Polivinilpirolidon Katkılı Polisülfon Membranlarda Üre Ve Kreatinin Difüzyonu / Tubanur Karakaş

Abstract

Hemodiyaliz yarı geçirgen bir membran aracılığıyla akut veya kronik böbrek yetmezliği çeken hastaların kanı ile normal kan elektrolitlerini içeren diyalizat çözeltisi arasında gerçekleşen bir değiş tokuş olayıdır. Bu değişme olayı hastanın kanından zehirli atık maddeleri uzaklaştırır ve aynı zamanda elektrolitleri de normale yakın bir biçimde dengeler. Hemodiyaliz tedavisi haftada birkaç kez düzenli olarak tekrarlanırsa teknik olarak böbrekleri artık çalışmayan hastaya sınırsız yaşama olanağı verebilir. Bu çalışmada polivinilpirolidon(PVP)/polisülfon(PS) polimerlerinin harmanlanması ile hemodiyalizde kullanıma uygun membranların hazırlanması, hazırlanan membranların üre ve kreatinin geçirgenliklerinin belirlenmesi ve membran hazırlama şartlarındaki değişikliklerin membran yapısına etkilerinin incelenmesi amaçlanmıştır. Geçirgenlik ölçümleri için arasına test edilecek membranın yerleştirildiği iki adet cam hazneden oluşan bir diyaliz hücresi kullanılmıştır. Bu hücrenin bir haznesine üre veya kreatinin bulunan metabolit çözeltisi diğer haznesine de deney sırasında sürekli sirkülasyonu sağlanan saf su konulmuştur. Deney sırasında metabolit çözeltisinden belirli zaman aralıklarında numuneler alınarak membrandan geçen üre ve kreatinin konsantrasyonları bir UV spektrofotometre yardımıyla belirlenmiştir. Deneylerde kullanılan PVP katkılı PS membranlar faz dönüşümü yöntemi uygulanarak hazırlanmıştır.Çözücü olarak N-metilpirolidon (NMP), çöktürme ortamı olarak ta saf su kullanılmıştır. Membran hazırlama çalışmalarında membran yapısına ve geçirgenliğine etki edebilecek üç önemli parametre incelenmiştir. Bu parametreler döküm çözeltisindeki PVP/PS oranı, çöktürme banyosunun içeriği ve gliserinleme son işlemidir. Yapılan bütün deneylerde üre geçirgenliğinin kreatinin geçirgenliğinden büyük olduğu gözlenmiştir. Üre molekülü kreatinin molekülüne kıyasla daha küçük olduğundan üre difüzyonunun kreatinin difüzyonundan daha hızlı olması beklenen bir sonuçtur. Membran matrisine gözenek oluşturucu madde olarak katılan PVP miktarı arttıkça geçirgenliklerin arttığı saptanmıştır. Deneylerde üre ve kreatininin membran malzemesi ile etkileşime girerek membran yüzeyinde adsorplandığı düşünülmektedir. Gliserinleme işleminin membranın gözenek yapısını genişleterek geçirgenliği arttırdığı görülmüştür. Çöktürme ortamına (su) çözücü (NMP) katılmasının membran geçirgenliğini azalttığı, aynı ortama şişme sağlayıcı bileşenin (izopropilalkol) katılmasının ise geçirgenliği arttırarak üre adsorpsiyonunu azalttığı gözlenmişir.

Since ancient times people have believed that diseases result from impurities in the body. Methods of purifying the organism and correcting the body's humoral balance have been disputed throughout the centuries. The blood purification health maintenance program of the 17 th and 18 th century for the well-to-do was adequate purgation every week, application of a strong emetic once a month, and blood-letting twice a year, in the spring and in the fall. In our modern times extra-corporeal blood purification techniques like hemodialysis are basically used to treat people which suffer from kidney failure. Hemodialysis is applied to the treatment of the patient which suffer from chronic and acute kidney failure to remove toxic metabolic wastes like urea, uric acid and creatinine from their blood. During a hemodialysis run arterial blood is passed over one side of the artificial kidney membrane, while a dialysate solution containing a buffered and isotonic mixture of dextrose and salts is circulated on the other side. The composition of the dialysate is set to maintain the correct ionic balance in the blood. The concentration difference across the membrane between blood and dialysate streams causes small solutes to diffuse through the membrane while larger molecules like proteins and blood cells are rejected. An additional aim of hemodialysis is the removal of excess body fluid, and therefore the process is also driven by a small pressure difference, typically of 0.2 bar. This pressure difference is high enough to produce 1-4 liter urine which is not produced by the kidney of the patient. People suffering from chronic and acute kidney failure should preferably have their blood cleaned continuously. For practical and economical reasons, dialysis is performed only two or three times a week. A typical hemodialysis treatment lasts from 4 to 6 hours. Approximately 460000 kidney failure patients are treated with hemodialysis in the world and the number of patients is increasing by 7 to 8 percent annually. During clinical hemodialysis, two physical processes are in operation simultaneously. The first process, diffusion, describes the movement of solutes, such as urea, creatinine, from the blood compartment to the dialysate across a semipermeable membrane, and the movement of substances such as calcium and bicarbonate from the dialysate into the blood. The driving force for this movement is the concentration gradient across the membrane. The amount of material that diffuses or fluxes across the semi permeable membrane is a function of the concentration gradient, the surface area of the membrane, and the diffusivity of the membrane which is a unique property dependent on the membrane material and temperature. The other principle operating during hemodialysis is convection or ultrafiltration. This involves bulk movement of solvent and solute across the membrane. Fluid moves under hydrostatic pressure from the blood to the dialysate compartment. The quantity of fluid ultrafiltered depends on the pressure difference between the blood and dialysate compartments. This transmembranes pressure (TMP) can be controlled by varying the pressure in the dialysate or blood compartments. Decreasing dialysate pressure will increase ultrafiltration. The rate of ultrafiltration is dependent on the pressure gradient across the membrane, the surface area of the membrane, and the ultrafiltration properties of the membranes. The transport of large molecular weight substances increase with increasing ultrafiltration rate but the main purpose of ultrafiltration is to remove excess body fluid. The primary purpose of the dialysis treatment is to remove the metabolic wastes which are normally eliminated by the kidney and to maintain mineral and water balance. There are a large number of materials which accumulate during renal failure other than urea, creatinine, and uric acid which may be important to remove but not known at this time. In the past there was a large search for 'uremic' toxin but now it appears evident that the uremic syndrome is probably not caused by the accumulation of a single substance, but is most likely the results of presence of a number of toxic agents. There are currently two views: Babb and Schribner at the University of Washington feel that the most important uremic toxins have a molecular weight in the range of 1000-2000 Dalton, so-called 'middle molecules' while many others feel that the major toxins are much smaller, being in the range of urea (100-200 Dalton). In hemodialysis, most important and useful characteristics of a dialyzer are clearance and ultrafiltration coefficient. Clearance describes the amount of blood that can be completely cleared of a given solute in unit time. Thus, if 100 ml of blood per minute is completely cleared of urea as it passes through the dialyzer, the dialyzer is said to have an urea clearance of 100 ml/min. The ultrafiltration coefficient (KUf) is the number of milliliters of fluid transferred across the membrane per hour when 1 mm Hg TMP is applied. For the patient who tends to gain large amounts of weight between treatments, it is necessary to use a dialyzer with an ultrafiltration capability high enough to allow removal of fluid gained. The dialyzer membrane is the main determinant of what and how much is removed during dialysis. As the most important component of the dialyzer, dialysis membranes are generally classified into cellulosic and non-cellulosic types. In the literature on dialysis membranes and their clinical applications, cellulosic membranes are referred to as that class of membranes that is based on the cellulose molecule. This molecule is XI synthesized in nature from a glucose monomer and may be used directly as a membrane polymer in a highly purified form. In addition to purified cellulose, chemically modified cellulose is also used as a basic polymer for dialysis membranes. The most commonly used cellulosic membranes are cellulose acetate, hemophan, cuprophan, and other modified cellulose. A second class of membranes is commonly referred to as synthetic. They are made of man-made non-cellulosic polymers. Examples of synthetic polymers are polysulfone, polyacrylonitrile, polymethylmethacrylate, and polypropylene. A common property of these membranes is that their monomer is not found in nature. Synthetic membranes have higher ultrafiltration rates and in general more biocompatible than cellulosic membranes. The properties of membranes with optimal performance in hemodialysis can be defined as follows: (a) The active membrane layer should be as thin as possible to obtain high transmembrane fluxes. (b) The porosity of the membrane at the surface as well as in the matrix should be as high as possible to provide high transmembrane fluxes. (c) The membrane structure should guarantee a certain minimum mechanical strength. (d) The diffusion coefficient in the membrane should be high. (e) The membrane should have good blood compatibility. (f) The pore size distribution should be as narrow as possible to obtain a sharp molecular weight cut-off. (g) All materials of the final membrane have to be nontoxic and chemically inert. The goal of this study is to prepare and characterize polysulfone membranes for hemodialysis applications and to investigate the effect of preparation parameters on the separation properties of the membranes and their structure. For this purpose permeabilities of urea and creatinine through polysulfone membranes were studied using a dialysis test cell. The dialysis cell is made from two detachable glass compartments and the membrane under investigation is placed between the two compartments. Urea or creatinine solution is placed in the left-hand side of the cell and distilled water is circulated in the right-hand side using a peristaltic pump. During the experiments samples from the left-hand side of the cell were taken out periodically. For the estimation of urea and creatinine concentration a UV spectrophotometer was used. All experiments were carried out in 37 °C in a water bath and before the start of each experiment, urea and creatinine solutions and the membrane was preconditioned at the required temperature. The membranes prepared in this study are polysulfone (PS) based asymmetric polymeric membranes. Polysulfone is used as the primary polymeric component of the membrane because of such beneficial characteristics as thermal stabilitv, resistance to XII acid, alkali, and salt solutions, high mechanical strength, etc. Polyvinylpyrrolidone (PVP) is added to the polysulfone polymer in order to modify the structure and surface characteristics of the polysulfone membranes. The membranes used in the experiments were prepared by phase inversion technique. Casting solutions were prepared by dissolving appropriate amounts of PS and PVP in N-methylpyrrolidone (NMP). The solution was mixed with a mechanical mixer to obtain a homogenous solution Then the casting solution was cast in the form of a thin film of a certain thickness on a glass plate using a casting knife. The cast films were then immersed a coagulation bath to obtain asymmetric structure. After coagulation bath, membranes could be soaked in a 20% (vol.) glycerine bath to fill the pores of the membranes with this hydrophilic fluid so as to enhance pore wetting. Finally membranes were dried at 60 C for 20 minutes. The effect of three significant preparation parameters on the permeability of membranes have been investigated: the PVP/PS ratio in the casting solution, the composition of the precipitation bath and glycerinization post treatment. All membranes exhibited higher permeabilities for urea than creatinine, as expected. Because the movement of molecules by diffusive transport is inversly proportional to their molecular weight urea due to it's lower molecular weight should exhibit faster permeation rate than creatinine. It was observed that urea and creatinine were adsorbed and accumulate on the membrane, for most of the membranes prepared. Adsorption of urea and creatinine to membrane can be explained by electrostatic interaction between membranes and the molecules. Accumulation of urea and creatinine at the membrane surface is called concentration polarization and is defined as the formation of a concentration boundary layer near the membrane. This phenomena delays the permeation of molecules through the membrane and decreases the permeabilities. Membranes prepared from casting solutions of six different PVP/PS ratios (0, 0.25, 0.40, 0.60, 0.80, 1.0, by weight) exhibited higher urea and creatinine permeabilities as the PVP/PS ratio in the casting solution were increased. Higher PVP/PS ratio in the casting solution results in higher porosity in the membranes.This is due to the fact that PVP is a water soluble polymer and diffuses into the coagulation bath since coagulation bath containing water. When membranes were soaked in 20% (vol.) glycerine bath, they exhibited increases in urea and creatinine permeabilities. Glycerinization post treatment enlargers the pores of the membranes and therefore enhances the permeabilities. The addition of solvent (NMP) into the precipitation bath decreased both urea and creatinine permeabilities. This behavior is in accordance with the expectation of small XIII pore structure due to the decreased precipitation rate when solvent is added into the precipitation bath. Indeed, it is even possible to change from porous to nonporous membrane by adding solvent to the coagulation bath. It was observed that the permeabilities of urea and creatinine of membranes precipitated in a coagulation bath containing 40% NMP were slightly more than the permeabilities of urea and creatinine of membranes precipitated in a coagulation bath containing 20% NMP. This situation can be explained by two effects: when solvent is added into the coagulation bath, delayed demixing tends to produce nonporous membranes with thick and dense top layers, whereas low interfacial polymer concentration tends to produce more open top layers which increases the permeabilities of molecules. Effect of addition of a swelling agent (Isopropylalcohol) into the precipitation bath was investigated by preparing membranes from casting solution of PVP/PS=T ratio. Isopropylalcohol (IPA) was added into the precipitation bath, both urea and creatinine permeabilities increased and the highest permeabilities of urea and creatinine were obtained in this case. The most important result was that the accumulation or adsorption of urea on the membrane surface was not observed. When IPA was added into the coagulation bath, it swells the polymer. The presence of the swelling agent acts in favor of the introduction of the precipitation medium into the casting solution, in exchange for the pore-former (PVP) and solvent (NMP) resulting in the formation of a membrane with high porosity. For creatinine, similar situation was not observed. It can be concluded that the pore size of membranes prepared from the coagulation bath containing IPA as a swelling agent was suitable for faster urea, but not creatinine. So the creatinine molecules accumulate on the membrane surface as occurred for the membranes prepared without presence IPA in the coagulation bath. XIV