JPH0298352A - Internal shunt type artificial vein - Google Patents

Abstract

PURPOSE:To obtain an internal shunt type artificial vein which can be easily pierced by a syringe and which can bear against frequent piercing of syringes by having a porous pipe-like member in which polyurethane elastic fibers are joined together and which includes a plurality of covering layers made of fibers in a part of the wall thereof, and by setting the amount of leakage after piercing of a syringe to a value less than 200ml/min. CONSTITUTION:Polyurethane elastic fibers applied for an artificial vein, are obtained by reaction among 500 to 600 molecular weights of polyol, block copolymer thereof or the like, less than 500 molecular weights of organic diisocyanate or the like, and a chain elongating agent such as, water, hydrazine, diamine, grycol or the like. The vein is made of a porous pipe-like member while the amount of leakage after piercing of a syringe should be less than 200ml/min. The polyurethane elastic fiber forming the artificial vein is monofilament preferably having an averaged diameter of less than 30mu, more preferably 5 to 20mu. With this arrangement, blood is rapidly blocked by slightly pressing the vein. Further, the recovery of a damage part is rapid after piercing of a syringe, and there are no increase in the thickness of the inner membrane and no blockage.

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to an artificial blood vessel. More specifically, the present invention relates to an artificial blood vessel suitable for producing an internal shunt type access for extracorporeal blood circulation such as artificial hemodialysis.

(Prior Art) Artificial dialysis therapy using a dialyzer has become established for patients with renal failure, which was said to be an incurable disease, and the survival rate of patients with renal failure is increasing year by year. When performing chronic dialysis therapy, the blood inlet and outlet through which blood is taken out from the patient, waste products are dialysed and returned to the patient via a dialyzer is called a blood access. There are various types of blood access (see Table 1), and each method is selected depending on the treatment purpose and the condition of the target patient. Because of the above problems, internal shunts are mainly used to create an arteriovenous anastomosis under the patient's skin.

An internal shunt is created by the patient's own peripheral arteriovenous anastomosis, autologous vein grafting, artificial blood vessel grafting, etc. Usually, the patient's own blood vessels are used, but in recent years the number of elderly patients or patients with diabetic nephropathy has increased,1 and it has been recognized that there are cases in which it is not possible to construct an internal shunt using the patient's own blood vessels. In such patients, there is a possibility of future AC bypass surgery due to arteriosclerosis, so autologous vein grafting cannot be performed and artificial blood vessel grafting must be performed.
In order to prevent compression or occlusion of other blood vessels due to the creation of an internal shunt, artificial blood vessel transplantation is performed in which the length and diameter can be freely selected.

(Problems to be Solved by the Invention) Table 2 lists grafts used as blood access. Among these, grafts made of E-PTFE are currently mainly used because they are relatively easy to handle, such as easy availability and freedom of choice in thickness and length. However, several problems have been recognized with this expanded polytetrafluoroethylene (EP T F E) artificial blood vessel. Firstly, plasma leakage and seroma development after transplantation, and secondly, rigid E-
Because PTFE is used as a material, a large hole is created at the needle puncture site during dialysis therapy, which is prone to the formation of blood clots, thickening of the intima, and emboli. . In addition, the occurrence of aneurysms has been observed at the site of transection caused by this puncture.As the conventionally used artificial blood vessels are greatly affected by the puncture, we have developed an artificial blood vessel that can withstand the puncture. This led me to consider the development of blood vessels. In other words, the conditions for an artificial blood vessel that can withstand puncture are as follows: +l) It is desirable that the wound site caused by the needle at the time of puncture be as small as possible, so that thickening of the intima and occlusion due to the puncture do not occur; (2) Removal of the puncture needle; The subsequent needle hole is small and bleeding stops quickly with light pressure. (3) No tearing or rupture occurs due to the fibers severed by the puncture needle.

(4) It has a strong bond with the surrounding living tissue and does not form a hematoma after needle puncture.

By improving the drawbacks of conventional blood access (shunt) artificial blood vessels as mentioned above, we have created an artificial blood vessel that can withstand needle puncture.
An artificial blood vessel has been proposed in which at least the blood contact surface is made of polyurethane or polyurethane urea, and a tube-shaped reinforcing material made of polyester fibers is disposed within the wall (see Japanese Patent Laid-Open No. 625354). . However, in this artificial blood vessel, it is thought that the needle puncture resistance becomes large due to the tubular reinforcing material made of W-woven polyester fibers.

In addition, although the purpose is not to increase needle puncture resistance, in order to approximate the compliance and stress-strain curve of an elastomer artificial blood vessel to that of a biological blood vessel, a tubular structure made of fibers is used as a part of a porous elastomer tubular body. Artificial blood vessels with a combination of
No. 53, JP-A-61-185271, JP-A-6
(See Publication No. 1244345). Furthermore, an artificial blood vessel that can be sterilized using high-pressure steam has also been proposed using the same technique (see Japanese Patent Laid-Open No. 64361/1983).

However, in these proposals, a pore-forming agent is used during molding to obtain porosity. For this reason, if these are insufficiently removed after molding, it may have an adverse effect on the living body.

Furthermore, in recent years, the importance of porosity (water permeability) to patency in synthetic artificial blood vessels has been recognized. That is,
It has been pointed out that even if artificial blood vessels are manufactured using segmented polyurethane with excellent antithrombotic properties, those with low water permeability will have poor patency.

However, in the above proposal, it is difficult to obtain an artificial blood vessel with increased water permeability and easy tissue penetration. Additionally, if you try to increase the water permeability, the pipe walls will become extremely weak and reinforcement will need to be strengthened. This leads to an increase in needle puncture resistance.

The object of the present invention is to overcome the above-mentioned drawbacks and to provide sufficient porosity (i3
The purpose of the present invention is to provide an artificial blood vessel suitable for use as an internal shunt artificial blood vessel, which has a high water content), is easy to puncture, and is resistant to puncture by a consultant.

(Means for Solving the Problems) That is, the present invention provides a porous tubular body in which polyurethane elastic fibers are mutually bonded, and a part of the wall of the tubular body has a coating layer made of fibers. and the amount of water leaked after needle puncture is 20
This is an artificial blood vessel for internal shunt with a flow rate of 0 m//min or less.

(Function) The polyurethane elastic fiber applied to the artificial blood vessel of the present invention is
These fibers are made of a known thermoplastic polyurethane elastomer, and contain polyols with a molecular weight of 500 to 6,000, such as dihydroxy polyether, dihydroxy polyester, dihydroxy silicone, dihydroxy polycarbonate, dihydroxy polyester amide, or a combination of these compounds. Polymers, etc., organic diisocyanates with a molecular weight of 500 or less, such as p,p'-diphenylmethane diisocyanate, tolylene diisocyanate, isophorone diisocyanate, 2,6-diythiomethylcaproate, hexamethylene diisocyanate, dicyclohexylmethane diisocyanate inert, metaxylylene diisocyanate, etc., and a chain extender such as water, hydrazine, etc.
It is a fiber made of a polymer obtained by reaction with diamine, glycol, etc. Particularly good among these polymers are those using polytetramethylene glycol, a block copolymer of polytetramethylene glycol and silicone, or a block copolymer of polyethylene glycol and silicone as the polyol. Moreover, p,p'-diphenylmethane diisocyanate is suitable as the organic diisocyanate. Moreover, glycol is suitable as a chain extender, and 1,4-butanediol or bis-β-hydroxyethoxybenzene is particularly suitable.

The basic structure of the artificial blood vessel according to the present invention is a porous tubular body in which the above-mentioned polyurethane elastic fiber aggregates are joined to each other at their contact points.

This basic tubular body can be manufactured by various methods, including, for example, the following method.

After melt-spinning the thermoplastic polyurethane elastomer, the substantially continuous filaments obtained by jetting high-temperature gas and thinning are laminated into a sheet, and the contact points of the laminated filaments are joined by the filaments themselves. A method of laminating 8 rods of polyurethane elastic fiber nonwoven fabric and forming a tubular body by heating and forming the same
(see publication).

(2) A liquid composition containing a fiber-forming polymer made of polyurethane is electrostatically spun to form fibers, and the thus-formed fibers are collected on a shaped molding tool to form a tubular body. Method of forming
No. 0.977, JP-A No. 54151.675, JP-A No. 5
No. 9-11.864 and JP-A-60-190,947
(Refer to each publication in issue).

(3) A method of forming a tubular body by rotating and winding the eight rods while extruding polyurethane elastic fibers onto a core (see Japanese Patent Laid-Open No. 157,465/1983) (4) Spreading the polymer solution through a nozzle A method in which a single fiber is formed by spraying through a fiber, and the fiber is wound around eight rods to form a tubular body (Japanese Patent Application Laid-open No. 59181.
(See Publication No. 149) (5) Other methods.

Therefore, among the above methods, method +11 is the most preferred.

The artificial blood vessel according to the present invention has a porous tubular body in which the polyurethane elastic fibers are mutually bonded, and a part of the tube wall of the tubular body is provided with a coating made of fibers. , includes not only the inside but also the inner and outer surfaces of the tube wall of the tubular body, that is, the coating layer may be located on the outer surface and/or the inner surface.

In order to maintain high strength even after the puncture of the advisor, it is preferable that the coating layer is firmly integrated with the tubular body, and
Considering the occurrence of cutting and fraying of the fibers of the coating layer by the puncture needle, it is preferable that these fibers are not exposed to blood flow. Taking these circumstances into consideration, it is preferable that the coating layer exists inside the tube wall.

The fibers constituting the coating layer of the present invention are not particularly limited as long as they are fully resistant to living organisms, have low in vivo deterioration, are sterilizable, and can form the intended coating layer.

However, from the viewpoint of processability, ease of availability, flexibility, and uniformity, recycled fibers, semi-synthetic fibers, and synthetic fibers are preferred; specific examples include cellulose-based, protein-based, polyamide-based, polyester-based, and polyurethane-based fibers. Examples include fibers of polyethylene, polypropylene, polyvinyl chloride, polyvinylidene chloride, polyacrylic, polyvinyl alcohol, polyfluoroethylene, and polyvinyl alcohol.

Among these, the fibers themselves have elasticity, such as polyurethane elastic fibers and polyester elastic fibers,
Highly processed yarns such as woolly nylon and woolly polyester, and covered yarns made of rubber or elastic yarns wrapped around other spun yarns or filament yarns, have elastic properties that can improve the elasticity of the tubular body. The polyurethane elastic fibers are preferably the same as the polyurethane elastic fibers constituting the tubular body or have approximately the same softening point as the polyurethane elastic fibers.

The reason for this is the above-mentioned most preferred manufacturing method (Japanese Unexamined Patent Publication No. 61
When manufacturing the artificial blood vessel of the present invention using the artificial blood vessel (see Publication No. 136,085), the strength of the artificial blood vessel is improved because it is more firmly integrated by heat treatment, and high strength can be maintained even after puncture. It is.

On the other hand, polyester fibers, poly-4-fluorinated ethylene fibers, polyethylene fibers, and polypropylene Ili fibers, which are stable for a long time in the body, are preferable because they have a large strength-improving effect. In this respect, polyester fibers are most preferred.

The coating layer of the present invention is a yarn made of the above-mentioned fibers, a woven fabric, a knitted fabric, a braided fabric using at least one kind of these yarns, a non-woven fabric made of the above-mentioned fibers, or a combination thereof.

In terms of integration with the tubular body, among the coating layers, threads, coarse woven fabrics, or knitted fabrics are suitable, and in the nonwoven fabric lamination heat forming method, which is the most preferable manufacturing method for the tubular body, It is optimal to form the coating layer with threads in terms of adhesion of each nonwoven fabric layer and adjustment of water permeability by peeling. In the above production method, the coating layer is formed by threads by wrapping the threads in a spiral shape at least once during the lamination of the polyurethane elastic fiber nonwoven fabric around the eight rods, or by heating and forming the threads, or after laminating a small amount of the nonwoven fabric. - Achieved by first heating and forming, then spirally winding a yarn thereon, then laminating a nonwoven fabric and heating and forming. Therefore, IIi! The existence of one or more complex layers is also possible.

The artificial blood vessel of the present invention is characterized in that it is made of the porous tubular body and has a water volume after puncture of 200 m17 minutes or less. This amount of water after puncturing the needle is defined as follows. In other words, the inner cavity is filled with water at 120 mmH by the water supply device.
A piece of artificial blood vessel with an effective length of 5 cm pressurized to
Puncture the artificial blood vessel with an indwelling needle with a G plastic jacket at an entry angle of 30° so that the needle enters the artificial blood vessel 2 cm from the tip and leave it for 5 hours. At this time, be careful not to damage the opposite wall of the artificial blood vessel with the needle. After 5 hours, remove it from the constant temperature water bath and remove the needle. The amount of water leaking from the needle hole after needle removal is measured, and the amount of water leaking for one minute from immediately after needle removal is called the amount of water after needle puncture. In addition, in the case of porous artificial blood vessels, the dog,
Use blood from cows, etc. that has been subjected to brecronoting. Also, the water supply device is 2000mJ at 12QmmHg! /
Use a device with a capacity of more than 1 minute. The puncture device is
If it is less than 200 m1/min, when used as an internal shunt, hemostasis after needle removal is sufficient, but if it is less than 150 m1/min,
/min has better hemostasis, and even 100 m
If it is less than 1/min, it is safe. Water leakage after needle puncture is 200
When it is larger than m1/min, when used as an internal shunt, hemostasis is reduced.

The average diameter of the polyurethane elastic fibers constituting the artificial blood vessel of the present invention is preferably 30 microns or less as a monofilament, and particularly preferably 5 to 20 microns. If the average diameter of the fibers exceeds 30 microns, the roughness of the inner wall of the artificial blood vessel will increase, making it easier for thrombi to form and reducing the flexibility of the entire tube. Furthermore, the resistance during needle puncturing may also increase, making puncturing difficult. Further, the 100% elongation recovery rate of the polyurethane elastic fiber is 50% or more, preferably 85%.
or more, more preferably 90% or more, most preferably 9
It is 5% or more. Furthermore, the apparent density of this artificial blood vessel is 0.
．． It is preferably 3 to 0.8 g/cm', and more preferably 0.5 to 0.8 B/cm3, that is, the apparent density exceeds 0.8 g/cm'. It becomes difficult to puncture the needle, and if it is less than 0.3 g/Cm', the strength is insufficient.

Although the diameter of the lumen of the present artificial blood vessel is not particularly specified, it is 2 to 20 mm, preferably 3 to 10 mm, and the wall thickness is particularly preferably 0.2 to 3 mm, 0.4 to 1.5 mm. preferable.

In the present invention, a "porous tubular body" refers to a tubular body that is composed of voids between fibers and has many I:J holes on its wall surface.The porosity of the tubular body is -S. can be expressed in terms of pore size distribution and porosity, but in the case of artificial blood vessels, it is common and practical to express it in terms of water permeability. The i3 water rate is 1cm of the wall of an artificial blood vessel under 120mm and 1g of pressure.
In the present invention, this water permeability can be easily controlled by adjusting the fiber diameter, thickness, amount of lamination, and coating layer of the nonwoven fabric used. This 1 water rate is 3000 ml/min or less, preferably 1
0"1500mA/min more preferably 150-1000
m (1/min.) If it exceeds 3000 ml/min, it will be difficult to briclot and it will take time to use it as an internal shunt.

Hereinafter, preferred embodiments of the present invention will be summarized.

(a) The artificial blood vessel for internal shunt according to claim 1, wherein the polyurethane is thermoplastic.

(0) The artificial blood vessel for internal shunt according to claim 1, wherein the polyurethane elastic fibers have an average diameter of 30 microns or less.

(c) The apparent density is 0.3 to 0.8 g/cm
The artificial blood vessel for internal shunt according to claim 1.

(d) The artificial blood vessel for internal shunt according to claim 1, wherein the coating layer is located inside the wall of the tubular body.

($) The artificial blood vessel for internal shunt according to claim 1, wherein the covering layer is made of polyurethane elastic fibers.

(f) The artificial blood vessel for internal shunt according to claim 1, wherein the covering layer is formed by spirally winding polyurethane elastic thread.

(g) The artificial blood vessel for internal shunt according to claim 1, wherein the covering layer is made of polyester fiber.

(h) The artificial blood vessel for internal shunt according to claim 1, wherein the covering layer is formed by spirally wound polyester thread.

(n) The artificial blood vessel for internal soyant according to claim 1, wherein water leakage after puncture is 150 me1 minute or less.

(l) The artificial blood vessel for internal shunt according to claim 1, wherein the amount of water leakage after puncture is 1 OOmf/min or less.

(t) i3 water rate is 3000mA! The artificial blood vessel for internal shunt according to claim 1, which has a flow rate of less than /min.

(iv) The artificial blood vessel for internal shunt according to claim 1, which has a water permeability of 10 to 15QQm17 minutes.

(Force) Inner diameter is 2-20 mm and thickness is 0.2-3
The artificial blood vessel for internal shunt according to claim 1, which is m m.

(3) The artificial blood vessel for internal shunt according to claim 1, wherein the polyurethane elastic fiber has an elongation recovery rate of 50% or more.

(Example) Next, the present invention will be described in further detail by giving examples.

Example 1 5548 parts of dehydrated polytetramethylene glycol having a hydroxyl value of 102 (hereinafter, all parts mean parts by weight) and 499 parts of p,p/-bishydroxyethoxybenzene were charged into a jacketed Nigu and stirred. After thoroughly dissolving the mixture while maintaining the temperature at 90°C, p,p'-diphenylmethane diisocyanate 195
3 parts were added and allowed to react. When stirring was continued, a powdered polyurethane was obtained in about 30 minutes, which was molded into a pellet shape using an extruder and had a relative viscosity of 2.5 g/100 ml at a concentration of 1 g/100 ml as measured in dimethylformamide at 25°C.
50 polyurethane elastomers were obtained.

Using the polyurethane elastic pellets obtained in this way as a raw material, a melt blow spinning device was used, which had nozzles with a diameter of 0.8 mm arranged in a row, and slots 7) for injecting heated gas on both sides. 235℃ 0.5 per minute per nozzle
The polymer was discharged at a rate of 0 g, and air heated to 200°C was injected through the slit at a pressure of 4.0 kg/cm'' to make it thin.
The nonwoven fabric was collected on a conveyor consisting of a wire mesh of 30 meshes installed at 300 m, and then sandwiched between rollers to obtain a nonwoven fabric. This nonwoven fabric was made up of opened and laminated monofilaments of polyurethane elastic fibers, and the intertwining points between the filaments were joined together by fusion. The physical properties of this nonwoven fabric were as follows.

Fabric weight: 25g/m” Tensile strength
0.18 kg/cm breaking elongation
550% 100% elongation recovery rate 92% Bending resistance 15 mm Filament diameter 15 microns Next, 20 cm of this nonwoven fabric was wrapped around 8 rods coated with fluororesin and 8 mm in diameter, and the polyurethane used in manufacturing the nonwoven fabric was wrapped on top of this. 1 piece of 35 denier polyurethane monofilament yarn obtained by melt spinning elastic pellets
, spirally wound at 3 mm intervals. This operation of winding in a U-shape was repeated 15 times. At this time, the polyurethane elastic threads were overlapped at approximately the same position, so that a -strand spiral was formed.

Next, 28 cm of the above-mentioned nonwoven fabric was wound on top of this, and a release paper was further wound around it, and then it was placed in a cylindrical mold with an inner diameter of 10 mm and heated at 150° C. for 30 minutes.

After cooling, it was taken out from the mold, the release paper was peeled off, and eight rods were pulled out to obtain a porous polyurethane tubular body.

This tubular body had a structure in which the nonwoven fabric and the polyurethane elastic thread were firmly bonded to each other and integrated, and the polyurethane monofilament thread was completely integrated to form a single helical zone.

The water leakage rate of this tubular body after puncturing was measured using the method described in this specification, and was found to be 25 mA/min.

The apparent density is 0.6 g/cm', i! Ice water ratio 185ml
/minute. Electronic S of the inner and outer surfaces after puncturing! Ili microscopic observation revealed that the needle hole was extremely small.

This tubular body was pre-cloned and anastomosed end-to-end to the carotid artery and vein of an adult mongrel to create a bypass. 16G for this bypass
Using an indwelling needle, we evaluated it as an artificial blood vessel for shunts such as puncture and removal and hemostasis. For comparison, a similar test was conducted using a commercially available artificial blood vessel made of poly(4-fluoroethylene). was also not recognized. moreover,
When puncturing with an indwelling needle, there was less penetration resistance and the risk of tip curling of the plastic needle and damage to the inner wall of the blood vessel caused by the metal needle during insertion was lower than with poly(4-fluorinated ethylene) needles. The retention force of the indwelling needle was also strong (there was little risk of it falling out. Wave timing showed that there was only slight bleeding immediately after, and hemostasis was completed within 5 minutes. In contrast, the needle made of poly(4-fluorinated ethylene) was easily removed. The subsequent bleeding was so intense that it took 30 minutes to stop the bleeding.

Example 2 20 cm of the same nonwoven fabric as in Example 1 was wrapped around eight fluororesin-coated rods each having a diameter of 8 mm, and a release paper was further wrapped over the rods, followed by heating at 145° C. for 25 minutes. After cooling, the release paper was peeled off, and #50 polyester sewing thread was wound spirally 3 times from above in the same manner as in Example 1.
Furthermore, 28cm of non-woven fabric! Next, a release paper was wrapped over this, and then it was placed in a cylindrical mold with an inner diameter of 10 mm and heated for 25 minutes. After cooling, it was taken out from the mold, the release paper was peeled off, and eight rods were pulled out to obtain a porous polyurethane tubular body. This tubular body had a structure in which the nonwoven fabric and polyester sewing thread were firmly bonded to each other and integrated.

This tubular body has a water volume of 30mm at the back of the puncture needle! /minute. The apparent density is 0.1 g/cm" and the water permeability is 260 m1.
/minute. Electron B microscopic observation after puncturing revealed that the needle hole was extremely small as in Example 1. Furthermore, when this tubular body was evaluated as an artificial blood vessel for shunting using a mongrel dog in the same manner as in Example 1, it showed good handling properties and hemostatic properties similar to those in Example 1.

(Needle puncture durability test) The tubular bodies of Examples 1 and 2 were cut 1 cm, and 1 cm was cut on the half circumference.
Punctures were made at random at 15 locations (15 times) using a 4G indwelling needle.

Insert two hardened pins with a diameter of 1 mm into the tubular body after puncturing, hold both ends of each bottle, and test with a constant speed tensile tester.
The strength was measured by pulling it up and down at a speed of 7 minutes. Separately, the similar strength of the tubular body without puncturing was measured, and the durability was evaluated based on the strength after puncturing and the strength retention rate relative to the strength before puncturing. The results are shown in Table 3, and the tubular body according to the present invention has high strength after puncture with a needle, and can be used safely even after puncturing with an open needle. In addition, the artificial blood vessel for internal shunt according to the present invention is excellent in terms of strength retention, and even after puncture, the tube wall does not peel off.Table 3 (Effects of the Invention) It is effective.

(1) It is made of a porous tubular body in which polyurethane elastic fibers are bonded to each other, and the water leakage after puncturing is less than 200 mj/min, so the needle hole after the puncturing needle is removed is minimized, and it can be quickly removed by light pressure. Stop bleeding.

(2) During needle puncture, the injury site caused by the needle is minimal and elastically recovers after the needle is removed, so the injury site can be repaired quickly (no thickening of the intima or occlusion).

(3) Polyurethane elastic fibers are mutually bonded and have a porous structure, so they have low needle puncture resistance and are easy to puncture, minimizing tearing and rupture of the fibers due to needle puncture. does not occur, and therefore can withstand invasive needle puncture.

(4) Since there is a coating layer made of tightly integrated fibers inside the pipe wall, high strength can be maintained even after puncturing at opening.

(5) Since it has a porous structure made of fibers and has sufficient water permeability, it is easy to invade the surrounding M weave and the bond is strong, so there is no formation of hematoma after needle puncture. Furthermore, since the neointima is strongly bonded to the artificial blood vessel on the inner surface, there is no peeling of the intima due to the puncture needle.

Claims (1)

[Claims] (1) A porous tubular body in which polyurethane elastic fibers are mutually bonded, which has a covering layer made of fibers on a part of the wall of the tubular body, and has a water leakage rate of 200 ml/min after puncturing. Artificial blood vessels for internal shunts as follows: