JPS5857186B2 - The basics of the future - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a medical tubular object to which air bubbles do not adhere, which is used for extracorporeal blood circulation, blood transfusion, and infusion.

For devices that circulate blood outside the body, such as heart-lung machines, auxiliary circulation devices, and hemodialysis devices, it is necessary to fill the tubes of the device with physiological saline, etc., and completely remove air bubbles before passing blood through the device. .

If air bubbles enter the blood vessels of the human body, serious accidents may occur, so this operation must be performed carefully.
They are often composed of hydrophobic polymeric substances with a critical surface tension of 45 dyne or less, and it takes a long time to remove bubbles.

Tubes for infusions and blood transfusions are often made of hydrophobic materials (polymer materials with a critical surface tension of 45 dyne/or less), and if blood transfusions or fluids are transfused over a long period of time, they may form in the tubes. The bubbles cannot easily escape upwards, causing various difficulties.

In order to solve these difficulties, methods such as silicone treatment of the inner surface of the tubular object have been carried out, but sufficient results have not been recognized.

The present invention solves the above problem, and provides a tubular object made of a polymer material with a critical surface tension of 45 dyneA-rI'L or less, in which the inner surface of the tubular object has a receding contact angle with water of 45 degrees or less. It is characterized by being coated with (meth)acrylate-based hydrophilic polymer.
This suppresses the generation of air bubbles and allows extracorporeal circulation of blood or blood transfusion or infusion to be carried out smoothly without any difficulty.

The present invention has the following findings: When blood and aqueous solutions of various drugs are introduced into an extracorporeal device, a critical surface tension of 45 d
Bubbles are likely to form on the surface of a tubular object made of a polymer material of yne/crrL or less, and are difficult to remove;
Polymer materials with properties suitable for use in extracorporeal blood circulation, blood transfusion, and infusions are often hydrophobic materials with good water resistance, critical surface tensions of 45 dyne/cx or less, and tubular objects. If the inner surface of the body is coated with an appropriate hydrophilic polymer, it may become difficult for air bubbles to adhere to it. This is based on the fact that damage during passage through tubular objects is also reduced.

In the present invention, the critical surface tension is a parameter proposed by Zis Kawayo, and is a physical property value related to the surface free energy of a solid.
"Surface Chemistry of Polymers" published by Sangyo Tosho Co., Ltd. on December 13, 1961, page 19.

In addition, the receding contact angle for water is a value measured by the tilting plate method.
The measurement method is described, for example, on page 77 of Nippon Kagaku Complete Edition "Experimental Chemistry Course 7, Surface Chemistry" published by Maruzen Co., Ltd. on May 20, 1955.

Note that the critical surface tension and the receding contact angle with respect to water are measured at a temperature of 25°C.

In the present invention, the inner surface of the tubular object can be coated with a hydrophilic polymer having a receding contact angle of 45° or less with respect to water by, for example, a graft polymerization method or a coating method.

The graft polymerization method uses gamma rays, electron beams, ozone, etc. to form a tubular object υ.
In this method, active sites such as radicals are generated on the inner surface, and a hydrophilic polymer monomer is brought into contact with the active sites and polymerized to form a coating.

Generation of active sites is carried out in the presence or absence of the monomer.

The coating method is a method in which a hydrophilic polymer is synthesized in advance, this solution or latex is applied to the inner surface of a tubular object, and the solvent is evaporated to form a coating of the hydrophilic polymer.

Another coating method involves melting a hydrophilic polymer and extruding it simultaneously when forming a tubular object (melt method).
is also included.

In the solution coating method, in order to improve adhesion, it may be preferable to subject the inner surface of the tubular object to a pretreatment such as chromium sulfuric acid treatment, sodium-naphthalene treatment, or ultraviolet treatment.

In terms of workability in forming the coating, the above-mentioned melting method is most preferred, but in consideration of the properties of the resulting coating, the grafting method is preferred.

Improvements in bubble adhesion and affinity with living cells in a tubular object can be achieved sufficiently even if the thickness of the inner surface coating of the hydrophilic polymer is extremely thin. It is preferably 5 mm or less, particularly 0.1 mm or less.

A thickness of the order of 10rrl11 is particularly suitable.

In order for such a thin coating layer to be stable, when a coating method is employed, the hydrophilic polymer must have a molecular weight of 10,000 or more, preferably 30,000 or more, and be water-insoluble. Ru.

Note that it is actually easier to handle the tubular object if only the inner surface is coated with the hydrophilic polymer.

In the present invention, (meth)acrylate-based hydrophilic polymers (acrylates and methacrylates are collectively referred to as (meth)acrylates) having a receding contact angle with water of 45° or less are particularly preferable for coating formation by a coating method. Examples include polymers of hydroxyethyl (meth)acrylate, hydroxypropyl (meth)acrylate, methoxyethyl acrylate, and ethoxyethyl acrylate.

Furthermore, copolymerization of the above monomers and other hydrophobic monomers such as hydroxylaethyl acrylate, hydroxypropyl acrylate, diethylene glycol (meth)acrylate, dimethylaminoethyl (meth)acrylate (and quaternized salts thereof), etc. Consolidation can also be used.

When the tubular body of the base material is flexible (which is actually often the case), the glass transition temperature of the hydrophilic polymer for coating is preferably below room temperature.

The most preferred hydrophilic polymer in the coating method is
It is a polymer prepared from hydroxyethyl (meth)acrylate, hydroxypropyl (meth)acrylate, etc.

Further, it is often effective to use a polymer of monomers containing a quaternary ammonium salt or a group that easily becomes a quaternary ammonium salt.

This has the advantage that heparin can be immobilized.

Thanks to the graft polymerization method, the receding contact angle with water is 45°.
The monomers described above are also advantageously used in forming the following coatings.

The critical surface tension (25℃) of the tubular object is 45 d
Examples of materials below yne/m include Teflon, polyethylene, polypropylene, natural rubber, polyisoprene, polybutadiene, styrene-butadiene rubber, neoprene, silicone rubber, polyvinyl chloride, ethylene-vinyl acetate copolymer, etc. However, polyvinyl chloride, silicone rubber, and polyethylene are materials that have excellent physical properties for injecting blood or various liquids into living organisms, and are particularly effective for applying the hydrophilic polymer coating according to the present invention. , polypropylene, and ethylene-vinyl acetate copolymer.

Materials to which the present invention is more applicable due to ease of handling of tubular objects, ease of forming surface coatings, stability, improvement effect on bubble adhesion, etc. are polyvinyl chloride, ethylene-vinyl acetate copolymer, and silicone. Rubber, especially a material based on ethylene-vinyl acetate copolymer.

The present invention will be specifically explained below using Examples.

Example 1 Critical surface tension is 39 dyne between inner diameter 10zH and outer diameter 15
/m of PVC heart-lung tube (containing 45% dioctyl phthalate as a plasticizer) in air.
After irradiation with Mrad's gamma rays, the tube was filled with hydroxyethyl acrylate, and after the tube was purged with nitrogen, the side end was closed with a silicone rubber stopper and kept at 80° C. for 10 hours.

Thereafter, unreacted hydroxyethyl acrylate was removed, and the tube was thoroughly washed with methyl alcohol and dried.

An extremely thin coating of hydroxyethyl acrylate polymer is formed on the inner surface of the vinyl chloride tube by graft polymerization, and the inner surface is extremely wettable with water.
The receding contact angle of water decreased from 71° before treatment to less than 20°.

When we used the above-mentioned untreated and treated tubes as tubes for an artificial heart-lung machine, we found that air bubbles tend to adhere to the untreated tubes, and when blood begins to flow, we frequently tap the tubes with our hands to vibrate the tubes. It was necessary to transfer the air bubbles inside the tube to the drip chamber.

On the other hand, almost no air bubbles were attached to the inner surface of the processing tube, so such an operation was unnecessary.

Example 2 150 parts of hydroxyethyl methacrylate, 50 parts of ethoxyethyl acrylate, 400 parts of methyl alcohol and 40.6 parts of t-butylperoxyoctoate were heated at 67°C.
The polymer solution polymerized for 12 hours at
After passing through the tube (for blood circuit), the remaining solution was allowed to drip, and air was forced into the tube to dry it.

The tube was kept in an oven at 60° C. for 5 hours to fix the inner coating.

As a result of the above operation, the receding contact angle of the inner surface of the tube with respect to water was reduced from 62° to 25°.

When physiological saline was circulated through the untreated and treated tubes, the air bubbles attached to the inner surface of the untreated tube did not come out easily, so the same operation as in Example 1 was performed to remove the air bubbles. I had to move it to a drip chamber.

On the other hand, almost no air bubbles were observed on the treatment tube.

Claims (1)

[Claims] 1 A tubular object used for extracorporeal blood circulation or blood transfusion or infusion, with a critical surface tension of 45 dyne/
In a tubular object made of a polymer material with crrL or less, the inner surface of the tubular object has a receding contact angle with water of 45
A tubular object to which air bubbles do not adhere, characterized by being coated with a (meth)acrylate-based hydrophilic polymer of less than or equal to .