JP2000325465A - catheter - Google Patents

Abstract

(57) [Problem] To provide a catheter excellent in operability without damaging tissues in the body. The styrene content is 30 to 50 mol%,
And the glass transition point determined by differential thermal analysis is 5 to 40 ° C.
Is a catheter formed by molding a styrene-ethylene random copolymer, which has a waist strength that can be easily inserted into the body, and exhibits flexibility when inserted into the body, Said catheter being reversible.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a catheter and a tube.

[0002]

2. Description of the Related Art In addition to the conventional infusion and transfusion, catheters for diagnosis, treatment and monitoring of the inside of the body have been actively used in recent years. Is being inserted.
In general, catheters and tubes (hereinafter referred to as catheters including tubes) have appropriate lumbar strength and flexibility, as well as radiation resistance (sterilization), biocompatibility,
Hemocompatibility is required. The tip of a catheter to be inserted or further placed in the body is inserted into a target site or tissue through a blood vessel and various body cavities according to the application and purpose. For example, after a vascular catheter is inserted into a blood vessel, the catheter is pushed through the blood vessel so that its distal end reaches a target site. Thereafter, a contrast agent or a drug is injected through the catheter. The one provided with a balloon at the distal end is used for the purpose of expanding the balloon at a stenosis site and expanding the stenosis site for treatment.

[0003] Since the catheter used in such a procedure is selectively inserted, a moderate waist strength for pushing, pulling, and rotating, that is, an elastic modulus and a torque transmitting force (torque). Control) is required. In addition, for example, peripheral blood vessels are three-dimensionally curved with a small curvature, and blood vessels with lesions are often brittle, and it may be difficult to insert the tip of the catheter to a target site. Attempting to force the insertion may cause damage to the patient's vascular wall or tissue at the catheter tip. Therefore, flexibility is particularly required at the tip.

[0004] A catheter having a sensor for monitoring labor in the uterus and a catheter having a sensor for monitoring exhalation during anesthesia in the oropharynx are used. This is because more accurate information can be obtained compared to a monitor on the body surface. Also,
When performing percutaneous coronary angioplasty (PTCA), PT
In order to smoothly introduce a treatment catheter such as a CA balloon catheter, a guiding catheter (guide catheter) is placed in a blood vessel. When placing these catheters, flexibility is also required to reduce discomfort and pain to the patient.

[0005] Further, in the balloon catheter, if slackness remains in the balloon or the like, blood flow becomes stagnant, which causes thrombus. In addition, since the gastrointestinal catheter is constantly exposed to peristaltic movement, it is desired that the permanent elongation be small.

Conventionally, as a catheter having a certain hardness and a flexible distal end, a catheter in which a distal tip formed of a flexible resin is joined to a main body is known.
There was a risk that the tip would fall off. As a solution to this, flexibility is achieved by immersing the distal end of a catheter integrally molded from a resin having a certain hardness without bonding into a solution containing a plasticizer to diffuse the plasticizer into the distal end. Is known (for example, JP-A-5-305144). Conversely, there is also known a method of hardening the proximal portion of a catheter containing a plasticizer by removing an appropriate amount of the plasticizer at the proximal portion of the catheter with a solvent. However, in these methods, since the operability is inferior if the flexible portion is too long or too short, the length for providing flexibility, that is, the length to be inserted and placed in the body is various. It is necessary to arrange them.

[0007]

SUMMARY OF THE INVENTION It is an object of the present invention to provide a catheter to be inserted and detained in a body, which has a flexible tip at least inside the body, and that the main body has a moderate waist strength. An object of the present invention is to provide a catheter which is excellent in balance among elastic modulus, torque transmitting force and flexibility, and permanent elongation, and which is integrally molded.

[0008]

Means for Solving the Problems As a result of intensive studies to solve the above problems, the present inventors have found that a styrene-ethylene random copolymer having a specific composition and a glass transition point (Tg) as a catheter material. Is well balanced with its moderate lumbar strength, flexibility, and permanent elongation, is biocompatible and blood compatible, and does not damage vascular walls or tissues when heated to body temperature The present inventors have found that a certain degree of flexibility is reversibly expressed, and have completed the present invention by applying it to the catheter material of the present invention with the suitability.

That is, the present invention is characterized in that it has a stiffness enough to be easily inserted into the body at room temperature, exhibits flexibility when inserted into the body, and is reversible. It is a catheter. This catheter has a styrene content of 30 to 50 mol% as a material, and a styrene-ethylene random copolymer having a glass transition point (Tg) of 5 to 40 ° C. measured by a tangent method by differential scanning calorimetry (DSC). This is a catheter formed by molding.

Preferably, at a temperature of 23 ° C., 1
The catheter comprising the styrene-ethylene random copolymer having a permanent elongation at 00% tensile strain of 30% or less.

The catheter of the present invention is flexible, flexible,
Suitable for mechanical strength such as elasticity and torque transmission force, and also suitable for radiation-resistant (sterile), biocompatible and blood-compatible medical materials, suitable for insertion into the body. Used.

The characteristics and physical properties of a catheter, especially a catheter to be inserted into the body, are important in terms of the operability of the treatment, such as the lumbar strength of the catheter, that is, the elasticity and the torque transmitting force. In the present invention, the elastic modulus means an elastic modulus at 0% elongation of a stress-strain curve of a tensile test. That is, in the stress-strain curve in the tensile test, it represents the Young's modulus of a low strain region (linear elastic region) according to Hooke's law. A specific measuring method is described in JIS K7113. The elastic modulus is preferably in a range of about 10 to 500 MPa. When a catheter molded from a material having an elastic modulus in this range is used, operations such as inserting the catheter into a target site, pushing, pulling, and rotating the catheter are performed. The properties are good. If the elastic modulus is too small, the catheter becomes stiff and it is difficult to insert it into the target site. The torque transmission force rotates the rear end of the catheter in the range of 180 to 360 °, and indicates the torque transmitted to the front end at that time. However, from the operability of the catheter, 5 to 30 g is appropriate. Preferably 10-2
0 g.

On the other hand, in order to prevent the body lumen wall and tissue from being damaged in the body, the distal end portion needs to have flexibility. The styrene-ethylene random copolymer has a glass transition point of 5 to 40 ° C and a body temperature (around 37 ° C).
When it is placed in a room, flexibility develops. This property is reversible and has the property of returning to its original hardness when it is taken out of the body (when it is returned to room temperature). The styrene-ethylene random copolymer has an elastic modulus of 5 at this body temperature (around 37 ° C.).
Since the displacement of the elastic modulus between room temperature and body temperature is in a range where the flexibility and the hardness for maintaining the torque transmitting property are well balanced, it is suitable as the material of the catheter of the present invention.

In order to reduce the slack when the catheter is used as a balloon catheter and the effect of the peristaltic motion of the digestive tract when the catheter is used by being inserted and placed in the digestive tract, the above-described elastic modulus and torque transmission are required. In addition to power,
A proper recovery from elongation, i.e. low permanent elongation, is required. If the permanent elongation is large, particularly in a balloon catheter, when the balloon is deflated, slack occurs, and there is a possibility that a blood clot is formed due to stagnation of blood flow. For this reason, the permanent elongation is preferably 30% or less, particularly preferably as low as 20% or less.

The catheter of the present invention can be made using one kind of the styrene-ethylene random copolymer resin described above, and can be integrally molded. Therefore, since there is no difference in dropping or leaking of the joining portion or difference in liquid sending resistance depending on the portion, the durability is excellent. Also, since it has flexibility in the body, it does not damage curved blood vessels, especially in catheters inserted into the trachea to monitor respiration through the nasal cavity and catheters inserted into the uterus to monitor accurate labor. The effect of alleviating discomfort and pain given to the patient is brought about. In particular, a styrene-ethylene random copolymer having a styrene content of 30 to 50 mol% exhibits a low permanent elongation of 30% or less, and can be suitably used for the catheter of the present invention.

Furthermore, since the catheter of the present invention does not contain chlorine, there is little problem of environmental pollution due to incineration.
Considering that catheters are often incinerated after use from the viewpoint of biohazard prevention,
This is a great advantage.

Next, the styrene-ethylene random copolymer used in the present invention will be described. The styrene-ethylene random copolymer used in the present invention is not particularly limited as long as it has the above-mentioned composition and properties, but preferably has a weight average molecular weight of 30,000 or more and 1,000,000 or less, and 60,000 or more and 600,000 or less. Are more preferred. By changing the molecular weight or styrene content, or both, the modulus and flexibility can be adjusted. In order to industrially obtain a styrene-ethylene random copolymer having such a molecular weight with high productivity, for example, JP-A-3-1630088, JP-A-7-53618, and EP-A-416815 disclose. CGCT catalyst described in JP-A-9-309925, EP-87249
There is a production method using a metallocene catalyst described in 2A2 publication and the like. However, a styrene-ethylene random copolymer particularly preferably used is the styrene-ethylene random copolymer having the above-mentioned molecular weight and obtained using the metallocene catalyst described in the above-mentioned literature. A so-called styrene-ethylene pseudo-random copolymer obtained using a CGCT catalyst tends to be slightly inferior in balance between elastic modulus and flexibility as compared with a metallocene-catalyzed styrene-ethylene random copolymer.

The catheter of the present invention may contain a stabilizer, an anti-aging agent, an ultraviolet absorber, a plasticizer, a softener, a lubricant, a processing aid, an anti-blocking agent, etc., if necessary, as long as its performance is not impaired. It can be added to the styrene-ethylene random copolymer that is the material. These may be used alone or in combination of two or more. In particular, the flexibility can be adjusted by adding a plasticizer.

Conventionally, catheters and the like made of soft vinyl chloride are generally sterilized using ethylene oxide gas (EOG). The catheter using the styrene-ethylene random copolymer of the present invention as a material is also preferable in that a gamma ray sterilization method can be applied in addition to EOG sterilization. According to the γ-ray sterilization method, a crosslinking reaction can be carried out simultaneously with sterilization, which is convenient in some cases.

Further, the catheter of the present invention has good biocompatibility. Also, blood compatibility is good. In particular, in the case of an application to be inserted into a blood vessel, the catheter of the present invention can impart antithrombotic properties to the surface in contact with the liquid. As a method for imparting antithrombotic properties, a known method can be used.For example, heparin, urokinase, or the like can be immobilized on a reactive functional group of a catheter substrate by covalent bonding, ionic bonding, adsorption, or the like. it can.

Examples of the method for producing the catheter of the present invention include known methods used for producing tubes such as extrusion molding. Further, for example, there is a method of forming a large diameter and then stretching it at a temperature lower than the melting point to a predetermined small diameter.

The catheter of the present invention will be specifically illustrated below, but the present invention is not limited thereto. A. Angiographic catheter, cerebrovascular catheter,
Thermodilution catheters, IVH catheters, intravascular or indwelling catheters. B. Various balloons or balloon catheters. C. Catheters, such as gastric tube catheters, feeding catheters, and tubes for tube feeding, which are inserted or placed in the digestive tract orally or nasally. D. Oral or nasal catheters such as oxygen catheters, oxygen cannulas, tubes and cuffs for endotracheal tubes, tubes and cuffs for tracheostomy tubes, and intratracheal suction catheters. E. FIG. Catheters inserted or placed in various body cavities or tissues such as suction catheters, waste catheters, peritoneal catheters, rectal catheters, urethral catheters, and trocars. F. Endoscope tube inserted into various body cavities. G. FIG. Catheter sheath introducer (introducer), guiding catheter (catheter guide).

[0023]

EXAMPLES Hereinafter, the catheter of the present invention will be further described based on examples, but these examples do not limit the present invention. First, a production example of a styrene-ethylene random copolymer used as a material in the present invention will be described below as an experimental example.

Experimental Example (1) Production of Styrene-Ethylene Random Copolymer P-1 Polymerization was carried out using a polymerization vessel having a capacity of 150 L, a stirrer and a jacket for heating and cooling. 36 L of dehydrated cyclohexane and 36 L of dehydrated styrene were charged, and the internal temperature was 40 ° C.
And heated and stirred. Triisobutyl aluminum 84m
mol, methylalumoxane (PMA manufactured by Tosoh Akzo)
84 mmol of O-3A) was added based on Al. Immediately after ethylene was introduced and the pressure was stabilized at 1 MPa, the transition metal catalyst component A96 was removed from the catalyst tank installed on the polymerization vessel.
About 100 mL of a toluene solution in which μmol was dissolved was added to the polymerization vessel. Heat generation started immediately, and cooling water was introduced into the jacket. The internal temperature rises up to 71 ° C. Thereafter, the temperature gradually decreased, and finally reached 70 ° C. Ethylene pressure is 1
Polymerization was carried out for 2 hours while maintaining the pressure at MPa. The polymerization solution was fed over 1 hour into 150 L of heated water containing a dispersant heated to 85 ° C. with vigorous stirring. Then 9
After stirring at 7 ° C. for 1 hour, hot water containing crumb was fed into cold water to collect crumb. The obtained crumb was blow-dried at 50 ° C. The above transition metal catalyst component A [rac dimethyl methylene bis (4,5-
Benzo-1-indenyl) zirconium dichloride]
Was synthesized by the method disclosed in EP-A-0872492A2.

The dried crumb is fed to a tandem extruder with a hot-cut pelletizer (Buss Co-Kneader PL).
K-46). The operation was performed under the following conditions. First extruder: cylinder temperature 80 ° C., screw rotation speed 120 rpm. Second extruder: cylinder temperature 120 ° C, die 135
° C, screw rotation speed 22 rpm.

Experimental Example (2) Production of Styrene-Ethylene Pseudorandom Copolymer CP-1 Using a transition metal catalyst component B under the polymerization conditions shown in Table 1, a 10 L capacity autoclave equipped with a stirrer and a cooling jacket for heating was used. Was used to polymerize styrene and ethylene. After the completion of the polymerization, the obtained polymerization liquid was poured little by little into excess methanol which was vigorously stirred to precipitate the produced polymer. After drying under reduced pressure at 60 ° C. until no change in weight was observed, 409 g of a copolymer having a styrene content of 40 mol% was obtained. The above transition metal catalyst component B used for the polymerization; complex CGCT (constrained geometric structure) type Ti complex, (tert-butylamido) dimethyl (tetramethyl-η5-cyclopentadienyl) silanetitanium dichloride is disclosed in It was synthesized with reference to JP-A-7-053168.

Experimental Example (3) Production of Styrene-Ethylene Pseudorandom Copolymer CP-2 Using the transition metal catalyst component B under the polymerization conditions shown in Table 1,
Styrene and ethylene were polymerized in the same manner as in Experimental Example (2) to obtain a copolymer.

The styrene-ethylene random copolymer P-1 obtained in Experimental Example (1), the styrene-ethylene pseudo-random copolymer CP-1 obtained in Experimental Example (2) and Experimental Example (3), Table 2 shows the styrene content, molecular weight, molecular weight distribution, tacticity of alternating styrene-ethylene structure, λ value, and glass transition point (Tg) of CP-2.

The molecular weight and the molecular weight distribution are determined by GPC measurement, the tacticity of the styrene-ethylene alternating structure in the copolymer, the λ value is determined by ¹³ C-NMR, and the determination of the styrene content in the copolymer is determined by ¹ H. -It was determined from NMR. These details will be described below.

[Molecular weight, molecular weight distribution] Instrument: HLC-8020 manufactured by Tosoh Corp. Procedure: Dissolve the sample in THF as a solvent, and use the above instrument, and determine the weight average molecular weight in terms of standard polystyrene by GPC method (gel permeation chromatography). The number average molecular weight was determined. [Tacticity, λ value] Equipment: JEOL α-500 or JNMGX-27
0 Solvent: deuterated chloroform or deuterated 1,1,2,2-tetrachloroethane Procedure: First, the shift value of the center peak of the triplet ¹³ C-NMR peak of deuterated 1,1,2,2-tetrachloroethane based on TMS. I decided. Next, the copolymer was weighted with 1,1,
It was dissolved in 2,2-tetrachloroethane and ¹³ C-NMR was measured, and each peak shift value was calculated based on the triplet center peak of heavy 1,1,2,2-tetrachloroethane. The shift value of the triplet center peak of heavy 1,1,2,2-tetrachloroethane was 73.89 ppm. The ¹³ C-NMR spectrum measurement for quantifying the peak area
By a proton gate decoupling method in which OE was erased, a pulse width of 45 ° was used, and the repetition time was 5 seconds as a standard. [Styrene content] Equipment: α-500 manufactured by JEOL Ltd. and AC-250 manufactured by BRUCKER Procedure: heavy chloroform solvent or heavy 1,1,2,2-
Using a tetrachloroethane solvent, a peak derived from a phenyl group proton (6.5 to 7.5 pp) was determined based on TMS.
m) and a proton peak derived from an alkyl group (0.8 to 3 p
pm).

The glass transition point was determined by differential thermal analysis (DSC). [Glass transition point (Tg)] Instrument: DSC200 manufactured by Seiko Denshi Co., Ltd. Procedure: The sample was measured at a heating rate of 10 ° C./min under a stream of N ₂ .

As a sample for measuring mechanical strength, flexibility and biocompatibility, a sheet having a predetermined thickness was separately press-molded at a temperature of 210 ° C. The methods for measuring and evaluating the physical properties were as follows. Since the physical properties of the catheter obtained here are substantially the physical properties of the catheter itself, the measured values were used as the physical properties of Examples 1 to 3 described later. Table 3 shows the results.

[Mechanical strength] A sheet having a thickness of 1 mm is prepared, a JIS-2 type test piece is punched from the sheet, and JIS K-711 is used by using the test piece.
Tensile speed 100 mm / min according to the tensile test method 3
The modulus of elasticity in tensile was obtained as an index of mechanical strength. [Permanent elongation] A sample pressed to a thickness of 1 mm as described above was punched into a No. 2 type dumbbell, and 100% (2%) between marked 1 cm marked lines was measured according to the test method of JIS K6301.
cm), stretched and held for 10 minutes, and then relieved. After standing for another 10 minutes, the length between the marked lines was measured to measure the residual permanent strain. Permanent elongation was expressed as a ratio (%) of elongation to the original length. [Flexibility] A sheet with a thickness of 2 mm is manufactured and is JIS K-
The durometer hardness of types D and A was determined according to the durometer hardness test method of No. 7215, and used as an index of flexibility. [MFR] The MFR was measured according to the flow test method for thermoplastics specified in JIS K-7210. The measurement was performed at a measurement temperature of 200 ° C. and a test load of 5 kgf.

Examples 1-3, Control Example Copolymer P-1, copolymer CP-1, copolymer CP obtained in Experimental Examples (1), (2) and (3) −
2, and as a control, soft vinyl chloride was extruded at a temperature of about 180 ° C. to obtain a hollow tube having an outer diameter of 2.67 mm, an inner diameter of 1.73 mm, and a length of 1100 mm. Torque transmission force,
The blood compatibility is shown below.

[Torque transmission force] The outer diameter 2.67 mm, inner diameter 1.73 mm, length 1100 m obtained in Examples 1 to 3
mm hollow tubes were each rotated by 180 ° at hand, and the force transmitted to the tip was measured. The results are shown in Table 3. [Blood compatibility] The tubes obtained in Examples 1 to 3 and the control were each inserted into a rabbit jugular vein and left for 7 days. At this time, the inside of the tube was filled with physiological saline, and the end protruding outside the body from the vein was sealed. The tube was removed from the rabbit jugular vein, washed with saline, fixed by treating the surface with glutaraldehyde and osmium oxide, and the outer surface of the tube was observed visually and with an electron microscope. On the outer surface, fibrin and platelets less than or equal to those of the soft vinyl chloride of the control example were observed in the tubes made of any of the resin compositions of Examples 1 to 3. It can be seen that catheters made of the resin compositions obtained in Experimental Examples 1 to 3 have good blood compatibility.

Further, a gamma sterilization test was conducted as follows. [Γ-ray sterilization test] A sheet having a thickness of 1 mm obtained by pressing the copolymer P-1 was placed in a polyethylene bag and placed in a cardboard box. Each cardboard box was irradiated with 25 kGray, which is a normal sterilization condition. A 1 mm thick polyethylene (PE) sheet was used as a control. After irradiation, mechanical strength,
Flexibility and MFR were measured. Table 4 shows the results. Like the PE, the copolymer showed a tendency to decrease in elongation after irradiation, indicating that a cross-linking reaction had occurred.

[0037]

[Table 1]

[0038]

[Table 2]

[0039]

[Table 3]

[0040]

[Table 4]

[0041]

The catheter of the present invention has an appropriate elasticity and torque transmitting force at room temperature, and exhibits excellent flexibility when placed inside the body, thereby being excellent in insertion and operability and being flexible in the body. By exhibiting the property, it becomes possible to reduce the pain and discomfort to the patient without damaging the body lumen and the tissue.

Claims (3)

[Claims] 1. A catheter characterized in that it has a stiffness that allows it to be easily inserted into the body at room temperature, exhibits flexibility when inserted into the body, and is reversible. 2. A styrene-ethylene random copolymer having a styrene content of 30 to 50 mol% and a glass transition point (Tg) determined by differential thermal analysis (DSC) of 5 to 40 ° C. A catheter having a stiffness enough to be easily inserted into the body at room temperature, and exhibiting flexibility when inserted into the body, which is reversible. . 3. Styrene having a permanent elongation of 30% or less.
3. The catheter according to claim 1, wherein the catheter is formed by molding an ethylene random copolymer.