JPH0696024B2 - Base material for artificial blood vessel and method for producing the same - Google Patents

Description

TECHNICAL FIELD The present invention relates to a flexible polyurethane-based artificial blood vessel substrate and a method for producing the same.

<< Prior art and its problems >> As a base material for artificial blood vessels, polyester fibers, for example, fibers such as Dacron (trade name) braided in a tubular shape,
Polyethylene tetrafluoride-based porous materials such as those based on Gore-Tex (trade name) are known. When this kind of base material is used in a living body as an artificial blood vessel, a thrombus is formed on the inner wall of a hollow tubular base material, a pseudointimal film is formed on the inner surface of the base material, and blood flows through the inside. From this point, if the tube diameter is reduced, the thrombus itself may cause the occlusion of the artificial blood vessel substrate.

For this reason, it has been said that these artificial blood vessel base materials that have been generally used conventionally are not suitable as a substitute for a blood vessel having an inner diameter of about 5 mm or less.

On the other hand, a method of preventing the formation of thrombus on the inner wall by grafting a hydrophilic polymer or the like on the inner wall of the artificial blood vessel base material has been proposed. According to this method, an artificial blood vessel with a small diameter is also possible. However, the base material itself is naturally required to have biocompatibility, resistance to bending, flexibility, and anastomotic compatibility.

As a method for producing such a small-diameter artificial blood vessel substrate,
The present applicant has proposed Japanese Patent Application No. 61-52353 as a method for making a polyurethane material porous.

The artificial blood vessel substrate obtained by the method according to this application,
It is provided with a smooth inner layer and a porous outer layer, and is provided as an artificial blood vessel by grouting a hydrophilic polymer as a substance that forms hydrous glue on the surface of this smooth inner layer.

By the way, an artificial blood vessel based on this type of porous urethane tube having a hydrous gel on the inner surface shows excellent antithrombogenicity and is expected to have a high patency rate, but the flexibility of the tube itself is expected. There was a problem that it was inferior to.

Therefore, increasing the thickness of the porous portion of the tube is sufficient for merely improving the flexibility, but in that case, the flexibility is reduced and the piercing property of the needle during anastomosis deteriorates. And other problems arise.

For this reason, the bending resistance is sacrificed, but the thickness of the porous portion is made thin. However, if the thickness is thin, the strength of the tube becomes small and there is a risk of bursting under high pressure.

In view of the above problems, the present inventors have earnestly studied for the purpose of improving the flex resistance without compromising the operability during compliance or anastomosis as an index of flexibility as the artificial blood vessel substrate, The present invention has been completed.

<< Means for Solving the Problems >> In order to achieve the above object, the present invention provides a base material for an artificial blood vessel, a tubular base material layer made of a porous elastomer material, and an inner periphery of the tubular base material layer. Inner layer, a monofilament reinforcing material spirally wound around the outer periphery of the tubular base material layer, and a porous material that partially surrounds the reinforcing material and is formed on the outer periphery of the tubular base material layer. And a peelable outer layer of elastomeric material.

Further, as a method for producing the base material for artificial blood vessel, after adjusting the viscosity by adding and mixing an inorganic salt to a solution in which an elastomeric material is dissolved in a solvent, a tubular base which is extruded annularly from an extruder and cut into a predetermined length. A material forming step, a reinforcing material winding step of spirally winding a monofilament-like reinforcing material around the outer periphery of the tubular base material after the solvent is removed and dried and solidified, and the reinforcing material is wound. An outer coating layer forming step of annularly extruding a coating material obtained by adding and mixing an inorganic salt to a material having compatibility with the elastomer material to the outer periphery of the tubular base material and coating under reduced pressure; The method is characterized by comprising an inner layer forming step of forming an inner layer on the circumference, and then a porous forming step of removing the inorganic salts of the tubular substrate and the outer coat layer to make them porous.

Examples of the elastomeric material used for the tubular base material layer, the smooth inner layer and the outer coating layer of the present invention include polyurethane, polyurethane urea, a blend thereof with a silicone polymer, and a silicone polymer. Polyurethane or polyurethane urea In terms of durability in vivo, a polyether type is preferable, and a polyether segmented polyurethane or a polyether segmented polyurethane urea is more preferable.

The above-mentioned elastomer material is used by being dissolved in a solvent, and the solvent that can be used in the present invention is, when the elastomer material is a polyether segmented polyurethane or a polyether segmented polyurethane urea,
Tetrahydrofuran and dimethylformamide may be mentioned.

Inorganic salts to be added and mixed for making porous are calcium carbonate, magnesium oxide, magnesium hydroxide,
Sodium chloride can be used, and any substance that can be eluted afterwards by an acid such as hydrochloric acid, sulfuric acid, or acetic acid nitric acid can be used, and the addition amount is 500 parts by weight or more based on 100 parts by weight of the elastomer from the viewpoint of forming continuous pores. desirable.

Further, as the monofilament-like reinforcing material, it is desirable to use a material such as polyethylene and polypropylene that has rigidity and is not likely to be decomposed and absorbed in the living body. The thickness of the filament and the spiral winding pitch are determined according to the specifications as an artificial blood vessel, but the winding pitch is 1 to 20 mm, more preferably 1 to 5 mm, and the monofilament is preliminarily coiled in winding. You may keep it.

The outer layer is extruded in an annular shape while covering it under a reduced pressure so as to have a slight gap without surrounding the entire outer circumference of the monofilament as a reinforcing material. It is important to join the tubular substrate layer to the extent that the layers can be peeled off.

Furthermore, when producing a substrate that can be directly used as an artificial blood vessel, as the hydrogel-forming layer, polyvinyl alcohol, particularly those having a polymerization degree of 500 to 10,000 and a saponification degree of 80 or more, or an ethylene-vinyl alcohol copolymer. Those having a high content of vinyl alcohol are not dissolved in cold water but tend to swell to form a hydrogel, which is preferable from the viewpoints of antithrombogenicity and durability.

<Example> Hereinafter, a preferred example of the present invention will be described with reference to the accompanying drawings.

Example 1 First, 100 parts by weight of polyether segmented polyurethane is dissolved in 600 parts by weight of tetrahydrofuran to obtain a viscous polymer solution. Next, 450 parts by weight of soft calcium carbonate having an average particle size of 1.7 μm and 90 parts by weight of magnesium oxide having an average particle size of 2 μ were added and kneaded to volatilize a part of tetrahydrofuran to give a cylinder diameter of 9.55 mm and an orifice. With a melt indexer with a diameter of 2.96 mm and a load of 2160 g, a paste-like material with a viscosity of about 1.25 g / 10 minutes at normal temperature was formed, which was fed to a screw type extruder 1 to have an inner diameter of 3 mm and an outer diameter. While extruding from a 4 mm annular die 2 and taking it out by a take-up machine 3, a tubular article A cut into a length of about 50 to 60 cm is produced. Then, as shown in FIG. 2, the tubular material A was immersed in the water tank 4 to remove the solvent and solidify, and then dried sufficiently.

Thereafter, a reinforcing material B made of polypropylene monofilament having a fiber diameter of about 0.3 mm is wound around the outer periphery of the tubular material A at a pitch of 1 mm, and this is passed through a coating device equipped with an annular die having an outer diameter of 7 mm and an inner diameter of 6.5 mm. Then, the same paste-like material as used for the tubular material A was coated to a thickness of 0.5 mm under a reduced pressure of 300 mm water column, immersed in a water tank to desolvate the coating layer, and then dried to coat Layer F was formed. Then, a 1-5N dilute hydrochloric acid was passed through the tubular material A for about 1 minute,
Part of the inner soft calcium carbonate and magnesium oxide was eluted and removed, and the inner porous layer C having a thickness of about 20 μm was formed.
Was formed.

After this, the tubular material A is washed with water and vacuum freeze-dried,
As shown in FIG. 3, after holding one end of the tubular material A in an upright state in a 5% aqueous solution of polyvinyl alcohol having a polymerization degree of 1700 and a saponification degree of 99% or more, by suctioning the upper end, After repeating the operation of raising the polyvinyl alcohol aqueous solution three times, this was dried and was embedded in the tubular article A by a thickness of 15 to 20 μm, which corresponds to the inner porous layer C, and a hydrogel layer having a thickness of 25 to 30 μm. D was formed.
Subsequently, this tubular material A is immersed in a pressure-resistant container filled with hydrochloric acid of 1 to 5 N (normal), and light calcium carbonate and magnesium oxide on the outside of the inner porous layer C are eluted under reduced pressure to have continuous pores. After forming the base material layer E and repeating rinsing with dilute hydrochloric acid and washing with water, in order to maintain its porous shape, a vacuum freeze-drying method is performed at a vacuum degree of 2 mmHg or less.
Dried for hours.

The artificial blood vessel substrate having the hydrogel layer D obtained in this Example 1 is used as it is as an artificial blood vessel,
It has a cross-sectional shape as shown in Fig. 4, inner diameter of about 3 mm and outer diameter of 3.7 m.
m, a smooth layer which is a part of the hydrogel layer D is about 10 μm, and the embedding thickness in the porous substrate is about 15 to 20 μm.
Hydrogel layer D of about 25-30 μm in total and about 320 μm
a porous base material layer E having a thickness of m, an average pore diameter of 6 to 10 μm and a porosity of about 80%, and a reinforcing material B made of polypropylene monofilament wound around the outer periphery thereof at a pitch of 1 mm;
It is composed of a porous outer layer F that partially surrounds the reinforcing material.

A tubular article A was obtained by using the same material and the same method as in Example 1. Then, this tubular material A was immersed in a water tank to remove the solvent and solidify, and was further dried sufficiently. Then, the reinforcing material B made of the same monofilament as that used in Example 1 is spirally wound around the outer periphery of the tubular material A at the same pitch as in Example 1 to form the outer cover layer F as in Example 1. Then, the solvent was removed and the product was dried.

Thereafter, the operation of raising the solution from below by holding one end in a standing state in a tank filled with a 5% solution of polyether segmented polyurethane in tetrahydrofuran and then sucking the other end is performed. By repeating this repeatedly, an inner layer G having a smooth inner surface with a thickness of about 50 μm was formed.

After this, the tubular material A is washed with water, and the aspirator is filled with about 5
The inner layer G was dried by connecting for a minute. Next, this tubular material A was immersed in a pressure-resistant container filled with hydrochloric acid, and treated under reduced pressure until hydrogen generation due to the reaction between the inorganic salt (calcium carbonate and magnesium oxide) and hydrochloric acid was no longer observed, and the inorganic salt was eluted. . After that, it was rinsed several times with dilute hydrochloric acid and further washed with water to remove hydrochloric acid and inorganic substances, and then dried by a vacuum freeze-drying method at a vacuum degree of 2 mmHg or less for 12 hours to maintain its porous shape.

The porous artificial blood vessel substrate thus obtained is
As shown in the figure, an inner layer G having an inner diameter of about 3 mm, an outer diameter of 3.8 mm and a thickness of about 50 μm on the inner diameter side, and a substantially non-perforated inner layer G having an average pore diameter of 6 to
A base material layer E having a porosity of 80% at 10 μm, a monofilament-like reinforcing material B wound around the outer periphery thereof and a thickness of about 0.2 mm which partially surrounds the reinforcing material B and an average pore diameter of 6 to 10 μm and a porosity of It is composed of 80% of outer layer F.

In each of the above examples, the base material layer E, the reinforcing material B, and the outer covering layer F are used.
There is a gap H between and.

The artificial blood vessel of Example 1 and the artificial blood vessel substrate of Example 2 had a minimum bending diameter of 0.5 cm when a sample having a length of 10 cm was bent, and had sufficient bending resistance.

Comparative Example 1 Compared to Example 1, except that a nylon monofilament having a fiber diameter of 0.4 mm was used as the reinforcing material B and this was adhered with a cyanoacrylate-based adhesive without being covered with the covering layer F. An artificial blood vessel was obtained in the same manner as in Example 1.

The artificial blood vessel in which the monofilament-like reinforcement is fixed to the outer periphery of the base material layer E has a significantly small compliance of 0.01 by the measurement method described below, and when implanted in the living body as an artificial blood vessel, the anastomotic part due to compliance mismatching. There was a concern that the tube would not bend when the bending stress was applied because the waist was too strong and the host blood vessel would bend and block.

The compliance and flexibility were measured by the following methods.

-Measurement of compliance For the compliance, a fixed amount of physiological saline is sent to the artificial blood vessel for each operation using a microsyringe dispenser, and a change in internal pressure is detected by a pressure sensor and recorded in a recorder via an amplifier. The compliance of the sample is obtained by the equation 1 from the amount of change in the internal pressure with respect to the amount of physiological saline injected into the sample.

Formula 1: C = ΔV / V ₀ However, ΔV: increment of the internal volume when the internal pressure changes from 50 mmHg to 150 mmHg.

V ₀ : Internal volume of the sample when the internal pressure is 50 mmHg.

・ Measurement of flexibility The measurement of flexibility was performed using the Olsen type flexibility measuring instrument.

When the flexural modulus of the sample is E and the moment of inertia of the sample is I, the value of ET can be obtained by the Olsen-type flexibility measuring instrument, so this value was used as a measure of flexibility.

Table 1 shows the physical properties of Examples and Comparative Examples obtained by these methods.

<< Effect of Action >> The artificial blood vessel substrate according to the present invention has a monofilament-like reinforcing material spirally wound around the outer periphery of a porous substrate layer, and the outer periphery encloses the entire cross-sectional outer periphery of the reinforcing material. If the tubular member is subjected to bending stress, for example, the compression-side jacket layer, which is the inner diameter side of the bend, is bent with a uniform curvature, since it is partially surrounded and covered, leaving a void. Without being deformed into a pleated shape, the contact force of the covering layer with respect to the reinforcing material changes, and the reinforcing material itself is also easily deformed. On the other hand, since the reinforcing material is spirally wound in the lengthwise direction, the tubular material is prevented from bending in the crushed state, so that it can be bent to a considerably small diameter. Further, since the outer coat layer is provided by the annular coating and has a gap between the outer cover layer and the reinforcing material, it can be peeled off from the base material layer if necessary.

Therefore, the artificial blood vessel or the artificial blood vessel substrate according to the present invention can be bent to a considerably small diameter, and at the time of anastomosis, the outer layer of the required portion, the reinforcing material can be peeled off, etc.
It is extremely easy to operate and practical.

Further, the method of the present invention is an extremely practical method for producing an artificial blood vessel or an artificial blood vessel substrate, since a tubular material having a layered structure made of a porous elastomer can be relatively easily produced.

As described above, according to the present invention, it is possible to provide a novel and useful artificial blood vessel or a base material for an artificial blood vessel and a method for producing them.

[Brief description of drawings]

FIG. 1 is an explanatory view showing a manufacturing process of a tubular article of the method of the present invention,
FIG. 2 is an explanatory view showing a desolvation step of the tubular article of the same method, and FIG. 3 is an explanatory view showing a hydrogel layer forming step of the same method,
FIG. 4 is a sectional view showing an embodiment of the artificial blood vessel substrate manufactured by the same method, and FIG. 5 is a sectional view showing another example of the substrate. A ... Tubular material, B ... Reinforcing material C ... Inner porous layer, D ... Hydrogel layer E ... Base material layer, F ... Outer layer G ... Inner layer, H ... Gap

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification code Office reference number FI technical display location B32B 5/24 101 7016-4F

Claims (5)

[Claims] 1. A tubular base material layer made of a porous elastomer material, an inner layer provided on the inner circumference of the tubular base material layer, and a monofilament-like reinforcement spirally wound around the outer circumference of the tubular base material layer. And a releasable covering layer made of a porous elastomer material, which partially surrounds the reinforcing material and is formed on the outer circumference of the tubular base material layer, for use in an artificial blood vessel. . 2. The artificial blood vessel substrate according to claim 1, wherein the inner layer is formed of an elastomer material on a smooth surface. 3. The artificial blood vessel substrate according to claim 1, wherein the inner layer comprises a hydrogel-forming layer, a part of which is embedded in the tubular substrate layer. 4. A tubular base material forming step of adding and mixing an inorganic salt to a solution of an elastomer material dissolved in a solvent to adjust the viscosity, and then extruding this annularly from an extruder and cutting it into a predetermined length; After the solvent in the material is removed and dried and solidified, a reinforcing material winding step of spirally winding a monofilament-shaped reinforcing material on the outer periphery thereof, and the outer peripheral surface of the tubular base material on which the reinforcing material is wound, Outer layer forming step of annularly extruding a coating material obtained by adding and mixing inorganic salts to a material compatible with an elastomer material and coating under reduced pressure, and then forming an inner layer to form an inner layer on the inner circumference of the tubular substrate. A method for producing a base material for artificial blood vessels, which comprises a step of forming a porous body by removing inorganic salts of the tubular base material and the outer coat layer to make the base material porous. 5. The inner layer forming step comprises forming a hydrogel layer in a state where the inner periphery of the tubular base material layer is partially made porous, and anchor-joining the inner layer and the tubular base material layer. The method for producing a base material for an artificial blood vessel according to claim 4, which is characterized in that.