JPH10127763A - Selective transmitting hollow string film - Google Patents

Abstract

PROBLEM TO BE SOLVED: To remove the detrimental substance in the middle and high molecular weight regions and hinder useful substances from flowing out by specifying the screening factor (SCDX) of dextran using a water solution of a dextran having a specific molecular weight, and also specifying the ratio SCAIb /SCDX, where SCAIb represents the screening factor of albumin after perfusion of bovine plasma for a specific time. SOLUTION: As the starting material, cellulose derivative, in particular acetyl cellulose, is used (example is cellulose diacetate). A hollow string film is formed where a thin dense layer is provided on the inner surface of hollow strings while a porous layer is provided on the outside. This hollow string film has such as structure that the screening factor (SCDX) of dextran using a water solution of a dextran having a molecular weight of 70000 is more than 0.05 and that the ratio of the screening factor (SCAIb ) of albumin after one-hour perfusion of bovine plasma to the value SCDX lies below 0.12. This enhances the performance of removing detrimental substance in the middle and high molecular weight regions such as β2 -microglobulin and allows hindering albumin, etc., from flowing away.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a selectively permeable hollow fiber membrane. More specifically, the ratio of the sieving coefficient of albumin in the bovine plasma system to the sieving coefficient of dextran in the aqueous solution system is equal to or less than a specific value, and has a selective permeability exhibiting excellent separation performance in the plasma system. , Hemodialysis,
It is an object of the present invention to provide a selectively permeable hollow fiber membrane suitable for blood treatment such as hemofiltration dialysis, and particularly suitable for removing harmful substances in a medium-high molecular weight region.

[0002]

2. Description of the Related Art Permselective hollow fiber membranes have been practically used in reverse osmosis and hemodialysis. In particular, hollow fiber hemodialyzers are often used at present for purifying blood of patients with renal failure. This is a method in which a dialysis membrane, for example, a number of hollow fiber membranes, is housed in a housing, a patient's blood flows inside the hollow, and a dialysate flows through the outside, that is, a hollow fiber gap, and a hollow fiber membrane is formed. In addition to removing wastes in the blood and correcting the electrolyte concentration by dialysis through the wall, a pressure difference is applied between the inside and outside of the hollow fiber to remove excess water in the blood by ultrafiltration. Furthermore, hollow fibers are sometimes used to separate plasma alone from blood or to remove specific components from the plasma to treat autoimmune diseases and the like. Recently, it has been confirmed that a therapeutic effect can be obtained by using hollow fibers in protein-permeable hemodialysis or protein-permeable hemofiltration dialysis.

As described above, a hollow fiber for blood treatment must selectively allow a specific substance to permeate according to the purpose. The performance is determined by the material of the hollow fiber, the porosity (the size and number of holes), the film thickness and the like.

[0004] In recent years, β which is considered to be a causative substance of dialysis amyloidosis is associated with long-term complications of dialysis patients.
_2- MG (microglobulin) (molecular weight 11,800)
Parathyroid hormone (molecular weight about 9,500), which is thought to be associated with pruritus and hyperlipidemia, erythroblast inhibitory factor involved in anemia, molecular weight 2 which is thought to be involved in arthralgia and bone pain
The need to remove harmful substances in the relatively high molecular weight region, such as 40,000 substances, is avoided. On the other hand, loss of albumin (molecular weight: 66,000), which is essential for the human body, must be avoided as much as possible. That is, there is a demand for a permselective membrane which is excellent in permeability of substances having a molecular weight of 40,000 or less and 50,000 or less, and which has good rejection of substances having a molecular weight of 60,000 or more and a good sharp cut property of a cut molecular weight.

However, conventionally, synthetic polymers such as polysulfone are disclosed in, for example, Japanese Patent Publication No.
As described in JP-A-54373, those which relatively satisfy the above requirements have been obtained. However, in the case of cellulose derivatives, particularly triacetate, for example, as shown in JP-B-58-34165, when hollow fibers are wet-spun. For the core agent,
In order to use non-coagulable triacetate spinning solution such as liquid paraffin, higher alcohol, and isopropyl myristate, it is necessary to increase the concentration of triacetate in the spinning solution to increase spinnability during spinning. In addition, a layer having a dense structure is formed on the outer surface of the hollow fiber in order to solidify the spinning stock solution from the nozzle and then solidify the outer surface of the hollow fiber with the coagulating liquid.

[0006] For these reasons, conventionally, a cellulose derivative hollow fiber has a smaller difference in density between a dense layer and a porous layer in structure than a synthetic polymer membrane, and is close to a uniform layer as a whole.
The permeability of the substance was not sufficient. For this purpose, the thickness of the film has been reduced and the permeability has been improved, but this is not sufficient. Furthermore, since the density difference between the dense layer and the porous layer having a membrane structure is unclear, there is room for improvement in the fractionation characteristics of the permeated substance.

[0007]

SUMMARY OF THE INVENTION An object of the present invention is to solve such problems of the prior art.
The purpose of the present invention is to provide a close-packed structure close to the structure of a conventional synthetic polymer by using a polymer of a cellulose derivative, and to impart high molecular weight fractionation characteristics. In particular, it is an object of the present invention to provide a selectively permeable hollow fiber membrane capable of removing harmful substances in the medium-high molecular weight region such as β ₂ -MG and preventing outflow of useful substances such as albumin in hemodialysis and hemodiafiltration. I have.

[0008]

Means for Solving the Problems As a result of the inventor's intensive efforts to achieve such an object, the ratio of the sieving coefficient of albumin in the bovine plasma system to the sieving coefficient of dextran in the aqueous solution system was determined. It has been found that a hemodialyzer using a hollow fiber having a value equal to or less than the value exhibits a remarkably enhanced separation performance of a medium-high molecular weight substance, and has reached the present invention.

That is, the present invention relates to a hollow fiber membrane having permselectivity, and a sieving coefficient (SC) of the dextran using an aqueous solution of dextran having a molecular weight of 70,000, which was measured by assembling the hollow fiber membrane as a dialyzer. _DX) is not less than 0.05, and for SC _DX, the ratio of the sieving coefficient of albumin after 1 hour perfused bovine plasma _{(SC AI b) SC AI b} /
A permselective hollow fiber membrane consisting essentially of a cellulose derivative, having an SC _DX of less than 0.12.

Hereinafter, the present invention will be described in more detail.

That is, the hollow fiber membrane of the present invention has a selective permeability, and is made of a cellulose derivative, particularly acetylcellulose. And a polymer composed of cellulose diacetate and cellulose triacetate. Note that “substantially” means that other polymers, additives, and the like may be contained as long as the properties of the cellulose derivative are not impaired.

The structure of the membrane wall of the hollow fiber membrane of the present invention is characterized by an ultra-thin dense layer that functions to separate and permeate the separation and permeation characteristics of the substance and the mechanical properties, and is capable of mechanically withstanding fluid pressure. A two-layer or multi-layer structure conventionally realized by a synthetic polymer, which has a porous layer having almost no permeation resistance, is preferable. In particular, when blood is processed through the inner surface of the hollow fiber membrane, it is desirable that there is a dense layer at least on the inner surface of the hollow fiber. If there is a porous layer on the inner surface, there is a concern that blood proteins may adhere to that portion or penetrate into the pores, thereby impeding the permeation of substances.

For example, as described above, in a membrane having a thin dense layer on the inner surface of a hollow fiber and a porous layer on the outer side, a medium- or large-molecule aqueous solution such as dextran (molecular weight 70,
000) shows a relatively high sieving coefficient, but the sieving coefficient of albumin of similar molecular weight in plasma or whole blood system is found to be lower. In this case, it was also found that the sieving coefficient by filtration of the medium and large molecular weight substances was significantly lower in the plasma system than in the aqueous system, while the permeability coefficient by diffusion had little effect.

As described above, in a hollow fiber membrane having a structure in which the reduction rate of the sieving coefficient of a medium-large molecule in a plasma system to an aqueous solution or the like shows a certain value or less, the permeation of the medium-large molecule by diffusion (Dialysis performance) can be reduced without lowering the permeation by filtration.
The separation characteristics of a substance having a molecular weight of about 7000 and a substance having a molecular weight of about 70,000 can be greatly improved.

This tendency of the cellulose derivative-based hollow fiber membrane has been demonstrated for the first time.

A conventional hollow fiber membrane for dialysis of a cellulose derivative such as triacetate or diacetate is generally a uniform membrane, and the ratio of the sieving coefficient of the medium and large molecules of the plasma to the aqueous solution is 0.12 or more. Indicated.

The sieving coefficient was measured based on the "Blood Purifier" evaluation standard of the Scientific Committee of the Japanese Society for Dialysis Therapy.

The hollow fiber membrane according to the present invention has a molecular weight of 70,00 in a dialyzer assembled using the hollow fiber bundle.
The dextran sieving coefficient SC _DX using an aqueous solution of dextran of 0 or more is 0.05 or more, and the ratio SC SC of the sieving coefficient of albumin (SC _{AI b} ) after perfusion of bovine plasma for 1 hour to SC _{DX AI b} / SC _DX is characterized in that less than 0.12. Preferably, it is 0.10 or less, and such a hollow fiber membrane is composed of water, a low molecular weight substance and a molecular weight of 1
The material permeability of dextran of 000 is good,
In addition, the permeability of albumin having a molecular weight of about 66,000 through the hollow fiber membrane is sufficiently prevented,
It has sharp fractionation characteristics between these molecular weights.

The thickness of the hollow fiber membrane is generally desirably small in view of the permeability of the substance.
In the case of a structure having two or more layers, the thickness is preferably 30 μm or more from the viewpoint of mechanical strength because of having a porous layer. The inner diameter of the hollow fiber membrane is 100 to 300 μm, and more preferably 150 to 250 μm.
m is preferred.

Further, in the present invention, the total mass transfer coefficient K ₀ of β ₂ -microglobulin measured in bovine plasma system is 5.0 × 10 ⁻⁵ cm / sec or more. As a method of measuring K ₀ , the clearance (CL) of β ₂ -microglobulin is measured by the evaluation method of the Japanese Society for Dialysis Medical Academic Committee (1994), and calculated using the following equation.

[0021]

(Equation 1)

Q _B : flow rate on blood side [ml / sec] Q _D : flow rate on dialysate side [ml / sec] A: effective membrane area of hollow fiber membrane [cm ² ]: inner diameter of hollow fiber membrane in wet state This is the reference film area.

The K ₀ of the hollow fiber membrane of the present invention is 5.0 ×
10 ^-5 cm / sec or more, more preferably 6.0 × 10
^-5 cm / sec or more.

As described above, when the hollow fiber membrane of the present invention is used in a hemodialyzer or hemofiltration dialysis, it has a high ability to remove harmful substances in a medium-high molecular weight region such as β ₂ -MG and has a low molecular weight region. In addition to the excellent performance of removing harmful substances, the selective permeation of albumin, which is beneficial to the human body, is small.

Although the method for producing the hollow fiber membrane of the present invention is not particularly limited, a tube-in-orifice nozzle is desirably prepared by using a spinning stock solution obtained by dissolving a cellulose derivative in an organic solvent and using an aqueous solution as a core agent. A method is adopted in which the liquid is discharged more, passes through a gas, and then passes through a water-soluble coagulating liquid and solidifies.

[0026]

EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited to these examples.

[Examples 1 to 6, Comparative Examples 1 to 5] Cellulose triacetate and triethylene glycol were uniformly dissolved in dimethyl sulfoxide (DMSO) (triethylene glycol / DMSO = 2/7 (wt / w)
Using t)) as a spinning dope, various fluids were discharged into the air from a tube-in-orifice type nozzle as a core agent, and then guided into a coagulating liquid to be solidified, washed with water, glycerin-adhering treatment, and then wound up. . The obtained hollow fiber membranes were dried and formed into a bundle, inserted and filled in a cylindrical container, and both ends were adhered and fixed with polyurethane to prepare a hemodialyzer having an effective area of about 1.5 m ² .

Table 1 shows the spinning conditions, in vitro characteristic values and dialysis performance. The hollow fiber of the present invention has a small sieving coefficient of albumin in a plasma system and a large dialysis performance of β ₂ -microglobulin.

When the hollow fiber membrane of the present invention is used to assemble a blood purifier using the bundle, not only the removal rate of harmful substances in the medium-high molecular weight region such as β ₂ -MG is high but also the dialysate of albumin It has an excellent effect that the amount of leakage into the inside is small.

[0030]

[Table 1]

Claims (4)

[Claims] 1. A hollow fiber membrane having permselectivity,
The hollow fiber membrane was assembled and measured as a dialyzer, and had a molecular weight of 7
The dextran sieving coefficient (SC _DX ) using an aqueous solution of dextran of 000 is 0.05 or more, and the sieving coefficient of albumin after perfusing bovine plasma with SC _DX for 1 hour (SC _{AI b} ) The ratio SC _{AI b} / SC _DX is 0.1
A permselective hollow fiber membrane substantially consisting of a cellulose derivative, wherein the number is less than 2. 2. The permselective hollow fiber membrane according to claim 1, wherein the permselective hollow fiber membrane has a dense layer at least on an inner surface. 3. The selectively permeable hollow fiber membrane has a thickness of 30 μm.
The selectively permeable hollow fiber membrane according to claim 1, which is as described above. 4. A patent wherein the total permeability coefficient of β ₂ -microglobulin in bovine plasma is 5.0 × 10 ⁻⁵ cm / sec or more, as measured by assembling and measuring the permselective hollow fiber membrane as a dialyzer. The selectively permeable hollow fiber membrane according to claim 1.