JP2710710B2 - Fluid separator - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a fluid separator using a selectively permeable hollow fiber made of a specific polymer. More specifically, the present invention provides a fluid separator using a permselective cellulose diacetate hollow fiber mainly composed of a cellulose diacetate polymer having a high average degree of polymerization different from that of the prior art. Is what you do.

[0002]

2. Description of the Related Art A fluid separator using a selectively permeable hollow fiber has been practically used in reverse osmosis and hemodialysis.

[0003] In particular, in order to purify the blood of patients with renal failure,
At present, hollow fiber hemodialyzers are often used. This is a dialysis membrane in the housing, for example, a number of hollow fiber membranes,
It is stored, the patient's blood is flowed into the hollow interior, the dialysate is flowed outside, i.e., between the hollow fibers, and dialysis is performed through the hollow fibers to remove waste products in the blood and correct the electrolyte concentration, A pressure difference is applied between the inside and the outside of the hollow fiber to remove excess water in blood by ultrafiltration. Furthermore, in order to separate only plasma from the blood, or to remove specific components from the plasma to treat autoimmune diseases and the like,
Hollow fibers are used. As described above, the 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 pores, etc.), the film thickness and the like.

[0004] As a material of a hollow fiber for a hemodialyzer, cellulose or cellulose acetate is generally often used. In particular, cellulose acetate can be produced relatively easily by commonly used spinning methods such as plasticizing melt spinning and wet spinning, and when the obtained hollow fiber is used for hemodialysis treatment, for example, compared to the case of a cellulose hollow fiber. Thus, there is an advantage that complement activity can be suppressed to some extent.

However, in the conventional cellulose diacetate hollow fiber, the degree of polymerization of cellulose itself tends to decrease at the stage of acetylating the cellulose, and a high degree of polymerization of only about 170 to 200 was obtained at most.

[0006]

SUMMARY OF THE INVENTION The present inventor has found that using conventional cellulose diacetate having a degree of polymerization of at most 200, if the concentration of the polymer is lowered to increase the material permeability, the viscosity of the spinning dope will be insufficient. In some cases, it is difficult to reduce the film thickness. In such a case, it is difficult to form a fin that extends in the axial direction. In order to improve the difficulty in obtaining a hollow fiber type fluid separator having permeability, diligent research was conducted.

[0007]

Means for Solving the Problems The present inventors have obtained cellulose diacetate having a higher polymerization degree than that of the conventional cellulose diacetate hollow fiber, and by using such a high polymerization degree cellulose diacetate. The present inventors have found that a permselective hollow fiber having more excellent properties can be obtained, and as a result, a fluid separator having desired properties can be easily obtained.

That is, the present invention relates to a hollow fiber type fluid separator containing a hollow fiber bundle having a permselective wall membrane consisting essentially of cellulose diacetate, wherein the average polymerization degree of the cellulose diacetate is substantially 230. And at least one fin extending along the axial direction on the outer surface side of the wall membrane, wherein the thickness of the fin-free portion of the wall membrane is 20 μm or less and the hollow fiber A fluid separator characterized in that the average cutting strength is 0.4 g / de or more.

The invention includes a fluid separator wherein the permselectivity of the wall membrane is a substance permselectivity for hemodialysis treatment.

The present invention, in addition to the above features, has a water permeability coefficient of the hollow fiber membrane at 37 ° C. of 10 ml / m ^2.
-Fluid separation characterized by a urea permeability coefficient of not less than 0.045 cm / min at 37 ° C when the flow rate on the blood side is 200 ml / min and the flow rate on the dialysate side is 500 ml / min. Vessel included.

Further, the present invention provides a method for preparing a hollow fiber wall membrane at 37 ° C.
Water permeability coefficient is 20 ml / m ² · hr · mmHg or more, blood side flow rate is 200 ml / min, dialysate side flow rate is 500
A fluid separator is characterized in that the dextran with a molecular weight of 10,000 per 1 m ² of effective membrane area at 37 ° C. has a dialysance of 20 ml / min or more at 37 ° C.

Hereinafter, the present invention will be described in more detail.
First, the selectively permeable cellulose diacetate hollow fiber of the present invention contains a substantial component of a substantially cellulose diacetate polymer. As such a substantial cellulose diacetate polymer, those which are within the range usually handled as cellulose diacetate, specifically, those having an average degree of acetylation within the range of 50 to 57 can be mentioned.

The cellulose diacetate polymer of the present invention is characterized in that the average degree of polymerization is from 230 to 400. Here, the average degree of polymerization means a value obtained by dividing the weight average molecular weight by the molecular weight of the repeating unit of the polymer. As a method for measuring the weight average molecular weight, for example, gel filtration chromatography, measurement of viscosity, measurement of sedimentation equilibrium,
Light scattering method may be used.

When the average degree of polymerization of the cellulose diacetate polymer is less than 230, it is difficult to obtain a cellulose diacetate hollow fiber having high fins and high permselectivity. Further, it is difficult to obtain a hollow fiber having a low rewetting elongation rate. The average degree of polymerization is more preferably from 240 to 350, and particularly preferably from 250 to 300.

When the average degree of polymerization of the cellulose diacetate polymer is 400 or more, it is difficult to produce the polymer itself, and when a hollow fiber is melt-spun, a very high temperature is required, and the decomposition of the cellulose diacetate is difficult. Easier to do.

The cellulose diacetate hollow fiber of the present invention contains such a cellulose diacetate polymer as a main component, and its specific content is preferably at least 50%, more preferably at least 70%. In addition, the components contained other than that are not particularly limited, for example, polymethyl methacrylate, polyethylene, polypropylene,
Organic polymers such as polyacrylonitrile, polyvinyl alcohol, and nitrocellulose are exemplified.

Further, the outer diameter (d) of the hollow fiber of the present invention may be, for example, 100 in the case of body fluid treatment such as hemodialysis.
~ 400μ, more preferably 200 ~ 300μ. The film thickness (h) is not more than 20 μm, and more preferably 5 to 20
μ, particularly preferably 10 to 15 μ.

The cellulose diacetate hollow fiber of the present invention has fins extending in the longitudinal direction at the outer peripheral portion. In this case, the ratio H / W of the height H to the width W of the fin is 0. It is desirable that it be not less than 0.5. Ratio H / W
Is less than 0.5, it is difficult to obtain the effect of preventing the hollow fibers from sticking together when housed in the fluid separator, which is not preferable. H / W is more preferably 0.8 or more. The width W of the fin means the width at half the height H of the fin.

Further, the number x of the fins of the hollow fiber in the present invention x
Is at least 1. However, when it is 11 or more, the effective membrane area is significantly reduced by the root portion of the fin. For example, the material dialysis performance and water permeation performance in a hemodialyzer are remarkably reduced, which is not practical. That is, such x is generally 1 to 10, more preferably 2 to 8, and the particularly effective range is 3 to 10.
~ 7.

In this case, the height (H) of the fin is 5
-100 μm, more preferably 9-60 μm. The ratio H / h between the fin height and the film thickness is preferably 0.5-3, more preferably 1-2. Furthermore, the ratio H / d of the average height H (μ) of the fins and the average outer diameter d (μ) of the hollow fibers excluding the fins.
Is preferably in the range of 0.01 to 1, more preferably in the range of 0.02 to 0.5, and particularly preferably in the range of 0.03 to 0.2.

The width of the root of the fin is desirably narrower than that of the upper part of the fin, but usually the root portion tends to become wider due to the surface tension of the stock solution after the stock solution is discharged from the spinneret. The width of the root is 15 to 50 μm, preferably 20 to 50 μm.
40μ is suitable.

A hollow fiber in such a range has good roundness and is preferable in that blood coagulation and residual blood in the hollow fiber hardly occur.

Further, the hollow fiber of the present invention has an average breaking strength of 0.4 g / de or more, particularly preferably 0.6 g / de or more. When the strength is less than 0.3 g / de, the shape retention is poor, and it is easily broken during the hollow fiber manufacturing process and the fluid separator manufacturing process. In particular, the outer diameter d is 100 to 300 μm and the film thickness is 5 μm. In the case of a hollow fiber in the range of 〜20 μ, the tendency is large. The upper limit of the strength is not particularly limited, and is, for example, generally 0.9 g / de or less.

Further, the hollow fiber of the present invention is characterized in that the rewetting elongation is 3% or less. Rewetting elongation rate is 3
%, The elongation of the hollow fibers when filled with water or an aqueous solution after being stored in a fluid separator substantially in a dry state and brought into a rewet state is too large, and the local adhesion between the hollow fibers is large. And the hollow fiber is liable to be bent, which is not preferable. The rewetting elongation is more preferably 2% or less. The lower limit of the rewetting elongation rate is not particularly limited, but if it is 0.5% or more, more preferably 1% or more, the hollow fiber exhibits an appropriate elongation at the time of rewetting in the fluid separator. Also, the effect of spreading the hollow fiber bundle throughout the fluid separator can be obtained. The rewetting elongation α is about 0.1 g / de when the length of the hollow fiber which is substantially dry is measured under a load of about 0.1 g / de, and the hollow fiber is wetted with water. the length L ₁ as measured under a load was measured, α = {(L
₁₋ L) / L｝ × 100. Here, the substantially dry state means a state in which the glycerin content obtained by immersing the hollow fiber in an aqueous glycerin solution and then drying is 30 to 60%, and the water content is 0.5 to 9%.

Further, among the hollow fibers having a small thickness according to the present invention,
Preferably, the material has a bending stiffness substantially in the range of 200 mg / 200 or more, and preferably has a burst pressure of 4 kg / cm ² or more as a pressure resistance when pressed into the hollow fiber when wet. In the range, the handling of the hollow fiber is easy at the time of manufacturing the fluid separator, etc., the length of each hollow fiber within the fluid separator tends to be uniform, and the pressure during the use of the separator is increased. An advantage is obtained that the hollow fiber is less likely to be damaged by the operation.

The method for producing the hollow fiber of the present invention may be any of melt spinning, wet spinning, semi-dry semi-wet spinning, and the like. That is, in the case of the melt spinning method, the spinning dope is a heated melt, and the melt is discharged from the spinneret to be cooled, thereby forming a finned hollow fiber, and then dissolving the cellulose diester polymer. A finned cellulose diacetate hollow fiber having selective permeability is obtained by extracting and removing at least a part of the additive in the finned hollow fiber with a solvent capable of dissolving the additive without using the solvent.

The fluid separator of the present invention contains a bundle of the above-described specific permeable cellulose diacetate hollow fibers as a fluid separation function part, and the hollow fibers have an average degree of polymerization of 230 to 400. And a fin-free portion having a fin having a ratio H / W of height H to width W of 0.5 or more, which preferably extends in the longitudinal direction at the outer peripheral portion and has a cellulose-based polymer as a main component. The thickness is 30 μm or less.

The filling rate of the hollow fibers in the fluid separator of the present invention is preferably 30 to 80%, more preferably 35 to 70%. If the filling ratio is less than 30%, even in the hollow fiber of the present invention having a good dispersion state, the non-uniform filling occurs, and the flow of the fluid such as the dialysate outside the hollow fiber tends to cause non-uniformity such as channeling. Not preferred. The filling rate is 8
If it is 0% or more, it is not preferable because filling of the hollow fiber bundle becomes difficult. In the case of a state having a relatively high filling rate within this range, the hollow fiber bundle is wound or covered with other members such as a tape-like material, a sheet-like material, a thread-like material, a net-like material, etc. It is effective to make the yarn bundle thin and store it in the container constituting the processor.

The fluid treatment device of the present invention is particularly suitable for housing a cellulose ester type hollow fiber having a rewetting elongation ratio of 3% or less and having a small expansion when water or an aqueous solution comes into contact with the hollow fiber. There is an advantage that local adhesion between the yarns, bending of the hollow fibers, and the like hardly occur. Particularly, when the filling rate of the hollow fiber is relatively high at 50% or more, the advantage is very effectively retained.

In the case where the fluid separator is a hemodialyzer, a form in which a blood distribution member and a blood collection member are provided outside each tube plate portion and a dialysate inlet / outlet is provided on the wall of the container is common. It is a target.

Specific applications of the fluid separator of the present invention include liquid separation such as dialysis, ultrafiltration, microfiltration, and reverse osmosis.
Oxygen enrichment, gas separation of artificial lungs and the like. Among them, it is suitable for a body fluid processor such as an artificial kidney, an artificial liver, a plasma separator, an ascites processor, and an artificial lung, and is particularly excellent as a hemodialyzer.

As one type of such a fluid separator for hemodialysis treatment of the present invention, which contains the cellulose diacetate hollow fiber as described above, has a water permeability coefficient at 37 ° C. of 10 ml / m ² ··· hr · mmHg or more, and the flow rate on the blood side, that is, the hollow part side is 200 ml / min, and the flow rate on the dialysate side, that is, the hollow fiber gap part is 500 ml.
/ Min and a urea permeability coefficient of 0.045 cm / min or more under the condition maintained at 37 ° C.

In this case, as compared with a conventional fluid separator using cellulose diacetate hollow fibers, the polymer concentration in the spinning solution of the hollow fibers is reduced and the film thickness is 20 μm or less, preferably 5 to 15 μm. Since a hollow fiber thinned to a degree can be used, the separation performance of low-molecular-weight harmful substances in blood represented by urea can be improved.

A preferred fluid separator of this type has a water permeability in the range of 5 to ²⁰ ml / m ² · hr · mmHg and a urea permeability of 0.045 to 0.055 cm.
/ Min, which has a good balance between high-level water removal and low-molecular-weight harmful substance removal. In this case, the average molecular weight of the cellulose diacetate is 25
It is desirable that the film thickness in the range of 0 to 300 and the portion without fins is in the range of 20 to 25.

The measurement of the urea permeability coefficient can be performed in a state where an aqueous solution containing urea at a rate of 0.01% by weight is introduced into the hollow part and water is introduced into the hollow fiber gap part.

As another type of the fluid separator for hemodialysis treatment of the present invention, the cellulose diacetate hollow fiber as described above has performance different from that of the previous type, that is, has a better material permeability. Containing a bundle of hollow fibers having a water permeability coefficient of 20 ml at 37 ° C.
/ M ² · hr · mmHg or more, and the flow rate on the blood side, that is, the hollow part side is 200 ml / min, and the flow rate on the dialysate side, that is, the hollow fiber gap side is 500 ml / min. A fluid separator characterized by a dialysance of 20 ml / min or more for dextran having a molecular weight of 10,000 per m ^{2 of} effective membrane area.

This type of fluid separator has a lower polymer concentration in the spinning stock solution and a thinner film thickness of about 18 to 20 μm than the hollow fiber in the previous type, and thus has a higher material permeation rate. Uses cellulose diacetate hollow fiber with enhanced properties, has a very high water permeability coefficient, and especially has a high permeability to harmful substances in blood having a large molecular weight corresponding to dextran having a molecular weight of 10,000. Has excellent permselectivity.

As a more preferred hemodialysis fluid separator excellent in removing large molecular weight harmful substances of this type, dextran having a water permeability coefficient of 15 to 40 ml / m ² · hr · mmHg and a molecular weight of 10,000 is used. Dialysance in the range of 15 to 40 ml / min. In this case, the average molecular weight of the cellulose diacetate is desirably 250 to 300, and the film thickness in the portion without fins is desirably 18 to 20.

The dialysance measurement is carried out in such a manner that a solution containing a dextran having a molecular weight of 10,000% at a rate of 0.01 wt% is introduced into the hollow part and water is introduced into the hollow fiber gap part. be able to.

Hereinafter, the present invention will be described in more detail with reference to Examples.
The present invention is not limited by these examples.

[0041]

Example 1, Comparative Example 1 To 100 parts of cellulose diacetate having an average degree of polymerization of 260 and 170, 170 parts of a mixture obtained by mixing polyethylene glycol (molecular weight: 400) and diglycerin at a ratio of 8 to 1 was added and mixed. Mix 180
The thicknesses of the membranes at the fin-free portions which were melted at a temperature of from 0 ° C. to 190 ° C. and tried to be spun using a die having double annular slits for finned hollow fibers were set to 12 μ and 14 μ, respectively.
Next, polyethylene glycol and diglycerin are extracted with hot water, and after winding, the hollow fiber bundle is turned into an effective membrane area of about 1.
A 5 m ² hemodialyzer was assembled. The following table shows the properties of the obtained hollow fiber and hemodialyzer.

As shown in Table 1, when the average degree of polymerization is 260, there is almost no breakage during spinning, and the permeability coefficient of urea can be increased to 0.045 cm / min or more by reducing the thickness of the hollow fiber.

[0043]

[Table 1]

[0044]

According to the present invention, the average degree of polymerization of the cellulose diacetate hollow fiber of the present invention is higher than usual, and the viscosity of the spinning solution at a certain polymer concentration becomes higher, so that the spinnability becomes very good. That is, yarn breakage during spinning is small, and yarn spots are reduced. Further, the polymer concentration at the time of spinning can be reduced, and the permeability of a substance such as UFR dialysance, particularly the permeability of a medium-high molecular weight region having a molecular weight of about 10,000 can be greatly improved.

Claims (4)

(57) [Claims] 1. A hollow fiber type fluid separator containing a hollow fiber bundle having a permselective wall membrane consisting essentially of cellulose diacetate, wherein said cellulose diacetate has an average degree of polymerization of 230 to 400. And at least one fin extending along the axial direction on the outer surface side of the wall film, and the thickness of the fin-free portion of the wall film is 20 μm.
And the average cutting strength of the hollow fiber is 0.4 g / de
A fluid separator characterized by the above. 2. The fluid separator according to claim 1, wherein the permselectivity of the wall membrane is a substance permselectivity for a hemodialysis treatment. 3. When the water permeability coefficient of the hollow fiber wall membrane at 37 ° C. is 10 ml / m ² · hr · mmHg or more, the flow rate on the blood side is 200 ml / min, and the flow rate on the dialysate side is 500 ml / min. The fluid separator according to claim 2, wherein the urea permeability coefficient at 37 ° C is 0.045 cm / min or more. 4. The method according to claim 1, wherein said hollow fiber wall membrane has a water permeability coefficient at 37 ° C. of not less than 20 ml / m ² · hr · mmHg, a flow rate on the blood side of 200 ml / min and a flow rate on the dialysate side of 500 ml / min. The molecular weight per 1 m ² of effective membrane area at 37 ° C.
3. The fluid separator according to claim 2, wherein the dextran has a dialysance of 20 ml / min or more.