JP2010194069A - Bioabsorbable material for treatment in blood vessel - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a bioabsorbable material for treatment in a blood vessel capable of manufacturing a spring coil from a bioabsorbable polymer and indwelling to the inside of a brain aneurysm. <P>SOLUTION: A bioabsorbable material is formed in a spring coil shape having a diameter for passing through the inside of a catheter. The material is passed through the inside of the catheter to fill the brain aneurysm therewith for making it possible to treat the brain aneurysm by the intravascular treatment method without a craniotomy procedure. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

The present invention relates to an intravascular treatment material that is made of a bioabsorbable polymer, is filled into an aneurysm, and is used for endovascular treatment.

A portion of a blood vessel, particularly a small to middle artery having a diameter of about 1 to 6 mm existing in the brain, is called a cerebral aneurysm. When a cerebral aneurysm becomes large, the surrounding nerve tissue may be compressed, causing oculomotor nerve palsy or causing cranial nerve palsy.

Leaving a cerebral aneurysm may cause rupture of the cerebral aneurysm, resulting in subarachnoid hemorrhage or large intracerebral hemorrhage. When a cerebral aneurysm ruptures, it often falls into a serious state and may die at the same time as the cerebral aneurysm ruptures or become comatose. The mortality rate is as high as about 50%, and even after treatment, there is a high possibility of rebleeding, and severe sequelae remain even after treatment.

Therefore, if a cerebral aneurysm is found by examination or the like and it is determined that the risk of the aneurysm rupturing is high, some kind of treatment must be performed. At present, it is impossible to prevent the rupture of the aneurysm by medical treatment using a drug, and it is necessary to physically block the blood flow into the cerebral aneurysm.

As a method of blocking the blood flow, there is a clipping technique in which the aneurysm is clipped with metal while opening and observing the affected part, and the aneurysm is closed to prevent rupture. Clipping is a method that reliably blocks blood flow because it is treated while observing the affected area under visual observation, but it is necessary to perform craniotomy under general anesthesia, and when a cerebral aneurysm occurs in the deep part of the brain Has the disadvantage of limited surgical field and difficult surgical operation.

Therefore, a catheter is inserted from the femoral artery at the base of the foot, guided through the aorta to the cerebral artery of the head, a thin metal coil is packed inside the cerebral aneurysm through this catheter, and blood is introduced into the cerebral aneurysm. An intravascular treatment method called coil embolization has been developed to block the inflow of water, and a metal coil as disclosed in Patent Document 1 has been put to practical use. Coil embolization is superior to clipping in that it can be treated under local anesthesia, without touching the brain directly, and even deeper in the brain. . In order to enhance the embolization effect, a material has also been developed in which a bioactive substance is combined with a metal coil using a polymer (Patent Document 2).

However, the filling rate of the cerebral aneurysm by the metal coil is not so high, and sufficient tissue to fill the cerebral aneurysm around the metallic coil is not regenerated. Therefore, a gap exists inside the cerebral aneurysm, blood flows into the gap, and the cerebral aneurysm may recur without obtaining the therapeutic effect as expected. In particular, a giant aneurysm may have a recurrence or re-rupture of the aneurysm. In addition, since the metal coil remains permanently, there is a risk that the coil may be displaced or jumped out of the knob. Furthermore, since the material is metal, there is also a problem that halation is likely to occur in post-operative image diagnosis. In order to solve such problems, an attempt has been made to produce a coil from a polymer (Patent Document 3).

Japanese Patent Publication No. WO2004 / 062509 JP 2005-526523 A JP-T-2005-503845

In view of the above-described situation, the present invention is flexible and capable of densely filling the inside of a cerebral aneurysm without damaging vascular tissue, and the material is gradually decomposed to cause a gentle biological reaction. It is an object of the present invention to provide a bioabsorbable endovascular treatment coil that is surely blocked by the blood flow into the aneurysm and does not affect postoperative image diagnosis.

The properties required for the materials used for endovascular treatment can be made compact enough to move the material to the target site through the blood vessels in the living body, and further, while moving the material to the target site. It is necessary to use a flexible material so as not to damage the inside of the blood vessel. Further, in order to densely fill the inside of the cerebral aneurysm, it is necessary that the filling material is flexible and has elasticity.

In addition, since the conventional material is a metal, it remains permanently in the living body, and this has an effect in observing the affected area, such as causing halation in image diagnosis after treatment. Therefore, the material according to the present invention is composed of a bioabsorbable polymer as a material that is gradually decomposed and absorbed in a living body after being treated and is replaced with a living tissue and does not affect image diagnosis.
The present invention is described in detail below.

The spring coil for endovascular treatment of the present invention is made of a bioabsorbable polymer. The bioabsorbable polymer is molded into a spring coil shape to form a spring coil for endovascular treatment. The bioabsorbable polymer is not particularly limited as long as it is a material that is gradually decomposed and absorbed in the living body, but natural polymers include collagen, gelatin, chitin, chitosan, and the like. Examples of polymers include homopolymers of lactic acid, glycolic acid, ε-caprolactone, dioxanone, trimethylene carbonate, and copolymers composed of at least two materials selected from these.

When the material composed of the bioabsorbable polymer is placed inside the cerebral aneurysm, granulation is formed around the cerebral aneurysm by a biological reaction, and the inside of the cerebral aneurysm is gradually filled with the biological tissue. In addition, since the material eventually decomposes and disappears from the living body, there is an advantage that chronic granulation reaction is reduced.

It should be noted that the material has a decomposition rate so that the material is broken during the decomposition of the bioabsorbable polymer, and the fragment of the material flows into the blood vessel so that it does not become an embolic substance in the blood vessel. Is preferred. In addition, in the initial stage of treatment, it is possible to fill the cerebral arteriovenous aneurysm as much as possible, and in order not to break the blood vessel wall, a flexible material is preferable. Furthermore, since the strength which can be extruded from a catheter is also required, as a material material having these properties, a copolymer of fatty acid polyester is preferable. In particular, in view of the decomposition rate and flexibility, a copolymer containing ε-caprolactone as a component is preferable. Examples of the material satisfying such requirements include a copolymer of ε-caprolactone and glycolic acid, or a copolymer of ε-caprolactone and lactic acid, and in order to achieve the object of the present invention, It is preferable to use a copolymer of ε-caprolactone and lactic acid having a slow decomposition rate.

The material according to the present invention needs to be deformed in accordance with the shape of the aneurysm in the arteriovenous vein, and the shape is preferably a spring coil shape so as not to accidentally damage the fragile blood vessel wall. . A spring coil shape is ideal because it can be bent at any position and has a stretchable structure. Also, if the material is a polymer material, if the material is heat set, even if it is inserted into the catheter with the coil released, a spring coil shape is formed when the material is pushed out of the catheter into the cerebral arteriovenous vein In addition, it is possible to use a spring coil having a diameter larger than that of the catheter.

The polymer material used as the spring coil material is most preferably a bioabsorbable suture that is widely used as a medical device. By changing the raw material and shape (monofilament, multifilament) and thickness of the suture to be used, and changing the pitch and diameter of the spring coil to be formed, various types can be adapted to the size and strength of the target aneurysm It is possible to produce a spring coil. In consideration of form stability and moldability, it is preferable to use monofilament yarn.

In order to obtain a therapeutic effect with a higher filling rate, a cell growth factor such as bFGF can be added to the material of the spring coil. By kneading the cell growth factor into the material, the spring coil can be used as a carrier for the growth factor, and the cell growth factor can be gradually released as the spring coil is decomposed. By the action of cell growth factor, tissue regeneration inside the aneurysm is accelerated, and it can be expected to shorten the treatment period.

As described above, according to the present invention, there is provided a spring coil for endovascular treatment for the purpose of filling the inside of a cerebral aneurysm with living tissue using the foreign body reaction of the living body and treating it by endovascular treatment. it can.

Spring coil side view The catheter is filled with a spring coil Aneurysm model used for evaluation Insertion method of spring coil into aneurysm model used for evaluation

1 Spring coil 11 Catheter 21 Blood vessel model tube 31 Aneurysm model polyethylene bag

Hereinafter, the present invention will be described with reference to examples. However, these examples do not limit the present invention.

Example 1
(1) Polymerization 288 g of L-lactide, 76 g of ε-caprolactone and 300 ppm of catalyst were placed in a glass ampule, polymerized at 140 ° C. for 48 hours, and then L-lactide / ε-caprolactone having a weight average molecular weight of 510,000 by GPC measurement. A polymer (molar ratio 75/25) (hereinafter referred to as P (L-LA / CL) (molar ratio 75/25)) was obtained.

(2) P (L-LA / CL) (molar ratio 75/25) obtained by spinning was extruded from a hole of 1 hole by an extruder, and then stretched under warm air to obtain a diameter of 0.092 mm ( A monofilament yarn of USP standard 6-0) was obtained.

(3) Formation of coil The obtained monofilament yarn corresponding to USP6-0 is wound and fixed on a fluororesin tube having a diameter of 1.5 mm. After heat setting at 130 ° C. for 2 hours in a vacuum dryer, the fluororesin tube was pulled out to obtain a spring coil having an outer diameter of 1.7 mm and an inner diameter of 1.5 mm.

(Example 2)
(1) P (L-LA / CL) (molar ratio 75/25) obtained by the method described in Spinning Example 1 was extruded from a hole of one hole by an extruder, and then stretched in warm air. To obtain a yarn having a diameter of 0.042 mm (equivalent to USP Standard No. 8-0).

(2) Coil formation The obtained yarn corresponding to USP standard 8-0 is wound and fixed on a fluororesin tube having a diameter of 0.9 mm. After heat setting at 130 ° C. for 2 hours in a vacuum dryer, the fluororesin tube was pulled out to obtain a spring coil having an outer diameter of 1.0 mm and an inner diameter of 0.9 mm.

(Example 3)
(1) P (L-LA / CL) (molar ratio 80/20) obtained by the method described in Spinning Example 1 was extruded from a 16-hole hole by an extruder and then stretched in warm air. To obtain a 16 filament yarn having a diameter of 0.23 mm (equivalent to USP standard 3-0).

(3) Formation of coil The obtained yarn corresponding to USP standard 3-0 is wound around a fluororesin tube having a diameter of 1.5 mm and fixed. After heat setting at 140 ° C. for 2 hours in a vacuum dryer, the fluororesin tube was pulled out to obtain a spring coil having an outer diameter of 2 mm and an inner diameter of 1.5 mm.

(Evaluation)
FIG. 1 shows a side view of the spring coil produced in Examples 1-3. As shown in FIG. 2, the coil produced by the method of Examples 1 to 3 was inserted into a catheter having an inner diameter of 1.5 mm. As shown in FIG. 3, a 15 mm diameter polyethylene bag was attached to the tip of a tube having a diameter of 5 mm and a length of 1 m to form an aneurysm model. As shown in FIG. 4, a catheter was inserted from the tube tip of the arteriovenous image and placed in a polyethylene bag portion at the tip.
The spring coil-shaped material produced from the absorbent polymer shown in each example can be deformed along the bag and can be filled in the bag because it is flexible.

ADVANTAGE OF THE INVENTION According to this invention, the bioabsorbable spring coil for endovascular treatment which can treat a cerebral aneurysm with an intravascular treatment method can be provided.

Claims (5)

A bioabsorbable endovascular treatment material that is made of a bioabsorbable polymer having a spring coil shape, can pass through the inside of a catheter, and is used to treat an aneurysm by being filled inside the aneurysm . The bioabsorbable endovascular therapeutic material according to claim 1, wherein the bioabsorbable polymer is an aliphatic polyester. The bioabsorbable intravascular therapeutic material according to claim 2, wherein the aliphatic polyester is a copolymer of ε-caprolactone. The bioabsorbable endovascular therapeutic material according to claim 3, wherein the aliphatic polyester is a copolymer of lactic acid and ε-caprolactone, or a copolymer of glycolic acid and ε-caprolactone. 5. The bioabsorbable endovascular treatment material according to claim 1, wherein the cell growth factor is complexed, and the cell growth factor is gradually released as the bioabsorbable polymer is decomposed.

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