JPH0624588B2 - Medical tube manufacturing method - Google Patents

Description

TECHNICAL FIELD The present invention relates to a medical tube having excellent patency, particularly to a method for producing a medical tube suitable for artificial blood vessels, and especially artificial blood vessels of medium and small diameter.

[Prior Art and its Problems] Conventionally, as a radical operation for securing the functions of the affected ureter, trachea, esophagus, and blood vessel, replacement with an artificial medical tube or bypass operation has been performed.

As these medical tubes, a tube in which polyester fibers are woven and pleated is used, and a tube in which polytetrafluoroethylene is molded and then stretched to have a fine fiber structure is used. ing.

When these medical tubes are applied as urethra, trachea, esophagus, and blood vessels having an inner diameter of 10 mm or more, relatively good patency results have been obtained, but they are still insufficient.
Further, the patency performance is extremely poor in a small-diameter blood vessel having an inner diameter of 7 mm or less, especially 6 mm or less, and the above-mentioned polytetrafluoroethylene made porous is used only for limited purposes.

In particular, an artificial blood vessel that can be applied to peripheral arteries with an inner diameter of 3 to 4 mm has been widely desired by the clinician for its application to coronary artery bypass surgery, and many studies on small and medium-sized blood vessels have recently been conducted. However, there is nothing that can be used yet.

In the artificial blood vessel in which the polyester fiber is reticulated, a thrombus layer having a thickness of 1 mm is formed in the lumen immediately after transplantation. Therefore, if this material is applied to small and medium-sized blood vessels, It is blocked by a blood clot.

Therefore, it is preferable to use a material having a superior antithrombotic property such that the material itself does not become blocked by the initial thrombus.

On the other hand, using several types of polyether polyurethane or polyurethane urea with different antithrombotic properties, a large number of artificial blood vessels with different cross-sections and inner surface structures were prototyped, and the results of a transplantation experiment in dogs showed that the It has been found that the surface structure of the surface affects patency performance with an extremely large effect. When these medical tubes are transplanted and placed in the body, in particular, ureters, trachea,
With suturing with tubular organs such as the esophagus and blood vessels, it is essential that a suture needle suitable for anastomosis is easy to pass through and does not bend (kinking resistance).

A medical tube having excellent antithrombogenicity, sutureability, anti-kinking property, etc., and a suitable inner surface structure,
It can be produced by a solution molding method for forming a porous wall by drying or gelling a solution of a polymer compound in a coagulation bath.

For example, a method of applying a known hollow fiber membrane spinning method or a method of gelating a solution adhering to the surface of a mandrel is generally known.

However, if the hollow fiber membrane spinning method is applied when the wall thickness of the tube reaches 0.2 to 0.3 mm or more, the time required for gelation is long and the cross-sectional shape or wall thickness is kept constant. It is extremely difficult to gel the gel as it is.

Further, in the method of dipping on the mandrel, the gelling action proceeds only from the outer surface side, so that the degree of freedom for controlling the surface structure of the inner surface is low and it does not meet the purpose.

[Means for solving problems]

The present invention relates to a method for producing a medical tube, characterized in that the step of inverting the inner surface and the outer surface of the tube obtained by gelling a solution of a polymer compound is included in the process. The structure of the inner surface of the medical tubing, which has a great influence on the patency performance of the cavity, overcomes the drawback of the conventional method in which it cannot be freely controlled.

The polymer compound used in the present invention is a substance excellent in compatibility with blood and tissues, that is, it has no acute or chronic toxicity, pyrogenicity, or hemolytic property, and even if it is placed in a transplanted place for a long period of time, Must be a polymer that does not cause inflammation in the tissues of Examples of such polymers include polyvinyl halides, polystyrene and derivatives thereof, polyolefin-based polymers, polyester-based condensates, cellulose-based polymers, polyurethane-based polymers, polysulfone-based polymers, polyamide-based polymers. And so on. Of course, a copolymer or mixture containing these may be used. From the viewpoint of mechanical properties, stability in vivo, and antithrombogenicity, the polyurethane type is preferable among them. Specific examples thereof include polyurethane, polyurethane urea, blends of these with silicone polymers, and those having an interpenetrating network structure. These also include segmented polyurethane or polyurethane urea,
Those containing polydimethylsiloxane in the main chain, hard,
Those including fluorine in the soft segment are included.
Polyether type polyurethane or polyurethane urea is preferable to polyester type because it is less susceptible to biodegradation.

Polytetramethylene oxide is most preferable as the polyether constituting the polyether segment of the polyurethane or the like, but other polyalkyl oxides (provided that the alkylene has 2 and / or 3 carbon atoms) are also preferable. Examples of these polyalkylene oxides include polyethylene oxide, polypropylene oxide, ethylene oxide-propylene oxide copolymer or block copolymer, or a mixture thereof.

The molecular weight of the polyether forming the soft segment is usually in the range of 400 to 3000, preferably 450 to
It is in the range of 2,500, more preferably in the range of 500 to 2,500, and among them, the most excellent polyether segment is a polytetramethylene oxide chain having a molecular weight of 800 to 2,500, and particularly a molecular weight of 1,300 to 2,000. If the molecular weight of this polyether soft segment exceeds 3000, the mechanical properties of the polyurethane medical tube will be poor, and if it is less than 400, it cannot be used because it is too hard to be molded as a medical tube.

Polyurethane is synthesized by reacting the above-mentioned polyether having hydroxyl groups at both ends with diisocyanate used in known polyurethane synthesis such as 4,4′-diphenylmethane diisocyanate, toluidine diisocyanate, 4,4′-dicyclohexylmethane diisocyanate and hexamethylene diisocyanate. To prepare a prepolymer of terminal isocyanate, and chain extend this with a diamine such as ethylenediamine, propylenediamine, tetramethylenediamine or a diol such as ethylene glycol, propylene glycol or butanediol.

The medical tube of the present invention can be manufactured, for example, as follows.

That is, a rigid core rod having a circular cross section is extruded concentrically from a circular orifice, whereby a solution of a polymer compound is attached to the entire circumferential surface of the core rod through a gap slit between the orifice and the core rod. After extrusion, the core rod is introduced into a coagulation bath, and the polymer compound is solidified around the core rod, then washed thoroughly with water to remove the solvent, and then the core rod is taken out to obtain a porous medical treatment. Tube can be obtained.

The solution used for molding is preferably set so that the viscosity at the molding temperature is 0.5 poise or more. If the viscosity is less than 0.5 poise, unevenness in wall thickness is likely to occur during the molding process. When it is 10 poises or more, restrictions on molding conditions are lessened, which is more preferable.

On the other hand, there is almost no saving on the high-viscosity side, and sufficient molding can be performed without the fluidity of the solution. When molding is performed by a known method for producing a hollow fiber using an annular nozzle, it is extremely difficult to form 500.
Even a solution of about 0 poise can be molded very easily. However, it is desirable from the viewpoint of production that the solution can be degassed relatively easily. Therefore, the porosity is preferably 3000 poises or less, more preferably 2000 poises or less.

As the solvent used for the solution of the polymer compound, a known solvent can be appropriately selected for each substance, but in order to avoid the solvent remaining in the product and from the viewpoint of the process cost, the water-soluble solvent is used. Are more advantageous. Examples of such a solvent include dimethylformamide, dimethylacetamide, dimethylsulfoxide, and N-methyl-2.
-Pyrrolidone, dioxane, tetrahydrofuran, acetone and the like. Further, in the production method of the present invention, the solution does not necessarily have to be in a good dissolved state. Therefore, a large amount of a poor solvent or a swelling agent such as urea can be mixed and used. This is extremely advantageous for the medical tube as the object of the present invention. That is, by selecting a wide range of solvent systems, it is possible to easily change a wide range of porosity (porosity) easily without a complicated process such as using a pore-forming agent.

The rigid rod used as the core may be one that does not dissolve in the solution and does not easily change its shape until it is introduced into the coagulation bath. Corrosion resistance is also required, so that stainless steel, steel, or brass plated with chrome or Teflon is preferable.

The core rod extruded in a state where the solution is attached to the entire surface of the core rod is introduced into the coagulation bath directly or after passing through a certain dry portion.

That is, a solution of a polymer compound discharged from a slit between a circular orifice and a core rod is wet coagulated directly discharged into a water-based coagulation bath, and a dry-wet solution introduced into a water-based coagulation bath after passing through a dry section. Either coagulation is applicable.

After drying the medical tube thus obtained,
Invert so that the inner surface of the medical tube is the outer surface.

By this operation, the portion which was the outer surface to which the direct gelation action is exerted, the tube having the inner surface is obtained, for example, by changing the composition of the coagulation bath,
The inner surface structure of the medical tubing according to the present invention can be widely and reproducibly controlled.

For example, a smooth surface can be obtained by inversion after gelling using a coagulation bath in which a water-soluble salt is dissolved in high concentration. Also, when the solution of the polymer compound attached to the mandrel gels, a porous surface is formed on the mandrel side, and by inverting this, a structure that promotes tissue adhesion on the outer surface can be easily formed. You can have it.

The present invention will be described in detail below with reference to examples. In addition,% shown below represents weight%.

Example Polytetramethylene glycol having a molecular weight of 1300 and having hydroxyl groups at both ends was reacted with 4,4'-diphenylmethane cisisocyanate to give a prepolymer of isocyanate at both ends, which was chain-extended with butanediol to synthesize polyurethane. . The synthesized polyurethane was purified by repeating reprecipitation three times with a tetrahydrofuran-ethanol solvent. This purified polyurethane was dissolved in dimethylacetamide to prepare a 20% solution.

From a circular orifice having a diameter of 6 mm, a stainless steel rod having an outer diameter of 4 mm set so as to be concentric with the orifice was extruded at a constant speed. From the extruded annular gap between the stainless steel rod and the orifice, the polyurethane solution was extruded while adhering to the entire circumferential surface of the rod, and then it was introduced into the coagulation bath shown in Table 1 as it was, It was cooled and solidified from the outside, and immersed in water for 48 hours to sufficiently remove the solvent.

The porous medical tube obtained by removing this rod was inverted from one end so that the inner surface became the outer surface, and then dried at 40 ° C. for 24 hours to produce artificial blood vessels with different lumen structures. did.

As is clear from Table 1, according to the production method of the present invention,
It is possible to obtain an artificial blood vessel in which the inner surface structure is widely changed.

[Effect of the Invention] According to the method for producing a medical tube of the present invention, it is possible to easily obtain an artificial medical tube that is used by being connected to a living organ with a changed inner surface structure. Examples of the medical tube include an artificial ureter, an artificial trachea, an artificial esophagus, and an artificial blood vessel, and are particularly suitable as a method for producing a medium- or small-sized artificial blood vessel having excellent antithrombogenicity, sutureability, or anti-kinking property. is there.

Claims (3)

[Claims] 1. A method for producing a medical tube, which comprises a step of inverting an inner surface and an outer surface of a tube obtained by gelling a polymer solution. 2. A high molecular polymer solution is polyurethane and / or
Alternatively, the method for producing a medical tube according to claim (1), which is a solution containing polyurethane urea as a component. 3. The method for producing a medical tube according to claim 1, wherein the medical tube is an artificial blood vessel.