JPS61113460A - Hollow yarn membrane for purifying blood - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a hollow fiber membrane used in a hollow fiber type artificial organ for blood purification. More specifically, it relates to hollow fiber membranes used for hemodialysis or blood purification by hemodialysis, which have excellent properties and stability for the treatment of patients with chronic or acute renal failure. be.

The objective is to control the filtration characteristics within a specified range.

[Conventional technology]

Currently, intermittent hemodialysis or hemodialysis using a blood pump is generally performed as a treatment for patients with chronic renal failure. On the other hand, for the treatment of patients with acute renal failure caused by complications after surgery, etc., it is necessary to quickly remove large amounts of water and solutes, and thus conventional intermittent treatment methods cannot be used. In this case, continuous hemodialysis and filtration are effective, but since they are used continuously for about 1 day to 2 weeks, the membrane used for this requires strict performance. Conventional commonly used hemodialysis membranes and hemofiltration membranes have problems in blood compatibility and compatibility, and blood clots occur within the large membrane, making continuous use difficult.

Furthermore, it is not recommended to use a blood pump, which puts a heavy burden on the patient's heart if used continuously for a long time.
In this case, it was impossible to use conventional membranes because blood flow fluctuates depending on the patient's blood pressure and blood flow decreases, which tends to cause thrombi to form within the tube.

! [Purpose of the Invention] The present inventors have conducted extensive research in an effort to obtain a hollow fiber membrane that can stably purify blood through long-term continuous hemodialysis or hemofiltration as described above. As a result of proceeding with
Made of polysulfone resin, transient ft with a fixed time range
It was discovered that the hollow fiber membrane of the present invention has extremely excellent performance, and based on this knowledge, various studies were carried out, resulting in the completion of the present invention.

[Structure of the invention]

That is, the present invention consists of polysulfone-based 1) i-fat,
The water permeability is within the range of 500-wooOml/wH1i 1 hour am', and the weight average molecular weight is 65,000.
The inhibition rate of dextran is ~75,000 and is 80-70
Must be within the range of %@:q! ! This is a hollow fiber membrane for blood purification.

Here, the terms will be explained as follows.

Filtration rate (Water permeability 1 (Go/Hpi・Time・Go) Amount of passed-through liquid (llIjJ p Overpressure tmH, FJ x Filtration time (hours) x Effective membrane area) 1 Rejection rate (%J However, for convenience, it is appropriate to take the Q value 15 to 10 minutes after the final opening time.Furthermore, the rejection rate of dextran is 0.2% by weight, so the dust Including □゛
aqueous solution, into the hollow fiber at a rate of 42 to 20 cm/sec.
Calculated from the dextran concentration of the 9F solution and the circulating fluid 5 minutes after the start of circulation. Similar measurement conditions were used in the following Examples and Comparative Examples.

To explain the present invention in more detail, the hollow fiber membrane made of polysulfone-based resin is made of polysulfone-based resin, the resin
The soluble polarity is dissolved in a mechanical solvent and added to form a spinning dope, which is spun into a hollow fiber membrane using a wet process, and then subjected to further appropriate treatment to impart a predetermined filtration property. It is made of stone.

Here, polysulfone resin and 1 are o @ construction, shoulder 6 is also O""6Bo spinning raw material a, l: l12
OM li', t.

~ Once the resin is 10 ~ 25 layers 1. In general, it is desirable to set the amount to 12 to zOt). Dimethylformamide, N-methyl-2-'pyrrolidone, and the like are used as polar organic bath agents for dissolving polysulfone-based lateral forces, but are not limited to these as long as they can dissolve polysulfone-based a-liquids.

Examples of additives include metal salts and non-vulgar agents of polysulfone resins. Examples of metal salts are monovalent or 21
) ffJ cationic metal salts, namely Llcl, LtB
r %NaC1, NaBr %KC1, KBr, M
Examples include, but are not limited to, gClxMgBr2, Ca(J2, CaBr1, etc.). Antioxidants for polysulfone resins include ketones, ethers, furans, organic compounds, organic acid anhydrides, and organic Examples include, but are not limited to, acid esters, surfactants, etc. Furthermore, it is also possible to combine a metal salt and a non-solvent, or to combine seven combinations of two or more types of non-bath agents.

The spinning stock solution is made by mixing the above components and heating it at room temperature to 100°C.
It is obtained by stirring and dissolving while heating to a certain degree.

Next, a hollow fiber membrane is obtained by a wet spinning method using a hollow fiber manufacturing nozzle having a double tube structure and discharging the spinning material from the outer annular opening into the spinning material at" and the core into the coagulation bath.

The composition of the internal coagulating liquid discharged from the nozzle core and coagulating from the inside of the spinning stock solution and the coagulating bath coagulating from the outside is preferably water alone from the viewpoint of operability. Ninth, by adding a polysulfone resin solvent and/or a polysulfone resin non-solvent, it is possible to change the structure of the intermediate layer of the separation membrane. K', Ni 1:1). i! ilKKffi
mL,,*;Ez4! dAtli+-! , LiCff
f, L8,8. .

NaCl-NaBr %KC1s KBr-MgCl
5, MgBr5, CaCA! Examples include, but are not limited to, 2, CaBr, 7Z, etc., and a combination of two or more metal salts is also possible. Further, solvents for polysulfone resins that can be added to the coagulation bath include, but are not limited to, dimethylformamide, N-methyl-2-pyrrolidone, etc., and a combination of two or more solvents is also possible. Non-solvents for polysulfone resins that can be added to the coagulation bath are:
Non-solvents include, but are not limited to, alcohol-based and ketone-based solvents, and combinations of 62 or more types of non-solvents are also possible.

Temperature control is mainly important when spinning hollow fibers, i.e., film forming conditions, and is usually carried out around room temperature, but if the composition of the spinning stock solution makes it unstable at room temperature, warm spinning is performed. The spinning temperature is suitably in the range of room temperature to 100°0. Furthermore, since the obtained film may contain additives that are insoluble in water, it is immersed in ethanol etc. to de-melt and remove additives. S''
'Ji9gCh;b・92. .

The performance of the yarn membrane can be freely controlled by appropriately combining the above-mentioned spinning dope composition, discharge conditions, and coagulation liquid composition. After producing the hollow fiber membrane, it may be immersed in a non-solvent of polysulfone resin and heat treated at a temperature of gO°0 to 150°C. ! Effective for sexual control. A heat treatment time of 80 minutes to 2 hours is usually sufficient, but about 1 hour is desirable.

Here, the water permeability is 2000 rtil/wiHji
1 hour - or more, and weight average molecular weight 65,000 to 7
If the rejection rate of dextran, which is 5000, is less than aO*, the inner surface of the hollow fiber membrane is clogged with blood cell components, proteins, etc., and blood coagulation within the hollow fiber is likely to occur, resulting in stable hemodialysis and blood flow. You will not be able to send P-mails. On the other hand, if the water permeability is less than 500 at/ymH9·hr and the rejection rate of dextran with a weight average molecular weight of 65,000 to 75,000 is 70% or more, the blood filtration flow rate will be extremely reduced and the effectiveness will be reduced. Standard hemodialysis and blood filtration become impossible. Even if the number of such hollow fiber membranes to be loaded is increased, the blood flow within the hollow fibers will decrease, and as a result, blood orange will be more likely to be produced.

〔Effect of the invention〕

The hollow fiber membrane made of the polysulfone resin of the present invention can perform hemodialysis or blood filtration efficiently (and stably) by controlling membrane performance such as water permeability and dextran rejection within an appropriate range. Therefore, in the treatment of patients with chronic or acute renal failure, in addition to blood purification using long-term continuous hemodialysis or blood filtration methods, which were previously considered difficult, extracorporeal methods without the use of blood pumps are needed. It is also extremely effective for blood purification through circulation methods.

Continuous hemofiltration is also effective for multiple organ failure, heart failure resistant to drug therapy, and Western species, and it is suitable as a blood filter that can be used stably for long periods of time in such cases. be. Furthermore, in the future, it is thought that it will be possible to use it for patients with chronic renal failure as well as for portable artificial kidneys, home dialysis, etc., and the range of applications is quite wide. In addition, even if the current intermittent treatment using blood pumps is used, it becomes possible to provide hemodialyzers and blood filters with better blood compatibility.Examples of the present invention will be described below. .

Example 1 Polysulfone (UCC a%UDEL P-1700)
t-16.5% by weight, dimethylformamide as a bath agent? 75.5% by weight and 8% by weight of methyl-n-butyl ketone as an additive were mixed at 80°C for 4 hours.

The mixture was heated and stirred to obtain a homogeneous solution. This spinning dope is discharged from the outer annular opening of the hollow fiber manufacturing nozzle and water is discharged from the troubled part, and is led to a coagulation bath consisting of water and coagulated.
Winding was carried out at a speed of m/min. Here, the spinning temperature, that is, the temperature of the spinning dope and the internal coagulating liquid, was 50°C.

The wound hollow fiber was immersed in water and left in a large state for 1) permanent residence at 0°C for 1 hour.

The obtained film had an inner diameter of 220μ and a film thickness of 45μ.

! To evaluate the rejection rate, dextran with a weight average molecular weight of approximately 70,000 (7 Almasia Chemiforces Co., Ltd., T?O
9 using j. Measurement results of water permeability and dextran rejection t-1st!5! Shown below.

Blood dialysis performance: 1 x 88,000 bottles, effective length 18a
A model was created using a peagle dog weighing 10 KP with ureteral ligation, and extracorporeal circulation was performed using a pump. The blood flow at this time was zoowt 7 minutes, which was 9. The circulation rate of dialysate is 5001) J/min, and the amount of heno(phosphorus) is 500 I
A continuous infusion of U/hour was given. As a result, the ability to remove low molecular weight substances and water removal was stable for over 100 hours, and almost no thrombus was observed within the membrane at the end of the test. blood g,
In the case of filtration, we performed the same procedure except for the dialysate, and found that there were 8 of the 90 or less examples and comparative examples that had sufficient water removal ability and stable filtration for more than 100 hours. Unless otherwise specified, the methods of film formation and performance evaluation were performed in the same manner as in this Example. Comparative Example 1 yH! j fis-ytcy (UCC@@, UDE
L P-170071'k1) Weight-1 N- as punishment
Methyl-2-pyrrolidone t83.5 wt., methyl-n-butylketone t''5.5 wt. as an additive, mixed;
The spun yarn was designated as IjKfIL. The water permeability and dextran rejection rate of the obtained hollow fiber membrane are shown in 1i - 1st construction cost.

In both blood dialysis and filtration, the inlet pressure gradually increases, and the water removal capacity also tends to decrease, 1) at 40 to bO hours! It became impossible to continue. Many thrombi were observed within the membrane at the time of completion. In addition, when hemodialysis and blood filtration were performed without using a blood pump, blood clots occurred in an even shorter period of time, and approximately 2
Natsufumi became unable to perform extracorporeal circulation at 0 hours.

Comparative Example 2 Polyether sulfone (ICI Exhibition, Victor
N-methyl-2- as solvent
A spinning stock solution was prepared by mixing 6% by weight of pyrrolidone t″ and 675% by weight of sodium dodecylbenzenesulfone (Kao Atlas Co., Ltd., Neoberetsu, Kusu 0675% by weight) as an additive.

The water permeability and dextran inhibition of the obtained hollow fiber membrane are shown in Table 1.

Blood dialysis and treatment were relatively stable regardless of the presence or absence of a blood pump, but after approximately 24 days, the dog's condition worsened and the dog exhibited symptoms characteristic of renal failure, such as vomiting.
- It was impossible to continue for more than 60 hours. This is presumed to be due to insufficient water removal ability and insufficient removal of low molecular weight substances from the blood.

Example 2 IJ s-f Luslun (manufactured by ICI, Vtctr)
e X800PJ was used in combination with 15% of weight, dimethylformamide was 76% by weight as a bath agent, and propyl alcohol and lacryl betaine (manufactured by Kao Atlas Co., Ltd., Amhitol 214B) were used in combination with 6% and 1% of dimethyl, respectively.
-i was mixed to obtain a spinning stock solution. Spinning temperature 40°0,
Winding speed 8971! /min, heat treatment temperature 100°0, and the inner diameter and thickness of the film were zOOμ and 8, respectively.
It was 5μ. Membrane performance t-shown in Table 1.

In blood dialysis and dialysis, it was extremely stable regardless of the presence or absence of a blood pump, and showed sufficient water removal ability for more than 100 hours, and the dog was in good condition.

Example 8 Polysulfone (manufactured by TJCC, UDEL P-170
0) 14% by weight, N-methyl-2-pyrrolidone 79% by weight, NaBr 2% by weight as additives and diglycidyl ether 53%! [It was mixed to obtain a spinning dope.

A film was formed in the same manner as in Example 2, and the film performance was evaluated as shown in Table 41. It showed extremely stable performance even after 100 hours of hemodialysis in animal experiments, and almost no blood orange was observed within the hollow fibers even after 100 hours of hemodialysis.

Claims (2)

[Claims] (1) Made of polysulfone resin, water permeability is 50
A hollow chamber for blood purification, characterized in that the rejection rate of dextran having a weight average molecular weight of 65,000 to 75,000 is within the range of 30 to 70%, and the rate is within the range of 0 to 2000 ml/mmHg/hour/m^3. Thread membrane. (2) Polysulfone resin is composed of a polymer having the following repeating units: A hollow fiber membrane for blood purification according to claim (1).