JPH11239613A - Catheter - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a catheter to be softened after being inserted into the body though it has a high elastic modulus before being inserted into the body. SOLUTION: In this catheter, at least a part of the catheter has <=0.5 in the ratio (E'/E) of a storage elastic modulus E' (dyne/cm<2> ) at 37 deg.C to a storage elastic modulus E (dyne/cm<2> ) at 20 deg.C. This E (dyne/cm<2> ) is <=1.0×10<12> , and E' (dyne/cm<2> ) is >=1.0×10<6> . The catheter preferably contains a polymer having a monomer having at least a 16-20 C straight chain alkyl group as a part of a constitutive component.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a catheter having a high elastic modulus before insertion into the body, but softening after being inserted into the body.

[0002]

2. Description of the Related Art Polyolefins, soft vinyl chlorides, Teflon-based materials, polyester elastomers, polyurethanes and the like are generally used as catheter materials. Among them, polyurethane having particularly excellent physical and mechanical properties is known as a material which softens at body temperature and is frequently used in various catheters. Polyurethanes are synthesized from three components: diisocyanates, polyglycols and chain extenders. Since polyurethane forms a microdomain structure called a hard segment and a soft segment, controlling the structure by its composition is a factor that determines the properties of the polymer. In fact, U.S. Pat. No. 5,061,
No. 254 reports that catheters composed of polyurethane composed of polyethylene oxide soft segments soften at body temperature.

As shown in US Pat. No. 5,061,254 and the like, there is a demand for material properties such that a catheter having a high elastic modulus before insertion into the body is softened after being inserted into the body. I have. A material with a high elastic modulus is easy to insert into blood vessels and has merit in the procedure of the operator,
It is a problem that a patient feels uncomfortable after placing a catheter in a body and damages a living tissue such as a blood vessel inner wall during placement. On the other hand, a material having a low elastic modulus rarely causes a patient to feel uncomfortable after placing a catheter, but has a problem that it is difficult for an operator to insert a catheter into a blood vessel. Further, the conventional body softening material mainly composed of urethane has a slow response to temperature and a small change in elastic modulus before and after softening, so that it is difficult to simultaneously satisfy the above two physical properties with one catheter.

[0004]

SUMMARY OF THE INVENTION The present invention seeks to provide a catheter which has a high modulus of elasticity before insertion into the body, but which softens after being inserted into the body.

[0005]

That SUMMARY OF THE INVENTION The present invention is, at least a portion of the catheter, the storage modulus E at 20 ℃ (dyne / cm ²⁾ and 37 storage modulus E at ℃ '(dyne / cm ²⁾ (E ′ / E) is 0.5 or less. Here, the E (dyne / cm ² ) is 1.0 × 1
0 ¹² or less and E '(dyne / cm ² ) is 1.0 × 10
It is preferably ⁶ or more. Furthermore, carbon number is 16-
It is preferable to contain a polymer containing at least one part of a component having at least 20 monomers having a linear alkyl group.

[0006]

DESCRIPTION OF THE PREFERRED EMBODIMENTS A catheter is a tubular device capable of passing a liquid (a gas when securing an airway) into or out of a body cavity. Examples include urethral catheters designed to pass through the urethra to drain residual urine from the bladder, angiographic catheters suitable for automatic contrast injectors for percutaneous puncture and angiography, large veins to arteries Examples include a Fogarty catheter used to remove emboli and thrombus and to remove stones from bile ducts, and an indwelling catheter used to supply infusions and the like and to stay in the bladder. Other acorn-type catheters, hyperbolic catheters, Boseman-Fritsch catheters, Brasch catheters, central venous catheters, conical catheters, double-tube (dual-lumen) catheters, Eustachian catheters, Gurley catheters, Neraton catheters, There are pacing catheters, pigtail catheters, Swan-Ganz catheters, and the like. The catheter of the present invention may belong to any of these types.

[0007] The catheter of the present invention has at least one of
Part is storage elastic modulus E (dyne / cm ² ) at 20 ° C.
And the ratio (E ′ / E) of the storage elastic modulus E ′ (dyne / cm ² ) at 37 ° C. to 0.5 or less, preferably 0.00
It is 1-0.5, particularly preferably 0.01-0.2.
This is because if E ′ / E exceeds 0.5, both the elasticity at room temperature and the flexibility during insertion into the body are not satisfied. Here, the storage modulus refers to the real value part of the complex modulus,
It is a measure of the energy stored and recovered during a load cycle.

[0008] In the catheter of the present invention, the portion where E '/ E is 0.5 or less, near or in the middle of the distal end of the tube,
Although it may be near the operating section or the whole catheter, it is preferably near the distal end of the tube because flexibility is required in the body.

[0009] In the catheter of the present invention, E
(Dyne / cm ² ) is 1.0 × 10 ¹² or less, preferably 1.0 × 10 ^{10 to} 1.0 × 10 ¹¹ , and E ′ (dyne / cm ² )
/ Cm ² ) is 1.0 × 10 ⁶ or more, preferably 1.0 × 1
It is preferably from 0 ^{8 to} 1.0 × 10 ⁹ . E (dy
(ne / cm ² ) exceeds 1.0 × 10 ¹² , it is too hard at room temperature, and if E ′ (dyne / cm ² ) is less than 1.0 × 10 ^6, it is too soft after insertion into the body and after insertion. Because it is inferior.

As such a catheter of the present invention,
Examples of the catheter include a polymer containing a monomer having a linear alkyl group having 16 to 20 carbon atoms and having at least one part of a component. The constituent components of such a polymer are not particularly limited, but are preferably (meth) acrylic monomers, vinyl monomers, dialcohol monomers,
Examples thereof include diamine-based monomers and dicarboxylic acid-based monomers, and the polymer used in the present invention includes at least a part of a component obtained by adding a linear alkyl group having 16 to 20 carbon atoms to these monomers. Due to these straight-chain alkyl groups, the polymer used in the present invention undergoes crystal melting at a specific temperature, so that the catheter of the present invention changes its elastic modulus according to a temperature change.

The polymer used in the catheter of the present invention is preferably a copolymer of an acrylic monomer having a straight-chain alkyl group and a methacrylic monomer from the viewpoint of ease of polymerization.

The following structural formula is shown as an example of the constituent components of such a polymer.

Embedded image

Among them, the preferable number of carbon atoms of the linear alkyl group from the viewpoint of the response temperature is, for example, 16 or 18 for acrylic monomers and 18 or 20 for methacrylic monomers.

Most preferred are copolymers of acrylic monomers having a stearyl group having 18 carbon atoms with various (meth) acrylic monomers and crosslinked products thereof. The (meth) acrylic monomer to be copolymerized is preferably a monomer that does not prevent crystallization of a linear alkyl group, and is not particularly limited, but preferably has a Tg of room temperature or higher from the viewpoint of moldability of a tube or the like. (Meth) acrylic monomers are preferred. Specific examples include methyl methacrylate and ethyl methacrylate.

As such a copolymer, a copolymer comprising stearyl acrylate and methyl methacrylate is exemplified. In this case, stearyl acrylate is preferably present in the copolymer in an amount of 25% by weight or more, more preferably. Is preferably in the range of 30% by weight to 80% by weight. When hexadecyl acrylate or stearyl methacrylate is used, the proportion in the copolymer is preferably 80% by weight or more.

The structure of the copolymer constituting the catheter of the present invention may be such that a long-chain alkyl group is bonded to the polymer skeleton in any form of random, block, or graft. Depending on the properties, a plurality of types of monomers that form a long-chain alkyl group or a polymer skeleton may be selected. Further, a crosslinked product of the polymer may be used.

The catheter of the present invention is used together with the above copolymer and other materials, for example, polyolefin, polyurethane, polyvinyl chloride, perfluoropolymer, styrene elastomer, polyamide, polyester, polyethylene terephthalate and other resin materials. You may. When the copolymer is used together with another resin material, the catheter may be blended with another material, or a layer of another material and a layer of the copolymer may be laminated or encapsulated. It may be used. Here, the inclusion is the figure 1 attached below.
As shown in (1), the copolymer used in the present invention does not have a cyclic structure and is partially used. For example, by mixing an X-ray contrast agent with the copolymer 2 used in the present invention and using the mixture in the catheter 1 of the present invention having another resin material 3, it has an X-ray contrast ability and has a softening property in vivo. An excellent catheter is obtained. Also, as shown in FIG. 2, if the catheter 1 of the present invention has a structure in which the copolymer 2 is used for the inner layer and a polyurethane resin is laminated on the outer layer, excellent mechanical properties can be obtained.

In the catheter of the present invention, the response temperature can be changed in a wide range by changing the copolymer composition. Specifically, changing the length of the linear alkyl group,
This can be achieved by changing the polymerization ratio of the monomer having a linear alkyl group and the monomer which is another component of the copolymer. The response temperature and the response speed can also be adjusted by changing the type of the polymer skeleton of the copolymer or by blending and using the copolymer with another resin.

According to the present invention, a catheter having a high modulus of elasticity at room temperature can exhibit the property of being softened by being brought into contact with a body fluid after being inserted into the body. The risk of injury to the patient is reduced, and the patient's discomfort when placed is reduced. Further, since the catheter made of the material of the present invention is non-swelling with respect to the aqueous solvent, the dimensions do not change even when touching a body fluid, so that stable performance can be exhibited. .

When the catheter is placed near the heart, the catheter constantly vibrates due to the pulsation of the heart, so that the catheter wall constantly stimulates the blood vessel wall, causing bleeding and the like due to wear. However, if the catheter of the present invention is used, the above problem can be solved because the catheter is softened and not a swellable material after insertion into the body.

That is, the catheter of the present invention can rapidly lower the elastic modulus by utilizing the order-disorder transition of a long-chain straight-chain alkyl group near body temperature, rapidly respond to body temperature and sufficiently respond to body temperature. Flexible.

[0022]

The present invention will be further described with reference to the following examples.
The present invention is not limited to these. (Example 1) 25 parts by weight of stearyl acrylate (SA), 25 parts by weight of methyl methacrylate (MMA),
4,4-azobisisobutyronitrile (AIBN)
A solution prepared by dissolving 05 parts by weight in 75 parts by weight of 1,4-dioxane was subjected to nitrogen bubbling for one hour to remove dissolved oxygen, then the temperature was raised to 80 ° C., and radical polymerization was performed for 18 hours. After completion of the reaction, the polymerization solution was poured into 2 L of methanol, and the precipitate was separated by filtration.

The operation of dissolving the filtered white product in tetrahydrofuran and injecting it into 2 L of methanol was repeated twice to purify the polymer. The purified polymer separated by filtration was dried under reduced pressure at room temperature for 18 hours to be dried. When the heat of fusion of the polymer after drying was measured by DSC, an endothermic peak due to crystal melting of the alkyl chain of SA was confirmed at around 36 ° C.

The polymer (Polymer-1) was used to prepare an R (manufactured by SHIMPO INDUSTRIAL CO., LTD.).
Using XM-90-G29A, die temperature 180 ° C
After extrusion, a catheter having an inner diameter of 0.70 mm and an outer diameter of 0.90 mm was produced.

The heat of fusion of the prepared catheter was measured by DSC, and was found to be 36 as in the case of Polymer-1.
A sharp crystal melting peak was observed around ℃, and it was confirmed that the catheter was softened.

Further, dynamic viscoelasticity measurement (TOYO BAL
DWIN RHEOVIBRON MODEL R
The storage elastic modulus obtained by using HEO-2000 and conforming to JIS K7196 (the same applies hereinafter) was (E) 1.0 × 10 ¹⁰ (dyne / cm ² ) at 20 ° C., but (E ′) at 37 ° C. ) 1.0 × 10 ⁸ (dyne / cm
² ), and it was confirmed that E ′ / E was reduced to 0.01.

Example 2 Stearyl acrylate (S
A) 30 parts by weight, methyl methacrylate (MMA) 2
0 parts by weight, 4,4-azobisisobutyronitrile (AI
BN) A solution in which 0.05 parts by weight of 1,4-dioxane was dissolved in 75 parts by weight was subjected to nitrogen bubbling for 1 hour to remove dissolved oxygen, then the temperature was raised to 80 ° C., and radical polymerization was performed for 18 hours. . After completion of the reaction, the polymerization solution is
L and the precipitate was filtered off.

The operation of dissolving the filtered white product in tetrahydrofuran and injecting it into 2 L of methanol was repeated twice to purify the polymer. The purified polymer separated by filtration was dried under reduced pressure at room temperature for 18 hours to be dried. The heat of fusion of the polymer after drying was measured by DSC, and an endothermic peak due to crystal melting of the alkyl chain of SA was confirmed at around 40 ° C.

The polymer (Polymer-2) was used to prepare an R (manufactured by SHIMPO INDUSTRIAL CO., LTD.).
Using XM-90-G29A, a tube (inner diameter 0.70 mm, outer diameter 0.90 mm) was formed at a die temperature of 200 ° C.

The heat of fusion of the catheter after molding was measured by DSC, and was found to be 40 as in the case of Polymer-2.
A sharp crystal melting peak was observed around ℃, and it was confirmed that the catheter was softened.

The storage elastic modulus determined by dynamic viscoelasticity measurement was (E) 8.0 × 10 ⁹ (dyne) at 20 ° C.
/ Cm ² ) at 37 ° C. (E ′) 8.0 ×
It was 10 ⁸ (dyne / cm ² ), and it was confirmed that E ′ / E was reduced to 0.1.

Comparative Example 1 Commercially available polyurethane (Pel)
lethane 2363-65D, was subjected to the same dynamic viscoelasticity measurement as in Example 1 and 2 also tube Dow Chemical Co. of Japan, Ltd.), the storage modulus at around 20 ° C. (E) is 6.3 × 10 ⁹ (dyne / cm ² ) and 3.3 × 10 ⁹ (dyne / c) around 37 ° C. (E ′).
m ² ) and E ′ / E decreased only to 0.52.

(Embodiment 3) Polyme described in Embodiment 1
r-1 and a commercially available polyurethane (Pandex T-50)
00, manufactured by Dainippon Ink Co., Ltd.)
About the thing blended by 5000 = 50/50 (Wt ratio), the dynamic viscoelasticity measurement was performed similarly and the change of the value of the storage elastic modulus was compared.

As a result, the storage elastic modulus (E) at 20 ° C. of 3.5 × 10 ⁸ (dyne / cm ² ) with T-5000 alone was changed to 2.8 × at 37 ° C. (E ′). 10 ⁸ (d
yne / cm ² ) and E ′ / E = 0.8. On the other hand, the blended product had a storage elastic modulus (E) of 2.0 × 10 ⁹ (dyne / cm ² ) at 20 ° C., but changed to 1.0 × 10 ⁸ (E ′) at 37 ° C. (E ′). dyne
/ Cm ² ), and E ′ / E decreased to 0.05.

Example 4 Polyme described in Example 1
r-1 20 g and a commercially available polyurethane (PANDEX)
T-5000 Dainippon Ink Co., Ltd.)
Extrusion molding was performed on a two-layer tube (outer diameter 1.5 mm, outermost diameter 2.5 mm) having 00 as the outer layer and Polymer-1 as the inner layer. The molding machine is SHIMPO INDUSTR
The test was performed at a die temperature of 200 ° C. using RX Co., Ltd. RXM-90-G29A.

The heat of fusion of the formed two-layer tube was measured by DSC.
As a result, the same SA as in Example 1 was observed around 37 ° C.
An endothermic peak due to crystal melting of the alkyl chain was confirmed. The storage elastic modulus determined by dynamic viscoelasticity measurement is
At 20 ° C., (E) 5.0 × 10 ⁹ (dyne / cm ² )
At 37 ° C. was (E ′) 5.0 × 10 ⁸ (d
yne / cm ² ), and it was confirmed that E ′ / E = 0.1.

Example 5 50 parts by weight of hexadecyl acrylate (HDA) and 0.05 parts by weight of 4,4'-azobisisobutyronitrile (AIBN) were dissolved in 75 parts by weight of 1,4-dioxane. The solution was bubbled with nitrogen for one hour to remove dissolved oxygen and then heated to 80 ° C.
Radical polymerization was performed for 18 hours. After completion of the reaction, the polymerization solution was poured into 2 L of methanol, and the precipitate was separated by filtration. The operation of dissolving the filtered white product in tetrahydrofuran and injecting it into 2 L of methanol was repeated twice to purify the polymer. The purified polymer filtered off was dried under reduced pressure at room temperature for 18 hours to be dried. When the DSC of the polymer after drying was measured, an endothermic peak due to crystal melting of the alkyl chain of HDA was confirmed at around 37 ° C. This polymer (Polymer-3) and a commercially available Shore hardness of 74
SHIMPO INDUSTRIA using a dry blend of polyurethane D at a weight ratio of 50/50
Using RXM-G29A manufactured by L Co., Ltd., it was extruded at a die temperature of 200 ° C. to prepare a catheter for indwelling in a blood vessel (inner diameter 0.70 mm, outer diameter 0.90 mm). When the DSC of the catheter after molding was measured, Polym
Similar to the result of er-3, a sharp crystal melting peak was observed at around 36 ° C., confirming that the catheter was softened. In addition, dynamic viscoelasticity measurement (TOYO BAL
DWIN RHEOVIBRON MODEL R
HEO-2000) is 20 ° C.
(E) was 4.3 × 10 ⁹ (dyne / cm ² ) at 37 ° C., and (E ′) was 1.4 × 10 ⁹ (dyne / cm ² ) at 37 ° C.
/ Cm ² ), and it was confirmed that E ′ / E was reduced to 0.33.

Comparative Example 2 The dynamic viscoelasticity of a commercially available catheter made of polyurethane having a Shore hardness of 74D was measured in the same manner as in Examples 1 and 2, and the storage elastic modulus (E) at around 20 ° C. was 1 .3 × 10 ¹⁰ (dyne / c
m ² ) was 7.0 × 10 around 37 ° C. (E ′).
⁹ (dyne / cm ² ) and E ′ / E decreased only to 0.54.

[0039]

According to the present invention, the temperature at which the catheter responds can be easily controlled by changing the copolymer composition, and the elastic modulus can be rapidly and rapidly increased by inserting the catheter into a living body. Temperature can be obtained.

[Brief description of the drawings]

FIG. 1 is a diagram showing a cross section of one embodiment of the catheter of the present invention.

FIG. 2 is a diagram showing a cross section of another embodiment of the catheter of the present invention.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 The catheter of this invention 2 The polymer used for this invention 3 Other resin materials

Claims (3)

[Claims] At least a portion of claim 1. A catheter, 'the ratio of ^{(dyne / cm 2) (E} ' storage modulus E at 20 ℃ (dyne / cm ²⁾ and the storage modulus E at 37 ° C. / E) is 0 A thermosoftening catheter having a temperature of not more than 0.5. 2. The E (dyne / cm ² ) is 1.0 × 10
¹² or less and E '(dyne / cm ² ) is 1.0 × 10 ⁶
The catheter of claim 1, wherein said catheter is a softening body. 3. The softening agent according to claim 1, wherein the polymer contains a monomer having at least 16 to 20 carbon atoms and having a straight-chain alkyl group as a component. catheter.