JP3236048B2 - Tube with contrast agent - Google Patents

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 a tube wall, for example, a tube containing a contrast agent suitable for use as an indwelling catheter or a catheter for angiography.

[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 polymer material in various modes is laminated on a tube made of a single material or another polymer 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 tubes containing a contrast agent, a fluororesin, polyolefin, vinyl chloride resin, or the like is used as a polymer material constituting the tube wall (Japanese Patent Publication No. 47-49394, Japanese Patent Application Laid-Open No. 56-119).
No. 263 and No. 51-108389).

[0003] Furthermore, recently, it has good flexibility, elasticity and mechanical strength, and is non-toxic, sterilizable, and safe.
Medical thermoplastic polyurethane having excellent antithrombotic properties is used as a material for this kind of tube containing a contrast agent, and among them, a polyether type is particularly awarded. On the other hand, such a polyurethane has the above-mentioned excellent properties, but has a property of easily deteriorating due to heat, so that the processing temperature range is narrower than other thermoplastic resins, and when this is extruded into a tube, Requires precise temperature control.

[0004]

In a tube containing a contrast agent made of polyurethane, barium sulfate has been used as an X-ray contrast agent, and a bismuth-based X-ray contrast agent having a higher contrast effect than barium sulfate has been used. Had not been used. One of the reasons is that the bismuth-based X-ray contrast agent has a function of catalytically promoting the thermal decomposition of the polyurethane in the molten state. When this is used, the melt viscosity of the polyurethane greatly changes in the extruder. In addition, stable tube formation cannot be performed, and low molecular weight substances due to decomposition may be mixed into the tube and eluted into blood. However, with advances in medical technology, catheters are becoming thinner or thinner, and the demand for polyurethane tubes mixed with a bismuth-based X-ray contrast agent having a high contrast effect has been particularly strong in recent years.

[0005] The present inventor has conducted intensive studies in view of such problems of the prior art, and as a result, if bismuth-based X-ray contrast agent particles having been subjected to surface treatment are used, polyurethane during molding processing can be obtained. Found that thermal decomposition of
The present invention has been made. That is, an object of the present invention is to provide a polyurethane tube mixed with a bismuth-based X-ray contrast agent having a high contrast effect.

[0006]

To achieve the above object, a tube containing a contrast agent according to the present invention comprises a bismuth-based X-ray contrast coated with a metal oxide selected from the group consisting of aluminum oxide, zirconium oxide and titanium oxide. The composition is such that agent particles are mixed into the inside of a tube wall made of polyurethane. In this configuration, as the metal oxide covering the surface of the bismuth-based X-ray contrast agent particles, aluminum oxide, zirconium oxide, and titanium oxide are particularly preferable, and the coating amount is determined by the amount of the bismuth-based X-ray contrast agent used. Although it varies depending on the type and particle size and the type of metal oxide, it is generally selected in the range of 0.05 to 10 parts by weight based on 100 parts by weight of the X-ray contrast agent. The reason is that when 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 when the amount of the metal oxide is 10 parts by weight or more, there is no difference in the effect of suppressing the thermal decomposition. Alternatively, the extrudability of the tube is reduced due to a factor other than the thermal decomposition.

In order to form the metal oxide film on the surface of the bismuth-based X-ray contrast agent particles, for example, the bismuth-based X-ray contrast agent particles are dispersed in an aqueous solution of a water-soluble salt of the metal, and this dispersion is dispersed. 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 and precipitates on the surface of the X-ray contrast agent particles, and the hydrated metal oxide is dehydrated by heating to obtain an anhydrous metal oxide. Becomes It is not always necessary to completely dehydrate.

Another method of forming a metal oxide film includes heating of an alkoxy metal. For example, X in an alcohol solution of alkoxysilane or alkoxytitanium
When the X-ray contrast agent particles are heated after being moistened and dried, the alkoxy metal is converted into a metal oxide, and a thin film of the metal oxide can be formed on the surface of the X-ray contrast agent particles. Further, in addition to the above-described chemical treatment method, a coating technique (referred to as Hosokawa Micron Co., Ltd.) that causes a mechanochemical reaction by applying a certain type of mechanical energy to a plurality of different material particles, called surface fusion. (Mechanofusion system), the bismuth-based X-ray contrast agent particles are used as a base, and the metal oxide can be fused to the surface.

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

[0010]

[Function] The mechanism by which the bismuth-based X-ray contrast agent promotes the thermal decomposition of thermoplastic polyurethane has not been sufficiently elucidated, but the thermal decomposition of polyurethane is catalyzed on the particle surface of the bismuth-based X-ray contrast agent. It was noted that there was an active site to promote. 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 that is chemically and thermally stable, so that the polyurethane in the molten state can be prevented. It is configured to prevent direct contact of bismuth-based X-ray contrast agent particles. Since this metal oxide film blocks the active sites present on the surface of the X-ray contrast agent particles and inactivates the catalytic action thereof, the thermal decomposition of polyurethane is remarkable during the tube molding as in the case of untreated. It is possible to obtain a clear effect that stable tube molding can be performed without being promoted, and generation of impurities such as low molecular weight substances due to thermal decomposition of polyurethane is eliminated.

[0011]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, a tube containing a contrast agent of the present invention will be described, but it is needless to say that the present invention is not limited to the embodiments, and modifications within the technical concept of the present invention are possible.
FIG. 1 is a cross-sectional view showing an example of a tube containing a contrast agent according to the present invention.
Is composed of a polyurethane composition containing bismuth-based X-ray contrast agent particles. In this case, the surface of the bismuth-based X-ray contrast agent particles is configured to be covered with a metal oxide film. Specifically, such a metal oxide film can be formed as follows.

Example 1 A 1 wt% aqueous solution of aluminum sulfate 14-18 hydrate was
100 parts by weight of bismuth oxide was dispersed in 10 parts by weight of aluminum sulfate, and this dispersion was adjusted with an aqueous sodium hydroxide solution so that the pH of the dispersion was in the range of 4 to 8. As a result of the neutralization, aluminum hydroxide was precipitated as a gel on the surface of the bismuth oxide particles. Next, the bismuth oxide particles covered with the aluminum hydroxide gel are dried, and then heated (400 ° C. or more,
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 were added to a medical polyether type polyurethane (Dow Chemi).
cal: Pellethane2363-90A
E, hardness Shore A90) 3 parts by weight, and kneaded with a twin-screw extruder to form a pellet. And
A mixture of the bismuth oxide-containing pellet and the bismuth oxide-free polyurethane pellet so that the bismuth oxide content is 40 wt% is supplied to a usual extruder, and the molding is performed under a molding condition at a resin temperature of 190 ° C. When extruded into a tube having an outer diameter of 2 mm and an inner diameter of 1 mm, no change was observed in the melt viscosity even after 48 hours of continuous operation, and a tube containing a contrast agent having a good appearance and high dimensional accuracy could be produced. . In this case, no resin accumulation was observed on the die surface.

The tube containing the contrast medium was tested according to the dissolution test of "Disposable blood transfusion set and transfusion set standard" determined by the Pharmaceutical Affairs Law.

A tube was formed under the same conditions as in Example 1 except that bismuth oxide not treated with aluminum sulfate was used. As a result, a change in viscosity due to decomposition of polyurethane was observed, and stable extrusion was performed. could not. This tube was not compatible with the eluate test.

Example 2 Using 100 parts by weight of bismuth oxide and 5 parts by weight of aluminum chloride hexahydrate, the polyurethane was converted to Ther.
Tecoflex EG- made by mo Electron
A tube containing a contrast agent was manufactured 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.

Reference Example A 1% aqueous solution of sodium silicate was mixed with sodium silicate 2
100 parts by weight of bismuth oxide particles were dispersed with respect to parts by weight, and sodium silicate in the 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 ignited to form a thin film of silicon oxide on the surface of the bismuth oxide particles. Then, when tube forming 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 was also suitable for the eluate test specified in the Pharmaceutical Affairs Law.

Example 3 In a 1% aqueous solution of zirconium oxychloride octahydrate, 100 parts by weight of bismuth oxide particles were dispersed with respect to 3 parts by weight of zirconium oxychloride, and the zirconium oxychloride in the dispersion was subjected to hydroxylation. The solution was neutralized with an aqueous potassium solution to form a gel. By this operation, the surface of the bismuth oxide particles was covered with zirconium hydroxide, and when the hydrogel was further ignited, it turned into zirconium oxide and a thin film of zirconium oxide was formed on the surface of the bismuth oxide particles. Then, tube formation was performed using the bismuth oxide particles under the same conditions as in Example 1 above. As a result, no problems in production were observed, and the test was suitable for the eluate test.

Further, separately from such a method of hydrolysis of a metal salt, the bismuth oxide particles are wetted 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 the surface treatment method can be obtained.

In the above embodiment, an example was described in which bismuth oxide was used as the bismuth-based X-ray contrast agent. However, although other bismuth-based X-ray contrast agents differed to a certain extent, the thermal decomposition of polyurethane during molding was carried out. The formation of a metal oxide film on the surface of bismuth-based X-ray contrast agent particles has been confirmed to stabilize a polyurethane tube containing a bismuth-based X-ray contrast agent with a high contrast effect, which was previously impossible. Could be manufactured. Similar effects were also observed when polyester-type polyurethane was used.

In the embodiment, an example was described in which the bismuth-based X-ray contrast agent subjected to the surface treatment was uniformly dispersed on the tube wall made of polyurethane.
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 X-ray contrast agent, or made of a fluororesin containing no X-ray contrast agent On the outer side of the inner layer, an outer layer made of a polyurethane composition containing bismuth-based X-ray contrast agent particles subjected to the same surface treatment is formed in a two-layer structure in which the outer layer is laminated. For example, 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.

Further, the metal oxide covering the surface of the bismuth-based X-ray contrast agent particles is not limited to the metal oxide shown in the above-described embodiment, and the surface treatment method or the coating amount may be changed. It is possible.

[0024]

As described above, 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 the metal oxide film, and the bismuth-based X-ray contrast image is formed by the metal oxide film. Since the direct contact between the agent and the polyurethane is prevented, the action of the bismuth-based X-ray contrast agent that promotes the thermal decomposition of the polyurethane is suppressed, and stable tube molding can be performed. And the polyurethane tube containing this bismuth-based X-ray contrast agent
Due to the excellent physical properties and high contrast effect of polyurethane, it is extremely convenient to use as a catheter.

[Brief description of the 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 tube with contrast agent 2 tube wall

Claims (2)

(57) [Claims] 1. A tube containing a contrast agent obtained by mixing bismuth-based X-ray contrast agent particles coated with a metal oxide selected from the group consisting of aluminum oxide, zirconium oxide and titanium oxide into the inside of a tube wall made of polyurethane. 2. The method according to claim 1, wherein the amount of the metal oxide coating the bismuth-based X-ray contrast agent particles ranges from 0.05 to 10 parts by weight based on 100 parts by weight of the bismuth-based X-ray contrast agent. The tube containing a contrast agent according to item 1.