JPH11123329A - Adsorbent for thromboplastin and external circulation column - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an adsorbent for thromboplastin which has a high degree of safety and can be generally used and adsorbs efficiently and selectively lipoprotein of low specific gravity, lipoprotein a, triglyceride, fibrinogen, etc., from body fluids. SOLUTION: The adsorbent for thromboplastin is prepared by graft-bonding an N-alkylated polyalkyleneimine, wherein an N-alkyl group has 4 or more carbon atoms, to a water-insoluble polymer. And an N-alkylated polyalkyleneimine, wherein the N-alkylation ratio is 1% or more and the ratio of the number of carbon atoms/the number of nitrogen atoms is 2.3-26, may be preferably used. The adsorbent is filled into a column for external circulation when it is used.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to cholesterol,
The present invention relates to an adsorbent for a thrombus-forming substance for removing a substance that induces formation of a thrombus if present in blood such as lipoproteins and fibrinogen, and an extracorporeal circulation column filled with the adsorbent. is there.

[0002]

2. Description of the Related Art In recent years, it has been revealed that lipid components such as low-density lipoprotein, lipoprotein a and triglyceride in blood cause arteriosclerosis. Also,
Fibrinogen is an important blood component having a hemostatic effect, but if it is too much, it becomes a risk factor for arteriosclerosis.
As atherosclerosis progresses, the possibility of serious circulatory symptoms such as myocardial infarction and cerebral infarction becomes very high, and mortality rate is high. Therefore, if it is possible to selectively adsorb and remove low-density lipoprotein, lipoprotein a, triglyceride, fibrinogen, and the like from body fluid components such as blood and plasma, it is possible to prevent the progression of the disease as described above or to alleviate symptoms. It is expected that healing will be further accelerated.

Conventionally, adsorbents for lipid components and the like for the above-mentioned purposes include dextran sulfate immobilized on a cellulose gel (JP-A-1-280469) and heparin immobilized on an agarose gel (Lupien). , PJ, e
t.al. Lancet, 2: 1261-1264, 1976), and vinyl polymers having a sulfonic acid group (Japanese Patent Publication No. 8-8928), and the like.
It activates kallikrein in the blood and induces the release of bradykinin, lowering blood pressure, which makes it difficult to use, and because they are granular, they have a small surface area and therefore a small adsorption capacity, and furthermore they have a large swelling property Since it is a hydrous gel, there is a problem that the liquid permeation resistance is large.

[0004]

SUMMARY OF THE INVENTION An object of the present invention is to disseminate generally and to selectively adsorb low-density lipoprotein, lipoprotein a, triglyceride, fibrinogen and the like from body fluids with high efficiency, and Another object of the present invention is to provide a highly safe thrombus-forming substance adsorbent.

Another object of the present invention is to provide an extracorporeal circulation column filled with the above-mentioned thrombus-forming substance adsorbent.

[0006]

In order to achieve such an object, the present invention has the following arrangement.

That is, the adsorbent for a thrombogenic substance of the present invention is characterized by comprising a water-insoluble polymer obtained by graft-bonding an N-alkylated polyalkyleneimine having an N-alkyl group having 4 or more carbon atoms. Is what you do.

[0008] The thrombogenic substance adsorbent of the present invention further includes the following preferred embodiments.

(1) The N-alkylated polyalkylenimine has an N-alkylation ratio of 1% or more and a carbon number / nitrogen number ratio of 2.3 to 26.

(2) The N-alkylated polyalkyleneimine is an N-alkylated ethyleneimine polymer having a degree of polymerization of 10 or more and 10,000 or less.

(3) The water-insoluble polymer is a polysulfone having an amine-binding group.

(4) The water-insoluble polymer is a poly (vinyl aromatic compound) having an amine-binding group.

(5) The water-insoluble polymer is a polyimide.

(6) The water-insoluble polymer is formed into a membrane, a fiber, a hollow fiber, a granular material, or an assembly using the same.

(7) The water-insoluble polymer is applied to the surface of a molded article such as a membrane, a fiber, a hollow fiber or a granular material.

(8) Heparin is adsorbed.

The extracorporeal circulation column of the present invention is packed with the adsorbent for the above-mentioned thrombus-forming substance.

[0018]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in more detail.

The adsorbent for a thrombus-forming substance referred to in the present invention is:
An N-alkylated polyalkyleneimine is added to the water-insoluble polymer, preferably having an amino group content of 0.1 to 10 mmol / g.
Any material may be used as long as it is graft-bonded so as to obtain, and there is no particular limitation.

The water-insoluble polymer used herein is not particularly limited as long as it is insoluble in water and can immobilize an N-alkylated polyalkyleneimine by a covalent bond. Specific examples of the water-insoluble polymer include an aromatic polyvinyl compound represented by polystyrene and poly (p-phenylene ether sulfone):-｛(p-C ₆ H ₄ )-
SO _2- (p-C ₆ H ₄ ) -O-｝ n- or Udel polysulfone:-｛(p-C ₆ H ₄ ) -SO _2- (p-C
_{6 H 4) -O- (p-} C 6 H 4) -C (CH 3) 2 -
_{(P-C 6 H 4)} -O} n- In _{addition, - {(p-C 6} H
_{4) -SO 2 - (p-} C 6 H 4) -O- (p-C
₆ H ₄ ) -O｝ n-,-｛(p-C ₆ H ₄ ) -SO _{2-
(P-C 6 H 4)} -S- (p-C 6 H 4) -O} n-,
-｛(P-C ₆ H ₄ ) -SO _2- (p-C ₆ H ₄ ) -O
_{- (p-C 6 H 4} ) -C (CF 3) 2 - (p-C
Polysulfone, polyetherimide, polyamide, polyimide, polyether, polyphenylene sulfide, etc. represented by ₆ H ₄ ) -O｝ n-
Those having a reactive functional group capable of immobilizing an alkylated polyalkyleneimine by a covalent bond are exemplified.

The reactive functional group includes an active halogen group such as a halomethyl group, a haloacetyl group, a haloacetamidomethyl group, a halogenated alkyl group, an epoxide group, a carboxyl group, an isocyanic acid group, a thioisocyanic acid group and an acid anhydride group. Among them, active halogen groups are particularly easy to produce, have high reactivity, can perform the immobilization reaction under mild conditions, and the covalent bond generated at this time is chemically stable. It is preferably used in the present invention.

Further, specific examples of the water-insoluble polymer having a reactive functional group include chloroacetamidomethylpolystyrene and chloroacetamidomethylated Udel®.
Examples thereof include polysulfone and chloroacetamidomethylated polyetherimide. Further, these polymers are particularly preferable if they are soluble in an organic solvent because they are easy to mold.

The molecular weight of the water-insoluble polymer and copolymer is not particularly limited as long as it can be molded, and is not particularly limited.
Usually, 5,000 to 1,000,000, especially 10,000 to 200,000 are preferably used.

In the present invention, the N-alkylated polyalkylenimine is a nitrogen atom of a polyalkylenimine represented by polyethyleneimine, polyhexamethyleneimine and poly (ethyleneimine / decamethyleneimine) copolymer. Is alkylated with a halogenated hydrocarbon singly or as a mixture represented by n-hexyl bromide, n-decanyl bromide, n-stearyl bromide and the like. Such an N-alkylated polyalkyleneimine has the length of the alkylene group in the main chain and the N-alkylated group.
Depending on the number of alkyl carbon atoms of the alkyl group and the N-alkylation ratio, the adsorption performance and the ease of processing vary.

As the parameter, in the present invention, N-
An N-alkylated polyalkyleneimine whose alkyl group has 4 or more alkyl carbon atoms is used. When the number of carbon atoms is small, there is a drawback that cholesterol adsorption is lowered. In addition, halides having a long alkyl group having an alkyl carbon number of 20 or more are generally expensive, and if too large, it is difficult to dissolve in the solvent of the N-alkylated polyalkyleneimine, and it is difficult to purify the imine-immobilized polymer. Therefore, usually 18 or less are used.

When the ratio of the number of carbon atoms to the number of nitrogen atoms in the whole molecule (hereinafter abbreviated as C / N ratio) and the N-alkylation ratio are used, when the C / N ratio is too small, the hydrophilicity is reduced. If it is too high and processing is difficult, on the other hand, if it is too large, the adsorptivity will decrease, so the C / N ratio is preferably 2.3 to 26, and particularly preferably 2.5 to 14. Also, N-
If the alkylation rate is too small, the adsorption capacity will decrease,
The N-alkylation rate is preferably at least 1%, in particular 1%.
It is preferably 0% or more.

Further, the higher the degree of polymerization (n) of the N-alkylated polyalkyleneimine, the higher the adsorption performance to a high molecular weight substance is. However, if the degree of polymerization is too large, the graft chain is fixed in an extended form. N = 10-10,000
Is preferable, and especially 20 to 300 is preferable. Further, a part of the alkylene portion of the main chain portion of the N-alkylated polyalkyleneimine may be substituted with a cyclohexane ring, a benzene ring, or the like, or may be substituted with an amide group, an ether group, a sulfone group, or the like. Is also good.

In the present invention, the density of immobilization of the N-alkylated polyalkyleneimine group is determined by the C / N ratio and the size of n of the N-alkylated polyalkylenimine and the chemical structure and application of the water-insoluble polymer serving as the trunk. Depends on
If the immobilization density is too low, its function will not be exhibited,
On the other hand, if the amount is too large, the moldability of the polymer after immobilization becomes poor, and the function as a blood treating agent also decreases. Therefore, the density is preferably 0.0001 to 0 per repeating unit of the water-insoluble polymer. .5, more preferably 0.001
０．１0.1 mol.

The preparation of the N-alkylated polyalkylenimine used in the present invention is carried out by mixing a solution of the polyalkylenimine with a halogenated hydrocarbon such as an alkyl bromide at a temperature from room temperature to 100 ° C. or less. It can be done easily. This reaction involves ethyl alcohol,
It proceeds quantitatively even at room temperature in polar solvents such as tetrahydrofuran and dimethylformamide. When the molecular weight of the polyalkyleneimine is large and the N-alkylation rate is high, the N-alkylated polyalkyleneimine becomes difficult to dissolve in the solvent, so that the low alkylation rate is reacted with the water-insoluble polymer. Further, the above-mentioned alkyl bromide is added to the reaction system to obtain a target alkylation ratio of N
A method for obtaining an alkylated polyalkyleneimine is convenient.

In order to produce the adsorbent for a thrombus-forming substance of the present invention, a method of a homogeneous reaction in which a water-insoluble polymer and an N-alkylated polyalkyleneimine are made into a solution and reacted,
There is a heterogeneous reaction method in which an N-alkylated polyalkyleneimine solution is brought into contact with a water-insoluble polymer molded article.

An example of a method using a homogeneous reaction is as follows.
By adding the corresponding polyamine to a solution of chloroacetamidomethylated polysulfone and reacting at a temperature of 0 to 100 ° C., it can be easily synthesized and produced. The amount of the polyamine is not particularly limited, but is preferably at least 1 mole per haloacetamidomethyl group in order to obtain a soluble polymer. In particular, in the case of a branched polyamine, it is preferable to use a large excess of the polyamine in order to obtain a soluble polymer.

As the reaction solvent for the reaction in a homogeneous system, tetrahydrofuran, dimethylsulfoxide, N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone and the like are preferably used.

In the present invention, a method for surface-treating a molded article is also possible. For this purpose, a solvent which does not dissolve polysulfone such as water, methanol or ethanol but dissolves polyamine is preferably used.

As an example of the method of the heterogeneous reaction, a molded article such as chloroacetamidomethylated polysulfone fiber or hollow fiber is immersed in an N-alkylated polyalkyleneimine solution in isopropanol, and then heated to a temperature of 0 to 100 ° C. And can be easily produced.

The adsorbent of the present invention can be used by directly shaping the adsorbent into a fibrous form or a film form. In addition, when the adsorbent of the present invention is applied to the surface of a molded article such as nylon fiber by coating or the like, a high-order molded article having a large surface area can be easily obtained, which is a practically preferred embodiment in the present invention. .

The coating can be easily performed by immersing a knitted fabric or woven fabric made of nylon fibers or the like in a solution or the like in which the adsorbent of the present invention is dissolved in a low boiling point solvent such as methylene chloride or tetrahydrofuran, and then evaporating the solvent. Can do it. Further, a wet coating method in which a solution dissolved in a solvent such as N, N-dimethylformamide is put into water or the like can also be used.

The molded article to be coated may be any of polyamide, polyurethane, polyimide, polysulfone, polyvinyl chloride, polyester and the like, as long as it has good adhesion to the adsorbent of the present invention. Although there is no limitation, the adsorbent of the present invention has excellent adhesiveness to amide-based polymers such as nylon and polyetherimide, and these polymers are preferably used.

The adsorbent of the present invention can be used for an extracorporeal circulation system. When used in the extracorporeal circulation system, it is preferable to use it after treating it with heparin, an anticoagulant, because it improves the blood compatibility and the ability to adsorb LDL. In particular, when the C / N ratio is high, the adsorbent becomes hydrophobic, but heparin treatment is preferable because the adsorbent becomes hydrophilic and the adsorbability increases.

The adsorbent of the present invention is packed in an extracorporeal circulation column or the like for the purpose of removing thrombus-forming substances such as cholesterol, phospholipids, neutral fats, LDL, lipoprotein A and fibrinogen in blood. Can be used for circulatory treatment. It can also be used for the purpose of removing fat components from blood for transfusion, serum, and plasma.

[0040]

The present invention will be described more specifically with reference to the following examples.

The analysis of components in blood in this example was performed according to the following evaluation method.

1. Total cholesterol (TC) and phospholipid (PL) components were determined by an enzymatic method.

2. Neutral fat (TG) was determined by an enzyme method (free glycerol elimination method).

3. β-lipoprotein (LDL) was determined by cellulose acetate membrane electrophoresis.

4. Albumin was determined by the BCG method.

5. HDL-C is heparin Ca2 +, Ni2 +
Determined by the precipitation method.

Example 1 A mixed solution of 8 mL of nitrobenzene and 16 mL of sulfuric acid was cooled to 0 ° C., and 2.1 g of N-methylol-α-chloroacetamide was added and dissolved. 3L of P3500
To a nitrobenzene solution (300 g / 3 L) with good stirring. It was further stirred at room temperature for 3 hours. Thereafter, the reaction mixture was placed in a large excess of cold methanol to precipitate the polymer. The precipitate was thoroughly washed with methanol and then dried to obtain 300 g of α-chloroacetamidomethylated polysulfone (substitution rate: 0.024; polymer-A).

Further, apart from the above, N-methylol-α-
The charge ratio of chloracetamide was increased, and the same treatment was carried out to obtain α-chloroacetamidomethylated polysulfone having a substitution rate of 10% (substitution rate: 0.1; polymer-B).

Next, polyethyleneimine (average molecular weight 1
0000 g: Wako Pure Chemical Industries, Ltd.) was dissolved in 200 mL of isopropanol, and 149 g of lauryl bromide (0.
6 mol), and the mixture was stirred at room temperature for 1 hour and heated by perfusion for 2 hours. To this was added an isopropanol solution containing 24 g of sodium hydroxide. The sodium bromide crystals generated here are filtered, and the filtrate is concentrated under reduced pressure to give N-laurylated polyethyleneimine (C / N) having a laurylation rate of 60%.
Ratio 9.2) was prepared. Separately, other N-alkylated polyalkyleneimines having different types of alkyl groups and different alkylation rates were prepared in the same manner.

Next, each of 200 mL of tetrahydrofuran solution containing 20 g of polymer-A or B was
20 containing 20 g of N-alkylated polyalkyleneimine
0 mL of a tetrahydrofuran solution was added, and the mixture was heated by perfusion for 2 hours. The reaction mixture was added to a large excess of isopropanol and the precipitated polymer was collected by filtration. The obtained polymer was vacuum-dried to prepare an N-alkylated polyalkyleneimine-immobilized polysulfone as an adsorbent of the present invention.

Next, a 20% dimethylacetamide solution of these polymers was applied on a glass plate, and this was put into water to form a film having a thickness of 100 μm. This has a diameter of 4.
It was cut into a 2 cm disk and used. For a heparinized sample, this membrane was coated with a 0.5 mg / mL heparin / PBS solution 4
After treatment in 0 mL at 60 ° C. for 20 hours, it was prepared by washing with physiological saline.

Two disc-shaped membranes (55.4 cm ² surface area)
Was placed in 4 mL of human serum and shaken at 37 ° C. for 4 hours.
Table 1 shows the results of the adsorption.

However, Sample 1 of the present invention is a polysulfone (C / N ratio of 3.2) membrane in which laurylated polyethyleneimine having a laurylation ratio of 10% (molecular weight of polyethyleneimine is 10,000) is immobilized on polymer-A. And the sample 2 of the present invention
A membrane of polysulfone (C / N ratio: 9.2) in which laurylated polyethyleneimine having a laurilation rate of 60% (molecular weight of polyethyleneimine: 10,000) was immobilized on polymer-B. Comparative sample 1 had a molecular weight of 10,000. Comparative Example 2 is a polysulfone membrane obtained by immobilizing polyethyleneimine on polymer-A.
Is a polysulfone membrane (20% polysulfone and 2% K30
A dimethylacetamide solution containing polyvinylpyrrolidone was applied on a glass plate and placed in water to form a film).
% Of a polysulfone (C / N ratio: 13.6) in which laurylated tetraethylenepentamine was immobilized. Comparative sample 4 was obtained by polymerizing polymer-A with ethylated polyethyleneimine (polyethylenimine) having an ethylation ratio of 100% Molecular weight of 70,000)
Is a polysulfone (C / N ratio 4.0) membrane on which is immobilized.

[0054]

[Table 1] As is clear from Table 1, it can be seen that the present invention samples 1 and 2 adsorb lipids well, and that when the C / N ratio is high, the lipid adsorbability is improved by heparinization. Further, when the N-alkyl group is a lower ethyl group, the adsorptivity is low, and C /
It can be seen that when the N ratio is low, the adsorptivity is low, and the adsorptivity is low with tetraethylenepentamine having a low degree of polymerization of polyalkyleneimine.

Example 2 After cooling a mixed solution of 16 mL of nitrobenzene and 32 mL of sulfuric acid to 0 ° C., 4.2 g of N-
Methylol-α-chloroacetamide was added and dissolved,
This was mixed with Udel polysulfone P3500 at 10 ° C.
L of nitrobenzene (300 g / 3 L) was added with good stirring. Further, the mixture was stirred at room temperature for 3 hours. Thereafter, the reaction mixture was placed in a large excess of cold methanol to precipitate the polymer. The precipitate was thoroughly washed with methanol, dried, and reprecipitated from dimethylformamide / methanol to obtain 303 g of α-chloroacetamidomethylated polysulfone (substitution rate: 0.05; polymer-
C) was obtained.

Next, polyethyleneimine (average molecular weight 1
0000: Wako Pure Chemical Industries, Ltd.) A solution of 60 g in 300 mL of dimethylformamide was added with 33 mL of lauryl bromide.
(0.1 mol) and heated at 60 ° C for 6 hours.
The mixture was mixed with 300 mL of a dimethylformamide solution containing 30 g of the polymer-C and stirred at room temperature for 24 hours. 160 mL (0.5-fold mol) of lauryl bromide was added thereto, and the mixture was further stirred at room temperature for 48 hours. The reaction mixture was added to a large excess of methanol, and the precipitated polymer was collected by filtration.
The obtained polymer was dried and further reprecipitated from dimethylformamide / methanol to prepare 27 g of N-alkylated polyalkyleneimine-immobilized polysulfone (adsorbent of the present invention).

In a solution of methylene chloride (250 ml) containing 5 g of the above adsorbent of the present invention, 20 g of cotton of nylon 66 fiber having a single denier fineness of 1 denier was immersed, and after 20 hours, the cotton was taken out. To obtain a coated cotton.

Next, 0.18 g of the coated cotton was treated with heparin, and the adsorbability was evaluated (4 hours at 37 ° C.) with 4 ml of human serum. The results shown in Table 2 were obtained.

[0059]

[Table 2] Table 2 shows a comparison sample using 0.7 mL of dextran sulfate beads (Liposorber). Table 2 shows that the sample of the present invention adsorbs lipid components well. [Example 3] N-alkylated polyalkylenimine-immobilized polysulfone (adsorbent of the present invention) 5 obtained in Example 2
g in a solution of 250 g of methylene chloride.
44 g of tubular knitted fabric made of 35 denier nylon 6 fiber
Was immersed, and after 20 hours, the tubular knitted fabric was taken out, squeezed, and air-dried to obtain 25 g of a coated knitted fabric.

7 g of the coated knitted fabric was packed in a 25 mL column, and a KHC rabbit (body weight: 3.1 kg) was anesthetized with Nembutal using heparin at a flow rate of 16 ml / min for 2 hours in whole blood extracorporeal circulation (DHP). did. Table 3 shows the results.

[0061]

[Table 3] Reduced cholesterol in hyperlipidemic rabbits. Since there is a difference in the cholesterol concentration before and after the column, it can be seen that the cholesterol is adsorbed.

[Example 4] A mixture of 46 parts of polystyrene ("Stanlon" 666) and 4 parts of polypropylene (Sumitomo "Noblen" WF-727-F) containing 50 parts of polypropylene (Mitsui "Noblen" J3HG) as an island component. Multi-core sea-island type composite fiber as sea component (16 islands, single fiber fineness of 2.6 denier, tensile strength of 2.9 g / d, elongation of 50%,
Filament number 42) 100 g of N-methylol-α
-100 g of chloroacetamide, 800 nitrobenzene
g, sulfuric acid 800 g and paraformaldehyde 1.70
g, and reacted at 20 ° C. for 1 hour. The fiber was taken out of the reaction solution, poured into ice water at 0 ° C. to stop the reaction, washed with water, and then nitrobenzene adhering to the fiber was extracted and removed with methanol.
This fiber was vacuum dried at 50 ° C. to obtain 140 g of chloracetamidomethylated fiber (hereinafter referred to as “fiber A”).

A laurylated polyethyleneimine having a laurylation ratio of 10% (polyethyleneimine having a molecular weight of 10,000: C / N
Ratio 3.2) A solution of 40 g in 250 mL of DMF was mixed with 16 g of fiber A sufficiently swollen in advance with DMF and 25 g of fiber A.
The mixture was mixed with 0 mL of a mixture of DMF and reacted at 80 ° C. for 4 hours. The fiber was thoroughly washed with tetrahydrofuran and isopropanol and then dried to obtain 20 g of the fibrous adsorbent of the present invention.

0.2 g of the fibrous adsorbent was added to human serum 4
and shaken at 37 ° C. for 4 hours to give total cholesterol from 122 to 73 mg / dl, neutral fat from 58 to 34 mg / dl and LDL from 245 to 140 mg / dl.
mg / dl. It was confirmed that the fat component was well adsorbed.

[0065]

As described above, the adsorbent of the present invention comprises a water-insoluble polymer,
The most characteristic feature is that the N-alkyl group is obtained by graft-bonding an N-alkylated polyalkyleneimine having 4 or more carbon atoms. Alternatively, it can be used as applied to the surface of a molded article such as fiber. These exhibited excellent properties as adsorbents for thrombus-forming substances, and their effects were confirmed in therapeutic experiments on hyperlipidemic rabbits. The column for extracorporeal circulation filled with the adsorbent of the present invention is useful for treating a patient having an occlusive disease in a coronary artery.

Claims (10)

[Claims] An N-alkyl group having 4 or more carbon atoms.
-An adsorbent for a thrombus-forming substance, comprising a water-insoluble polymer grafted with an alkylated polyalkyleneimine. 2. The N-alkylated polyalkyleneimine has an N-alkylation ratio of 1% or more and a carbon number / nitrogen number ratio of 2.3 to 26. An adsorbent for the thrombogenic substance according to the above. 3. The thrombus formation according to claim 1, wherein the N-alkylated polyalkyleneimine is an N-alkylated ethyleneimine polymer having a degree of polymerization of 10 or more and 10,000 or less. Adsorbent for volatile substances. 4. The method according to claim 1, wherein the water-insoluble polymer is a polysulfone having an amine-bonding group.
3. The adsorbent for a thrombogenic substance according to any one of 3. 5. The adsorbent for a thrombus-forming substance according to claim 1, wherein the water-insoluble polymer is a poly (vinyl aromatic compound) having an amine-bonding group. . 6. The adsorbent for a thrombogenic substance according to claim 1, wherein the water-insoluble polymer is polyimide. 7. The adsorbent for a thrombus-forming substance according to claim 1, wherein the water-insoluble polymer is molded. 8. The adsorbent for a thrombus-forming substance according to claim 1, wherein the water-insoluble polymer is applied to the surface of a molded article. 9. The adsorbent for a thrombus-forming substance according to claim 1, wherein heparin is adsorbed. 10. An extracorporeal circulation column packed with the adsorbent for the thrombogenic substance according to any one of claims 1 to 9.