JPH0362447B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a membrane that can be used for diaphragm separation in ultrafiltration, dialysis, etc., and particularly to a hollow fiber membrane suitable for hemodialysis. An object of the present invention is to provide a hollow fiber membrane with excellent dialysis performance, superior performance, biocompatibility, and physical properties. In recent years, with the progress of hemodialysis therapy, the characteristics required of dialyzers have widened, and various improvements have been made in terms of performance, quality, and safety. However, among the various functions of living kidneys, current dialyzers only have the function of removing substances stored in the body, mainly small molecular weight substances, and dehydration; Imperfections are coming to the surface and becoming a problem. Typical examples include anemia and abnormalities in calcium bone metabolism, which cause dialysis difficulties such as dialysis imbalance syndrome. Dialysis therapy relies on the principle of mass transfer by diffusion following the solute concentration gradient between blood and dialysate, which is fundamentally different from the principle of mass removal by pores in biological glomeruli. For this reason, current dialysis membranes have an extremely low ability to remove substances with a molecular weight of 500 or more (so-called medium-high molecular weight substances), and the accumulation of these substances that are not removed is thought to be one of the causes of uremic symptoms that are not improved by dialysis therapy. There is. HF (Hemofiltration), which was recently developed to address these problems with dialysis therapy,
The effects of new dialysis therapy and HDF (Hemodiafiltration) are attracting attention. HF and
The new dialysis treatment for HDF uses a medium-high molecular weight membrane with improved permeability to remove substances with a molecular weight of 500 to 1400, which are insufficiently removed with current dialysis membranes.
Furthermore, it also selectively removes high molecular weight substances with a molecular weight of 1,400 to several tens of thousands. It has been recognized to be effective in improving various dialysis symptoms and is attracting attention as a new dialysis therapy. The characteristics of the dialysis membrane used for these HF and HDF are that the ultraviolet characteristics are 2 to 5 ml/m ² · mm
A higher level of 8 to 40 ml/ ^m2.mmHg.Hr is required compared to Hg.Hr, and permeability to medium and high molecular weight substances is required to be about 1,400 to tens of thousands of molecular weight substances. Therefore, the object of the present invention is to provide a selectively permeable cellulose ester hollow fiber that has high water removal ability that can be applied to new dialysis therapy and has excellent fractionation characteristics for medium-high molecular weight substances. Special Publication of 1972-1999 was applied to the conventional manufacturing method of permeable cellulose ester hollow fibers.
There is a technique disclosed in Publication No. 14215 in which a membrane is formed from a cellulose ester composition containing a plasticizer, and then the plasticizer is extracted to obtain a membrane suitable for desalination of can water by reverse osmosis. Since this membrane is intended to be a hollow fiber for reverse osmosis, high pressure is required to increase water permeability, and there is substantially no solute permeability. As a technology to increase water permeability,
In No. 112511 and No. 50-112512, cellulose ester and polyethylene glycol are mixed and melt-spun, and the resulting hollow fibers are treated with an alkaline aqueous solution to extract polyethylene glycol and de-esterify it, ultimately producing regenerated cellulose. The manufacturing method is described. This method reduces the blood compatibility of cellulose esters. As a method for manufacturing hollow fibers having high water permeability without losing the properties of cellulose ester, Japanese Patent Application Laid-Open No. 54-42420 discloses a process in which a homogeneous mixture of cellulose ester, polyethylene glycol, and glycerin is melt-spun. It is known to subject this to solvent extraction treatment. Here, glycerin has the effect of preventing adhesion or welding between hollow fibers obtained by melt spinning, and also improving the permeation performance of the membrane. With this manufacturing method, the water permeability is approximately 2 to 6 ml/ ^m2・mmHg・
Although it is stated that hollow fibers having a high water permeability can be obtained, the above-mentioned effects of glycerin are not sufficient to easily produce hollow fibers having high water permeability. As mentioned above, various improvements have been attempted in order to obtain a method for industrially easily manufacturing hollow fibers having permselectivity, particularly high permeability to water, by melt spinning cellulose ester. The present invention provides cellulose ester hollow fibers that have high water permeability, which could not be obtained by conventional melt spinning, and have excellent permselectivity for medium- and high-molecular weight substances with a molecular weight of 1,400 to 100,000. As a result of intensive research on methods for improving spinnability and operability and for easy industrial production, we have developed cellulose esters, polyhydric alcohols, and glycerin derivatives (glycerin or polyethers in which at least one residue is composed of glycerin). A general term for at least one or more mixtures.Hereinafter, it will be used in this sense.)
The present invention was achieved by discovering that a cellulose ester composition having the above-mentioned characteristics satisfies the above-mentioned purpose. That is, the present invention provides cellulose ester
100 parts by weight, X parts by weight of a water-soluble polyhydric alcohol having a plasticizing effect, and parts by weight of at least one type Y from the group of polyethers in which at least one residue is composed of glycerin, respectively, by the following formulas (i) to ( iii) Melt-spinning a mixture containing in the range of 70≦X+Y≦200 (i) 60≦X≦140 (ii) 10≦Y≦80 (iii) into a hollow fiber form,
After that, extraction treatment was carried out with an aqueous solution at 80 to 99℃, and the ultimate permeability coefficient KUFR was 10.
~40ml/ ^m2・mmHg・Hr, plasma protein permeation inhibition rate is 88% or more, plasma albumin permeation rejection rate is 89% or more, and inulin permeation rate is 90% or more.
% or more, and the permeability of dextran having a molecular weight of 10,000 is 60% or more. The present invention will be explained below. The cellulose esters used in the present invention are esters of cellulose such as mono-, di-, and triacetates, and mixtures thereof. Water-soluble polyhydric alcohols having a plasticizing effect on cellulose ester include copolymers of ethylene glycol, propylene glycol, tetramethylene glycol, polyethylene glycol, polypropylene glycol, and mixtures thereof. When using a dihydric alcohol polymer, its molecular weight is less than 2000, more preferably about 100.
-1000, and those exceeding 2000 cannot be used in the present invention because their plasticizing effect on cellulose ester is significantly reduced. The polyether group of glycerin derivatives in which at least one residue is glycerin consists of the hydroxyl group of glycerin, ethylene glycol, propylene glycol,
The following formula obtained by the dehydration reaction of polyethylene glycol, polypropylene glycol, or a copolymer of ethylene glycol or propylene glycol with a hydroxyl group However, R ₁ , R ₂ , and R ₃ are H or CH ₃ a, b, and c are 0 or an integer, and the polyether is represented by 1≦a+b+c≦20 and the degree of polymerization is from 2 to
10 polyethers, which are polymers of glycerin, and mixtures thereof. The molecular weight of the polyether that can be applied to the present invention is within the range shown above; if the molecular weight exceeds this range, the plasticizing effect of the polyhydric alcohol on cellulose ester is weakened, and the spinnability in melt spinning is impaired. The mixing ratio of the cellulose ester composition of the present invention is such that the total amount of polyhydric alcohol (X) and glycerin derivative (Y) is 70 to 200 parts by weight per 100 parts of cellulose ester, especially as shown in the following formula. It is mixed in proportion. 70≦X+Y≦200 (i) 60≦X≦140 (ii) Where, Hollow fibers having a desired shape and good circularity can be stably spun for a long time using a known melt spinning method for obtaining hollow fibers. On the other hand, if the glycerin derivative in the above formula is less than 10 parts by weight, the dependence of the melt viscosity on temperature becomes significantly large, and stable spinning becomes difficult because the melt viscosity changes greatly even with a small temperature difference. Become. Furthermore, if the amount of glycerin derivative exceeds 80 parts by weight, the plasticity of the polyhydric alcohol will be weakened, and yarn breakage will easily occur during spinning, and the polyhydric alcohol and glycerin derivative will precipitate and separate on the fiber wall, causing the fibers to become loose after the extraction process. impairs the fractionation properties for solutes. The main part of this invention is to spin a composition consisting of cellulose ester, polyhydric alcohol, and glycerin derivative, and to develop desired water removal performance and material permeability from hollow fibers. Much depends on the composition between the three components of the alcohol and the glycerin derivative, and the formation of the hollow fiber membrane based on this composition. When there is a small amount of glycerin derivative in the composition, the polyhydric alcohol has a strong affinity for cellulose ester, resulting in a composition that is almost uniform at the molecular level of cellulose ester. Therefore, even if the extraction process is performed, the desired permeability will not be achieved. However, when the glycerin derivative is contained in the above proportion, in the hollow fiber obtained by melt spinning,
The presence of glycerin derivatives, which have virtually no affinity with cellulose esters and have a strong affinity with polyhydric alcohols, weakens the apparent affinity for cellulose esters, making it difficult for cellulose esters to interact with polyhydric alcohols. A microphase-separated structure is generated between the glycerin derivative mixture and the glycerin derivative mixture. On the other hand, if the concentration of the glycerin derivative is lower than the lower limit of formula (iii) and/or the concentration of polyhydric alcohol is higher than the upper limit of formula (ii), microphase separation will be insufficient. Furthermore, when the concentration of the glycerin derivative is higher than the upper limit of formula (iii) and/or the concentration of polyhydric alcohol is lower than the lower limit of formula (ii), the polyhydric alcohol and glycerin derivative mixture undergoes microphase separation and stably exists. It becomes undesirable because it stops shrinking and bleeds to the outside of the fiber wall. Therefore, excellent permselectivity can be exhibited by extracting hollow fibers having a microphase separation structure that is appropriate both quantitatively and qualitatively with a high temperature aqueous solution in the method described later. The cellulose ester composition can be obtained as a homogeneous mixture by heating and mixing at 150 to 250°C. Industrially, it is preferable to use a Ruder type extruder. The composition can be melt-spun using a known method, for example, a Luder-type extrusion spinning machine is equipped with a double-tube type spinneret, an inert gas, air, etc. is introduced into the inner port, and the melt is extruded from the outer port at 150 to 230°C to stabilize the spinning process. Hollow fibers with constant dimensions and good circularity can be obtained. Polyhydric alcohols and glycerin derivatives are extracted and removed from the hollow fibers obtained by melt spinning using a known method, that is, using an aqueous solution that is a non-solvent for cellulose ester. The extraction process can be carried out in conventional equipment, such as a water bath containing hot water. The desired substance permeability and ultrafiltration performance are obtained by extracting polyhydric alcohols and glycerin derivatives at a temperature of 80 to 99° C. when using an aqueous solution. The mechanism by which high permeability is developed in the hollow fiber membrane by treating the aqueous solution at a high temperature is thought to be due to the aggregation of cellulose ester molecules during the treatment of the high temperature aqueous solution. Ru. When extracted at low temperatures, the microphase-separated structure generated during the spinning process is dominantly expressed. However, this alone does not provide sufficient permeability to medium-high molecular weight substances with a molecular weight of several tens of thousands, and hollow fibers with desired fractionation characteristics cannot be obtained. On the other hand, by performing extraction treatment at high temperature, products with excellent fractionation characteristics can be obtained. This is because when the processing temperature increases, the swelling and dissolution effects of the aqueous solution increase, and at the same time, the thermal movement of cellulose ester molecules becomes active. This is thought to be due to the formation of loosely packed molecular chains near molecules with a low degree of esterification. However, if the extraction temperature exceeds 100°C, industrial production will be disadvantageous in terms of energy consumption and the high temperature and pressure of the extraction means. As a result of intensive efforts, the present invention has succeeded in producing a cellulose ester-based hollow fiber with excellent fractionation characteristics for medium-high molecular weight substances and a method for producing the same by combining the polymer composition and extraction temperature conditions. The cellulose ester hollow fibers obtained by the present invention have excellent permselectivity and can be used in fields such as medicine, food industry, and wastewater treatment. Since cellulose ester has excellent biocompatibility and safety, it is particularly useful as a hollow fiber material for artificial organs in the medical field. The present invention will be illustrated below by way of examples. Example Cellulose diacetate flakes with an acetylation degree of 55.0% were made into a powder using a pulverizer, and 100 parts by weight of this powder was uniformly mixed with polyethylene glycol having a molecular weight of 400 and polyether shown in the table while changing the weight ratio to make a liquid 130. The weight parts were mixed using a ribbon blender at 50°C to obtain a homogeneous mixture of cellulose diacetate, polyethylene glycol and polyether. The mixture was then melted at 150-200°C using a Ruder extruder and extruded and cut into chips. This was dried in a dryer until the moisture content was 0.5% or less. These dried chips were melt-spun into hollow fibers by extruding nitrogen gas from the inner port of the double tube type spinneret and extruding the melt from the outer port at a spinning temperature of 175°C using a melt spinning machine equipped with a double tube type spinneret. It also had good spinnability and could be easily rolled up. Subsequently, the obtained hollow fibers were placed in a hot aqueous solution at 90-95°C for 15 seconds, then in a hot water bath at 55°C for 6 seconds, then 45%
Polyethylene glycol and polyether were extracted from the hollow fibers by continuous immersion in glycerin solution at 55° C. for 15 seconds to obtain cellulose diacetate hollow fibers. In order to measure the water permeability and molecular weight fractionation properties of hollow fibers, we made a module by bundling 200 fibers and fixed both ends with thermosetting urethane resin, and measured the water permeability and molecular weight fractionation properties of hollow fibers using the following method. protein,
Plasma albumin permeability was measured. (1) Water permeability is determined by filling a module with water, sealing one end of the module, attaching a graduated glass tube filled with water to the other end, and pressurizing the water surface in the glass tube to 100 mmHg. The velocity of the falling water surface was measured at 25°C, and the amount of water permeating through the fiber wall was determined in ml/m ² ·mmHg ·Hr. (2) Measurement of molecular weight fractionation characteristics Molecular weight fractionation characteristics can be measured using inulin (molecular weight fractionation characteristics).
5000) When aqueous solutions (37°C) with dextran average molecular weights of 10,000 and 40,000 were flowed through the module incorporating the hollow fibers at a constant flow rate of 200 ml/min under a pressure of 150 mmHg, they permeated through the fiber walls. The transmittance was calculated using the following formula from the concentration of the aqueous solution and the concentration of the stock solution. Transmittance (%) = Concentration of the measured substance after permeating the hollow fiber wall / Concentration of the stock solution of the measured substance × 100 To measure the permeation inhibition rate of plasma proteins and plasma albumin, use fresh pig blood and pass through the fiber wall in the same manner as above. The transmittance was calculated using the above formula from the concentrations of protein and albumin in the permeating plasma components and the respective concentrations of the original blood, and the permeation inhibition rate was determined from (100 - transmittance).
The results obtained are shown in the table. As a comparative example for the present invention, a mixture of cellulose diacetate and polyethylene glycol (molecular weight 400), a mixture of cellulose diacetate and polyethylene glycol, and a mixture of cellulose diacetate and polyethylene glycol (molecular weight 400) were prepared in the same manner as in Examples 1 to 4. Hollow fibers were made from a mixture of glycerin, etc., and their spinnability was examined, as well as their water permeability and fractionation characteristics for medium- and high-molecular weight substances. The results are shown in the table below.

【table】

[Table] As shown in the table, the hollow fibers of Examples 1 to 4 obtained by the method of the present invention have better water permeability and molecular weight in the range of 5,000 to 70,000 than Comparative Examples 1 to 6. It is clear that the fractionation characteristics of medium and high molecular weight substances are all excellent. As shown in the examples, it is clear that a high extraction treatment temperature is superior. In addition, the poor spinnability described in Examples and Comparative Examples refers to the narrow temperature range in which spinnability occurs, and the change in melt viscosity in that temperature range is large, making it difficult to stably wind up fibers of a desired shape. This indicates that it is extremely difficult to do so.

Claims (1)

[Scope of Claims] 1. 100 parts by weight of cellulose ester, X parts by weight of a water-soluble polyhydric alcohol having a plasticizing action, and Y parts by weight of at least one type from the group of polyethers in which at least one residue is composed of glycerin. Each formula below
(i) to (iii) 70≦X+Y≦200 (i) 60≦X≦140 (ii) 10≦Y≦80 (iii) Melt spinning a mixture in the form of hollow fibers,
After that, extraction treatment was carried out with an aqueous solution at 80 to 99℃, and the ultimate permeability coefficient KUFR was 10.
~40ml/ ^m2・mmHg・Hr, plasma protein permeation inhibition rate is 88% or more, plasma albumin permeation rejection rate is 89% or more, and inulin permeation rate is 90% or more.
% or more, and the permeability of dextran having a molecular weight of 10,000 is 60% or more.