JP2006320729A - Adsorbent of toxic shock syndrome toxin-1, use of the adsorbent and adsorber filled with the adsorbent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an adsorbent, efficiently adsorbing and removing toxic shock syndrome toxin-1 (TSST-1) in body fluid, use of the adsorbent and an adsorber filled with the adsorbent. <P>SOLUTION: This adsorbent 3 of TSST-1 is formed by fixing a compound whose logP value (P is a distribution coefficient in octanol-water system) is 2.50 or more to a water-insoluble carrier. In a method of adsorbing and removing TTST-1 in body fluid, body fluid containing TSST-1 is brought into contact with the adsorbent. This adsorber 7 for TSST-1 is constructed so that the interior of a container having an inlet and an outlet for body fluid, and provided with an outflow preventing means 4, 5 for preventing an adsorbent from flowing to the outside of the container is filled with the adsorbent 3. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to an adsorbent for toxic shock syndrome toxin-1, use of the adsorbent, and an adsorber filled with the adsorbent.

  Toxic shock syndrome toxin-1 (hereinafter referred to as TSST-1) is an exotoxin (exotoxin) composed of a soluble protein having a molecular weight of about 20-30 kDa produced by Staphylococcus aureus, and is a typical superantigen.

  Sepsis refers to a condition where there is an infection somewhere in the body and thus causes a systemic inflammatory reaction. When this inflammatory symptom increases, shock symptoms occur (septic shock), organ damage (organ failure), and multi-organ failure occur. The source of infection is mainly bacteria, which are roughly divided into gram-positive and gram-negative bacteria.

  When infected with Staphylococcus aureus, a kind of Gram-positive bacteria, TSST-1 produced by the infected Staphylococcus aureus causes T cells to proliferate and activate, thereby causing sepsis. Recently, methicillin-resistant Staphylococcus aureus (MRSA) infection and the accompanying septic shock have attracted attention as an important infectious agent of nosocomial infection and have been a major social problem for several years (Tomoyuki Kawamata et al. 7: 631 (1995)).

  On the other hand, when infected with Gram-negative bacteria, endotoxin (endotoxin) present in the cell wall enters the blood and causes sepsis. Furthermore, since TSST-1 activates the immune system as a superantigen and enhances the toxicity of endotoxin several thousand times in recent years, sepsis is also caused by the presence of a low concentration of endotoxin that does not cause sepsis clinically. It is shown. That is, when Gram-positive and Gram-negative bacteria are combined, the possibility of causing sepsis is very high.

  Antibiotics as a countermeasure against infection and γ-globulin for activating resistance to infection are used for the treatment of sepsis, but still show a high mortality rate. Therefore, it is desired from a medical standpoint to remove TSST-1 and endotoxin that cause sepsis from body fluids.

  Regarding endotoxins, adsorbents for removal from body fluids are known. For example, Japanese Examined Patent Publication No. 1-16389 discloses an adsorbent in which polymyxin known as an endotoxin antidote is immobilized on a suitable carrier. Further, the present inventors have disclosed in JP-A-8-173803 that endotoxin can be adsorbed by a styrene-divinylbenzene copolymer into which a sulfonic acid group has been introduced. These adsorbents can be expected to have a significant effect on infection with gram-negative bacteria. However, the effect is reduced when TSST-1 and endotoxin coexist due to complex infection by Gram-positive and Gram-negative bacteria. Furthermore, if only Gram-positive bacteria are infected and TSST-1 enters the body fluid, no effect can be expected. Various adsorbents for endotoxin are known, but since the adsorbent for TSST-1 is not known, development of the adsorbent has been strongly desired.

  An object of the present invention is to provide an adsorbent capable of efficiently adsorbing and removing TSST-1 in a body fluid, use of the adsorbent, and a TSST-1 adsorber.

  The present inventors diligently studied an adsorbent capable of efficiently adsorbing and removing TSST-1 present in a body fluid. As a result, it was found that an adsorbent obtained by immobilizing a compound having a log P value of 2.50 or more on a water-insoluble carrier can efficiently adsorb and remove TSST-1 present in the body fluid, thereby completing the present invention.

  That is, the present invention relates to (1) an adsorbent for TSST-1 in which a compound having a log P (P is a partition coefficient in an octanol-water system) value of 2.50 or more is fixed to a water-insoluble carrier.

  The present invention further relates to (2) the adsorbent according to item (1), wherein the water-insoluble carrier is a water-insoluble porous carrier.

  The present invention further relates to (3) the adsorbent according to the above item (2), wherein the water-insoluble porous carrier has a globular protein exclusion limit molecular weight of 10,000 to 600,000.

  Furthermore, the present invention relates to (4) use of the adsorbent for toxic shock syndrome toxin-1 according to (1) above for the production of an adsorber for adsorbing and removing toxic shock syndrome toxin-1 in body fluids.

  Furthermore, the present invention provides (5) a TSST comprising a container having an inlet and an outlet for bodily fluids and provided with a means for preventing the adsorbent from flowing out of the container. -1 adsorber.

  According to the present invention, TSST-1 in a body fluid can be efficiently adsorbed and removed by using an adsorbent obtained by immobilizing a compound having a log P value of 2.50 or more on a water-insoluble carrier.

  “TSST-1” in the present invention is an exotoxin composed of a soluble protein having a molecular weight of 20 to 30 kDa produced by Staphylococcus aureus.

  The body fluid refers to blood, plasma, serum, ascites, lymph, intra-articular fluid, fractional components obtained therefrom, and other biological components derived from living bodies.

The log P value is a hydrophobic parameter of a compound, and the partition coefficient P in a typical octanol-water system is obtained as follows. First, the compound is dissolved in octanol (or water), and an equal amount of water (or octanol) is added thereto, and then Griffin Flask shaker (Griffin & George Ltd., Griffin & George Ltd.). )) For 30 minutes. Thereafter, the mixture is centrifuged at 2000 rpm for 1 to 2 hours, and each concentration of the compound in the octanol layer and the aqueous layer is measured by various methods such as spectroscopic or GLC, and the following formula is obtained.
P = Coct / Cw
Coct: Compound concentration in the octanol layer
Cw: Compound concentration in the water layer

  The adsorbent of the present invention is formed by fixing a compound having a log P value of 2.50 or more obtained as described above to a water-insoluble carrier.

  So far, many researchers have measured the log P values of various compounds, and the measured values of the log P have been arranged by C. Hansch et al. (“Partition Coefficiens and Zea”).・ Eugez; Chemical Reviews (Partial COEFFICIENTS AND THEIR USES; Chemical Reviews), 71, 525 (1971)).

  For compounds for which the actual measurement values are not known, R. F. Rekker wrote the book “THE HYDROPHOBIC FRAGMENTAL CONSTANT”, Elsevier Scien. A value (Σf) calculated using the hydrophobic fragment constant f shown in Elsevier Sci. Pub. Com., Amsterdam (1977) is a reference. The hydrophobic fragment constant is a value indicating the hydrophobicity of various fragments determined by statistical processing based on a number of logP actual measurement values. The sum of the f-values of each fragment constituting the compound almost coincides with the logP value. In the present invention, the logP value means a Σf value for a compound whose logP value is not known.

  In searching for a compound effective for adsorption of TSST-1, compounds having various log P values were immobilized on a water-insoluble carrier, and the adsorption ability for TSST-1 was examined. As a result, a compound having a log P value of 2.50 or more, preferably 2.80 or more, more preferably 3.00 or more is effective for adsorption of TSST-1, and most compounds having a log P value of less than 2.50 are TSST. It was found that the adsorption ability for -1 was not exhibited. For example, when an alkylamine is immobilized as a compound on a water-insoluble carrier, when the alkylamine is changed from n-hexylamine (logP = 2.06) to n-octylamine (logP = 2.90), TSST- It was found that the adsorptive capacity for 1 increased dramatically. From these results, the adsorptive capacity for TSST-1 by the adsorbent of the present invention is determined by the hydrophobic mutual relationship between TSST-1 and the atomic group introduced onto the support by immobilizing the compound having a log P value of 2.50 or more. This is considered to be due to the action, and it is considered that a compound having a log P value of less than 2.50 does not exhibit an adsorption ability for TSST-1 because the hydrophobicity is too small.

In the present invention, as a compound immobilized on a water-insoluble carrier, any compound having a log P value of 2.50 or more can be used without any particular limitation. However, when a compound is immobilized on a carrier by a chemical bonding method, a part of the compound is often eliminated, but when this leaving group contributes greatly to the hydrophobicity of the compound, that is, due to elimination. In view of the gist of the present invention, when the hydrophobicity of the atomic group fixed on the carrier is less than 2.50 when represented by the Σf value, it is not suitable as the compound used in the present invention. One typical example is when isopentyl benzoate (Σf = 4.15) is fixed to a carrier having a hydroxyl group by transesterification. In this case, the atomic group actually fixed to the carrier is C ₆ H ₅ CO—, and the Σf value of this atomic group is 1 or less. Whether such a compound is suitable as a compound to be used in the present invention may be determined based on whether the logP value of the compound in which the leaving group is replaced with hydrogen is 2.50 or more.

  Among compounds having a log P value of 2.50 or more, compounds containing oxirane rings such as unsaturated hydrocarbons, alcohols, amines, thiols, carboxylic acids and derivatives thereof, halides, aldehydes, hydrazides, isocyanates, glycidyl ethers, and halogens A compound having a functional group that can be used for bonding to a carrier, such as silane fluoride, is preferable. Representative examples of such compounds include, for example, n-heptylamine, n-octylamine, decylamine, dodecylamine, hexadecylamine, octadecylamine, 2-aminooctene, naphthylamine, phenyl-n-propylamine, diphenylmethylamine Amines such as n-heptyl alcohol, n-octyl alcohol, dodecyl alcohol, hexadecyl alcohol, 1-octen-3-ol, naphthol, diphenylmethanol, 4-phenyl-2-butanol and alcohols thereof Carboxylic acids such as n-octanoic acid, nonanoic acid, 2-nonenoic acid, decanoic acid, dodecanoic acid, stearic acid, arachidonic acid, oleic acid, diphenylacetic acid, and phenylpropionic acid Carboxylic acid derivatives such as acid halides, esters, amides, halides such as octyl chloride, octyl bromide, decyl chloride, dodecyl chloride, thiols such as octanethiol, dodecanethiol, n-octyltrichlorosilane, octadecyltri Examples thereof include halogenated silanes such as chlorosilane, and aldehydes such as n-octylaldehyde, n-caprinaldehyde, and dodecylaldehyde.

  In addition to these, the log P value of the compounds in which the hydrogen atom of the hydrocarbon portion of the above exemplary compound is substituted with a substituent containing a hetero atom such as halogen, nitrogen, oxygen, sulfur, or other alkyl group Of 550 to 613 in the above-mentioned review by Si Hansh et al., “Partition Co-Efficients and There Uses; Chemical Reviews, Vol. 71, 525, (1971)” A compound having a log P value of 2.50 or more shown in the table can be used, but the present invention is not limited thereto.

  Each of these compounds may be used alone, or any two or more of them may be combined, and further, may be used in combination with a compound having a log P value of less than 2.50.

  The water-insoluble carrier in the adsorbent of the present invention means a carrier that is solid at room temperature and normal pressure and water-insoluble.

  Examples of the shape of the water-insoluble carrier in the present invention include, for example, a granular shape, a plate shape, a fiber shape, and a hollow fiber shape. However, the shape of the carrier is not particularly limited.

  Examples of the water-insoluble carrier in the present invention include inorganic carriers such as glass beads and silica gel, crosslinked or uncrosslinked polyvinyl alcohol, crosslinked or uncrosslinked polyacrylate, crosslinked or uncrosslinked polyacrylamide, and crosslinked or uncrosslinked polystyrene. Synthetic carriers and organic carriers comprising crystalline cellulose, cross-linked or non-cross-linked cellulose, cross-linked or non-cross-linked agarose and cross-linked or non-cross-linked dextrins, and organic-organic obtained by combinations thereof, A typical example is a composite carrier such as organic-inorganic.

  Among these, a hydrophilic carrier is preferable because nonspecific adsorption is relatively small and the adsorption selectivity of TSST-1 is good. The hydrophilic carrier here means a carrier having a contact angle with water of 60 degrees or less when the compound constituting the water-insoluble carrier is formed into a flat plate shape. Typical examples of such carriers include cellulose, polyvinyl alcohol, saponified ethylene-vinyl acetate copolymer, polyacrylamide, polyacrylic acid, polymethacrylic acid, polymethyl methacrylate, polyacrylic acid grafted polyethylene, poly Examples of the carrier include acrylamide-grafted polyethylene and glass.

  Among these, the porous cellulose gel (1) is relatively high in mechanical strength and tough, so it is unlikely to be broken or finely formed by operations such as stirring. It does not become compacted or clogged even when flowing at a flow rate, and the pore structure is not easily changed by high-pressure steam sterilization. (2) Since the gel is composed of cellulose, it is hydrophilic, There are many hydroxyl groups that can be used for binding, and there is little non-specific adsorption. (3) Even if the pore volume is increased, the strength is relatively high so that the adsorption capacity is not inferior to that of a soft gel, and (4) It has excellent properties such as higher safety than synthetic polymer gels, and is one of the most suitable carriers for use in the present invention. The carrier used in the present invention is preferably a hard gel whose flow rate does not increase proportionally with increasing pressure. However, the present invention is not limited to these. In addition, each said support | carrier may be used independently, and arbitrary 2 or more types may be mixed and used for it.

  The property required for the water-insoluble carrier used in the present invention is to have a large number of pores of an appropriate size, that is, to be porous. TSST-1 which is an adsorption target of the adsorbent of the present invention is a protein having a molecular weight of about 20 to 30 kDa. To efficiently adsorb this protein, TSST-1 can penetrate into the pores with a certain high probability. It is preferable that other proteins do not enter as much as possible. The exclusion limit molecular weight is generally used as a measure of the molecular weight of a substance that can enter the pore diameter. Exclusion limit molecular weight means that it cannot penetrate into pores in gel permeation chromatography as described in the books (for example, Hiroyuki Hatano, Toshihiko Hanai, “Experimental High Performance Liquid Chromatograph”, Chemical Dojin) (exclusion) Is the molecular weight of the smallest molecule. The exclusion limit molecular weight is generally well examined for globular proteins, dextran, polyethylene glycol and the like. In the case of the water-insoluble porous carrier used in the present invention, it is suitable to use a value obtained using a globular protein.

  As a result of studies using carriers having various exclusion limit molecular weights, the range of pore diameters of the supports suitable for adsorption of TSST-1 was from 10,000 to 600,000. That is, when a carrier having an exclusion limit molecular weight of less than 10,000 is used, the amount of TSST-1 adsorbed is small, and thus the practicality is lowered. In addition, when a carrier having an exclusion limit molecular weight exceeding 600,000 is used, the amount of protein (mainly albumin) other than TSST-1 increases, and its practicality is lowered in terms of selectivity. Accordingly, the preferred exclusion limit molecular weight of the water-insoluble carrier used in the present invention is 10,000 to 600,000, more preferably 15,000 to 400,000, and particularly preferably 20,000 to 300,000.

Next, regarding the porous structure of the carrier, considering the adsorption capacity per unit volume of the adsorbent, the total porosity is preferable to the surface porosity, the pore volume is 20% or more, and the specific surface area is 3 m ² / g. The above is preferable.

  Further, the carrier preferably has a functional group that can be used for ligand immobilization reaction. Typical examples of these functional groups include a hydroxyl group, an amino group, an aldehyde group, a carboxyl group, a thiol group, a silanol group, an amide group, an epoxy group, a halogen group, a succinimide group, and an acid anhydride group. However, it is not limited to these.

As the water-insoluble carrier used in the present invention, either a hard carrier or a soft carrier can be used. However, when used as an adsorbent for extracorporeal circulation, clogging occurs when the column is packed and passed through. It is important that no mechanical strength is required. Therefore, the water-insoluble carrier used in the present invention is more preferably a hard carrier. The hard carrier here is, for example, in the case of a granular gel, as shown in the following reference example, the relationship between the pressure loss ΔP and the flow rate when the gel is uniformly packed in a cylindrical column and an aqueous fluid is flowed is 0. .Those that have a linear relationship up to 3 kg / cm ² .

  The adsorbent of the present invention can be obtained by immobilizing a compound having a log P value of 2.50 or more on a water-insoluble carrier, and various immobilization methods can be used without any particular limitation. . However, when the adsorbent of the present invention is used for extracorporeal circulation treatment, it is important for safety to suppress the desorption and elution of the ligand as much as possible during sterilization or treatment. For this purpose, the adsorbent is immobilized by a covalent bond method. It is preferable.

  In addition, the adsorbent in the present invention is preferably one in which an appropriate amount of a compound having a log P value of 2.50 or more is fixed. If the fixed amount is too small, the adsorption of TSST-1 is not observed. If the fixed amount is too large, adhesion of adhesive components such as platelets may occur when blood is used as a body fluid. Therefore, the fixed amount of the compound having a log P value of 2.50 or more is preferably 0.1 μmol to 10,000 μmol, more preferably 1 μmol to 200 μmol, most preferably 5 μmol per unit volume (1 ml) of the water-insoluble carrier. 100 μmol.

  There are various methods for adsorbing and removing TSST-1 from body fluids using the adsorbent according to the present invention. As the simplest method, a body fluid is taken out and stored in a bag or the like, adsorbent is mixed with this to adsorb and remove TSST-1, and then the adsorbent is filtered to obtain a body fluid from which TSST-1 has been removed. Can be given. As another method, there is a method in which an adsorbent is filled in a container equipped with a filter having a body fluid inlet and outlet, at least at the outlet through which the body fluid passes but the adsorbent does not pass, and the body fluid is allowed to flow therethrough. Either method can be used, but the latter method is easy to operate, and by incorporating it into an extracorporeal circuit, TSST-1 can be efficiently removed online from a patient's body fluid, particularly blood, The adsorbent of the present invention is suitable for this method.

  In this extracorporeal circuit, the adsorbent of the present invention can be used alone, but can also be used in combination with other extracorporeal circulation treatment systems. Examples of the combination include, for example, an artificial dialysis circuit, and can be used in combination with dialysis therapy.

  Next, the TSST-1 adsorber of the present invention using the TSST-1 adsorbent will be described with reference to FIG. 1 which is a schematic cross-sectional explanatory diagram of one embodiment. In FIG. 1, 1 is a body fluid inlet, 2 is a body fluid outlet, 3 is a TSST-1 adsorbent of the present invention, and 4 and 5 are capable of passing through the body fluid and components contained in the body fluid, but the TSST-1 adsorbent passes through. Incapable filter (adsorbent spill prevention filter), 6 is a column, and 7 is a TSST-1 adsorber. However, the TSST-1 adsorber is not limited to such a specific example, and is provided in a container having an inlet and an outlet for body fluid and a means for preventing the TSST-1 adsorbent from flowing out of the container. What is necessary is just to fill the adsorbent.

  Examples of the outflow prevention means include filters such as meshes, non-woven fabrics, and cotton plugs. The shape, material, and size of the container are not particularly limited, but preferred specific examples include a transparent or translucent cylindrical container having a capacity of about 150 to 400 ml and a diameter of about 4 to 10 cm. Particularly preferred are materials having sterilization resistance, and specific examples include silicon-coated glass, polypropylene, vinyl chloride, polycarbonate, polysulfone, and polymethylpentene.

  EXAMPLES Hereinafter, although this invention is described further in detail based on an Example, this invention is not limited only to a following example.

Reference Example Agarose gel (Biogel A-5m, particle size 50-100 mesh, Bio-Rad (BIO-RAD)) on a glass cylindrical column (inner diameter 9 mm, column length 150 mm) fitted with a filter with a pore size of 15 μm at both ends ), Vinyl polymer gel (Toyopearl HW-65, particle size 50-100 μm, manufactured by Tosoh Corporation) and cellulose gel (Cellulofine GC-700 m, particle diameter 45-105 μm, manufactured by Chisso Corporation) are uniform. Then, water was allowed to flow using a peristaltic pump, and the relationship between the pressure loss ΔP and the flow rate was determined. The results are shown in FIG.

As shown in FIG. 2, the flow rate of Toyopearl HW-65 and Cellulofine GC-700m increases almost in proportion to the increase of pressure, whereas Biogel A-5m causes consolidation and increases the pressure. It can be seen that the flow rate does not increase. In the present invention, as in the former case, the one in which the relationship between the pressure loss ΔP and the flow rate is a linear relationship up to 0.3 kg / cm ² is called a hard gel.

Example 1
Cellulofine GC-200m (spherical protein exclusion limit molecular weight: 140,000, manufactured by Chisso Corporation) is added to 170 ml of cellulose-based porous gel to make the total amount 340 ml, and then 90 ml of 2M aqueous sodium hydroxide solution is added to 40 ° C. It was. To this, 31 ml of epichlorohydrin was added and reacted at 40 ° C. with stirring for 2 hours. After completion of the reaction, it was thoroughly washed with water to obtain an epoxidized gel.

  To 10 ml of this epoxidized gel, 200 mg of n-octylamine (log P = 2.90) was added, and the mixture was allowed to react in a 50 (v / v)% ethanol aqueous solution at 45 ° C. for 6 days to be immobilized. After completion of the reaction, 50 (v / v)% ethanol aqueous solution, ethanol, 50 (v / v)% ethanol aqueous solution, and water were sufficiently washed in this order to obtain an n-octylamine-immobilized gel.

  TSST-1 serum (TSST-1 concentration 5 ng / TSST) prepared by adding TSST-1 (manufactured by Toxin Technology) to fetal bovine serum (manufactured by Flow Laboratories) with respect to 0.2 ml of the immobilized gel (adsorbent). ml) 1.2 ml was added and incubated at 37 ° C. for 2 hours. The same operation was performed for 0.2 ml of physiological saline instead of the adsorbent. The concentration of TSST-1 in the supernatant solution before and after incubation was measured by the ELISA method, and the adsorption rate was calculated. The adsorption rate was determined by dividing the supernatant concentration when the adsorbent was contained by the concentration when physiological saline was used (percentage).

  The ELISA method for TSST-1 was performed as follows. Primary antibody rabbit anti-TSST-1 IgG (manufactured by Toxin Technology) was diluted 1600 times with a coating buffer and dispensed in 100 μl aliquots onto a microplate. After overnight at 4 ° C., the microplate was washed. Each 200 μl of 3% bovine serum albumin solution was dispensed onto a microplate, allowed to stand at room temperature for 2 hours, and then the microplate was washed. There, the standard solution of TSST-1 and the supernatant solution before and after incubation were placed in a 100 μl microplate. Washed after 2 hours at room temperature. Secondary antibody rabbit anti-TSST-1 HRPO (manufactured by Toxin Technology) was diluted 400 times with 1% bovine serum albumin solution and dispensed in 100 μl aliquots. Washed after 2 hours at room temperature. The orthophenylenediamine solution was dispensed in 100 μl aliquots and allowed to stand at room temperature for 10 minutes. 100 μl of 4N sulfuric acid was dispensed, and the absorbance at 492 nm was measured. The TSST-1 concentration of the supernatant solution before and after incubation was determined by comparison with the absorbance of the standard solution.

Example 2
A cetylamine-immobilized gel was obtained in the same manner as in Example 1 except that n-octylamine (log P = 2.90) was changed to cetylamine (Σf = 7.22) and the solvent for the fixation reaction was changed to ethanol. Using this adsorbent, an adsorption experiment was conducted in the same manner as in Example 1, the concentration of TSST-1 was measured, and the adsorption rate was calculated.

Example 3
A cetylamine-immobilized gel was obtained in the same manner as in Example 2 except that Cellulofine GC-200m was changed to Cellulofine GC-700m (spherical protein exclusion limit molecular weight 400,000, manufactured by Chisso Corporation). Using this adsorbent, an adsorption experiment was conducted in the same manner as in Example 1, the concentration of TSST-1 was measured, and the adsorption rate was calculated.

Example 4
10 ml of Cellulofine GC-200m was taken, 10 ml of t-butyl alcohol and 2.0 g of potassium butoxide were added thereto, and the mixture was stirred at 40 ° C. for 1 hour. Next, 2.0 ml of cetyl bromide (Σf = 9.71 after immobilization) was added and stirred for 4 hours. After the reaction, the gel was separated by filtration, washed with ethanol and water, and a cellulose gel having a cetyl group fixed by an ether bond was obtained. Using this adsorbent, an adsorption experiment was conducted in the same manner as in Example 1, the concentration of TSST-1 was measured, and the adsorption rate was calculated.

Comparative Example 1
An n-butylamine-immobilized gel was obtained in the same manner as in Example 1 except that n-octylamine (log P = 2.90) was changed to n-butylamine (log P = 0.97). Using this adsorbent, an adsorption experiment was conducted in the same manner as in Example 1, the concentration of TSST-1 was measured, and the adsorption rate was calculated.

Comparative Example 2
An n-hexylamine-immobilized gel was obtained in the same manner as in Example 1 except that n-octylamine (log P = 2.90) was changed to n-hexylamine (log P = 2.06). Using this adsorbent, an adsorption experiment was conducted in the same manner as in Example 1, the concentration of TSST-1 was measured, and the adsorption rate was calculated.

  Table 1 shows the logP value or Σf value and the calculated adsorption rate (%) of the compounds used in each Example and Comparative Example.

It is a schematic sectional explanatory drawing of one Example of the TSST-1 adsorption device of this invention. It is a graph which shows the result of having investigated the relationship between flow volume and pressure loss (DELTA) P using three types of water-insoluble support | carriers.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Body fluid inlet 2 Body fluid outlet 3 TSST-1 adsorbent 4, 5 Adsorbent outflow prevention filter 6 Column 7 TSST-1 adsorber

Claims (5)

An adsorbent for toxic shock syndrome toxin-1 in which a compound having a log P (P is a partition coefficient in an octanol-water system) value of 2.50 or more is immobilized on a water-insoluble carrier. The adsorbent according to claim 1, wherein the water-insoluble carrier is a water-insoluble porous carrier. The adsorbent according to claim 2, wherein the exclusion molecular weight of the globular protein of the water-insoluble porous carrier is 10,000 or more and 600,000 or less. Use of the adsorbent for toxic shock syndrome toxin-1 according to claim 1 for the production of an adsorber for adsorbing and removing toxic shock syndrome toxin-1 in body fluids. An adsorber for toxic shock syndrome toxin-1 comprising an adsorbent according to claim 1 filled in a container having a body fluid inlet and outlet and a means for preventing adsorbent from flowing out of the container.

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