JPH05154192A - Contrast tube - Google Patents

Abstract

(57) [Abstract] [PROBLEMS] To provide a polyurethane tube containing particles of a bismuth-based X-ray contrast medium having a high contrast effect. A bismuth X-ray contrast agent is prepared by dispersing bismuth X-ray contrast agent particles in an aqueous solution of a water-soluble salt such as aluminum or silicon, neutralizing the dispersion with an alkali or an acid, and heating the dispersion. A thin film of a metal oxide such as aluminum oxide or silicon oxide is formed on the surface of the particles. Then, the surface-treated bismuth-based X-ray contrast agent particles are mixed with polyurethane to form a tube. [Effect] The thin film of metal oxide suppresses the action of bismuth-based X-ray contrast agent particles to accelerate the thermal decomposition of polyurethane, and enables stable tube molding.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a tube containing an X-ray contrast agent in the tube wall, which is suitable for use as, for example, an intravascular catheter or an angiography catheter.

[0002]

2. Description of the Related Art Conventionally, a tube in which an X-ray contrast agent such as barium sulfate or bismuth oxide is mixed in a tube wall made of a polymeric material in various modes is used alone or laminated on a tube made of another polymeric material. For example, it is used as an indwelling catheter for maintaining communication with the inside of a blood vessel when performing blood transfusion or infusion, or a catheter for diagnosis or treatment. In these contrast agent-containing tubes, fluorine-based resins, polyolefins, vinyl chloride resins, etc. are used as the polymeric material forming the tube wall (Japanese Patent Publication No. 47-49394, Japanese Patent Laid-Open No. 56-119).
263, Jitsukai Sho 51-108389, etc.).

Further, recently, it has good flexibility, elasticity and mechanical strength, and is nontoxic in terms of safety, sterilizable,
Medical-use thermoplastic polyurethane having excellent antithrombogenicity is used as a material for a tube containing a contrast agent of this type, and among them, a polyether type is particularly favored. While such polyurethane has the excellent characteristics as described above, it has a property of being easily deteriorated by heat, and therefore has a narrow processing temperature range as compared with other thermoplastic resins. Requires precise temperature control.

[0004]

By the way, in a tube containing a contrast agent made of polyurethane, barium sulfate has been used as an X-ray contrast agent up to now, and a bismuth-based X-ray contrast agent having a higher contrast effect than barium sulfate is not available. It was never used. One of the reasons is that the bismuth-based X-ray contrast agent has a function of catalytically promoting the thermal decomposition of polyurethane in a molten state. When this is used, the melt viscosity of the polyurethane in the extruder fluctuates greatly. In addition to being unable to perform stable tube molding, a low molecular weight substance due to decomposition may be mixed in the tube and eluted into blood. However, with advances in medical technology, catheters are becoming thinner or thinner, and in recent years, there has been a particularly strong demand for a polyurethane tube containing a bismuth-based X-ray contrast agent having a high contrast effect.

Therefore, as a result of intensive studies made by the present inventor in view of the above-mentioned problems of the prior art, if surface-treated bismuth-based X-ray contrast agent particles are used, polyurethane during molding is processed. Found that the thermal decomposition of
The present invention was conceived. That is, an object of the present invention is to provide a polyurethane tube containing a bismuth X-ray contrast agent having a high contrast effect.

[0006]

In order to achieve the above object, in a tube with a contrast agent according to the present invention, bismuth-based X-ray contrast agent particles coated with an oxide of a metal other than bismuth are added to a tube wall made of polyurethane. The structure is mixed inside. In this structure, the metal oxide covering the surface of the bismuth-based X-ray contrast medium particles is aluminum oxide,
Silicon oxide, zirconium oxide, and titanium oxide are particularly preferable, and the coating amount thereof generally varies depending on the type of bismuth-based X-ray contrast agent used, the particle size, and the type of metal oxide. It is selected within the range of 0.05 to 10 parts by weight with respect to 100 parts by weight of the contrast agent. The reason is that if the coating amount of the metal oxide is 0.05 parts by weight or less, the effect of suppressing the thermal decomposition of polyurethane is small, and if it is 10 parts by weight or more, there is no difference in the effect of suppressing the thermal decomposition, which is not economical. However, since the extrudability of the tube is deteriorated due to a factor other than thermal decomposition, it is desirable to carry out the treatment within the above range.

In order to form the above-mentioned metal oxide film on the surface of the bismuth-based X-ray contrast medium particles, for example, the bismuth-based X-ray contrast medium particles are dispersed in an aqueous solution of a water-soluble salt of the above metal, and this dispersion is used. It is obtained by neutralizing with an alkali or an acid, drying it, and then igniting it. in this case,
The water-soluble metal salt is hydrolyzed to form a hydrated metal oxide, which is deposited on the surface of the X-ray contrast medium particles, and the hydrated metal oxide is dehydrated by heating to form an anhydrous metal oxide. Becomes It is not always necessary to completely dehydrate.

Another method for forming the metal oxide film is heating an alkoxy metal. For example, X with an alcohol solution of alkoxysilane or alkoxytitanium.
When the X-ray contrast medium particles are moistened, dried and then heated, the alkoxy metal is changed into a metal oxide, and a thin film of the metal oxide can be formed on the surface of the X-ray contrast medium particles. Furthermore, in addition to the chemical treatment method as described above, a coating technique called surface fusion, in which a certain kind of mechanical energy is applied to a plurality of different material particles to cause a mechanochemical reaction (for example, Hosokawa Micron Of the bismuth-based X-ray contrast medium as a matrix, and the metal oxide can be fused to the surface of the particles.

In the present invention, examples of the bismuth X-ray contrast agent include bismuth oxide, bismuth oxychloride, bismuth subcarbonate, bismuth nitrate and bismuth tungstate.
-60% is preferable, but it can be appropriately changed depending on the purpose of use of the tube containing the contrast medium, the conditions of use, and the like.

[0010]

The mechanism by which the bismuth X-ray contrast agent accelerates the thermal decomposition of the thermoplastic polyurethane has not yet been fully elucidated. It was found that there were active sites that promoted. Therefore, in the tube containing the contrast agent according to the present invention, the surface of the bismuth-based X-ray contrast agent particles is covered with a thin film of a metal oxide such as aluminum oxide which is chemically and thermally stable, so that the polyurethane in a molten state is protected. The bismuth-based X-ray contrast medium particles are prevented from coming into direct contact with each other. This metal oxide film blocks the active sites present on the surface of the X-ray contrast agent particles and inactivates its catalytic action, so that the thermal decomposition of polyurethane during tube molding is remarkable as in the case of untreated. Stable tube molding is possible without being accelerated to the above, and the clear effect that the generation of impurities such as low molecular weight substances due to the thermal decomposition of polyurethane is eliminated is recognized.

[0011]

EXAMPLES The tube containing a contrast medium of the present invention will be described below, but the present invention is not limited to the examples, and modifications can be made within the technical concept of the present invention.
FIG. 1 is a cross-sectional view showing an example of a tube containing a contrast agent according to the present invention.
Is made of a polyurethane composition containing bismuth-based X-ray contrast agent particles, and in this case, the surface of the bismuth-based X-ray contrast agent particles is covered with a metal oxide film. Specifically, such a metal oxide film can be formed as follows.

Example 1 In a 1 wt% aqueous solution of aluminum sulfate 14-18 hydrate,
100 parts by weight of bismuth oxide was dispersed in 10 parts by weight of aluminum sulfate, and the pH of the dispersion was adjusted to 4 to 8 with an aqueous sodium hydroxide solution. By this neutralization, aluminum hydroxide was deposited as a gel on the surface of the bismuth oxide particles. Then, after drying the bismuth oxide particles covered with the aluminum hydroxide gel, a strong heat (400 ° C. or higher,
After 2 hours, the aluminum hydroxide on the surface of the bismuth oxide particles was dehydrated and changed to aluminum oxide, and a thin film of aluminum oxide was formed on the surface of the bismuth oxide particles.

Next, 2 parts by weight of the bismuth oxide particles are added to a medical polyether type polyurethane (Dow Chemi).
Cal: Pellethan 2363-90A
E, hardness Shore A 90) 3 parts by weight, and this was sufficiently kneaded by a twin-screw extruder to form pellets. And
The pellets containing the bismuth oxide and the polyurethane pellets containing no bismuth oxide were blended so that the content of bismuth oxide was 40 wt% and the mixture was fed to an ordinary extruder under a molding condition of a resin temperature of 190 ° C. When extruded into a tube with an outer diameter of 2 mm and an inner diameter of 1 mm, no change in the melt viscosity was observed even during continuous operation for 48 hours, and a tube with a contrast agent that had a good appearance and high dimensional accuracy could be manufactured. .. In this case, no resin accumulation was found on the surface of the die.

The tube containing the contrast agent was tested according to the eluate test of "Disposable blood transfusion set and infusion set standard" defined by the Pharmaceutical Affairs Law, and it was found to be suitable.

When bismuth oxide which had not been treated with aluminum sulfate was used and the tube molding was carried out under the same conditions as in Example 1 except that the viscosity change due to the decomposition of polyurethane was observed and stable extrusion molding was performed. could not. Also, this tube did not meet the eluate test.

Example 2 Using 100 parts by weight of bismuth oxide and 5 parts by weight of aluminum chloride hexahydrate, polyurethane was used in Ther.
Tecoflex EG- manufactured by mo Electron
A tube containing a contrast agent was manufactured by using the same procedure as in Example 1 except that the tube was changed to 85A.

Even when the water-soluble aluminum salt was changed, no particular change was observed in the polyurethane during molding, and good extrusion molding could be performed. In addition, there was no problem in terms of eluate.

Example 3 Sodium silicate 2 was added to a 1% aqueous solution of sodium silicate.
100 parts by weight of bismuth oxide particles were dispersed with respect to parts by weight, and sodium silicate in this dispersion was neutralized with dilute hydrochloric acid and gelled. By this operation, the surface of the bismuth oxide particles was covered with hydrous silicic acid, and the hydrogel was further ignited to form a thin film of silicon oxide on the surface of the bismuth oxide particles. Then, when tube molding was performed using the bismuth oxide particles under the same conditions as in Example 1, no problems in production occurred. further,
The tube containing the contrast agent also complied with the eluate test prescribed by the Pharmaceutical Affairs Law.

Example 4 100 parts by weight of bismuth oxide particles were dispersed in 3% by weight of zirconium oxychloride in a 1% aqueous solution of zirconium oxychloride octahydrate, and zirconium oxychloride in this dispersion was hydroxylated. The solution was neutralized with an aqueous potassium solution and gelled. By this operation, the surface of the bismuth oxide particles was covered with zirconium hydroxide, and when the hydrogel was further ignited, it was converted to zirconium oxide, and a thin film of zirconium oxide was formed on the surface of the bismuth oxide particles. Then, when tube molding was performed using the bismuth oxide particles under the same conditions as in Example 1, no production problems were observed and the eluate test was also satisfied.

Further, apart from such a method of hydrolyzing a metal salt, the bismuth oxide particles may be moistened with an alcohol solution of an alkoxy metal such as alkoxysilane or alkoxytitanium, dried, and then heated. A metal oxide film can be formed on the surface of the particles, and even when a metal oxide film is formed on the surface of the particles by surface fusion, the same effect as that of the surface treatment method can be obtained.

In the above-mentioned embodiment, an example in which bismuth oxide is used as the bismuth X-ray contrast agent has been described, but other bismuth X-ray contrast agents have different degrees, but the thermal decomposition of polyurethane during molding Suppressing effect of the bismuth-based X-ray contrast agent is formed. By forming a metal oxide film on the surface of the bismuth-based X-ray contrast agent particles, the polyurethane tube containing the bismuth-based X-ray contrast agent, which has a high contrast effect, which was previously impossible, is stabilized. Could be manufactured. Similar effects were observed when polyester type polyurethane was used.

In the examples, the case where the surface-treated bismuth X-ray contrast agent is uniformly dispersed on the tube wall made of polyurethane has been described. For example, bismuth X
A three-layer structure in which a polyurethane layer containing no X-ray contrast agent is provided on the inner and outer surfaces of an intermediate layer made of a polyurethane composition mixed with a line contrast agent, or made of a fluororesin containing no X-ray contrast agent A two-layer structure is formed by laminating an outer layer made of a polyurethane composition containing bismuth-based X-ray contrast agent particles that have been similarly surface-treated on the outer side of the inner layer, or a polyester-type polyurethane instead of the polyether-type polyurethane. The structure of the tube and the type of polyurethane can be appropriately changed according to the purpose of use of the tube containing the contrast agent and the like.

Furthermore, the metal oxide covering the surface of the bismuth-based X-ray contrast medium particles is not limited to the metal oxides shown in the above-mentioned examples, and the method of surface treatment or the amount of coating may be changed. It is possible.

[0024]

As described above, in the tube containing a contrast agent according to the present invention, the surface of the bismuth X-ray contrast agent particles is covered with a metal oxide film, and the metal oxide film is used for bismuth X-ray contrast imaging. Since the composition prevents direct contact between the agent and the polyurethane, the action of the bismuth-based X-ray contrast agent to accelerate the thermal decomposition of the polyurethane is suppressed, and stable tube molding becomes possible. The polyurethane tube containing the bismuth-based X-ray contrast agent is
The excellent physical properties and high contrast effect of polyurethane make it extremely convenient for use as a catheter.

[Brief description of drawings]

FIG. 1 is a sectional view showing an embodiment of a tube containing a contrast agent according to the present invention.

[Explanation of symbols]

 1 Contrast tube 2 Tube wall

Claims (3)

[Claims] 1. A contrast agent-containing tube obtained by mixing bismuth-based X-ray contrast agent particles coated with a metal oxide other than bismuth into a tube wall made of polyurethane. 2. The contrast agent-containing tube according to claim 1, wherein the metal oxide is selected from the group consisting of aluminum oxide, silicon oxide, zirconium oxide and titanium oxide. 3. The metal oxide coating the bismuth X-ray contrast medium particles is in a range of 0.05 to 10 parts by weight based on 100 parts by weight of the bismuth X-ray contrast medium. The contrast agent-containing tube according to item 1 or 2.