JPH0783767B2 - Blood purification device - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial field of application) The present invention relates to a blood purification device for returning a blood component changed due to various diseases to a normal state, in particular, a centrifugal plasma separation device to remove whole blood from a whole blood. Flow the separated plasma through an adsorption column,
The present invention relates to a blood purification device that adsorbs and removes a body fluid component in plasma.

(Prior art and its problems) With recent advances in science and technology such as medicine and engineering, the components increased in blood of patients due to various diseases are adsorbed and removed by an adsorption column to remove components in blood. Attempts have been made to prevent or treat the deterioration of various diseases by returning to a state close to normal, and the effects have been improved in various diseases.

For example, an adsorption column that adsorbs bilirubin that increases in blood of patients with liver disease, an adsorption column that adsorbs and removes poisoning-inducing substances from the blood of drug poisoning patients, is used for collagen diseases, autoimmune diseases, etc. An adsorption column that selectively adsorbs and removes malignant substances such as antibodies and immune complexes, an adsorption column that selectively adsorbs and removes low-density lipoproteins that are the cause of disease development from the blood of hyperlipidemic patients, An adsorption column that selectively adsorbs and removes immunosuppressive substances from the blood of cancer patients,
An adsorption column or the like that adsorbs blood group substances in blood of a blood type incompatible pregnant patient can be given as an example of the blood purification device.

The adsorption column for blood purification described above is designed to flow the plasma separated by the plasma separation device. When whole blood is flown, the column may become clogged due to adhesion of white blood cells and platelets, and if particulates are washed away from the adsorbent, there is no means to remove them and there is a problem that particulates are mixed into the blood of the patient. Yes, it cannot process whole blood. Therefore, the blood is first separated into a blood cell component and a plasma component by the plasma separation device, and the separated plasma component is flowed to the adsorption column. Also in this case, it is necessary to attach a particle removal filter for removing the particles to the downstream side of the adsorption column, considering that the particles may flow out from the adsorption column. The particle removal filter usually uses an ultrafiltration membrane with a pore size of 0.2 to 0.5 μm, and because the priming volume cannot be increased, the membrane area cannot be increased, and the membrane area is 20 to 40 cm ² . Usually there is. When a membrane-type plasma separator is used as the plasma separator, the separated plasma does not contain any blood cell components, so this particulate removal filter does not become clogged. In the case of using the blood plasma separator, the separated plasma contains a small amount of platelets. Therefore, when using a centrifugal plasma separator,
The fine particle removal filter causes clogging,
It was not possible to process a sufficient amount of plasma on the adsorption column.

On the other hand, centrifugal plasma separators have been widely used in various hospitals, and it has been strongly desired to develop a blood purification device of a type capable of treating plasma separated by centrifugal plasma separators with an adsorption column.

(Object of the Invention) In view of the above problems, an object of the present invention is to remove fine particles even if blood plasma contains platelets in a blood purification apparatus that processes plasma separated by a centrifugal plasma separation apparatus by an adsorption column. It is an object of the present invention to provide a blood purification device which can process a sufficient amount of plasma in an adsorption column without clogging of the filter.

(Structure of the Invention) As a result of intensive research conducted by the present inventors in line with the above object,
By installing a platelet removal filter between the centrifugal plasma separator and the particulate removal filter to remove most of the platelets contained in plasma, clogging of the particulate removal filter can be completely prevented, resulting in a sufficient amount. The present invention has been completed by finding that the plasma can be treated with an adsorption column, and that when a fibrous substance is used as a platelet removing material for a platelet removing filter, the platelet removing ability is particularly remarkable and the priming volume can be reduced. It is a thing.

That is, the present invention, the blood flow path formed between the blood inlet and blood outlet is provided with a centrifugal plasma separator,
The plasma channel connected to the plasma separation device is provided with an adsorption column on the upstream side and a particulate removal filter on the downstream side, and the plasma channel on the downstream side of the particulate removal filter is downstream from the centrifugal plasma separation device. In the blood purification apparatus connected to the blood circuit on the side, the blood purification apparatus is characterized in that a platelet removal filter is arranged in the plasma flow path upstream of the particulate removal filter.

The present invention is also a blood purification apparatus in which the main component of the platelet removal material of the platelet removal filter is a fibrous substance.

The centrifugal plasma separator referred to in the present invention is a device capable of separating plasma from whole blood by utilizing centrifugal force, such as a continuous centrifugal separator or a simplified centrifugal separator, and a commercially available device can be used. . The adsorption column is a known adsorbent packed in a container having an inlet and an outlet for plasma. Examples of the adsorbent include activated carbon, anion exchange resin, amino acid-immobilized porous material, polyanion-immobilized porous material, and antibody-immobilized porous material. Examples of the adsorbent include a hydrophobic compound-immobilized porous body and porous glass.
The adsorbent is not limited to this example, and includes any substance that can remove harmful substances in plasma and is safe for the human body. The fine particle removal filter may be a filter using a known ultrafiltration membrane, and examples of the membrane material include cellulose acetate, cellulose nitrate, regenerated cellulose, polyamide, polysulfone, ethylene vinyl alcohol copolymer and the like. . The pore size of the filter is 0.1 to 1 μm, preferably 0.2 to 0.5
μm, and the membrane area is 10 to 200 cm ² , preferably
20 to 100 cm ² can be used.

The platelet removal filter referred to in the present invention may be any one that can remove platelets contained in plasma by adhesion. For example, hydrophobic beads having a size of 0.05 to 3 mm, beads having a cation surface, columns packed with beads such as glass beads, 0.1 to 50 μm
Examples of the filter include a filter filled with a fibrous substance having an average diameter of 1 to 1, and a porous body having an average pore diameter of 1 to 200 μm. Among them, the filter filled with fibrous material is
It is recommended because it has excellent platelet removal efficiency and low pressure loss when plasma is flown.
The average diameter of the fibrous substance is a diameter when converted to a circle in the case of a modified cross-section yarn, but a diameter of 0.1 to 50 μm can be used. The smaller the diameter, the larger the pressure loss when used as a filter, and the larger the diameter, the poorer the platelet removal efficiency. The preferred average diameter range is 0.2 to 20μ
m, more preferably 0.3 to 10 μm, most preferably 0.5 to 5 μm. As the material of the fibrous substance, various materials such as synthetic fiber, semi-synthetic fiber, regenerated fiber, natural fiber, and inorganic fiber can be used, and synthetic fiber is preferably used because its fiber diameter can be easily adjusted. Examples thereof include polyester polymers such as polyethylene terephthalate, polyamide polymers such as nylon 6, and vinyl polymers such as polyethylene, polypropylene, polystyrene, polymethacrylate ester and polyacrylate ester. Among synthetic fibers, a polymer having a particularly high hydrophobicity or a polymer having a cation surface has high adhesion efficiency to platelets and is recommended. In addition, even in the case of a polymer with a hydrophilic surface, use a coating agent to further enhance the adhesion efficiency of platelets,
Due to the scientific modification of the fiber surface, it can be used by increasing the adhesion efficiency of platelets. As a coating agent for fibrous substances,
Examples thereof include polymers having a basic functional group or polymers having a hydrophobic functional group. Examples of the basic functional group include a primary amino group, a secondary amino group, a tertiary amino group, and a quaternary amino group.
Examples thereof include a primary ammonium group, a pyridyl group and an imidazolyl group.

Monomers used in synthesizing the polymer having a basic functional group include vinylamine; dimethylaminoethyl (meth) acrylate, diethylaminoethyl (meth) acrylate, dimethylacinopropyl (meth) acrylate, and 3-dimethylamino. Derivatives of acrylic acid and methacrylic acid such as 2-hydroxypropyl (meth) acrylate; styrene derivatives such as p-dimethylaminomethylstyrene and P-diethylaminoethylstyrene; 2-vinylpyridine, 4-vinylpyridine, 2-
Vinyl derivatives of nitrogen-containing aromatic ring compounds such as methyl-5-vinylpyridine, 4-vinyl-2-ethylimidazole and N-vinyl-2-methylimidazole; and quaternary ammonium salts of the above vinyl compounds with alkyl halides and the like. The derivative can be mentioned. The monomer having these basic nitrogen-containing functional groups may be used alone or in combination.
One or more species and another polymerizable monomer having no basic nitrogen-containing functional group may be copolymerized by ordinary vinyl polymerization.

Examples of the surface modification of the fibrous substance include a method of plasma-grafting a polymerizable monomer having a polyamine chain on the fiber surface, chemical treatment, ultraviolet irradiation, low-temperature plasma treatment, and the like. The amount of the fibrous substance to be filled in the container can be arbitrarily determined according to the amount of plasma to be treated, but when treating 3 l of plasma, it may be determined to be 3 to 12 g. The form of the fibrous substance may be any of a woven fabric, a cotton fabric, a non-woven fabric and the like, but the non-woven fabric is particularly preferred from the viewpoint of platelet removal performance and pressure loss when used as a filter. The place for installing the platelet removal filter may be anywhere in the plasma flow path between the centrifugal plasma separation device and the particulate removal filter. It may be installed alone as a platelet removal filter, or may be installed on the plasma inlet side or outlet side of the adsorption column, or in the middle,
It may be installed by being installed on the inlet side of the particulate removal filter. Further, it may be installed not only in one place but also in several places.

Hereinafter, embodiments of the present invention will be described in more detail with reference to the drawings.

The figure is a schematic view showing an example of the present invention. Blood is introduced from the blood introduction port 1 and then introduced into the centrifugal plasma separation device 2. Here, the blood is separated by centrifugal force into blood cell-rich components and plasma components, and the plasma is sent to the platelet removal filter 3. Most of the platelets contained in plasma are removed by the platelet removal filter 3, plasma containing almost no platelets is sent to the adsorption column 4, and the adsorbed component (adsorption target substance) in plasma is adsorbed and removed. Next, fine particles are removed by the fine particle removal filter 5 and mixed with the blood cell-rich component separated by the centrifugal plasma separation device 2, and then the blood outlet port 6
Derived from. Since "plasma containing almost no platelets", from which platelets have been removed by the platelet removal filter 3, is flown through the particle removal filter 5, the particle removal filter 5 does not cause clogging. The arrangement position of the platelet removal filter 3 may be between the adsorption column 4 and the particulate removal filter 5, may be incorporated in the adsorption column 4, or may be incorporated on the inlet side of the particulate removal filter 5. Is also good.

(Effects of the Invention) As described above, by using the blood purification apparatus of the present invention, platelets are clogged in the particulate removal filter in the conventional method, and it has been difficult to process a small amount of plasma. On the other hand, it has become possible to process a sufficient amount of plasma in a state of low pressure loss. The present invention is very useful for various blood purification treatment methods using an adsorption column.

Hereinafter, the present invention will be described in more detail with reference to Examples.

(Example) (Example 1) An IBM2997 plasma component separation device was used as a centrifugal plasma separation device, and an adsorption type plasma purifier Imsorber was used as an adsorption column.
PH-350 (manufactured by Asahi Medical Co., Ltd.) was used. As the fine particle removing filter, a cellulose acetate ultrafiltration membrane (manufactured by Fuji Film Co., Ltd.) having a pore diameter of 0.45 μm was cut into a diameter of 69 mm and filled in a container. As a platelet removal filter, a polypropylene non-woven fabric having an average diameter of 1.1 μm was cut into 67 mm square pieces, and 29 sheets were stacked and used by filling the container. The weight of the non-woven fabric was 7.1 g. The platelet removal filter was previously wetted with alcohol and then washed with physiological saline. Each of the above parts was assembled into the blood purification device shown in the attached drawings.

Blood was mixed with 7 fresh whole blood of ACD pigs and 5 l
Was used. Blood flow rate is 50ml / min, centrifugation speed is 1900r
The plasma collection rate was 20 ml / min. Blood was pooled in a tank and recirculated. Under this condition, 3 l of plasma was passed through the adsorption column, and the pressure difference before and after the particulate removal filter was stable at an average of 60 mmHg.

Comparative Example 1 The same experiment as in Example 1 was performed except that the platelet removal filter was not used in Example 1. As blood, 5 l was used from the same pool.

As a result, when the plasma 1 was passed through the adsorption column, the pressure difference before and after the particulate removal filter exceeded 300 mmHg, and no more plasma could be passed.

(Example 2) As a material of the platelet removal filter in Example 1,
An experiment was carried out in the same manner as in Example 1 except that a container was prepared by stacking 20 sheets (6.7 g) of polyester nonwoven fabric having an average diameter of 1.5 μm, and coating the polymer with diethylaminoethyl methacrylate.

The polymer coating was performed by filling a polyester non-woven fabric into a container, filling the container with a 1% by weight polymer / ethanol solution, and then drying by sending dry air.
As a result of the experiment, when 3 l of plasma was flown through the adsorption column, the pressure difference before and after the particulate removal filter was stable at an average of 56 mmHg.

[Brief description of drawings]

 FIG. 1 is a schematic diagram showing an embodiment of the present invention. 1 ... Blood inlet 2 ... Centrifugal plasma separator 3 ... Platelet removal filter 4 ... Adsorption column 5 ... Fine particle removal filter 6 ... Blood outlet

Claims (2)

[Claims] 1. A centrifugal plasma separator is provided in a blood channel formed between a blood inlet and a blood outlet, and a plasma channel connected to the plasma separator is provided on the upstream side thereof. In a plasma purification device in which an adsorption column is provided with a particulate removal filter on the downstream side, and the plasma flow path on the downstream side of the particulate removal filter is connected to a blood circuit downstream of the centrifugal plasma separation device, a particulate removal filter A blood purification device characterized in that a platelet removal filter is arranged in the plasma flow path on the upstream side. 2. The blood purification apparatus according to claim 1, wherein a main constituent element of the material for removing platelets of the platelet removal filter is a fibrous substance.