JPS6222658A - Low specific gravity lipoprotein adsorbing apparatus - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to an apparatus for adsorbing and removing low-density lipoproteins from body fluids such as blood and plasma using an adsorbent.

Increases in lipids in the blood, especially low-density lipoproteins, are thought to be closely related to the cause or progression of arteriosclerosis.As arteriosclerosis progresses, it can lead to cardiovascular problems such as myocardial infarction and cerebral infarction. The chance of developing severe symptoms is much higher, and the mortality rate is also high. Therefore, by selectively adsorbing and removing low-density lipoproteins from body fluid components such as blood and plasma, it is expected to prevent the progression of the above-mentioned diseases, alleviate symptoms, and even hasten the healing process. Ta.

(Prior art) Existing technologies that are capable of achieving the above purpose include adsorption (Lupie) using an adsorbent in which heparin is immobilized on agar gel.
n,P-J,et,at,:A newW app
reach to management of
familiar hypercholestero
lemia.

Rem6val of plasma-cholest
erol based on the principle
e of affinity chromatogra
phy, Lancet.

Chromat.
graphic 5eparation of se
rum 1ipoprotein glasspo
wder columns +Description
of the method and some
applications-clin, Chim
+Acta.

5:52a-538.1960. ).

The present inventors conducted extensive research to further improve the low-density lipoprotein adsorption ability of the low-density lipoprotein adsorbent, and found that the adsorbent has polyanion moieties with numerous negative charges in the molecule on its surface. He discovered that it adsorbs proteins at a high rate and hardly adsorbs useful proteins such as high-density lipoproteins and albumin, and has already applied for a patent 7'C (Japanese Patent Application No. 58-80777, Patent Application No. 58-80778). ).

(Problems to be Solved by the Invention) Low-density lipoproteins having polyanion moieties on the surface have excellent ability to grow low-density lipoproteins and selectivity for high-density lipoproteins, albumin, etc. Because it has many negatively charged moieties, it has the property of easily adsorbing cationic inorganic electrolytes, especially polyvalent cations such as calcium and magnesium. For this reason, treating body fluids with the adsorbent reduces the amount of cationic inorganic electrolytes in the body fluids, which is not preferable.

c) Means for Solving Problems) As a result of intensive research to solve the above problems, the present inventors have found that an inorganic electrolyte replenisher is provided at a specific location in the circuit of a low-density lipoprotein adsorption device. We have discovered that it is surprisingly easy to stably control the electrolyte concentration in body fluids without reducing the adsorption amount of low-density lipoproteins, and we have also developed a system for transporting body fluids to low-density lipoprotein adsorbers. The present invention was completed by confirming that the electrolyte concentration in body fluids can be automatically and stably controlled by operating an inorganic electrolyte replenisher in conjunction with a liquid container.

That is, the present invention provides a body fluid inlet, a body fluid outlet, and a low-density lipoprotein adsorbent that is located between the body fluid inlet and the body fluid outlet and is filled with a low-density lipoprotein adsorbent having a polyanion moiety on the surface. In a low-density lipoprotein adsorption device consisting of a container and a liquid feeder for sending body fluid to the low-density lipoprotein adsorption device, an inorganic A low-density lipoprotein adsorption device characterized by being equipped with an electrolyte replenisher,
Preferably, the low-density lipoprotein adsorption device is provided such that an inorganic electrolyte replenisher is operated in conjunction with a liquid feeder for sending body fluid to the low-density lipoprotein adsorption device.

The target adsorbent of the present invention is low-density lipoprotein, and to explain in more detail, it has a molecular weight of 2.2
06 to 3.5
-"!-', lipoproteins with diameters from 20.0 to 50.0 nm (5CANU, A, M,: plasma 1ip
oproteins: an 1ntroducti
on.

” The Biochemistry of Ath
erosclerosis”ed.

by 8CANU A≧M,,197? ,P,3~B,
). This is a lipoprotein with a smaller specific gravity, that is, a buoyancy coefficient (1,065) of 20 x 10"
Lipoproteins larger than m-5ee-", dyn-" and 9-1 may be adsorbed, but high-density lipoproteins with high specific gravity are preferably not adsorbed.

The body fluid introduction part and the body fluid discharge part as used in the present invention are used for the purpose of introducing or drawing out body fluid, and tubes that are safe for living organisms such as vinyl chloride tubes, polyethylene tubes, silicone tubes, etc. can be used. Also,
The liquid pump referred to in the present invention can be a pump such as a blood pump used in normal hemodialysis, but it must be able to send liquid safely to living organisms without damaging blood, plasma, etc. You can use whatever you have.

In the present invention, the polyanion moiety of the low-density lipoprotein adsorbent refers to a functional group having a molecular weight of 600 or more and a trap negative charge in the molecule, that is, a carboxyl group (C0
OH, C00-), sulfonic acid group (80, H, so, ″
), etc., which have many functional groups that exhibit negative charges in plasma. Examples include vinyl-based synthetic borian anions such as polyacrylic acid, polyvinyl sulfonic acid, polyvinyl phosphoric acid, and polymethacrylic acid, polystyrene sulfonic acid, and polyvinyl sulfonic acid.
Copolymers of nostyrene polyanions such as α-methylstyrene sulfonic acid and follistyrene phosphate, vinyl anions, polyanions such as styrene maleic acid copolymers, synthetic peptide polyanions such as polyglutamic acid and polyaspartic acid, polyU XpolyA
Examples include synthetic nucleic acid polyanions such as polyphosphoric acid, polyphosphate ester, alginic acid, heparin, dextran sulfate, and the like.

Among them, polyanions obtained by synthesis are
It is a natural product because it has excellent chemical stability, and it is easy to obtain products that are stable against high-pressure steam sterilization, gamma ray sterilization, ethylene oxide sterilization, etc., and the molecular weight can be adjusted relatively easily. Excellent, can recommend. In addition, polyanions obtained by synthesis are preferable because polyanions that do not easily cause complement activation as seen in natural polysaccharides can be easily obtained. Furthermore, substances such as vinyl anions that can be directly grafted onto a carrier,
This method provides more favorable results in that a polyanion having a large molecular weight can be immobilized in a high retention amount on the carrier.

In addition, since the low-density lipoprotein, which is the substance to be adsorbed, is a huge lipoprotein with a diameter of about 200 mm, it is preferable that the structure of the polyanion part is a chain structure, and it is better that it extends long from the surface of the adsorbent. preferable. Further, it is preferable that the polyanion moiety has at least one negative charge density per molecular weight of 300. More preferably, the molecular weight is 2
The number is one or more per 00, and preferably one per unit of molecular weight 70 to 150. The molecular weight referred to here includes the molecular weight of a functional group that exhibits a negative charge. The molecular weight of the polyanion moiety needs to be at least 600, since it becomes difficult to adsorb low-density lipoprotein as it becomes small. A value of 2,500 or more is preferred, and a range of 10,000 to 5,000,000 is more preferred.

A structure that shows the large number of negative charges possessed by the polyanion moiety.
It is thought that the functional groups bind low-density lipoproteins with strong Coulomb force by recognizing multiple points on low-density lipoproteins.

Among the functional groups showing negative charge, carboxyl group (C0O
H,Coo-) gives particularly favorable results.

Since it is a weaker acid than the sulfonic acid group (5o3H, so; ), it has low adsorption to useful proteins such as albumin. In addition, blood coagulation system proteins are less adsorbed and less likely to be activated. Furthermore, complement system proteins are also difficult to adsorb.

Among the above-mentioned polyanion moieties, polycarboxylic acids such as polyacrylic acid and polymethacrylic acid are particularly stable and are recommended.

The density of negative charge is from 1μeq to 1meq per adsorbent.
This range is an appropriate range that has good adsorption performance for low-density lipoproteins, good adsorption selectivity, and little influence on the coagulation fibrinolytic system and the complement system. When the negative charge density is lower than 1 μeq 7'm/m, the adsorption ability of low-density lipoproteins falls short of practical performance, and when it exceeds 1 meq, non-selective adsorption increases, which adversely affects the coagulation fibrinolytic system and the complement system. ) The preferred range is 5μ
eq/- to 700 μeq/ld, more preferably 10 μsq/- to 500 μeq/-.

The negative charge density can be measured according to a conventional method for measuring the ion exchange capacity of a cation exchange resin.

Examples of the method for producing the low-density lipoprotein adsorbent according to the present invention include a method of activating a carrier and covalently bonding a polyanion, and a method of graft polymerizing an anion monomer to the carrier to form a polyanion graft chain. It will be done.

The carrier only needs to be able to immobilize the polyanion, and both hydrophilic and hydrophobic carriers can be used. However, when using a hydrophobic carrier, non-specific adsorption of albumin to the carrier sometimes occurs, so a hydrophilic carrier is preferable. gives the desired result.

The shape of the insoluble carrier may be any known shape such as particulate, fibrous, hollow fiber, or membrane. Preferably.

The carrier may be made of any material as long as it can fix the polyanion. Usable carriers include organic or inorganic porous materials such as cellulose gel, dextran gel, agarose gel, vinyl polymer gel, polyacrylamide gel, polyhydroxyethyl methacrylate gel, porous glass, and silica. I can do it,
All carrier materials used in normal affinity chromatography can be used, but the adsorbed substance, low-density lipoprotein, has a diameter of 200 to 300X and a molecular weight of 2.2×I06' to 3.5X10'. The exclusion limit molecular weight of the carrier is 2.2 million or more, and the pore diameter is 2.
The adsorption efficiency is higher when it is 00X or more.

Among the above-mentioned carriers, carriers made of cross-linked copolymers whose main component is vinyl alcohol units are particularly hydrophilic, so their interaction with solutes such as proteins in plasma is small, and non-specific adsorption is minimized. lower. Furthermore, it has extremely excellent properties such as not interacting with the complement system and coagulation system in plasma. In terms of physical properties, it exhibits an excellent pore size distribution, has heat resistance, enables heat sterilization, and has excellent physical and mechanical strength, which is a characteristic of synthetic polymers. When used as a carrier for whole blood adsorbents, there is little interaction with blood cell components, preventing thrombus formation, non-specific adhesion of blood cell components,
It also has extremely excellent properties such as keeping residual blood to a minimum.

A crosslinked polymer having vinyl alcohol units as a main component can be synthesized by polymerizing a monomer having a hydroxyl group or by introducing a hydroxyl group through a chemical reaction of the polymer, or by using both methods in combination.

As the polymerization method, a radical polymerization method can be used. The crosslinking agent may be introduced through copolymerization during polymerization, or may be introduced through a chemical reaction between polymers (between polymers or between the polymer and the crosslinking agent), or both may be used in combination.

For example, it can be produced by copolymerizing a vinyl monomer and a vinyl or allyl crosslinking agent. Examples of the vinyl monomer in this case include vinyl esters of carboxylic acids such as acetate and vinyl propionate, and vinyl ethers such as methyl vinyl ether and ethyl vinyl ether.

Examples of crosslinking agents include allyl compounds such as triallyl isocyanurate and triallyl cyanurate, di(meth)acrylates such as ethylene glycol dimethacrylate and diethylene glycol dimethacrylate, butanediol divinyl ether, diethylene glycol divinyl ether, and tetravinyl. Polyvinyl ethers such as glyoxal, polyallyl ethers such as diarylidene pentaerythritol and tetraallyloxyethane, and glycidyl acrylates such as glycidyl methacrylate can be used. Moreover, copolymerization of other comonomers can also be used, if necessary.

In the case of vinyl copolymers, triallylisocyanurate crosslinking of polyvinyl alcohol obtained by copolymerizing a vinyl ester of carboxylic acid and a vinyl compound (allyl compound) having an isocyanurate ring and hydrolyzing the copolymer. The body provides a particularly good carrier in terms of strength and chemical stability.

All known methods such as covalent bonding, ionic bonding, physical adsorption, embedding, and precipitation insolubilization on the polymer surface can be used to immobilize the polyanion on the surface of the insoluble carrier. Considering this, it is preferable to use it after being fixed and insolubilized by covalent bonding. For this purpose, we usually use immobilized enzymes, known carrier activation methods used in affinity chromatography, binding methods with ligands, and graft polymerization methods in which the carrier or activated carrier is used as a backbone polymer and polyanions are used as branches. can be used.

Examples of activation methods include the halogenated cyanide method, epichlorohydrin method, biseboxide method, halogenated triazine method, buttetramoacetylbromide method, ethyl chloroformate method, 1,1'-sibonyldiimidazole method, etc. I can give it to you. The activation method of the present invention is not limited to the above examples as long as it can perform a substitution and/or addition reaction with a nucleophilic reactive group having active hydrogen such as an amino group, a hydroxyl group, a carboxyl group, or a thiol group of the ligand. However, in consideration of chemical stability, thermal stability, etc., a method using an epoxide is preferable, and an epichlorohydrin method is particularly recommended.

In addition, for phases with silanol groups such as silica-based and glass-based, r-glycidoxyglobiltrimethoxysilane, γ-aminopropyltriethoxysilane, γ-mercaptoglobiltrimethoxysilane, vinyl Various silane coupling agents such as trichlorosilane are preferably used.

Examples of graft polymerization methods include methods that utilize chain transfer reactions, methods that utilize reactions such as dehydrogenation and dehalogenation by K such as radiation and ultraviolet light, and methods that utilize the formation of peroxides. A method of craft polymerizing an anionic monomer onto a carrier having a reducing group such as , thiol, aldehyde, or amine using a cerium salt, iron salt, or the like as an initiator is simple and recommended. In addition, a graft polymerization system is preferably used because a polyanion having a relatively large molecular weight can be fixed to the inside of the carrier.

Two or more types of polyanions may be bound to the carrier.

Although the method for manufacturing a low-density lipoprotein adsorbent in which a polyanion is bonded after activating a carrier has been described above, the method is not limited to this.

The low-density lipoprotein adsorbent is one in which the above-described low-density lipoprotein adsorbent is filled and held in a container equipped with an inlet and outlet for body fluids.

In FIG. 1, numeral 1 indicates an example of a low-density lipoprotein adsorber containing a low-density lipoprotein adsorbent;
A cap having a body fluid inlet is screwed into an opening at one end of the cylinder 2 through a backing 4 with a filter 3 stretched inside, and a backing 4 with a filter 3' stretched inside the opening at the other end of the cylinder 2. A cap 8 having a body fluid lead-out lower part is fitted with a screw through the cap 8 to form a container, and a low-density lipoprotein adsorbent is filled and held in the gap between the filters 3 and 3' to form an adsorbent layer 9. It is something.

The adsorbent layer 9 may be filled with a low-density lipoprotein adsorbent alone, or may be mixed or laminated with other adsorbents. Other adsorbents that can be used include, for example, activated carbon, which has a wide range of adsorption capacities. This can be expected to have a wide range of clinical effects (depending on the synergistic action of the adsorbent). When used for extracorporeal circulation, the volume of the adsorbent layer 9 is 50~
Approximately 400 yen is appropriate.

- When using the device of the present invention equipped with this low-density lipoprotein adsorber for extracorporeal circulation, there are two methods as shown below. First, blood taken from the body is separated into plasma components and blood cell components using a centrifuge or a model plasma separator, and the plasma components are passed through the device to be purified and then separated into blood cell components. One method is to return the blood to the body along with the blood, and the other method is to directly pass the blood taken out from the body through the device and purify it.

The method for passing body fluids may be continuous or intermittent, depending on clinical needs or equipment conditions.

171 The low-density lipoprotein adsorption device of the present invention is configured as shown in FIG. 2, for example.

In the figure, 10 is a body fluid inlet, 1) is a body fluid outlet, 12 is a low-density lipoprotein adsorber, 13 is a liquid feeder, and 14 is an inorganic electrolyte replenisher.

Hereinafter, a method for adsorbing and removing low-density lipoproteins from plasma using the low-density lipoprotein adsorption device of the present invention will be described as an example.

First, plasma is passed through the body fluid introduction section 10 and transferred to the liquid feeder 131C.
It is then sent to a low-density lipoprotein adsorption device 12.

Here, as the liquid feeder 13, a pump similar to a blood pump used in normal artificial dialysis can be used. From the plasma sent to the low-density lipoprotein adsorber 12, low-density lipoproteins are removed, and polyvalent cations such as calcium and magnesium are adsorbed and removed.

Next, the plasma from which low-density lipoproteins and polyvalent cations have been removed is sent to an inorganic electrolyte replenisher 14, where it is replenished with inorganic electrolytes containing polyvalent cations such as calcium and magnesium. After returning the electrolyte balance to normal, the body fluid is drawn out through the body fluid drawing unit 1). In this way, the low-density lipoprotein adsorption device of the present invention can process body fluids while maintaining a high low-density lipoprotein adsorption capacity, and can correct the electrolyte concentration downstream of the low-density lipoprotein adsorption device. Therefore, the electrolyte concentration can always be controlled at a constant level, making it safe.

Next, there is a method of electrolyte balance control using an inorganic electrolyte replenisher, but the electrolyte concentration in body fluids is stable or constant unless there is a specific disease, and polyvalent cations caused by low-density lipoproteins are Since the degree of adsorption can be known in advance, there is no need to measure the electrolyte concentration of the body fluid after it has passed through the low-density lipoprotein adsorbent.If you know the amount of body fluid that has passed through the adsorbent, you can calculate the appropriate amount. Polyvalent cation supplementation makes it possible to restore electrolyte concentrations in body fluids to normal values. The most suitable control method for automatically carrying out this process is to link the liquid feeder and inorganic electrolyte replenisher for sending body fluid to the low-density lipoprotein adsorbent, and to adjust the amount of body fluid that has passed through the adsorber to match the volume of body fluid that has passed through the adsorber. This is done by replenishing the amount of inorganic electrolytes. That is, this method replenishes a predetermined amount of cationic electrolyte when a certain amount of body fluid passes through the low-density lipoprotein adsorber.

Examples of devices for achieving this are shown in FIGS. 5 and 4.

FIG. 3 shows a system in which a liquid feeder 15 for sending body fluids and an inorganic electrolyte replenisher 14 are linked by a control device 15. Pump, inorganic electrolyte replenisher 1
4, an infusion pump using a syringe can be used, and when the liquid feeding speed of the liquid feeding device 13 changes, the control device 15 controls the injection speed of the supply device 14 in conjunction with the speed. It is something to do. The method of control may be intermittent injection of the inorganic electrolyte, but it is preferably carried out continuously and in proportion to the speed of the liquid feeder.

In Fig. 4, both the liquid feeder 15 and the inorganic electrolyte replenisher 14 are operated by one roller pump. The difference in flow rate can be controlled by making the tubes thinner.

By using a device such as the one described above, the electrolyte concentration is automatically corrected, which is extremely convenient.

(Effects of the Invention) By using the low-density lipoprotein adsorption device of the present invention, while maintaining the low-density lipoprotein adsorption capacity of the low-density lipoprotein adsorbent at a high level, calcium adsorbed by the adsorbent, It has become possible to return the concentration of polyvalent cations such as magnesium to normal values, and its control has become very simple.

In addition, by using automated equipment, we are able to more stably and easily control body fluid electrolyte concentrations.
became.

(Example) Using the apparatus shown in FIG. 2, an adsorption experiment of low-density lipoprotein was conducted.

Soft vinyl chloride tubes are used for the body fluid inlet and body fluid outlet, a blood pump with a roller to squeeze the soft vinyl chloride tube is used as the fluid feeder for body fluids, and a syringe is used as the inorganic electrolyte replenisher. An infusion pump was used.

The low-density lipoprotein adsorber has an inner diameter of 1.40M and a length of 6.
A container with 5 scratches and an internal volume of 10 cm filled with 10 cm of low-density lipoprotein adsorbent was used.

The low-density lipoprotein adsorbent was manufactured by the method described below.

Vinyl acetate 1000f,) realyl isocyanurate 4
14 f, ethyl acetate 1000 f, heptane 1000
f, polyvinyl acetate (degree of polymerization 500) 701 and 2.
A homogeneous mixture of 2'-azobisisobutyronitrile 361, 1 part by weight of polyvinyl alcohol, 0.05% by weight of IJ um dihydrate and disodium hydrogen phosphate, and water. Pour 4 tons of water in which 1.5 weight percent of the compound was dissolved into a flask, stir thoroughly, and then heat to 65C.
Suspension polymerization was carried out by heating and stirring at 75C for 18 hours and then for 5 hours at 75C to obtain a granular copolymer. During the polymerization, the stirring speed was controlled to keep the particle size small. After filtration, washing with water, and extraction with acetone, the copolymer was transesterified in a solution consisting of caustic soda 4651 and 20 tons of methanol at 40C for 18 hours. The average particle size of the particles obtained was 40 Jlm.

This gel was packed into a stainless steel column with an inner diameter of 7.5mm and a length of 120mm, and aqueous solutions of dextran and polyethylene glycol with various molecular weights, albumin, immunoglobulin G, inter-immunoglobulin 1β-lipoprotein, tobacco, and mosaic were added. When the virus was measured in a phosphate buffered salt solution, each virus was eluted in descending order of molecular weight.

The exclusion limit molecular weight of Dextra/ is approximately 5 x 10', and the exclusion limit molecular weight of protein is approximately 2 x 1 G? Met.

Furthermore, when solutions of human γ-globulin and human albumin were passed through an aqueous solution containing 0.3M sodium chloride and 0.1M sodium phosphate as a solvent, almost 100% recovery rate was obtained, and gelation was achieved. The nonspecific adsorption of was very low.

All sample measurements were performed at a flow rate of 1 ml/1 nl JI.

Next, the gel was transesterified, thoroughly washed with water, and dried. was suspended in a solution consisting of 18.00 d of dimethyl sulfoxide and 1200 d of epichlorohydrin, and 150 d of a 50% aqueous sodium hydroxide solution was added.
The reaction was carried out at 0C for 5 hours with stirring. After the reaction was completed, it was filtered through a glass filter and washed with 3/= dimethyl sulfoxide and then with 20 tons of water to obtain an epoxy group-bonded gel.

The amount of epoxy group bonded in this gel is 1! 0.1 per +1/
) mmol. Using the epoxy group-bonded gel, polyacrylic acid (weight average molecular weight 9×10 4 , manufactured by Aldrich, USA) was bound as a ligand to prepare an adsorbent.

500m7 of polyacrylic acid 4.51 with distilled water! KL,
This was used as a ligand solution. 100 yd of the epoxy group-binding gel was added to this ligand solution, and the ligand binding reaction was carried out at 50C for 16 hours with shaking.

After this, the polyacrylic acid is thoroughly washed with water, dehydrated by suction for 7'C, then immersed in a 0.1N sodium hydroxide solution for 30 minutes to convert the polyacrylic acid into a sodium form, and then washed with a sufficient amount of water. It was used as a low-density lipoprotein adsorbent.

Adsorption experiments were performed using plasma from patients with familial hypercholesterolemia.

First, the plasma flow circuit and the inside of the low-density lipoprotein adsorption device are primed with physiological saline, and then the patient's plasma is introduced into the body fluid inlet at a flow rate of 1.67 tdl-.
A blood pump) was introduced. At the same time, calcium and magnesium were supplied using an infusion pump. The concentrations of calcium and magnesium are each s
A mixed solution was prepared at Eq/l and 2.5f/61. The flow rate of the infusion pump was 1.67 μt/−. After discarding the first 10-mL extracted from the body fluid extraction section, the plasma 100-mL that came out was sampled, and the calcium concentration, magnesium concentration, and total cholesterol concentration were measured and compared with the plasma concentration before the adsorption experiment. , calcium concentration is 5. Omeq/l became 4.9 meq/l\
The 7g' concentration was stably controlled from 2.5 η/dt to 2.4 η/dt, while the total cholesterol concentration decreased significantly from 420 η/dt to 160 η/dt.

Comparative Example The same low-density lipoprotein adsorber as in Example 1 was used, except that calcium and magnesium were not supplemented.
An adsorption experiment was conducted in the same manner as in Example 1. As a result, the calcium concentration was 5.0 meq/1 to 0.2 meq/l.
Ks Magnesium concentration is 2.5mg/dL is 0.1
m97dt was mostly adsorbed and did not remain. However, the total cholesterol concentration is 420 drops/dt, which is 158η.
/dt, indicating good adsorption.

[Brief explanation of drawings]

Figure 1 is a schematic diagram showing an example of a low-density lipoprotein adsorption device;
FIG. 2 is a schematic diagram showing an example of the low-density lipoprotein adsorption device of the present invention, and FIGS. 5 and 4 are schematic diagrams showing automated examples of the low-density lipoprotein adsorption device of the present invention.

Claims (2)

[Claims] (1) A body fluid inlet, a body fluid outlet, a low-density lipoprotein adsorbent located between the body fluid inlet and the body fluid outlet, and filled with a low-density lipoprotein adsorbent having a polyanion portion on the surface; In a low-density lipoprotein adsorption device comprising a liquid feeder for sending body fluid to the low-density lipoprotein adsorption device, an inorganic electrolyte is supplied between a body fluid outlet and a body fluid outlet of the low-density lipoprotein adsorption device. A low-density lipoprotein adsorption device characterized by being equipped with a container. (2) Adsorption of low-density lipoproteins according to claim 1, wherein an inorganic electrolyte replenisher is provided to operate in conjunction with a liquid feeder for sending body fluids to the low-density lipoprotein adsorption device. Device.