Sample E, and a filter 7 prepared with a mesh subjected to the second
additional step using PEI (LUPASOL (registered trade mark) SK, manufactured by
BASF) was provided as Sample F.
[0141]
Samples E and F used for endovascular treatment aiding devices 1 were
2 0 subjected to evaluation by the human whole blood test. The results are shown in
Table 2. As shown in 'fable 2, no thrombus adhesion (--) was found in the
evaluation by the human whole blood test.
[0142]
Example 4
2 5 The first coating step was carried out by the same operation as in the case of
Mesh B in Example 2, and the mesh was then soaked in an aqueous solution of 0.5
wt% DMT-MM and 0.5 wt% PAA (manufaclurcd by Wako Pure Chemical Industries

49
Ltd.), followed by allowing the reaction to proceed at 30°C for 2 hours (first
additional step). The aqueous solution after the reaction was removed, and the
mesh was washed with an aqueous sodium carbonate solution and distilled water.
L0I43J
5 The mesh was further soaked in an aqueous solution of 0.5 wt% DMT-MM
and 5.0 wt% PEI, and the reaction was allowed to proceed at 30°C for 2 hours (second additional step). The aqueous solution after the reaction was removed, and the mesh was washed with distilled water. The quaternary ammonium modification step using ethyl bromide was earned out by the same operation as in the case of
10 Mesh C in Example 2, and the second coating step was then carried out. The same
reagents as in Example 2 were used except for the antithrombogenie compound. [0144]
Here, a filter 7 prepared with a mesh subjected to the second additional step using PEI (average molecular weight, about 600; manufactured by Wako Pure
15 Chemical Industries, Ltd.) was provided as Sample G; a filter 7 prepared with a mesh
subjected to the second additional step using PEI (LUPASOL (registered trade mark) P, manufactured by BASF) was provided as Sample H; and a filter 7 prepared with a mesh subjected to the second additional step using poly(allylamine hydrochloride) (hereinafter referred to as "PAH") (weight average molecular weight, 900,000;
20 manufactured by Sigma-Aldrich) was provided as Sample I.
[0345]
Samples G to I used for endovascular treatment aiding devices 1 were subjected to evaluation by the human whole blood test. The results are shown in Table 2. As shown in Table 2, no thrombus adhesion (—) was found in the
25 evaluation by the human whole blood test.
[0146] Example 5

50
The first coating step was carried out by the same operation as in Rxample 2
except that PAH (weight average molecular-weight, 900,000; manufactured by
Sigma-Aldrich) or poly-L~lysine hydrobromide (hereinafter referred to as PLys)
(average molecular weight, 30,000 to 70,000; manufactured by Sigma-Aldrich) was
5 used instead of PEI. The quaternary ammonium modification step using ethyl
bromide was earned out by the same operation as in the case of Mesh C in Example 2 using ethyl bromide, and the second coating step was then carried out. The same reagents as in Example 2 were used except for the antithrombogenic compound. [0147]
10 Here, a filter 7 prepared with a mesh subjected to the first coating step using
PAII instead of PEI was provided as Sample J, and a filter 7 prepared with a mesh subjected to the first coating step using PLys instead of PEI was provided as Sample K. The same reagents as in Example 2 were used except for the antithrombogenic compound.
15 [0148]
Samples J and K used for endovascular treatment aiding devices 1 were subjected to evaluation by the human whole blood test. The results are shown in Table 2. As shown in Table 2, no thrombus adhesion (-) was found in the evaluation by the human whole blood test.
20 [0149]
Example 6
A filter 7 prepared with a mesh subjected to the second coating step by the same operation as in the case of Mesh C in Example 2 except that dextran sulfate sodium (Wako Pure Chemical Industries, Ltd.) was used instead of heparin sodium
2 5 (manufactured by Organon API Inc.) was provided as Sample L. The same reagent*
as in Example 2 were used except for the antithrombogenic compound. [0150]

51
Sample L used for an endovascular treatment aiding device 1 was subjected to
evaluation by the human whole blood test. The results are shown in Table 2. As
shown in Table 2, no thrombus adhesion (-) was found in the evaluation by the
human whole blood test.
5 [0151]
Example 7
A mesh was soaked in an aqueous solution of 5% PEI, and irradiated with 5 kGy of y-ray using a type JS-8500 Cobalt 60 y-ray irradiator (manufactured by Nordion International Inc.) to allow covalent bonding (first coating step). The
10 aqueous solution after the reaction was removed, and the mesh was washed with
Triton-XlOO (manufactured by Sigma-Aldrich), physiological saline, and distilled water. The quaternary ammonium modification step using ethyl bromide was carried out by the same operation as in the case of Mesh C in Example 2, and the second coating step was then carried out. The same reagents as in Example 2 were
15 used except for the antithrombogenic compound.
[0152]
Here, a filter 7 prepared with a mesh treated with PEI (average molecular weight, about 600; manufactured by Wako Pure Chemical Industries, Ltd.), but not subjected to the quaternary ammonium modification step, was provided as Sample
2 0 M; a filter 7 prepared with a mesh treated with PEI (average molecular weight, about
600; manufactured by Wako Pure Chemical Industries, Ltd.) and ethyl bromide was provided as Sample N; a filter 7 prepared with a mesh treated with (P; manufactured by BASF) and ethyl bromide was provided as Sample O; and a filter 7 prepared with a mesh treated with PEI (LUPASOL (registered trade mark) SK, manufactured by
2 5 BASF) and ethyl bromide was provided as Sample P.
[0153]
Samples M to P used for endovascular treatment aiding devices 1 were

52
subjected to evaluation by the human wliole blood test. The results are shown in
Table 2. As shown in Table 2, no thrombus adhesion (-) was found for Samples M,
N, and P, and no thrombus adhesion (--) was found for Sample O, in the evaluation
by the human whole blood test.
5 [0154]
Example 8
A mesh was soaked in an aqueous solution of 5% PEI, and heated at 80°C for 2 hours, thereby covalently binding PEI to the mesh by aminolysis reaction (first coating step). The aqueous solution after the reaction was removed, and the mesh
10 was washed with distilled water. The quaternary ammonium modification step
using ethyl bromide was carried out by the same operation as in the case of Mesh C in Example 2, and the second coating step was then carried out. The same reagents as in Example 2 were used except for the antithrombogenic compound. [0155]
15 Here, a filter 7 prepared with a mesh subjected to the first coating step using
PEI (average molecular weight, about 600; manufactured by Wako Pure Chemical Industries, Ltd.) was provided as Sample Q; a filter 7 prepared with a mesh subjected to the first coating step using PEI (LUPASOL (registered trade mark) P, manufactured by BASF) was provided as Sample R; and a filter 7 prepared with a
2 0 mesh subjected to the first coating step using PEI (LUPASOL (registered trade mark)
SK, manufactured by BASF) was provided as Sample S. [0156]
Samples Q to S used for endovascular treatment aiding devices 1 were subjected to evaluation by the human whole blood test. The results are shown in
2 5 Table 2. As shown in Table 2, no thrombus adhesion (-) was found in the
evaluation by the human whole blood test. [0157]

53
Example 9
A filter 7 prepared with a mesh subjected to the first coating step using PE1
(LUPASOL (registered trade mark) P, manufactured by BASF) and then to the
quaternary ammonium modification step using ethyl bromide by the same operation
5 as in the case of Mesh C in Example 2, but not subjected to the second coating step,
was provided as Sample T. The same reagents as in Example 2 were used except
for the antithrombogenic compound.
[0158]
Sample T used for an endovaseular treatment aiding device 1 was subjected to
10 evaluation by the human whole blood test. The results are shown in Table 2. As
shown in Table 2, thrombus adhesion (+) was found in the evaluation by the human
whole blood test.
[0159]
Example 10
15 A filter 7 prepared with a mesh subjected to neither the first coating step
using PEI nor the quaternary ammonium modification step, but subjected to the
second coating step by the same operation as in the case of Mesh C in Example 2,
was provided as Sample U. The same reagents as in Example 2 were used except
for the antithrombogenic compound.
2 0 [0160]
Sample U used for an endovaseular treatment aiding device 1 was subjected
to evaluation by the human whole blood test. The results are shown in Table 2.
As shown in Table 2, thrombus adhesion (+) was found in the evaluation by the
human whole blood test.
25 [0161]
Example 11
The first coating step was carried out by the same operation as in Example 2

54
except that polyvinyl pyrrolidone (hereinafter referred to as "PVP") (K-90,
manufactured by ISP) was used instead of PEL A filter 7 prepared with a mesh
subjected to the quatemaiy ammonium modification step using ethyl bromide by the
same operation as in the case of Mesh C in Example 2 and then to the second coating
5 step was provided as Sample V. The same reagents as in Example 2 were used
except for the antithrombogenic compound. [0162]
Sample V used for an endovascular treatment aiding device 1 was subjected to evaluation by the human whole blood test. The results are shown in Table 2.
10 As shown in Table 2, thrombus adhesion (+) was found in the evaluation by the
human whole blood test. [0163] Example 12
The first coating step was carried out by the same operation as in Example 2
15 except that benzalkonium chloride (manufactured by Wako Pure Chemical Industries,
Ltd.) was used instead of PEL A filter 7 prepared with a mesh subjected to the quaternary ammonium modification step using ethyl bromide by the same operation as in the case of Mesh C in Example 2 and then to the second coating step was provided as Sample W. The same reagents as in Example 2 were used except for
2 0 the antithrombogenic compound.
[0164]
Sample W used for an endovascular treatment aiding device 1 was subjected to evaluation by the human whole blood test. The results are shown in Table 2. As shown in Table 2. thrombus adhesion (■!-) was found in the evaluation by the
25 human whole blood test.
[0165]
The endovascular treatment aiding devices of the present invention were

55
evaluated by the following methods for the antithrombogenicity, the retrieval sheath
delivery performance, and catching in a treatment device such as a stent or a guiding
catheter during retrieval.
[0166]
5 (Evaluation 1: Human Whole Blood Test)
Filters 7 to which antithrombogenic compounds are bound (Samples A to W), and the same material as the untreated filter 7 (positive control), were cut into test pieces each having an effective surface area of 1.0 cm . The test pieces were soaked in physiological saline at 37°C for 30 minutes, and then placed in 2-mL microtubes.
10 After adding Heparin Sodium Injection (manufactured by Ajinomoto
Pharmaceuticals Co., Ltd.) to fresh human blood to a concentration of 0.5 U/mL, 2 mL of the resulting human blood was added to each microtube, and the microtube was then incubated at 37°C for 2 hours. Thereafter, the test piece was removed, and rinsed with PBS(-) (manufactured byNissui Pharmaceutical Co., Ltd.), followed by
15 quantifying the weight of thrombi attached. The thrombus weight was determined
by measuring the dry weights of the test piece before the test and the test piece after the rinse, and calculating the difference between these weights. The test was carried out for each of Samples A to W and the positive control in three replicates. In cases where the mean of the relative values of the thrombus weight measured in three
2 0 replicates, calculated according to the following Equation 3, was not less than 20%,
the sample was judged as having thrombus adhesion, and rated as (+). In cases where the mean was less than 20% or less than 10%, the sample was judged as having no thrombus adhesion, and rated as (-) or (—), respectively. [0167]
2 5 Relative value of thrombus weight (%) = (Bt / Bp) x 100 ... Equation 3
Bt: thrombus weight on a filter 7 to which an antithrombogenic compound is bound

56
Bp: thrombus weight of the positive control [0168]
(Evaluation 2: Comparative Experiments on Catching of Endovascular Treatment
Aiding Device during Retrieval)
5 To carry out comparative experiments, a guiding catheter for 6Fr was inserted
from Femoral approach using a PCT TRAINER for BEGINNERS (commercially available from Medialpha), which is a two-dimensional blood vessel model, and the distal end of the guiding catlieter was placed at the inlet of the portion corresponding to the coronary artery in the two-dimensional blood vessel. In the middle of the
10 coronary artery model, a stent was placed, and the endovascular treatment aiding
device of Example 2 was allowed to pass through the inside of the guiding catheter and the stent, to place the filter section in the distal side relative to the stent. [0169]
In this state, comparative experiments were carried out in 10 replicates for
15 each experiment in order to investigate whether or not the endovascular treatment
aiding device of Example 2 is caught in the stent or the guiding catheter during its retrieval. The results are shown in Table 1. Table 1 also shows the results of the Comparative Example 1 and the Comparative Example 2. [0170]
20 [Table 1]

Table 1
Specification

Shaft

Example 2 Antithr omb o gen ic endovascular treatment aiding device 1 Yes (shaf
Comparative Example 1 Antithr omb ogenic endovascular treatment aiding device 10 Yes (shaf 2)
Comparative Example 2 Filtrap (registered trademark) FTS-35-18S Yes

Table 2
Sample Antilhrombogenie compound Abundance ratio of sulfur atoms (atomic percent) Abundance ratio of nitrogen atoms (atomic percent) Surface amount based on anti-factor Xa activity (mIU/cm2) Thic antith comp (am)

Cationic polymer Anionic sulfur compound having anticoagulant activity

Example 2 A PEI Heparin 1.4 3.4 15.7 14

B PEI Heparin 4.0 8.3 64.2 58

C PEI Heparin 3.8 8.2 83.5 58

D PEI Heparin 3.9 8.0 88.6 61
Example 3 E PEI Heparin 3.3 8.0 Not less than 100 510

F PET Heparin 3.5 8.2 Not less than 100 415
Example 4 G PEI Heparin 4.3 8.9 Not less than 100 395

H PEI Heparin 3.9 9.8 Not less than 100 585

I PEI, RAH Heparin 3.4 6.5 55.4 368
Example 5 J PAH Heparin 3.2 7.3 52.3 10

K PLys Heparin 3.2 7.1 41.5 12
Example 6 L PEI Dextran sulfate 3.6 8.2 - 60
Example 7 M PEI Heparin 1.0 2.5 3.2 6

N PEI Heparin 1.0 2.4 8.2 6

0 PEI Heparin 3.1 6.4 25.5 20

P PEI Heparin 1.0 2.9 8.4 11
Example 8 0 PEI Heparin 1.1 2.6 8.8 9

R PEI Heparin 1.1 3.4 10.5 10

s PEI Heparin 1.1 3.1 10.1 10
Example 9 T PEI - 0.3 8.1 - 49
Example 10 U - Heparin 0.8 - 0 <1
Example ] 1 V PVP Heparin 1.2 2.5 0.5 10
Example 12 W Benzalkonium chloride Heparin 1.5 2.9 2.3 10

59
[0172]
The present invention can be used as an endovascular treatment aiding devic
when an endovascular treatment such as balloon angioplasty or stenting using a
balloon catheter or a stent is carried out.
5 DESCRIPTION OF SYMBOLS
[0173]
1. Endovascular treatment aiding device
2. Shaft
3. Filter section
10 4. Annular member
5. Outer tube
6. Elastomer member
7. Filter section
8. Ring
15 9. Supporting member
10. Endovascular treatment aiding device
11. Annular member

60
CLAIMS
1. An endovascular treatment aiding device comprising:
a flexible shaft;
a filter fixed to said shaft such that a closed-end section is formed in the distal
5 side in the longitudinal direction of the shaft, and an opening section is formed in the
proximal side in said longitudinal direction, which filter can be opened and closed in an umbrella-like manner;
a supporting member composed of linear members each of which is fixed to
the end portion in the opening-section side of said filter and a part of said shaft such
10 that these are connected to each other, which linear members enable to close said
filter by tension caused by application of an external force to the proximal side in said longitudinal direction; and
an elastomer member which is a member composed of an elastomer in which
a penetrating hole (A) is formed, said elastomer member being arranged in the
15 proximal side relative to the opening section of said filter in said longitudinal
direction such that said shaft penetrates said penetrating hole (A), wherein the outer
diameter of the end face in which said penetrating hole (A) is formed is larger than
the outer diameter of the opening-section side of said filter when said filter is closed;
and comprising:
2 0 an outer tube in which a penetrating hole (B) is formed, said outer tube being
arranged in the proximal side relative to the opening section of said filter in said
longitudinal direction such that said shaft penetrates said penetrating hole (B) in a
state which allows movement of said shaft in said longitudinal direction;
wherein said elastomer member is fixed in the distal side of said outer tube in said
2 5 longitudinal direction.
2. The endovascular treatment aiding device according to claim 1, further
comprising an annular member in which a penetrating hole (C) is formed, said

61
annular member being arranged in the proximal side relative to the opening section
of said filter in said longitudinal direction such that said shaft penetrates said
penetrating hole (C) in a state which allows movement of said shaft in said
longitudinal direction, said annular member having a thick section whose outer
5 diameter is smaller than the outer diameter of the opening-section side of said filter
when said filter is closed, and whose outer diameter is larger than the inner diameter of said elastomer member.
3. The endovascular treatment aiding device according to claim 1 or 2, wherein,
when said outer tube is slid toward the distal side in said longitudinal direction, said
10 filter is closed by bundling of said supporting member.
4. The endovascular treatment aiding device according to any one of claims 1 to
3, wherein, when said outer tube is slid toward the distal side in said longitudinal
direction to close said filter, said endovascular treatment aiding device can have a
shape in which said elastomer member covers said thick section, and said thick
15 section is pressed into said penetrating hole (A).
5. The endovascular treatment aiding device according to any one of claims 1 to
4, which can be contained in a sheath when said filter is in a closed state.
6. The endovascular treatment aiding device according to any one of claims 1 to
5, wherein a cationic polymer containing, as constituent monomers, at least one
2 0 compound selected from the group consisting of alkylencimine, vinylamine,
allylamine, lysine, protamine, and diallyldimethylammonium chloride is covalently bound to said filter, and an anionic sulfur compound having anticoagulant activity is bound to said filter and/or said cationic polymer.
7. The endovascular treatment aiding device according to any one of claims 1 to
2 5 6, wherein the ratio of the abundance of nitrogen atoms to the abundance of total
atoms on the surface of said filter as measured by X-ray photoclectron spectroscopy (XPS) is 7.0 to 12.0 atomic percent.

62
8. The endovascular treatment aiding device according to any one of claims 1 to
7, wherein the ratio of the abundance of sulfur atoms to the abundance of total atoms
on the surface of said filter as measured by X-ray photoelectron spectroscopy (XPS)
is 3.0 to 6.0 atomic percent.
5 9. The endovascular treatment aiding device according to any one of claims 1 to
8, wherein said anionic sulfur compound having anticoagulant activity is at least one
selected from the group consisting of heparin and heparin derivatives.
10. The endovascular treatment aiding device according to any one of claims 1 to
9, wherein the surface amount of said anionic sulfur compound having anticoagulant
10 activity on said filter after soaking in physiological saline at 37°C for 30 minutes as
measured based on the anti-factor Xa activity is not less than 30 mlU/cm .
11. The endovascular treatment aiding device according to any one of claims 1 to
10, wherein said cationic polymer and said anionic sulfur compound having
anticoagulant activity form an antithrombogenie compound layer with a thickness of
15 1 to 600 nm on the surface of said filter.
12. The endovascular treatment aiding device according to any one of claims 1 to
11, wherein said filter is formed with polyester.