JP2014135976A - Adsorbent of basic fibroblast growthfactor and utilization thereof - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an adsorbent and an adsorption removal system of basic fibroblast growthfactors which can adsorb and remove selectively the basic fibroblast growthfactors regarded as aggravating factors in various kinds of nephrotic syndromes including diabetic nephropathy from liquid such as body fluid containing the basic fibroblast growthfactors.SOLUTION: An adsorption removal system uses an adsorption removal column 7 of basic fibroblast growthfactors characterized in that an adsorbent 3 of the basic fibroblast growthfactors made by stabilizing ligand having an acid functional group to a porous carrier having water-insoluble and hydrophilic properties is packed in a column 6 having a liquid entrance 1 and exit 2 with packing outflow inhibition mechanisms 4 and 5.

Description

The present invention relates to an adsorbent for basic fibroblast growth factor, an adsorption removal system using an adsorbent for basic fibroblast growth factor, and a method for adsorbing and removing basic fibroblast growth factor from a liquid.
By treating a liquid such as a body fluid containing a basic fibroblast growth factor with the adsorbent for basic fibroblast growth factor according to the present invention, the liquid can be cleaned. The present invention also relates to a system for adsorbing and removing basic fibroblast growth factor, which can be expected as a method for treating or preventing various diseases that are considered to be associated with an increase in the amount of basic fibroblast growth factor in the body.

  Basic fibroblast growth factor (b-FGF, FGF-2) is a potent angiogenic factor widely distributed in the human body belonging to the fibroblast growth factor (FGF) family, fibroblasts, In addition to epidermal cells and vascular endothelial cells, it is known to show cell proliferation action in various cells. Basic fibroblast growth factor has a strong affinity for heparin and a basic isoelectric point (basic pI), and its molecular weight is known to be about 13,000 to 19,000. ing.

  In certain types of nephrotic syndrome, the concentration of basic fibroblast growth factor in the patient's blood is increased, and it is known that the basic fibroblast growth factor signal is an exacerbation factor (Non-Patent Documents 1 to 3). 5).

  Among nephrotic syndrome in which basic fibroblast growth factor signal is an exacerbation factor, diabetic nephropathy, which is a primary disease of patients with chronic renal failure introduced into dialysis therapy, tends to increase (Non-Patent Document 6). ).

  Treatment methods include early nephropathy, glycemic control (less than 6.5% HbA1c), blood pressure control (less than 130/80 mmHg, mainly ACE inhibitors and angiotensin receptor antagonists), lipid management (statins), low It is recommended that patients with diabetic nephropathy who have actively intervened by administration of dose aspirin, lifestyle guidance, etc., and that have advanced stage of disease, together with diet therapy such as protein restriction (Non-patent Document 7).

  Further, as a method for adsorbing basic fibroblast growth factor, a method in which a basic fibroblast growth factor-containing solution is brought into contact with a strong cation exchange matrix is known. (Patent Document 1).

  However, this adsorption method is a method of adsorbing basic fibroblast growth factor derived from a lysate derived from a crude cell culture or a tissue such as the pituitary gland. There is no known method for adsorbing and removing factors. Development of a method for adsorbing and removing basic fibroblast growth factor from a fluid such as a body fluid is required as a fundamental treatment method for removing a pathogenic substance from the body.

Japanese Patent Laid-Open No. 11-315097

Pediatr Nephrol, 1999, 13, 586-593 J Am Soc Nephrol, 2001, 12, 2787-2796. J Clin Invest, 1995, 96, 2809-2819 Kidny Int, 1995, 48, 1435-1450 Am J Physiol Renal Physiol, 2009, 296, 1452-1463 Japan Dialysis Medical Association Statistical Survey Committee, Current Status of Chronic Dialysis Therapy in Japan, as of December 31, 2011 Japan Nephrological Society, CKD Clinical Practice Guidelines 2009

  The problem to be solved by the present invention with respect to the above-mentioned problems of the prior art is that basic fibroblast growth factor, which is considered an exacerbation factor in various nephrotic syndromes including diabetic nephropathy, To provide an adsorbent for basic fibroblast growth factor that can be selectively removed from a liquid containing fibroblast growth factor, and a system for adsorbing and removing basic fibroblast growth factor composed of the adsorbent There is.

  As a result of intensive studies to solve the above-mentioned problems, the present inventors have come up with the present invention. That is, the present invention relates to an adsorbent for basic fibroblast growth factor obtained by immobilizing a ligand having an acidic functional group on a water-insoluble and hydrophilic porous carrier.

  In the present invention, the acidic functional group-containing ligand is preferably at least one ligand having at least one functional group selected from the group consisting of a sulfate group, a carboxyl group, and a sulfo group, and the acidic functional group It is preferable that the ligand having is at least one selected from the group of dextran sulfate, polyacrylic acid, and polystyrene sulfonic acid.

  The present invention also relates to a method for adsorbing and removing basic fibroblast growth factor, comprising contacting the adsorbent for basic fibroblast growth factor with a liquid containing basic fibroblast growth factor.

  The liquid is preferably a method for adsorbing and removing a basic fibroblast growth factor, which is blood or plasma.

  The present invention also provides the basic fibroblast growth factor adsorbent, which is packed in a column having a liquid inlet and outlet and having a packing outflow prevention mechanism. This relates to an adsorption removal column.

  The present invention also relates to a basic fibroblast growth factor adsorption / removal system comprising the basic fibroblast growth factor adsorption / removal column.

  The present invention also relates to the adsorbent for basic fibroblast growth factor, which is used for treating a disease exhibiting nephrotic syndrome.

  Further, the disease exhibiting nephrotic syndrome in the present invention is preferably diabetic nephropathy, hemolytic uremic syndrome, peritoneal fibrosis, focal glomerulosclerosis, and membranous nephropathy.

  The present invention also provides a method for adsorbing and removing a basic fibroblast growth factor, which is used for treating a disease exhibiting the nephrotic syndrome.

  The present invention also relates to an adsorption / removal column for basic fibroblast growth factor, which is used for treating a disease exhibiting the nephrotic syndrome.

  The present invention also relates to an adsorption removal system for treating a disease exhibiting the nephrotic syndrome.

  According to the present invention, it is possible to remove basic fibroblast growth factor considered to be an exacerbation factor of various nephrotic syndromes including diabetic nephropathy from a fluid containing basic fibroblast growth factor such as body fluid. It becomes possible.

  By using the present invention, treatment or prevention of various diseases that are considered to be associated with an increase in the amount of basic fibroblast growth factor in the body can be expected.

  Moreover, according to the present invention, it is possible to clean a liquid by treating the liquid such as a body fluid that may contain a basic fibroblast growth factor with the present invention.

It is a figure which shows one embodiment of the adsorption removal column of the basic fibroblast growth factor in this invention.

  Hereinafter, an embodiment of the present invention will be described, but the present invention is not limited thereto.

  The present invention relates to a basic fibroblast growth factor adsorbent obtained by immobilizing a ligand having an acidic functional group on a water-insoluble and hydrophilic porous carrier, and the adsorbent as a basic fibroblast growth factor. A basic fibroblast growth factor characterized in that it is packed in a column having a liquid inlet and outlet, and having a packing outflow prevention mechanism, the method comprising adsorbing and removing the liquid; The present invention relates to an adsorption removal column and a system for adsorbing and removing a basic fibroblast growth factor comprising the adsorption removal column.

  In the adsorbent of the present invention, the acidic functional group refers to a functional group that is negatively charged near a neutral pH. Representative examples of such functional groups include, but are not limited to, carboxyl groups, sulfate ester groups, sulfo groups, silanol groups, phosphate ester groups, phenolic hydroxyl groups, and the like. Moreover, the acidic functional group which the adsorption material of this invention has may be one type, and may be 2 or more types.

  Examples of ligands having an acidic functional group immobilized on a porous carrier that can be used as an adsorbent in the present invention include polyacrylic acid, polyvinyl sulfuric acid, polyvinyl sulfonic acid, polyvinyl phosphoric acid, polystyrene sulfonic acid, polystyrene phosphor Synthetic polyanionic compounds such as acid, polyglutamic acid, polyaspartic acid, polymethacrylic acid, polyphosphoric acid, styrene-maleic acid copolymer, polysaccharides having acidic functional groups such as heparin, dextran sulfate, chondroitin sulfate, phosphomannan, etc. However, the present invention is not limited to these representative examples. Among them, a polymer compound having an acidic functional group is preferable because it has a high affinity for basic fibroblast growth factor and can easily introduce many acidic functional groups per unit amount of the porous carrier. Furthermore, a polymer compound having an acidic functional group having a molecular weight of 1000 or more is more preferable in view of affinity for basic fibroblast growth factor and introduction of many acidic functional groups. The number of the ligand having an acidic functional group may be one, or two or more, but preferably the ligand having an acidic functional group is selected from dextran sulfate, polyacrylic acid, and polystyrene sulfonic acid. It is derived from at least one compound and may be derived from two or more compounds.

  When adsorbing basic fibroblast growth factor, the ligand having an acidic functional group in the present invention is preferably contained in an amount of 100 nmol to 10 mmol per unit volume (1 ml) of the water-insoluble carrier. Preferably, it is 1 μmol to 200 μmol, most preferably 5 μmol to 100 μmol. When the amount is less than 100 nmol, the effect of the ligand having an acidic functional group is small. When the amount is more than 10 mmol, nonspecific adsorption other than the basic fibroblast growth factor occurs.

The carrier that can be used in the present invention is a water-insoluble material that is solid at normal temperature and pressure and has extremely low solubility in water. Examples of the shape of the carrier include, but are not limited to, a granular shape, a plate shape, a fiber shape, a hollow fiber shape, and a non-woven fabric. Examples of the water-insoluble carrier include inorganic carriers such as glass beads, silica gel, and alumina, synthetic polymer carriers such as crosslinked polyvinyl alcohol, crosslinked polyacrylate, crosslinked polyacrylamide, and crosslinked polystyrene, crystalline cellulose, crosslinked cellulose, Organic carriers composed of polysaccharides such as cross-linked agarose and cross-linked dextran, and organic-organic, organic-inorganic and other composite carriers obtained by a combination thereof can be used. Among these, a hydrophilic carrier is preferable because nonspecific adsorption is relatively small and the adsorption selectivity of basic fibroblast growth factor is good. The hydrophilic carrier here refers to a carrier having a contact angle with water of 60 ° or less when the compound constituting the carrier is formed into a flat plate shape. Such carriers include polysaccharides such as cellulose, chitosan, sepharose, dextran, polyvinyl alcohol, saponified ethylene-vinyl acetate copolymer, polyacrylamide, polyacrylic acid, polymethacrylic acid, polymethyl methacrylate, polyacrylic. Representative examples include carriers made of acid-grafted polyethylene, polyacrylamide-grafted polyethylene, glass and the like. Among these, porous cellulose gel is
(A) Since the mechanical strength is relatively high and tough, it is less likely to be broken or generated by operations such as stirring, and when packed in a column, it will become compacted even if the body fluid flows at a high flow rate, It is not clogged, and the pore structure is not easily changed by high-pressure steam sterilization.
(B) Since the gel is composed of cellulose, it is hydrophilic, there are many hydroxyl groups that can be used for ligand binding, and there is little non-specific adsorption.
(C) Even if the pore volume is increased, an adsorption capacity not inferior to that of a soft gel can be obtained because of its relatively high strength.
(D) It has excellent points such as high safety compared to synthetic polymer gels and the like, and is a carrier that can be suitably used in the present invention.
In the present invention, the carrier is not limited to the above. In addition, each said support | carrier may be used independently, and arbitrary 2 or more types may be mixed and used for it.

  In addition, as a method for immobilizing a ligand having an acidic functional group on a water-insoluble carrier, when the acidic functional group itself is introduced directly into the water-insoluble carrier, or an acidic functional group having a moiety other than the acidic functional group in the molecule is used. The case where the compound which has it is introduce | transduced into a support | carrier solid substance is mentioned. A typical example of introducing an acidic functional group directly into a water-insoluble carrier is a method of directly introducing a sulfate ester group or a sulfonic acid group by reacting a reagent such as chlorosulfonic acid or concentrated sulfuric acid with a water-insoluble carrier. Although it is mentioned, it is not limited to these.

  In addition, when introducing a compound having an acidic functional group having a moiety other than an acidic functional group in the molecule, a physical adsorption method, an ionic bond method, a covalent bond method, a method of performing chemical treatment with acid, alkali, etc., heat treatment Various methods known in the art such as hydrolysis, radiation and plasma treatment to introduce graft chains can be used without any particular limitation. However, in order to maintain the storage stability and stability of the adsorbent, acidic functionalities can be used. Since it is important that the compound having a group does not leave, a covalent bond method capable of strong fixation is desirable.

  In the case of immobilizing a compound having an acidic functional group by covalent bond, it is preferable that the compound having an acidic functional group is multifunctional having a functional group that can be used for immobilization in addition to the acidic functional group. You may fix using a functional group.

  Representative examples of functional groups that can be used for immobilization include amino groups, amide groups, carboxyl groups, acid anhydride groups, succinimide groups, hydroxyl groups, thiol groups, aldehyde groups, halogen groups, epoxy groups, and silanol groups. However, it is not limited to these.

  For example, when a compound having a sulfate ester group is immobilized on a water-insoluble carrier by a covalent bond, typical examples of the compound having a sulfate ester group include sulfated products of compounds having a hydroxyl group such as alcohol, saccharide and glycol. However, among them, the partial sulfate ester of polyhydric alcohol, especially the sulfate ester of polysaccharide contains both sulfate ester group and functional group necessary for immobilization, and it is easily immobilized on water-insoluble carrier. This is particularly preferable because it can be performed.

  In addition to the above-described method for immobilizing a ligand having an acidic functional group on a water-insoluble carrier, an acidic functional group or a compound having a functional group that can be converted to an acidic functional group is used as a monomer or a cross-linking agent to perform polymerization or copolymerization. There is also a method of forming a water-insoluble carrier having an acidic functional group. Representative examples of the monomer having an acidic functional group include, but are not limited to, acrylic acid, methacrylic acid, and styrene sulfonic acid. In addition, the monomer that can be converted to an acidic functional group is not particularly limited as long as it can be converted to an acidic functional group, but an acrylic acid ester, a methacrylic acid ester, and the like can be easily converted to an acidic functional group by a reaction such as alkali saponification. Can be preferably used.

  And the water-insoluble support | carrier which has an acidic functional group can be obtained by superposing | polymerizing the monomer which has an acidic functional group represented by these, or copolymerizing using 2 or more types. Furthermore, a water-insoluble carrier having an acidic functional group can also be obtained by copolymerizing a monomer having an acidic functional group typified by these and a monovinyl monomer typified by, for example, styrene or chlorostyrene. Furthermore, it can be obtained by copolymerizing a polyvinyl monomer represented by divinylbenzene, trivinylbenzene or the like as a crosslinking agent.

  The adsorbent in the present invention can adsorb basic fibroblast growth factor only by its outer surface, but has pores of an appropriate size for adsorbing more basic fibroblast growth factor. It is preferable to use a carrier having a large porous structure. Although it is not particularly limited as long as it has a porous structure, a carrier having a three-dimensional structure such as a polymer network, a monolith carrier in which at least a part of pores in the carrier penetrates, etc. Can be mentioned.

  In addition, the water-insoluble carrier having a porous structure as described above has a high probability that the basic fibroblast growth factor is contained in the pores in order to efficiently adsorb the basic fibroblast growth factor to be adsorbed. It is preferred that it can penetrate and 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 pores. Exclusion limit molecular weight means the molecular weight of the smallest molecular weight that cannot enter (exclude) into the pores in gel permeation chromatography (Hiroyuki Hatano, Toshihiko Hanai, Experimental High Performance Liquid Chromatograph, Chemistry) Coterie). The exclusion limit molecular weight is generally examined for globular proteins, dextran, polyethylene glycol, and the like, but in the case of the carrier used in the present invention, it is appropriate to use values obtained using globular proteins.

  In the adsorption of basic fibroblast growth factor, the amount of basic fibroblast growth factor adsorbed and removed tends to be lower when a carrier whose exclusion molecular weight is smaller than that of basic fibroblast growth factor is used. is there. Therefore, the carrier used for adsorption of the basic fibroblast growth factor is preferably a carrier having an exclusion limit molecular weight of 20,000 or more, more preferably 30,000 or more.

  As long as plasma or serum is used as the liquid containing the basic fibroblast growth factor, there is no particular upper limit on the exclusion limit molecular weight, but when using blood, the exclusion limit molecular weight is preferably 5 million or less, preferably 2 to 500 It is especially preferable that it is 10,000, and it is still more preferable that it is 3-5 million. When the exclusion limit molecular weight exceeds 5,000,000, the rate of platelet adhesion tends to increase, and when the adsorbent of the present invention is used in a direct blood perfusion (DHP) type blood purification system, sufficient performance is not necessarily exhibited. There is a tendency not to. Note that the preferable range of the exclusion limit molecular weight is basically the same even if the water-insoluble carrier is granular, plate-like, or fiber-like.

  Liquids that can be treated in the present invention include blood, plasma, serum, ascites, lymph, intra-articular fluid, bone marrow fluid, fraction components obtained therefrom, and other basic components such as liquid components derived from living organisms. A liquid such as a body fluid containing fibroblast growth factor can be mentioned, but it is not particularly limited as long as it is a liquid containing basic fibroblast growth factor, and water or a buffer solution may be used.

  Regarding the method for adsorbing and removing the basic fibroblast growth factor in the present invention, as a preferred embodiment, the basic fibroblast is removed from the liquid by bringing the adsorbent of the basic fibroblast growth factor into contact with a liquid such as a body fluid. A method of adsorbing and removing growth factors can be mentioned. More specifically, body fluid is taken out and stored in a bag or the like, adsorbent is mixed with this to adsorb and remove the basic fibroblast growth factor, and then the adsorbent is filtered to remove basic fibroblast growth factor. A column with a batch method, a body fluid inlet and outlet, and a container equipped with a filter equipped with a filter that allows body fluid to pass through the inlet and outlet but not through the adsorbent. Can be obtained by flowing a body fluid under normal pressure or under pressure to obtain a body fluid from which basic fibroblast growth factor has been continuously removed. A combination of an equation and a continuous equation can also be used. Either method can be preferably used, but the continuous method using the column packed with the adsorbent is easy to operate, and by incorporating it into the extracorporeal circuit, it can be efficiently and online from the patient's body fluid, Basic fibroblast growth factor can be removed, and the adsorbent of the present invention can be suitably used in this method.

  When the adsorbent is packed in a column and used, it is preferable that the body fluid can be passed. In other words, it is preferable that a gap can be created through which cells contained in the body fluid can sufficiently pass. For example, when the adsorbent is granular and the basic fibroblast growth factor is adsorbed, it is desirable that the average particle diameter is 5 μm to 1000 μm. Preferably, the average particle size is 25 to 1000 μm, and most preferably the average particle size is 50 to 300 μm. If the average particle size is 5 μm or less, the body fluid cannot be stably passed at a high flow rate for a long time. If it is 1000 micrometers or more, adsorption | suction efficiency will fall. In the case of particles, it is more preferable that the particle size distribution is narrow.

  When the adsorbent is fibrous and hollow, the inner diameter is preferably 5 μm or more, and preferably 20 to 1000 μm, most preferably from the viewpoint that the basic fibroblast growth factor can be adsorbed in a high yield. Is 30-300 μm.

  Moreover, when the inside is a dense fibrous form, the diameter is preferably 1 μm or more, and preferably 2 to 500 μm, most preferably the basic fibroblast growth factor can be adsorbed in a high yield. Preferably, it is 5-200 micrometers.

  The surface of the water-insoluble carrier is preferably smooth, and a rough surface is not preferable because nonspecific adsorption increases and selectivity decreases.

  There are no particular limitations on the shape and material of the container when the adsorbent is packed in a column, and preferred specific examples include a cylindrical container having a capacity of about 150 to 400 ml and a diameter of about 4 to 10 cm.

  In addition, the basic fibroblast growth factor adsorption / removal system of the present invention more effectively adsorbs and removes basic fibroblast growth factor in addition to at least one basic fibroblast growth factor adsorption / removal column. An instrument for the purpose may be incorporated. For example, a pump for flowing a liquid may be arranged, and one or more basic fibroblast growth factor adsorption / removal columns made of adsorbents of two basic fibroblast growth factors are arranged in parallel. Alternatively, they may be incorporated in series.

  The adsorbent of the present invention is a nephrotic syndrome in which basic fibroblast growth factors such as diabetic nephropathy, hemolytic uremic syndrome, peritoneal fibrosis, focal glomerulosclerosis, and membranous nephropathy are considered as exacerbating factors. Can be suitably used for the treatment of diseases and the like. Moreover, it is not limited only to these diseases, It can use suitably also for the disease considered that the increase in the body of other basic fibroblast growth factors is related.

Example 1
(Adsorbent preparation example)
100 ml of porous cellulose beads (exclusion limit molecular weight of globular protein: 5 million, particle size: 45 to 105 μm), 100 ml of water, 50 ml of 2N sodium hydroxide and 17 ml of epichlorohydrin were mixed in a reaction vessel and reacted at 40 ° C. for 2 hours. After the reaction, the beads were sufficiently washed with water to obtain epoxidized cellulose beads. To the obtained epoxidized cellulose beads, 107 ml of a 58% sodium dextran sulfate aqueous solution (sulfur content 18%) was added, adjusted to pH 9 and shaken at 45 ° C. for 22 hours. Thereafter, the gel was separated by filtration and washed with water, and then 1.2 ml of monoethanolamine was added and shaken at 45 ° C. for 2 hours to seal unreacted epoxy groups. Thereafter, it was sufficiently washed with water to obtain dextran sulfate-fixed cellulose beads (adsorbent A).

(Preparation example of basic fibroblast growth factor solution)
Basic fibroblast growth factor (recombinant Human FGF basic (146aa), manufactured by R & D Systems) was prepared at a predetermined concentration in phosphate buffered saline (PBS) 0.1% BSA.

(Evaluation of adsorbent)
Dextran sodium sulfate-immobilized cellulose beads were equilibrated with physiological saline. 0.5 ml of this bead was taken into a test tube, and excess physiological saline was removed. To this, 3 ml of human serum containing about 3000 pg / ml of human basic fibroblast growth factor was added, shaken at 37 ° C. for 2 hours, and 2.5 ml of supernatant was extracted (supernatant A).

  Separately, 3 ml of human serum containing about 3000 pg / ml of human basic fibroblast growth factor was added to 0.5 ml of physiological saline instead of the adsorbent, and the mixture was shaken at 37 ° C. for 2 hours to serve as a control solution.

(Analysis method)
Using the ELISA kit for human basic FGF measurement manufactured by R & D Systems, the basic fibroblast growth factor concentration in the supernatant extracted in the above evaluation was measured, and the obtained basic fibroblast growth factor The adsorption rate was calculated from the concentration of.
The calculation formula for the adsorption rate is shown below.

Adsorption rate (%) = {(Cc1-Ca1) ÷ Cc1} × 100
Cc1: Concentration of basic fibroblast growth factor in control solution Ca1: Concentration analysis result of basic fibroblast growth factor in supernatant A is shown in Table 1.

(Example 2)
(Adsorbent preparation example)
A DALI adsorbent (Fresenius) using polyacrylamide beads as a carrier and polyacrylic acid as a ligand was used (adsorbent B).

(Preparation of basic fibroblast growth factor solution)
Prepared similarly to the method described in Example 1.

(Evaluation of adsorbent)
The DALI adsorbent was equilibrated according to the priming method described in the DALI system instruction manual. 0.5 ml of this adsorbent was placed in a test tube to remove excess priming solution. To this, 3 ml of human serum containing about 3000 pg / ml of human basic fibroblast growth factor was added, shaken at 37 ° C. for 2 hours, and 2.5 ml of supernatant was extracted (supernatant B).

  Separately, 3 ml of human serum containing about 3000 pg / ml of human basic fibroblast growth factor was added to 0.5 ml of the priming solution instead of the adsorbent, and the mixture was shaken at 37 ° C. for 2 hours to serve as a control solution.

(Analysis method)
Analysis was carried out in the same manner as described in Example 1. The analysis results are shown in Table 1.

1. 1. Liquid inlet 2. Liquid outlet 3. Adsorbent of basic fibroblast growth factor 4. Filter that can pass liquid and components contained in liquid but cannot pass through adsorbent of basic fibroblast growth factor. 5. Filter that can pass liquid and components contained in liquid but cannot pass through adsorbent of basic fibroblast growth factor. Column 7. Adsorption removal column of basic fibroblast growth factor

Claims (12)

A basic fibroblast growth factor adsorbent obtained by immobilizing a ligand having an acidic functional group on a water-insoluble and hydrophilic porous carrier. 2. The ligand according to claim 1, wherein the ligand having an acidic functional group is at least one ligand having at least one functional group selected from the group consisting of a sulfate group, a carboxyl group, and a sulfo group. Adsorbent for basic fibroblast growth factor. 3. The basic fibroblast according to claim 1, wherein the ligand having an acidic functional group is at least one selected from the group of dextran sulfate, polyacrylic acid, and polystyrene sulfonic acid. Cell growth factor adsorbent. A method for adsorbing and removing a basic fibroblast growth factor, comprising contacting the adsorbent according to any one of claims 1 to 3 with a liquid containing a basic fibroblast growth factor. The method for adsorbing and removing a basic fibroblast growth factor according to claim 4, wherein the liquid is blood or plasma. A basic fibroblast growth factor characterized in that the adsorbent according to any one of claims 1 to 3 is packed in a column having a liquid inlet and outlet and having a packing outflow prevention mechanism. Adsorption removal column. A system for adsorbing and removing basic fibroblast growth factor, comprising the adsorption removing column according to claim 6. The adsorbent for basic fibroblast growth factor according to any one of claims 1 to 3, which is used for treatment of a disease exhibiting nephrotic syndrome. The basic fibroblast proliferation according to claim 8, wherein the disease exhibiting nephrotic syndrome is diabetic nephropathy, hemolytic uremic syndrome, peritoneal fibrosis, focal segmental glomerulosclerosis, and membranous nephropathy. Factor adsorbent. The method for adsorbing and removing the basic fibroblast growth factor according to claim 5 for treating a disease exhibiting nephrotic syndrome. The column for adsorbing and removing the basic fibroblast growth factor according to claim 6, which is used for treating a disease exhibiting nephrotic syndrome. The system for adsorbing and removing a basic fibroblast growth factor according to claim 7 for treating a disease presenting with nephrotic syndrome.

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