Since 1981 we have been reporting our clinical results with protein permeable hemodialysis using a special filter capable of removing small molecules to low molecular weight proteins. This filter and dialyzer began to see widespread use in Japan as of 1985 for application as a protein-permeable membrane filter or dialyzer, so much so that over 40% of present hemodialysis is performed with protein-permeable membrane dialysis. Protein-permeable membrane dialysis has brought a marked reduction in symptoms such as neuropathy anemia and pruritus, which conventional dialysis could not overcome, and it has also reduced the arthralgia caused by dialysis-induced amyloidosis. In termes of serum β₂-M removal. protein-permeable membrane dialysis has a 40-50% per treatment, and protein-permeable membrane diafiltration up to 60-70% per treatment. Through the use of a protein-permeable membrane filter for continuous hemofiltration or hemodiafiltration, the β₂-M can be consistently maintained below 20m/l with 5-10l/day of filtration, and more favorable conditions can be maintained for small molecules, electrolytes and acid base balance than by the usual intermittent therapy.

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The mechanism of structure formation and the characteristic of solute permeation on regenerated cellulose hollow fiber membrane for hemodialysis are discussed.
Coagulation process of cuprammonium cellulose solution is dominated by the interfacial potential, caused at the interface between cellulose solution and coagulant solution, and thus the coagulation mechanism can be classified into three types.
They are copper ion removal type, Normann reaction type and ammonia removal type. According to these dynamics it is possible to generate the various type of membrane pore structure. And the characteristics of solute permeation of the membrane is to be controlled by the pore structure of the membrane.
Thus the characteristics of solute permeation is to be controlled by the coagulation process.
And how to characterize the generated pore structure of the membrane is indispensable for the membrane architecture. Validity of the image analysis of SEM for the characterization of pore structure of the membrane is shown. Futhermore, SAXS analysis has been developed and studied for the analysis of pore structure, the possibility of this method is also discussed.

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By combining a polyacrylonitrile (PAN) -polyethyleneoxide (PEO) membrane with ionically heparin-bound catheter, tubing, and module header, a totally antithrombogenic continuous ultrafiltration system (ACUS) was developed. Antithrombogenicity of PAN-PEO hollow fiber membrane was considered to be due to the presence of highly concentrated PEO near the inner surface of the membrane wich has a finely dispersed microstructure. ACUS was clinically applied to 24 patients without systemic anticoagulation and one PAN-PEO filter functioned for average 32 hrs without deteriorating their bleeding tendencies.

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The recent advancement in blood purification, including artificial Kidney and plasma separation techniques, is remarkable. In the course of this development, various types of membranes have played an important role.
In developing a plasma separator, due consideration should be given to the module design as well as to that of the membrane so that a high shear rate can be obtained under a given set of operating conditions. Use of plasma sepation membrane makes it possible to separate plasma components from blood components almost completely. Meanwhile, plasma fractionation membranes are capable of separating one solute from another satisfactorily, such as IgM fractions from albumin or cholesterol from albumin, if they are different enough in size. However, it remains to be shown whether some solutes of almost the same size, like albumin and IgG fractions, can be satisfactorily separated with the membrane alone.
Since blood purification is applied for living organisms, the safety and blood compatibility of the membranes are of the most importance. Almost all membranes used for blood purification are made of general-purpose polymeric materials, which have been originally developed for industial use. Opinions are divided on the interaction of the blood and the membrane. In developing new membranes for blood purification, it is one of the most important theme whether the membrane should be as inactive as possible or it should active the blood positively.
At present, plasma separation is conducted on the principle of using the difference of size in solutes, but there is a limit to this principle. To solve the problem, new plasma separation procedures combining physical and chemical methods, like electric charge, adsorption and temperature, are now under development by some researchers.

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This article reviewed the recent advance in the development of a new type of oral drug delivery system with a, timer, function, and the sigmoidal release system (SRS) is introduced as one of the most promising system for the time-controlled drug delivery, which was recently developed in our laboratory.
Eudragit RS has been widely used as a controlled release barrier of pharmaceuticals. Because this polymer contains a small amount of quarternary ammonium group in its lipophylic polymer chain, the film, when prepared from aqueous suspension, exhibits a distinctive structure and can electrostatically interact with various organic acids. In fact, the hydration and hence the drug permeability of the Eudragit RS film was found to be drastically enhanced in various organic acid solutions. Thus, the SRS was designed on the basis of the physicochemical interaction between Eudragit RS film and organic acids. This technology was applied for many types of drugs, in which succinic acid was used as a release enhancer. In the dissolution study, each of SRSs provided a very unique S-shaped dissolution profile in water with an extended lag time prior to the beginning of drug release. The lag time and the release rate thereafter were both controllable by altering the amount of coating and the loading amount of succinic acid in the drug layer, respectively. The in vivo performance of SRS was also examined by a series of beagle dog studies, and it was found that the in vivo lag time was well coincident with in-vitro lag time in every case.

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There has been a demand for such hemodialysis membranes of better biocompatibility the use of which would reduce the incidence of complications in patients who have been under long hemodialysis treatment.
We have developed a surface modification technique, consisting of forming efficiently a synthetic polymer layer on the inside of the regenerated cellulose hollow fiber without impairing fiber performance. Our newly-developed membrane has an excellent biocompatibility by modifying the inner surface and by immobilizing Vitamin E (α-tocopherol), which serves as an antioxidant, to the modified surface.

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Dielectric measurement coupled with measurement of steady voltage-current (V-I) characteristics was carried out on cation-exchange membrane CMV and anion-exchange membrane AMV immersed in aqueous NaCl solution under application of de bias voltage. A marked dielectric relaxation was observed when the bias voltage exceeds the voltage that yields the critical current density (CCD). The dielectric relaxation was analyzed on the basis of the dielectric model which consists of a Nernst diffusion layer, a thin salt depletion layer and a bulk solution phase. The values of the thickness of the diffusion layer were 0.062 cm for the CMV membrane and 0.026 cm for the AMV membrane, being in good agreement with those values, 0.05 cm for the CMV membrane and 0.03 cm for the AMV membrane, calculated from the values of CCD obtained by the V-I characteristics. The thickness of the salt depletion layer is 0.7-1.6 μm for the both ion-exchange membranes and the conductivity of the depletion layer is 0.2-0.25 μSem^-1 for the CMV membrane and 0.6-0.8 μScm^-1 for the AMV membrane. The conductivity of the depletion layer at the AMV membrane/solution interface is higher than that at the CMV membrane/solution interface, which may suggest that the water splitting takes place at the AMV membrane/solution interface.

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The biocompatibility and the mechanism of structure formation on regenerated cellulose hollow fiber membranes for hemodialysis are discussed. The biocompatibility can be improved by grafting polyethylene glycol chains to hydroxyl groups of regenerated cellulose. The coagulation process of cuprammonium cellulose solution is mainly dominated by the interfacial potential at the interface between cellulose solution and coagulant solution. And the performance of solute permeation of the membrane can be controlled through the coagulation process of cellulose solution. Consequently we have achieved the biocompatible and high permeable cellulose membrane.

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