JP4825085B2 - Adsorbent for blood purification or plasma purification, module filled with the adsorbent, and blood or plasma purification method using the module - Google Patents

Description

  The present invention relates to an adsorbent for blood purification or plasma purification, and more specifically, a pathogenic protein such as bilirubin in blood or a pathogenic protein such as bilirubin in plasma obtained by separating a formed component from blood efficiently. The present invention relates to an adsorbent to be removed by adsorption. Furthermore, the present invention relates to a module filled with the adsorbent and a blood or plasma purification method using the module.

  Red blood cells that have aged in vivo are destroyed by the reticuloendothelial cells of the liver and spleen, and hemoglobin in the blood cells changes to free bilirubin (hemobilylbin). This free bilirubin (hereinafter sometimes referred to as indirect bilirubin) is fat-soluble, and when it increases in the blood, it deposits while dissolving in lipids in the nucleus of brain cells and exerts neurotoxin, causing nuclear jaundice To do. In the human body, albumin and a part of α2-globulin bind to this free bilirubin and are carried on the blood to the liver for detoxification. That is, free bilirubin receives glucuronic acid (GA) from uridine diphosphate glucuronic acid (UDPGA) by the action of glucuronic acid converting enzyme, which is one of the liver enzymes in the liver, and smooth endoplasmic reticulum undergoing microsomal division in liver cells. Is subjected to glucuronide conjugation by bilirubin UDP glucuronyltransferase contained in, and becomes bilirubin glucuronide (a kind of conjugated bilirubin, and the conjugated bilirubin may be directly referred to as bilirubin hereinafter) and becomes water-soluble (detoxification). In general, two molecules of glucuronic acid bind to one molecule of bilirubin to form bilirubin diglucuronide (conjugated bilirubin, directly bilirubin), which is further excreted from the hepatocytes into the bile duct and duodenum, and the total bilirubin concentration in the blood of healthy subjects (The sum of indirect bilirubin and direct bilirubin) is maintained in an almost constant concentration range, although there are fluctuations due to diet, muscle work, and the like. However, if discharge to the duodenum is inhibited due to liver parenchymal disorder or bile duct obstruction, the total bilirubin concentration in the blood rises, manifests jaundice and develops hyperbilirubinemia, somnolence from consciousness disorder, In addition, it is not uncommon for the patient to become comatose and to develop a renal disorder that progresses from oliguria to anuria.

  As an initial blood purification method for such symptoms, direct blood adsorption with activated carbon (Direct hemoperfusion) was performed, but although direct bilirubin was removed, indirect bilirubin was insufficiently removed, and the therapeutic effect was sufficient. Could not be raised.

Subsequently, a method of easily separating blood into a tangible component and plasma was established by a blood centrifugation method (Hemonetic) and a plasma separation method using a membrane such as a hollow membrane. Along with this, even if there is irritation (coagulation promoting action) to platelets, bilirubin can be efficiently removed from the separated plasma, and the adsorbent does not significantly affect the plasma coagulation-fibrinolysis system. The search continues. Under such circumstances, based on the concept that an anionic adsorbent would be effective for the two carboxylic acids in the molecule of free bilirubin, the styrene / divinylbenzene copolymer currently has amino groups as active sites. Anionic ion exchange resins having (NH ₂ ), quaternary ammonium groups (N ^+. (CH ₃ ) ₃ .Cl ⁻ ) and the like are in clinical use. However, such ion exchange resins are also poorly compatible with plasma, and in order to improve it, the above disadvantages can be avoided by coating with a blood compatible polymer material such as polyhydroxymethacrylate (PHEMA). An improved method is adopted (Japanese Patent Laid-Open No. 63-275351, Shuhei Nakaji et al.). However, this treatment causes the disadvantage of reducing the pore volume and surface area of the ion exchange resin that contributes to the removal of bilirubin. In addition, the ion exchange resin in water does not have sufficient mechanical strength, and there may be a disadvantage that it is crushed during use. Furthermore, it is not possible to employ a method other than the high-pressure steam sterilization method for sterilization, which is an essential condition for clinical use, and the resistance to the sterilization conditions (130 ° C., 10 minutes) is not sufficient.

  Therefore, the inventors of the present invention first overcomes the above-mentioned drawbacks of the ion exchange resin, and uses titanium dioxide having specific physical properties as an adsorbent that has improved properties even for a treatment method using bilirubin removal using the activated carbon. Proposed (see Patent Document 1).

JP 2001-245973 A

Patent Document 1 discloses that titanium dioxide obtained by firing at 300 to 600 ° C. has a specific surface area of 20 to 80 m ² / g, an average pore diameter of 150 to 200 kg, and a pH value of 6 to 7.5. Titanium dioxide has physical properties, has high adsorption performance for bilirubin, especially direct bilirubin, and coagulation characteristics when contacted with human fresh plasma are substantially the same as when not contacted (blank). Although described to be compatible with plasma, the adsorption performance of indirect bilirubin is not sufficient, and further improvement is desired.

In order to improve the indirect bilirubin adsorption performance of titanium dioxide, the present inventors focused on the surface charge of titanium dioxide, whereas the isoelectric point of normal titanium dioxide is about 5 to 6 in water, For example, aluminum oxide can be supported and the isoelectric point of titanium dioxide can be controlled to 7.5 or more, and it has a positive surface charge in blood or plasma that is actually used, and therefore adsorbs indirect bilirubin. The present invention has been completed by finding out that it can be easily performed.
That is, the present invention is an adsorbent for blood purification or plasma purification characterized by containing titanium oxide having a positive surface charge in blood or plasma.

  Since the adsorbent of the present invention has excellent indirect bilirubin adsorption performance, it is useful for adsorption removal of pathogenic proteins such as bilirubin in blood or plasma. Further, since the adsorbent of the present invention has compatibility with blood or plasma, and has sufficient mechanical strength and resistance to sterilization, it is suitable for purification of blood by the direct blood adsorption method. It is also suitable for the purification of plasma obtained in

It is important that the adsorbent for blood purification or plasma purification of the present invention contains titanium oxide having a positive surface charge in blood or plasma, and the indirect bilirubin is made of titanium oxide by holding the positive charge. Adsorbs quickly on the particle surface.
In order for titanium oxide to maintain a positive surface charge in blood or plasma, the isoelectric point of titanium oxide in water needs to be higher than the pH of blood or plasma. Since the pH of blood and plasma is usually 7.4, if the isoelectric point of titanium oxide is at least about 7.5, a positive surface charge can be maintained in blood or plasma, and at least 7.8. If it is about, the amount of indirect bilirubin adsorbed is increased, preferably about 8.0, more preferably about 8.5. The upper limit value of the isoelectric point is not particularly limited, but a high isoelectric point of about 14 which is a theoretical upper limit value is often not required. Therefore, the upper limit value of the isoelectric point is preferably about 13, more preferably about 12. Preferably, about 11 is more preferable. The isoelectric point is the pH at which the zeta potential of a dispersion in which titanium oxide is dispersed in water is 0, and is a normal method using a zeta potential measuring device (for example, Otsuka Electronics Co., Ltd. (ELS-6000)). Can be measured.

The titanium oxide of the present invention includes, in addition to titanium dioxide, hydrated titanium dioxide which is a hydrate of titanium dioxide, hydrous titanium dioxide, metatitanic acid, β-titanic acid, and titanium hydroxide. These include titanium hydroxide, orthotitanic acid, and alpha titanic acid. They are a group of compounds such as a titanium atom and an oxygen atom, and are similar in composition, and are usually handled as a group of compounds. This titanium oxide may contain anatase-type crystal, rutile-type crystal or brookite-type crystal when viewed in X-ray, and includes amorphous titanium oxide which does not have a clear peak in X-ray diffraction. It may be.
Ordinary titanium oxide has an isoelectric point in water of about 5 to 6 and the pH of blood and plasma is about 7.4, so it is usually negatively charged in blood or plasma. The titanium oxide having a positive surface charge in the blood or plasma of the present invention is obtained by supporting a metal oxide or metal hydroxide having a relatively high isoelectric point on the titanium oxide particle surface, or The isoelectric point of the titanium oxide is controlled within the above range by treating the surface of the titanium oxide with an alkaline solution.

  Regarding the metal oxide and metal hydroxide supported on the titanium oxide particle surface, the isoelectric point of the metal oxide has been investigated conventionally, and the titanium oxide particle surface supported on the titanium oxide particle surface It is also known to control the surface charge, and it is possible to select a supported material and a supporting method as appropriate with reference to such documents and techniques (titanium oxide-physical properties and applied technology, Manabu Kiyono, Gihodo Publishing Co., Ltd.) Company, 1991, 60-62, 225-228; Journal of Coatings Technology, Vol. 61, No. 776, P57-P63, September, 1989; Coloring Material, 40 (1967), P163- P166; USP 3,015,573; 3,076,719). For example, since the isoelectric point of aluminum oxide is 8-9, zinc oxide is 9, and magnesium oxide is 10, and the hydroxides thereof are considered to be the same, at least one element selected from aluminum, zinc, and magnesium These metal oxides and / or metal hydroxides can be preferably used. On the other hand, since the isoelectric point of silicon oxide is about 2 to 3 and tin oxide is 5, these metal oxides are not suitable for use, but the isoelectric point varies depending on the loading method. The surface charge of the object may change to a suitable range. For this reason, it is necessary to actually carry a metal oxide and / or a metal hydroxide on the surface of titanium oxide particles and measure its isoelectric point to judge suitability. In addition to metal oxides, metal oxides include hydrated metal oxides and hydrated metal oxides that are hydrates of metal oxides.

  By supporting metal oxide and / or metal hydroxide, the surface charge of titanium oxide can be controlled and the isoelectric point can be in an appropriate range, and the supported metal oxide and metal hydroxide are also indirectly It has the ability to adsorb pathogenic proteins such as bilirubin and may have an auxiliary adsorption effect. The supported amount can be appropriately set to an amount that can be adjusted to a desired isoelectric point, for example, about 0.1 to 40% by weight with respect to titanium oxide, preferably 1.0. About 35% by weight, more preferably about 5.0-30% by weight. If the loading amount is more than 40% by weight, the surface of the titanium oxide is covered with a supporting material such as a metal oxide and the adsorption active sites are reduced. Is not preferable because it becomes insufficient.

In the present invention, a preferred embodiment of the titanium oxide to be used preferably contains more rutile type titanium dioxide crystals having excellent thermal stability and good safety and biocompatibility to living tissue. More preferably at least 50% by weight, more preferably at least about 60% by weight, more preferably at least about 70% by weight, based on the product itself (supported metal oxide, titanium oxide excluding metal hydroxide). Preferably, almost all of at least about 90% by weight is rutile type titanium dioxide. In addition to the rutile type titanium dioxide crystal, anatase type crystal, brookite type crystal and amorphous titanium dioxide having no clear peak in X-ray diffraction may be contained. The respective contents of the rutile, anatase, and brookite crystals can be determined by X-ray diffraction.
In addition, since the adsorption performance of indirect bilirubin and the adsorption performance of direct bilirubin are high, the titanium oxide to be used preferably has a large specific surface area, and further, metal oxide or metal hydroxide is formed on the titanium oxide particle surface. Even in a state of supporting the carbon, those having a large specific surface area are preferable, and those having a specific surface area of about 10 to 250 m ² / g are more preferable, and about 15 to 150 m ² / g are more preferable. The specific surface area is measured by the BET method. The average pore diameter is preferably about 150 to 200 mm as described in JP-A No. 2001-245973.

  The titanium oxide used by this invention can use what was obtained by the well-known method. Specifically, (1) a method of hydrolyzing or neutralizing an inorganic titanium compound such as titanium sulfate, titanyl sulfate, titanium chloride, and titanium nitrate, or an organic titanium compound such as titanium alkoxide and titanate, (2) A method in which the suspension of the product obtained by the method (1) is heated in a temperature range of about 40 to 250 ° C. In this case, hydrothermal treatment performed in an autoclave pressure device is preferable in order to carry out at a boiling point or higher. 3) A method of firing the products obtained in the above (1) and (2) in a temperature range of about 150 to 900 ° C. Furthermore, commercially available sulfuric acid method, titanium dioxide pigment obtained by chlorine method, ultrafine titanium dioxide obtained by wet hydrolysis method, flame hydrolysis method and the like can also be used.

In order to carry a metal oxide and / or a metal hydroxide on the surface of titanium oxide particles, a known surface treatment technique of titanium oxide can be used. Specifically, a method of adding a component to be a support to a suspension of titanium oxide and neutralizing or hydrolyzing it to precipitate can be used. The product thus obtained may be filtered, washed and dried at a temperature of about 80 to 150 ° C. as necessary. Further, the suspension of the product obtained by neutralization or hydrolysis may be heated in a temperature range of about 40 to 250 ° C. if necessary, or the product may be heated to 150 to 900 as necessary. You may bake in the temperature range of about degreeC.
After producing the supported titanium oxide in this way, dry pulverization may be performed by a known method as necessary. For the dry pulverization, an impact pulverizer such as a hammer mill or a pin mill, a grinding pulverizer such as a pulverizer, an airflow pulverizer such as a jet mill, or a spray dryer can be used.
Furthermore, among the commercially available sulfuric acid method, titanium dioxide pigment obtained by the chlorine method, ultrafine titanium dioxide obtained by wet hydrolysis method, flame hydrolysis method, etc., the isoelectric point by the surface treatment agent etc. A suitable one may be used.

  On the other hand, as another method for controlling the surface charge of titanium oxide, there is a method of treating the surface of titanium oxide with an alkaline solution. Specifically, an alkali solution is added to a suspension of titanium oxide, stirred, filtered, and dried at a temperature of about 80 to 150 ° C. In the case of stirring, it may be heated in a temperature range of about 40 to 250 ° C. as necessary, and after drying, it may be fired in a temperature range of about 150 to 900 ° C. if necessary. Examples of the alkali include alkali metal or alkaline earth metal hydroxides such as sodium hydroxide, potassium hydroxide and calcium hydroxide, alkali metal or alkaline earth metal carbonates such as sodium carbonate and potassium carbonate, and ammonia. And ammonium compounds such as ammonium carbonate and ammonium nitrate, and at least one of them can be used.

In order to use titanium oxide having a positive surface charge in blood or plasma as an adsorbent, the module is filled with the adsorbent, and blood or plasma is fed from the upper side or the lower side of the module. During the passage, pathogenic proteins such as bilirubin in blood and plasma are adsorbed and removed. Specifically, a module in which titanium oxide is granulated and formed to an appropriate size, or a module in which titanium oxide is fixed on glass beads or polymer particles can be used. A known granulator and molding machine such as a rolling granulator and an extrusion molding machine can be used for granulation and molding of titanium oxide, and the shape can be any shape depending on the granulator and the like. it can. The size can be appropriately set according to the scale of the module, and about 0.5 to 5 mm is appropriate. In addition to titanium oxide, the granulated product and molded product may contain a binder component, a filler, an antibacterial agent, an adsorbent, and the like as necessary. Therefore, the content of the titanium oxide in the granulated product and the molded product can be appropriately set, and for example, about 10 to 100% by weight is appropriate.
As another method of use, titanium oxide powder, granulated material, or molded product fixed on a sheet can be laminated, or wound into a coil and filled into a module. As the sheet for fixing the titanium oxide, for example, a sheet made of cellulose, cellulose diacetate, cellulose triacetate, ethylene-vinyl alcohol copolymer (ethylene content about 30 mol%), polysulfone, polyacrylonitrile, or the like is used. be able to.
The size of the module can be appropriately set according to the amount of blood or plasma processed. Further, the shape of the module can be appropriately set in consideration of efficiency. For example, a cylindrical shape or a polygonal cylindrical shape as shown in FIG. 6 is preferable. The upper side of the module for feeding blood or plasma may not be the uppermost part of the module, but may be from an appropriate location on the upper side of the module. Further, the lower part side of the module may not be the lowermost part of the module, but may be from an appropriate place at the lower part of the side surface of the module. The feeding speed of blood or plasma can be appropriately set according to the size of the module, and is preferably 30 to 120 ml / min, for example. Blood or plasma discharged from the module may be circulated and sent to the module again if the amount of adsorption is insufficient.

  The present invention will be specifically described below, but the present invention is not limited to the following examples.

Example 1
While maintaining a titanium tetrachloride aqueous solution having a concentration of 200 g / liter as TiO ₂ at 30 ° C., it is neutralized with an aqueous sodium hydroxide solution to precipitate colloidal amorphous titanium hydroxide. Titanium dioxide (sample a) having a rutile crystal was obtained by aging at a temperature of not lower than 2 ° C. for 2 hours.
Next, sodium aluminate (150 g / liter as Al ₂ O ₃ ) and 10% sulfuric acid were simultaneously added to the titanium dioxide suspension (sample a) with stirring to adjust the pH of the suspension to 8-9. Maintained. Then, after filtering, washing, and repulping, and subsequently treating with hot water at a temperature of 80 ° C. for 2 days in order to remove sodium content, filtering, washing, drying at a temperature of 105 ° C. for 3 hours, A rutile type titanium dioxide (sample A) carrying 15% by weight of aluminum oxide was obtained.

Example 2
Sample A obtained in Example 1 was calcined at a temperature of 330 ° C. for 3 hours to obtain rutile titanium dioxide (sample B) carrying 15% by weight of aluminum oxide.

Example 3
Sample A obtained in Example 1 was calcined at a temperature of 705 ° C. for 3 hours to obtain rutile titanium dioxide (sample C) carrying 15% by weight of aluminum oxide.

Example 4
In accordance with the method described in Example 1, rutile titanium dioxide (sample D) carrying 10% by weight of aluminum oxide was obtained.

Example 5
According to the method described in Example 1, rutile type titanium dioxide (sample E) carrying 20% by weight of aluminum oxide was obtained.

Comparative Example 1
To obtain a titanium dioxide suspension corresponding to sample a according to the method described in Example 1, and then filtering, washing, and repulping the suspension, followed by removal of sodium. After 2 days of warm water treatment at a temperature of 80 ° C., filtration, washing, and drying at a temperature of 105 ° C. for 3 hours, rutile titanium dioxide (sample F, no surface treatment) was obtained.

Comparative Example 2
Sample F obtained in Comparative Example 1 was calcined at a temperature of 330 ° C. for 3 hours to obtain rutile titanium dioxide (sample G, no surface treatment).

Comparative Example 3
Sample F obtained in Comparative Example 1 was calcined at a temperature of 705 ° C. for 3 hours to obtain rutile type titanium dioxide (sample H, no surface treatment).

Comparative Example 4
In accordance with the method described in Example 1, a titanium dioxide suspension corresponding to sample a was obtained, and sodium silicate (150 g / liter as SiO ₂ ) and 10% sulfuric acid were then added to the suspension with stirring. At the same time, the pH of the suspension was maintained at 8-9. Then, after filtering, washing, and repulping, and subsequently treating with hot water at a temperature of 80 ° C. for 2 days in order to remove sodium content, filtering, washing, drying at a temperature of 105 ° C. for 3 hours, A rutile type titanium dioxide (sample I) carrying 5% by weight of silicon oxide was obtained.

Comparative Example 5
Sample I obtained in Comparative Example 4 was calcined at a temperature of 330 ° C. for 3 hours to obtain rutile-type titanium dioxide (Sample J) carrying 5% by weight of silicon oxide.

Comparative Example 6
Sample I obtained in Comparative Example 4 was calcined at 705 ° C. for 3 hours to obtain rutile-type titanium dioxide (sample K) carrying 5% by weight of silicon oxide.

As a result of examining the crystal structures of Samples A to K obtained in Examples 1 to 5 and Comparative Examples 1 to 6 by the X-ray diffraction method, it was confirmed that any sample was attributed to rutile titanium dioxide.
Table 1 shows the results of measuring the isoelectric points of Samples A to K using a zeta potential measurement device (manufactured by Otsuka Electronics Co., Ltd. (ELS-6000)) and the measurement results of specific surface area. The isoelectric point of titanium dioxide carrying aluminum oxide of samples A to E is in the range of 7.8 to 8.5, higher than the pH of blood and plasma, and has a positive surface charge in blood or plasma. I understood. On the other hand, the isoelectric points of the samples F to H not supporting aluminum oxide are in the range of 4.9 to 5.3, and the isoelectric points of the samples I to K supporting silicon oxide are 3.3 to 3.3. It was in the range of 4.7, lower than the pH of blood and plasma, and was found to have a negative surface charge in blood or plasma.

The bilirubin adsorption removal ability of the samples A to C and F to K obtained in Examples 1 to 3 and Comparative Examples 1 to 6 was measured by the following method.
A. Method for preparing albumin containing conjugated bilirubin for adsorption test a. Reagent: 0.12 g of bilirubin (Wako Pure Chemical Industries, Ltd.) was dissolved in 50 mL of 0.1 N sodium hydroxide aqueous solution.
b. 7.50 g of bovine serum albumin (Wako Pure Chemical Industries, Ltd., purity 98-99%) was dissolved in 50 mL of distilled water.
Next, the a solution and the b solution were mixed, and 50 mL of a 0.1 N hydrochloric acid aqueous solution was added to the mixed solution. A 5N aqueous sodium hydroxide solution was added thereto to adjust the pH to 7.2, and 1.06 g of sodium chloride was added to obtain a total bilirubin standard solution.
B. Measurement of adsorption performance of bilirubin of titanium oxide The adsorption performance of bilirubin of the powders (particle diameter: 213 to 300 μm) of samples A to C and F to K was measured. 0.1 mg of each sample was collected in a disposable container made of polyethylene having a volume of 5.0 mL, immersed in 1.0 mL of physiological saline, and deaerated for 1 hour in a vacuum desiccator. 3 mL of the total bilirubin standard solution prepared in advance was added thereto, and the mixture was shaken in a constant temperature bath at 37 ° C. for a predetermined time (5 hours) in the dark. After shaking, the samples were filtered through a disposable filter having a pore size of 0.45 μm, and the total bilirubin (T.Bil) and conjugated (direct) bilirubin (D.Bil) concentrations in the solution were determined using a clinical test kit [Wako Pure Chemical Industries, Ltd. Co., Ltd., Bilirubin BII-Test Wako]. The free (indirect) bilirubin (In.Bil) concentration was calculated from the difference between the total bilirubin concentration and the conjugated (direct) bilirubin concentration. The total bilirubin (T.Bil), indirect bilirubin (In.Bil), and direct bilirubin (D.Bil) adsorption performance [(g) per unit weight] of each sample is shown in FIGS.

As is apparent from FIGS. 1 to 5, it was found that the indirect bilirubin adsorption performance of samples A to C carrying aluminum oxide was high, and the total bilirubin adsorption performance was also high accordingly. On the other hand, it was found that Samples I to K carrying silicon oxide also have low indirect bilirubin adsorption performance and low total bilirubin adsorption performance.
From the results of this adsorption performance and the isoelectric point of each sample, the higher the isoelectric point, the better the adsorption performance of indirect bilirubin. The isoelectric point of the sample is higher than the pH of blood and plasma, and positive in blood or plasma. It has been found that the adsorption performance of indirect bilirubin is particularly good when it has a surface charge.

  The module shown in FIG. 6 is filled with the sample A of Example 1 which is shaped into a sphere with a diameter of about 1 mm, and the plasma is fed at a rate of about 50 ml / min. As a result, indirect bilirubin in the plasma is adsorbed and removed. I was sure that.

  Since the adsorbent of the present invention has excellent indirect bilirubin adsorption performance, it is useful for adsorption removal of pathogenic proteins such as bilirubin in blood or plasma. In addition, since the adsorbent of the present invention has compatibility with blood or plasma and has sufficient mechanical strength and resistance to sterilization, it can be used for blood purification by the direct blood adsorption method. It can also be used to purify plasma obtained by the plasma separation method.

It is a graph which shows the total bilirubin adsorption | suction performance of sample AC obtained by Examples 1-3 and Comparative Examples 1-6, F-K. In FIG. 1, ◯ represents samples A to C, ● represents samples F to H, and Δ represents the total amount of bilirubin adsorbed at the drying and firing temperatures of samples I to K. It is a graph which shows the indirect bilirubin adsorption | suction performance of sample AC obtained by Examples 1-3 and Comparative Examples 1-6, FK. In FIG. 2, ◯ represents samples A to C, ● represents samples F to H, and Δ represents indirect bilirubin adsorption amounts at the drying and baking temperatures of samples I to K. It is a graph which shows the direct bilirubin adsorption | suction performance of sample AC obtained by Examples 1-3 and Comparative Examples 1-6, F-K. In FIG. 3, ◯ represents samples A to C, ● represents samples F to H, and Δ represents the amount of direct bilirubin adsorption at the drying and firing temperatures of samples I to K. It is a graph which shows the total bilirubin adsorption | suction performance of sample AC obtained by Examples 1-3 and Comparative Examples 1-6, F-K. In FIG. 4, ◯ indicates the relationship between the sample A to C, ● the sample F to H, and Δ the sample I to K isoelectric point and the total bilirubin adsorption amount. It is a graph which shows the indirect bilirubin adsorption | suction performance of sample AC obtained by Examples 1-3 and Comparative Examples 1-6, FK. In FIG. 5, ◯ indicates the relationship between the samples A to C, ● indicates the samples F to H, and Δ indicates the relationship between the isoelectric points of the samples I to K and the amount of indirect bilirubin adsorption. It is a schematic diagram of the module of this invention.

Claims (6)

Blood in the blood or plasma viewing containing titanium oxide having a positive surface charge, wherein the titanium oxide is a metal oxide and / or titanium oxide with metal hydroxide is supported on the particle surface Adsorbent for purification or plasma purification.   The adsorbent for blood purification or plasma purification according to claim 1, wherein the isoelectric point of titanium oxide in water is 8 or more. The blood purification or plasma purification according to claim 1 or 2 , wherein the metal element of the metal oxide and / or metal hydroxide supported on the titanium oxide is at least one selected from aluminum, zinc and magnesium. Adsorbent. The adsorbent for blood purification or plasma purification according to any one of claims 1 to 3 , wherein the titanium oxide has a rutile crystal. A blood purification or plasma purification module, which is filled with the adsorbent according to any one of claims 1 to 4 . 6. A method for purifying blood or plasma, comprising feeding blood or plasma from the upper side or the lower side of the module according to claim 5 at a rate of 30 to 120 ml / min.

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