JP3308034B2 - Saccharified denatured protein adsorbent - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an adsorbent for removing a glycated denatured protein contained in a body fluid, a method for removing the glycated denatured protein using the adsorbent, and a glycated denatured protein adsorption device.

[0002]

BACKGROUND OF THE INVENTION When diabetes develops, pathological changes begin to appear in the renal glomeruli in almost all cases several years later. The cause of death of diabetic patients is often due to renal impairment, and recently the proportion of people with renal failure due to diabetic nephropathy has been increasing year by year. This is due to vascular disorders in the glomeruli of the kidney ("Diabetes and renal vascular arteries; PRACTICE, 3
Vol., P. 298, 1986 "and" Relationship between diabetes and blood vessels; Record of the General Meeting of the Diabetes Association of Japan, p. 1, 1988 ").

[0003] A large amount of sugar is present in the blood of a diabetic patient as compared to a healthy person, and it is known that glucose present in such blood binds to proteins and the like without the involvement of enzymes. I have. Non-enzymatically conjugated sugars become glycosylated proteins which subsequently deposit on the blood vessel wall and cause vascular damage, which in turn leads to severe diabetic complications. Glycosylated proteins vary in their forms, but one example is Advanced Glycosylation End Products.
End Products (AGEs)) are known. This refers to crosslinked glycated proteins that are thought to be the causative agent of diabetic complications ("Non-enzymatic Glycosylation and the Pasogenesis of Diabetic Completion"). Applications: Anals of Internal Medicine (Nonen
zymatic Glycosylation and the Pathogenesis of Diab
eticComplications; Annals of Internal Medicine)
, 101, 527, 1984, "Advanced Glycosylation End Products in Patients with Diabetic Nephropathy; The New England Journal of Medicine (A
advanced Glycosylation End Products in Patients wit
h Diabetic Nephropathy; The New England Journal o
f Medicine), 325, 836, 1991 ”).

[0004] Currently, treatment of such diabetic complications relies on intensified insulin therapy and antihypertensive therapy. However, if clinically manifest nephropathy develops, it becomes difficult to stop the progress. There is currently no effective treatment for non-insulin dependent diabetes.

[0005]

SUMMARY OF THE INVENTION An object of the present invention is to provide a safe and inexpensive adsorbent capable of efficiently adsorbing and removing glycated and denatured proteins present in a large amount in the blood of diabetic complication patients. It is.

[0006]

SUMMARY OF THE INVENTION The present invention provides a saccharified modified protein adsorbent comprising a porous water-insoluble carrier and a compound having a logP value (P is a partition coefficient in an octanol-water system) of at least 2.50. A saccharified denatured protein, which comprises contacting a saccharified denatured protein adsorbent obtained by immobilizing a compound having a logP value (P is a partition coefficient in an octanol-water system) of 2.50 or more on an insoluble carrier, with a body fluid containing the glycated denatured protein. In a container having an inlet and an outlet for the liquid and a device for preventing the saccharified denatured protein adsorbent from flowing out of the container, a logP is added to the porous water-insoluble carrier.
(P is a partition coefficient in an octanol-water system) The present invention relates to a saccharified denatured protein adsorption device filled with a saccharified denatured protein adsorbent obtained by fixing a compound having a value of 2.50 or more.

[0007]

EXAMPLES In the present invention, the term "glycated protein" refers to any protein in which a reducing sugar is non-enzymatically bound to an amino group of a protein, nucleic acid, hormone or the like and denatured. These include those that have been saccharified to Schiff bases, those that have undergone Amadori transfer to ketoamines, and those that have been cross-linked to each other ("Advanced Glycosylation End Products in Tissue"). And the biochemical basis of diabetic complications; The New England Journal of Medicine (Advanced Glyc
osylation End Products in Tissue and the Biochemic
al Basis of Diabetic Complications; The New Englan
d Journal of Medicine), 318, 1315, 1988 ''
reference).

[0008] Body fluids include blood, plasma, serum, ascites,
Lymph fluid, intra-articular fluid and fraction components obtained therefrom, as well as other liquid components derived from living organisms.

The adsorbent of the present invention comprises a compound having a logP value (P is a partition coefficient in an octal-water system) of at least 2.50 fixed on a porous water-insoluble carrier.

The logP value is a parameter of the hydrophobicity of the compound, and a method of obtaining a distribution coefficient P in a typical octanol-water system is as follows. First, the compound is dissolved in octanol (or water), an equal amount of water (or octanol) is added thereto, and Griffin flask Shaker (Griffin & George Ltd. )
Shake) for 30 minutes. Thereafter, the mixture is centrifuged at 2000 rpm for 1 to 2 hours, and the concentration of the compound in the octanol layer and the aqueous layer is measured by various methods such as spectroscopy or GLC.

P = Coct / Cw Coct: the concentration of the compound in the octanol layer Cw: the concentration of the compound in the aqueous layer
Although the values have been measured, the measured values have been arranged by C. Hansch et al. ("Partition COEFFICIENTS AND THEI;
R USES; Chemical Reviews), 71, 525, 1971 ''
reference).

For compounds whose actual measured values are not known, RFRekker (RFRekker) wrote a book (“THE HYDROPHOBIC FRAGMENTAL CONSTANT”, Elsevier Scientific). -The value (Σf) calculated using the hydrophobic fragment constant f shown in the Publishing Company (Elsevier Sci. Pub. Com.), Amsterdam (1977) is useful. Is a value indicating the hydrophobicity of various fragments determined by performing a statistical process based on the measured logP value of the above, and the sum of the f values of each fragment constituting the compound is almost equal to the logP value.

When searching for compounds effective for adsorbing glycated denatured proteins, compounds having various logP values were fixed and examined. As a result, compounds having a logP value of 2.50 or more were effective for adsorbing glycated denatured proteins, and had a logP value of 2.50. It was found that less than less compounds showed little ability to adsorb glycated denatured proteins. For example, when alkylamine is fixed,
It was found that when the alkylamine was changed from n-hexylamine (logP = 2.06) to n-octylamine (logP = 2.90), the ability to adsorb glycated denatured protein dramatically increased during this period. From these results, the adsorption of the glycated denatured protein to the adsorbent of the present invention is due to the hydrophobic interaction between the glycated denatured protein and the atom group introduced on the carrier by immobilizing the compound having a logP value of 2.50 or more. It is considered that a compound having a logP value of less than 2.50 does not exhibit the ability to adsorb glycated denatured protein because the hydrophobicity is too small.

In the present invention, as the compound immobilized on the porous water-insoluble carrier, any compound having a logP value of 2.50 or more can be used without any particular limitation. However, when a compound is bonded to a carrier by a chemical bonding method, a part of the compound is often detached. However, when the leaving group greatly contributes to the hydrophobicity of the compound, that is, the desorption occurs. The hydrophobicity of the atomic group fixed on the carrier by separation increases.
When f is smaller than 2.50, the compound is not suitable for use in the present invention in view of the gist of the present invention. One typical example is when isopentyl benzoate (Δf = 4.15) is immobilized on a carrier having a hydroxyl group by transesterification. In this case, the atomic group actually fixed on the carrier is C ₆ H ₅ CO—, and Δf of this atomic group is 1 or less. Whether such a compound is suitable as the compound used in the present invention is determined by determining the log P value of the compound in which the leaving group is replaced with hydrogen by 2.50.
The determination may be made based on whether or not the above is true.

Among the compounds having a logP value of 2.50 or more, compounds such as alcohols, amines, thiols, carboxylic acids and derivatives thereof, halides, aldehydes, hydrazides, isocyanates, oxirane ring-containing compounds such as glycidyl ether, and halogenated silanes. Compounds having a functional group that can be used for binding to a carrier are preferred. Representative examples of such compounds include n-heptylamine, n-octylamine, decylamine, dodecylamine, hexadecylamine, octadecylamine, 2-aminooctene,
Amines such as naphthylamine, phenyl-n-propylamine, diphenylmethylamine, n-heptyl alcohol, n-octyl alcohol, dodecyl alcohol, hexadecyl alcohol, 1-octen-3-ol, naphthol, diphenylmethanol, 4-phenyl Alcohols such as 2-butanol and glycidyl ethers of these alcohols, n-octanoic acid, nonanoic acid, 2-nonenoic acid, decanoic acid, dodecanoic acid, stearic acid, arachidonic acid, oleic acid, diphenylacetic acid, phenylpropion Carboxylic acids such as acids and their acid halides, esters, carboxylic acid derivatives such as amides, octyl chloride, octyl bromide, decyl chloride, halides such as dodecyl chloride, octanethiol, thiols such as dodecanethiol, n- Okuchi Trichlorosilane, halogenated silanes such as octadecyl trichlorosilane,
Aldehydes such as n-octylaldehyde, n-caprinaldehyde, dodecylaldehyde and the like can be mentioned. In addition to the above compounds, among the compounds in which the hydrogen atom of the hydrocarbon portion of the exemplified compounds described above is substituted with a substituent containing a hetero atom such as halogen, nitrogen, oxygen, or sulfur, or another alkyl group, etc. Compounds having a logP value of 2.50 or more, as described in the above-mentioned review by C. Hansch et al., "Partition COEFFICIENTS AND THEIR;
USP; Chemical Reviews), vol. 71, p. 525, 1971 ", the logP value shown in the table on pages 555 to 613 is 2.50.
The above compounds and the like can be used, but the present invention is not limited to these.

These compounds may be used alone or in combination of two or more. Further, they may be used in combination with a compound having a logP value of less than 2.50.

Examples of the water-insoluble carrier used in the present invention include inorganic carriers such as glass beads and silica gel, synthetic polymers such as cross-linked polyvinyl alcohol, cross-linked polyacrylate, cross-linked polyacrylamide and cross-linked polystyrene, crystalline cellulose, cross-linked cellulose, cross-linked cellulose and the like. Organic carriers composed of polysaccharides such as agarose and cross-linked dextran, and organic-organic, organic-
Representative examples include composite carriers such as inorganic,
Among them, hydrophilic carriers are preferred because nonspecific adsorption is relatively small and glycated denatured protein adsorption selectivity is good. As used herein, the hydrophilic carrier refers to a carrier having a contact angle with water of 60 degrees or less when a compound constituting the carrier is formed into a plate. Such carriers include cellulose, polyvinyl alcohol, saponified ethylene-vinyl acetate copolymer, polyacrylamide, polyacrylic acid, polymethacrylic acid, polymethyl methacrylate, polyacrylic acid-grafted polyethylene, polyacrylamide-grafted polyethylene,
A typical example is a carrier made of glass or the like.
(1) Porous cellulose gel has relatively high mechanical strength and is hardly broken or generates fine powder due to operation such as stirring. When packed into a column, it flows a body fluid at a high flow rate. Even if it is not compacted or clogged, it can be flowed at a high flow rate, and the pore structure is not easily changed by high-pressure steam sterilization.
(2) The gel is composed of cellulose and therefore hydrophilic, has many hydroxyl groups available for ligand binding, and has little non-specific adsorption. (3) Relatively strong even if the pore volume is increased It has an excellent adsorption capacity that is not inferior to that of a soft gel because of its high molecular weight. (4) It has excellent features such as higher safety than synthetic polymer gels and the like, and is one of the most suitable carriers used in the present invention. One. The present invention is not limited to only these. The above carriers may be used alone, or two or more of them may be used as a mixture.

The first required property of the water-insoluble carrier used in the present invention is that it has a large number of pores of a suitable size.
That is, it is porous. The saccharified denatured protein to be adsorbed by the adsorbent of the present invention is a non-enzymatically saccharified protein, and therefore cannot be specified because of its wide molecular weight. In order to adsorb this protein efficiently, the glycated and denatured protein can enter the pores with a high probability to some extent, but it is preferable that entry of other proteins does not occur as much as possible. Although the mercury intrusion method is most often used for measuring the pore diameter, it is often not applicable to the porous water-insoluble carrier used in the present invention.
In such a case, it is appropriate to use the exclusion limit molecular weight as a measure of the pore size. As described in a compendium (eg, Hiroyuki Hatano and Toshihiko Hanai, Experimental High-Performance Liquid Chromatography, Chemical Doujinshi) etc., the molecular weight cannot be eliminated (excluded) in gel permeation chromatography. The molecular weight of the one having the smallest molecular weight among the molecules. The exclusion limit molecular weight is generally well examined for globular proteins, dextran, polyethylene glycol and the like. In the case of the carrier used in the present invention, it is appropriate to use the values obtained using globular proteins.

As a result of examination using carriers having various exclusion limit molecular weights, it has been found that a pore size suitable for adsorption of glycated denatured protein has an exclusion limit molecular weight of 20,000 or more. That is, when a carrier having an exclusion limit molecular weight of less than 20,000 is used, the amount of glycated and denatured protein adsorbed and removed is small, and its practicality is reduced. Therefore, the preferred exclusion limit molecular weight of the carrier used in the present invention is 20,000 or more.

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

The shape of the carrier can be arbitrarily selected, such as a granular shape, a fibrous shape, or a hollow shape, and the size is not particularly limited.

Further, it is convenient that a functional group which can be used for a reaction for immobilizing a ligand is present on the surface of the carrier. Representative 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 succinylimide group, and an acid anhydride group.

As the carrier used in the present invention, any of a hard carrier and a soft carrier can be used. When the carrier is used as an adsorbent for extracorporeal circulation treatment, the carrier is filled in a column and passed therethrough. It is important that clogging does not occur in such cases, and for that purpose, sufficient mechanical strength is required. Therefore, the carrier used in the present invention is more preferably a hard carrier. The term “hard carrier” as used herein means, for example, in the case of a granular gel, as shown in Reference Examples below, the gel is uniformly filled in a cylindrical column, and the relationship between the pressure loss ΔP and the flow rate when flowing an aqueous fluid is 0.3 kg / Cm ^{2 in a} linear relationship.

The adsorbent of the present invention can be obtained by immobilizing a compound having a logP value of 2.50 or more on a porous water-insoluble carrier. As the immobilization method, various known methods can be used without any particular limitation. it can. However, when the adsorbent of the present invention is used for extracorporeal circulation treatment, it is important for safety to minimize desorption and elution of the ligand during sterilization or treatment, and for that purpose, immobilization by a covalent bonding method is required. Is preferred.

There are various methods for using the adsorbent of the present invention for therapy. The simplest method is to derive a body fluid such as a patient's blood outside the body and store it in a blood bag. Is returned to the patient. This method does not require a complicated apparatus, but has the disadvantage that the amount of processing performed at one time is small, the processing takes time, and the operation becomes complicated.

In the following method, the adsorbent is packed in a column, incorporated into an extracorporeal circuit, and adsorbed and removed on-line. Treatment methods include a method of directly perfusing whole blood and a method of separating plasma from blood and then passing the plasma through a column. The adsorbent of the present invention can be used in any method, but is most suitable for online processing as described above.

Although the adsorbent of the present invention can be used alone in the extracorporeal circulation circuit, it can be used in combination with another extracorporeal circulation treatment system. Examples of the combination include an artificial dialysis circuit and the like, and can be used in combination with dialysis therapy.

Next, the glycated and denatured protein adsorption device of the present invention using the glycated and denatured protein adsorbent will be described with reference to FIG. 1 which is a schematic sectional view of one embodiment of the device.

In FIG. 1, 1 is a body fluid inlet, 2 is a body fluid outlet, 3 is a saccharified and denatured protein adsorbent of the present invention, and 4 and 5 are saccharified and denatured components which can pass through the body fluid and components contained in the body fluid. A filter through which the protein adsorbent cannot pass, 6 a column, and 7 a saccharified denatured protein adsorption device. However, the glycated denatured protein adsorption device is not limited to such a specific example, but is provided in a container having an inlet and an outlet for a liquid and having a device for preventing the glycated denatured protein adsorbent from flowing out of the container. Any material may be used as long as it is filled with the adsorbent. Examples of the outflow prevention device include a filter such as a mesh, a nonwoven fabric, and a cotton plug. 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 is a material having sterilization resistance, and specific examples include silicon-coated glass, polypropylene, vinyl chloride, polycarbonate, polysulfone, and polymethylpentene.

Hereinafter, the adsorbent of the present invention will be described in more detail based on examples, but the present invention is not limited to these.

REFERENCE EXAMPLE Agarose gel (Biogel A-5m, manufactured by Bio-rad, particle size: 50 mm) was placed on a cylindrical glass column (inner diameter: 9 mm, column length: 150 mm) equipped with a filter having a pore size of 15 μm at both ends.
-100 mesh), vinyl polymer gel (Toyopearl HW-65 manufactured by Tosoh Corporation, particle size 50-100 μm) and cellulose gel (Cellulofine GC manufactured by Chisso Corporation)
-700m, particle size 45 ~ 105μm)
Water was flowed by a peristaltic pump, and the relationship between the flow rate and the pressure loss ΔP was determined. The result is shown in FIG.

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

Example 1 GCL-2000m, a cellulosic porous hard gel (manufactured by Chisso Corp., molecular weight cutoff of globular protein of 3,000,000) 1
After adding water to 70 ml to make the total amount 340 ml, 90 ml of 2M sodium hydroxide was added to bring the temperature to 40 ° C. To this, 31 ml of epichlorohydrin was added and reacted at 40 ° C. with stirring for 2 hours. After the completion of the reaction, the resultant was sufficiently washed with water to obtain an epoxidized gel.

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

To 0.2 ml of the adsorbent was added 0.1 M PBS (pH 7.
1.2 ml of plasma of a diabetic patient diluted 10-fold with 2, calcium and magnesium) was added, and the mixture was shaken in a thermostat at 37 ° C for 1 hour. The mixture was centrifuged at 3000 rpm for 5 minutes to precipitate the adsorbent, and the concentration of glycated denatured protein and the total amount of protein in the supernatant were measured. There are many methods for measuring the concentration of glycated denatured protein.
Glycosylation End Products in Patients with Diabetic Nephropathy;
The New England Journal of Medicine (Advanced Glycosylation End Products in Patient
s with Diabetic Nephropathy; The New England Journ
al. Medicine), vol. 325, p. 836, 1991, p. 838, and measured with a fluorometer (excitation wavelength: 390 nm, fluorescence wavelength: 450 nm). The total amount of protein was measured by an absorptiometer (280 nm) according to a conventional method. Table 1 shows the results.

Example 2 A dodecylamine-immobilized gel was obtained in the same manner as in Example 1 except that n-octylamine was changed to dodecylamine (Δf = 5.10). Using this adsorbent, an adsorption experiment was performed in exactly the same manner as in Example 1. Table 1 shows the results.

Example 3 A cetylamine-immobilized gel was obtained in the same manner as in Example 1, except that n-octylamine was changed to cetylamine (Δf = 7.22). Using this adsorbent, an adsorption experiment was performed in exactly the same manner as in Example 1. Table 1 shows the results.

Example 4 10 ml of t-butyl alcohol and 2.0 g of potassium butoxide were added to 10 ml of the same gel GCL-2000m as used in Example 1, and the mixture was stirred at 40 ° C. for 1 hour. Next, 2.0 ml of cetyl bromide (Δf = 9.31 after immobilization) was added, and the mixture was stirred for 4 hours. After the reaction, the gel was separated by filtration and washed with ethanol and water to obtain a cellulose gel having cetyl groups immobilized with ether bonds. Using this adsorbent, an adsorption experiment was performed in exactly the same manner as in Example 1. Table 1 shows the results.

Example 5 N-octylamine was replaced with cetylamine (Δf) by using a carrier as a porous cellulose gel, GC-700m (manufactured by Chisso Corp., molecular weight of exclusion limit of globular protein was 400,000 after immobilization of ligand). = 7.22), and a cetylamine-immobilized gel was obtained in the same manner as in Example 1. Using this adsorbent, an adsorption experiment was performed in exactly the same manner as in Example 1. Table 1 shows the results.

Example 6 N-octylamine was replaced with cetylamine (Δf) by using a carrier made of GC-100m, a cellulosic porous gel (manufactured by Chisso Corp., the molecular weight of exclusion of spherical proteins was 30,000 after immobilization of ligand). = 7.22), except that cetylamine-immobilized gel was obtained in the same manner as in Example 1. Using this adsorbent, an adsorption experiment was performed in exactly the same manner as in Example 1. Table 1 shows the results.

Example 7 1 ml of the cetylamine-immobilized gel obtained in Example 3 was mixed with a small polypropylene column, Sepacol Mini PP.
(Trade name, manufactured by Seikagaku Corporation)
MPBS (pH 7.2, calcium and magnesium free)
6 ml of a 10-fold diluted plasma of a diabetic patient was flowed. The flow rate was adjusted to about 0.1 ml / min with a peristaltic pump. The concentration of glycated denatured protein and the total amount of protein in this effluent were measured. The measurement was performed in the same manner as in Example 1. Table 1 shows the results.

Comparative Example 1 n-octylamine was converted to n-hexylamine (log P = 2.06)
A hexylamine-immobilized gel was obtained in the same manner as in Example 1 except that the gel was changed to 1. Using this adsorbent, an adsorption experiment was performed in exactly the same manner as in Example 1. Table 1 shows the results.

Comparative Example 2 n-hexylamine was prepared in the same manner as in Example 1 except that the carrier was changed to GC-100m which is a cellulosic porous gel, and n-octylamine was changed to n-hexylamine (logP = 2.06). An immobilized gel was obtained. Using this adsorbent, an adsorption experiment was performed in exactly the same manner as in Example 1. The results are shown in Table 1. Comparative Example 3 The carrier was GCL-90m (manufactured by Chisso Corporation, the exclusion limit molecular weight of globular protein was 15000 after immobilization of the ligand) as a cellulose-based porous gel, and n-octylamine was cetylamine. A cetylamine-immobilized gel was obtained in the same manner as in Example 1 except that (Δf = 7.22) was used. Using this adsorbent, an adsorption experiment was performed in exactly the same manner as in Example 1. Table 1 shows the results.

Comparative Example 4 The procedure of Example 7 was repeated except that the cetylamine-immobilized gel was changed to GCL-2000m, a cellulose-based porous hard gel (manufactured by Chisso Corp., molecular weight cut-off of globular protein of 3,000,000). An adsorption experiment was performed. Table 1 shows the results.

[0045]

[Table 1]

[0046]

The adsorbent of the present invention is inexpensive and has the effect of efficiently adsorbing and removing saccharified denatured proteins contained in body fluids.

[Brief description of the drawings]

FIG. 1 is a schematic cross-sectional view of one embodiment of a glycated and denatured protein adsorption device of the present invention.

FIG. 2 is a graph showing the results of examining the relationship between flow rate and pressure loss using three types of gels.

[Explanation of symbols]

DESCRIPTION OF SYMBOLS 1 Inlet of body fluid 2 Outlet of body fluid 3 Saccharified denatured protein adsorbent 4, 5 Filter which can pass the body fluid and the components contained in the body fluid but cannot pass the glycated denatured protein adsorbent 6 Column 7 Saccharified denatured protein adsorption device

──────────────────────────────────────────────────続 き Continued on front page (58) Field surveyed (Int.Cl. ⁷ , DB name) B01J 20/00-20/34

Claims (5)

(57) [Claims] 1. A saccharified and denatured protein adsorbent obtained by immobilizing a compound having a logP value (P is a partition coefficient in an octanol-water system) of 2.50 or more on a porous water-insoluble carrier. 2. The saccharified and denatured protein adsorbent according to claim 1, wherein the exclusion limit molecular weight of the porous water-insoluble carrier is 20,000 or more. 3. The saccharified and denatured protein adsorbent according to claim 1, wherein the porous water-insoluble carrier is hydrophilic. 4. A saccharified denatured protein adsorbent obtained by immobilizing a compound having a logP value (P is a partition coefficient in an octanol-water system) of 2.50 or more on a porous water-insoluble carrier is brought into contact with a body fluid containing a saccharified denatured protein. A method for removing a glycated and denatured protein, the method comprising: 5. In a container having an inlet and an outlet for a liquid and provided with a device for preventing the saccharified denatured protein adsorbent from flowing out of the container, a porous water-insoluble carrier contains logP (P is octanol-
A saccharified denatured protein adsorption device comprising a saccharified denatured protein adsorbent obtained by immobilizing a compound having a value of a partition coefficient in an aqueous system of 2.50 or more.