KR20130131598A - Leukocyte removal bi-filter for preventing of blood transfusion - Google Patents

Abstract

The present invention is a two-stage leukocyte removal step for preventing transfusion side effects in which a first filter material having a pore size through which leukocytes do not pass and a second filter material made of a polymer material grafted with a functional group for adsorbing and separating leukocytes are sequentially connected. It relates to a system filter.

Description

Leukocyte removal bi-filter for preventing of blood transfusion

The present invention is connected to the first filter material which can separate the white blood cells by the pore size difference, and the second filter made of a polymer material grafted with a functional group capable of adsorbing and separating the white blood cells, minimizing the remaining white blood cells It is about a two stage filter which can be done.

Recently, a method for removing white blood cells from blood for transfusion uses a pre-preservation leukocyte removal filter which rapidly filters whole blood before separating, adjusting, and preserving each blood product after blood collection. Accordingly, there is a need for a filter that removes leukocytes in a short time and has improved filtration efficiency.

Hematopoietic blood products cause various transfusions, and blood infections such as mad cow disease and various infectious diseases have made the use of blood products more and more difficult, and the testing and screening procedures for screening for blood stability and quality are strictly strengthened. The development of high purity filter material for blood product separation is a very important industry.

In addition, studies on leukocyte removal are important because non-blood-forming blood products, such as fresh frozen plasm, are known to have leukocytes with sufficient viability to cause allogeneic immunity and transfusion-related graft-versus-host disease. It is emerging as an issue.

In the United States, Europe, and Japan, the use of leukocyte-free blood products has already been mandated, but in some general hospitals, leukocyte-free blood products are used, and transfusion reactions such as fever reactions, alloimmune reactions, and viral infections have occurred. The situation is high risk. In order to efficiently remove leukocytes in the blood product, a technique for providing the separation characteristics of the filter material in a balanced manner and a filter structure design for smoothly adsorbing leukocytes are the most important.

At present, centrifugation with physiological saline, sedimentation, washing, dextran sedimentation, filtration using nylon filter, microaggregating filter, etc. are commonly used for the purpose of removing white blood cells in blood products. The removal rate is high and the use is simple. However, the transfusion side effect of the remaining white blood cells is still a problem.

Japanese Patent Laid-Open No. 2004-215873 (2004.08.05) relates to stacking two kinds of filters having different average fiber diameters, and has a mean fiber diameter of 5.0 µm to 10 µm. Two types of filters, a phosphorus transfer filter (A) and a main filter (B) having an average fiber diameter of 1.2 µm to 2.0 µm, and directing each filter (A), (B) from the blood inlet to the outlet portion; The leukocyte removal filter laminated | stacked in order of (A), (B) is described. The present invention is to remove leukocytes by varying the diameter of the fibers of the two-stage filter, by removing the leukocytes by adjusting the pore size of the filter by varying the diameter of the fiber, the filter having a different pore size in one housing To remove the white blood cells due to the difference in pores as the blood flows down from top to bottom, but it is not easy to control the pore size of the fabric produced only by the diameter of the fiber, especially three kinds of granulocytes, three kinds Because of the different size and characteristics of each of the leukocytes, which are composed of nongranulocytes, it is impossible to remove all leukocytes only by the porosity of the fabric. In addition, even if the filtration efficiency of the leukocyte itself is only 100%, the filter performance is not excellent unless the recovery rate of red blood cells and platelets, which is a very important factor in determining the performance of the blood filter.

There is no description of a technique for applying a polymer material having a functional group as in the present invention.

In addition, Korean Patent Laid-Open Publication No. 2003-0034981 (2003.05.09) discloses an immune factor on a general-purpose polymer film using inductively coupled plasma chemical vapor deposition and ultraviolet light to selectively adsorb, separate, and remove leukocytes by biochemical factors. The present invention relates to a filter in which an absorber is grafted. The present invention relates to a manufacturing method of grafting an immune factor absorber by an antigen-antibody reaction onto a polymer film so as to utilize the migration and adsorption of leukocytes by an antigen-antibody reaction. The patent is prepared using an organic solvent in order to graf the immune factor absorber to the polymer film, so there may be a risk of human toxicity due to red blood cells and platelet contamination by organic solvents and residual organic solvent in the leukocyte removed blood filter after the filter. have.

In addition, Japanese Patent Application Laid-Open No. 2009-148567 (2009.07.09) relates to a filter for removing leukocytes in which a porous element is grafted onto polyethylene oxide, and grafting the porous element through a plasma treatment, ionizing radiation, or electron beam irradiation. The method is described. However, the patent also uses an organic solvent in the manufacture of the filter, there may be a risk of human toxicity due to red blood cells and platelet contamination by the organic solvent and residual organic solvent in the leukocyte removed blood filter after the filter.

Further, Japanese Laid-Open Patent Publication No. 2003-230627 (19.08.2003) is by irradiation with an electron beam to the filter substrate and improving adhesion between a hydrophilic polymer is coated with a base material by modifying the surface of the filter and chairs, C ₈ to the surface It is described to coat a hydrophilic polymer to a filter substrate having a functional group of H ₂₀ N and / or C ₁₂ H ₂₄ N. However, the patent is a film-like filter medium, when the film-like filter medium is the same volume compared to the fibrous or bead phase, the surface area is significantly reduced, so when introducing the functional group, the film is the introduction rate of the functional group is lowered, As a result, the filtration rate may also drop.

Korea has imported and used all leukocyte removal filters from overseas. Currently, most products such as Immugard IG 500Y (Terumo, Japan), Sepacell R-500TM (Asahi, Japan), Pall RC100TM (Pall Co., USA) It is used.

Therefore, it is necessary to develop Korea's own technology. Accordingly, the present invention seeks to solve the problems of high cost and bacterial infection, which are disadvantages of the conventional leukocyte removal filter. In addition, the conventional filter is intended to solve the problem that Lymphocyte (lymphocyte) is left while the neutrophil (neutrophil leukocyte) of leukocytes is completely removed, and to reduce the residual leukocytes and increase the erythrocyte and platelet recovery rate.

Specifically, the present invention is a leukocyte removal filter material consisting of a two-stage filter material so as to minimize the remaining white blood cell count, in the first step to separate the white blood cells from red blood cells, platelets, plasma with the same function as the existing filter material In the second filter, the filter material has a functional group capable of absorbing leukocytes effectively, and the functional group can be easily introduced into the filter material using radiation. Etc.) can be overcome.

In addition, since the remaining white blood cell count can be effectively lowered in one step, an additional removal process for removing the remaining white blood cells is not required from the blood product prepared primarily as in the conventional method, and thus, time and economic efficiency can be expected to increase. .

Japanese Laid-Open Patent Publication No. 2004-215873 (2004.08.05) Korean Unexamined Patent Publication No. 2003-0034981 (2003.05.09) Japanese Laid-Open Patent Publication No. 2009-148567 (2009.07.09) Japanese Laid-Open Patent Publication No. 2003-230627 (2003.08.19)

The present invention is to provide a filter connected in this step to minimize the remaining white blood cell count. Specifically, leukocytes are firstly separated according to the pore size, and the second separation is performed by using a polymer material having a functional group capable of separating and adsorbing leukocytes.

In addition, the present invention can be manufactured in a fibrous or bead phase polymer material having a functional group capable of separating and adsorbing the white blood cells, and when the bead phase is manufactured regardless of the shape and size of the filter case as a housing The present invention provides a filter for leukocyte removal that can be filled and used.

It is also an object of the present invention to provide a filter medium having a functional group capable of adsorbing and separating leukocytes using radiation instead of chemical reagents, which are the main cause of environmental pollution and human toxicity.

In addition, the present invention does not use organic solvents that are harmful to the human body at the time of manufacture is environmentally friendly, less toxic to the human body, and when discarded after use to remove leukocytes applied to the filter medium without the problem of environmental pollution because natural or synthetic polymer harmless to the human body To provide a filter for.

The present invention provides a first filter material made of a polymer material having a pore size through which leukocytes do not pass, and a second filter material made of a polymer material grafted with a functional group for adsorbing and separating leukocytes. It relates to a two-stage filter for leukocyte removal.

The two-stage filter for leukocyte removal according to the present invention can effectively remove leukocytes in one process, and the removal efficiency is very excellent.

In addition, the second filter material for adsorbing and removing leukocytes in the manufacture of the filter to improve the removal efficiency by grafting a functional group excellent in leukocyte removal efficiency, and also using an organic solvent by grafting with radiation when grafting. As a result, it is possible to provide a filter having low human toxicity and no environmental pollution.

In addition, by manufacturing and using a fibrous or bead-like filter medium using a biocompatible polymer as a filter material for adsorption and removal of white blood cells, the filter can be used regardless of the shape and size of the filter case as a housing. A leukocyte removal filter can be provided.

1 illustrates an example of a two-stage filter of the present invention, in which a first filter material 10 is inserted into a first filter case 100 and a second filter material 20 is a second filter case 200. It can be made to be inserted into.
2 shows an example of a two-stage filter of the present invention.
3 shows an example of a two-stage filter of the present invention, in which the first filter case 100 into which the first filter material 10 is inserted and the second filter case 200 into which the second filter material 20 is inserted. ) Is connected by a connection part 31, the connection part 31 may be formed with a step with the inlet 11 and outlet 21 to allow the blood to move.

Hereinafter, the present invention will be described in detail.

The present invention relates to a filter used to separate and remove leukocytes, wherein the first filter material for firstly separating and removing white blood cells by adjusting porosity and the second filter material grafted with a functional group capable of adsorbing and separating leukocytes sequentially The present invention relates to a two-stage filter for leukocyte removal that can be completely separated in a single process.

More specifically, one embodiment of the present invention prevents side effects of transfusion in which the first filter material having a pore size through which leukocytes do not pass and the second filter material made of a polymer material grafted with a functional group for adsorbing and separating leukocytes are sequentially It is a two-stage filter for leukocyte removal.

In addition, in one aspect of the present invention, the first filter material may be a fibrous filter material having a pore size of 0.5 to 10 ㎛.

In addition, in one aspect of the present invention, the first filter material may be a fibrous filter material consisting of fibers having an average fiber diameter of 0.1 to 3 ㎛.

In addition, in one aspect of the present invention, the second filter material may be a functional group for adsorbing and separating white blood cells to the polymer material by irradiation with radiation.

In addition, in one aspect of the present invention, the polymer material may be a fibrous filter material, a film filter material or a bead filter material.

In addition, in one aspect of the present invention, the fibrous filter medium used in the second filter material is polyvinylpyrrolidone, polyvinylalcohol, hydroxyethylcellulose, hydroxypropyl cellulose. , Hydroxypropylmethylcellulose, (meth) acrylic acid, (hydroxyethylmethacrylate), hydroxyethylmethacrylate, carrageenan, silicone rubber, polyethyleneglycol, Polyacrylamide, polyhydroxyethylmethacrylate, polydioxolane, polyacrylacetate, polyacrylamide, polyvinylchloride, polyethyleneoxide ), Methylcellulose, polya Polyacrylic acid, gelatin, agar, alginate, chitosan, poly lactic acid, polycaprolactone, polyglycolic acid, Poly (L-lactide-co-ε-caprolactone) (Poly (L-lactide-co-ε-caprolactone)), poly (L-lactide-co-glycolide A fibrous filter medium may be prepared by electrospinning a biocompatible polymer including any one or two or more mixtures selected from), and a functional group for adsorbing and separating leukocytes may be irradiated and grafted.

In addition, in one embodiment of the present invention, the bead filter medium used in the second filter material is polyvinylpyrrolidone (polyvinylpirrolidone), polyvinyl alcohol (polyvinylalcohol), hydroxyethyl cellulose (hydroxyethylcellulose), hydroxy propyl cellulose (hydroxypopylcellulose ), Hydroxypropylmethylcellulose, (meth) acrylic acid, (meth) acrylic acid, hydroxyethylmethacrylate, carrageenan, silicone rubber, polyethyleneglycol , Polyacrylamide, polyhydroxyethylmethacrylate, polydioxolane, polyacrylacetate, polyacrylamide, polyacrylamide, polyvinylchloride, polyethylene oxide ( polyethyleneoxide, methylcellulose, polya Polyacrylic acid, gelatin, agar, alginate, chitosan, poly lactic acid, polycaprolactone, polyglycolic acid, Poly (L-lactide-co-ε-caprolactone) (Poly (L-lactide-co-ε-caprolactone)), poly (L-lactide-co-glycolide Radiation-grafted functional groups for adsorbing and separating leukocytes may be used on beads prepared from biocompatible polymers including any one or two or more mixtures selected from

In addition, in one aspect of the present invention, the functional group for adsorbing and separating the leukocytes is positively charged and the terminal group of the grafted monomer after grafting the monomer having a double bond at the end by irradiation with the polymer material The grafted immune factor absorber capable of adsorbing and separating leukocytes to some or all of them may be used.

In addition, in one aspect of the present invention, the functional group for adsorbing and separating the leukocytes may be grafted to 0.05 ~ 5 uM / mg.

In one embodiment of the present invention, the radiation may be a gamma ray, an electron ray, an ultraviolet ray or an X-ray.

In addition, in one aspect of the present invention, the radiation dose may be 1 ~ 100 kGy.

In addition, in one aspect of the present invention, the first filter material and the second filter material may be inserted into and connected to each filter case.

In addition, in one aspect of the present invention, the filter case may be made of a transparent material so that the inside can be observed.

Hereinafter, each component will be described in more detail.

Referring to the two-stage filter of the present invention, the first filter material and the second filter material of the present invention are sequentially connected, and after the blood passes through the first filter material and is primarily filtered by the pore difference, the second filter material White blood cells can be effectively removed by a functional group capable of adsorbing and removing white blood cells while passing through the filter material.

More preferably, as shown in FIG. 1, the first filter material 10 is inserted into the first filter case 100, and the second filter material 20 is inserted into the second filter case 200 and sequentially. Can be connected. The shapes of the filter cases 100 and 200 and the filter materials 10 and 20 are not limited to those of FIG. 1.

At this time, the filter case is not limited, but preferably made of a transparent material so that the inside can be observed. More specifically, it is preferable to use a transparent resin such as acrylic resin, polycarbonate, polyethylene, polypropylene, but is not limited thereto.

In the present invention, the first filter material is preferably made of a fiber material having a pore size capable of separating and removing leukocytes, and in order to separate leukocytes, it has a pore size of 0.5 to 10 μm, more preferably 0.5 to 3 μm. It is preferable. In the range of less than 0.5㎛ pore size is too fine delays the filter time, the pores are blocked by the collected white blood cells can be difficult to pass through the red blood cells or platelets, If the thickness exceeds 10 ㎛ the efficiency of separation and removal of white blood cells Can be degraded. Since the size of white blood cells is typically 12-16 μm, excellent removal efficiency can be achieved in a range of 0.5 to 10 μm, and 0.5 to separate platelets of 2-5 μm and red blood cells of 8-10 μm in size Better removal efficiency can be achieved in the range of ˜3 μm.

The fiber material is not limited, but it is preferable to use one made of fibers having an average fiber diameter of 0.1 to 3 µm. If the average diameter of the fiber is less than 0.1 μm, the micropore size between the fibers is so small that the collected leukocytes can block the micropores, which makes it difficult to pass erythrocytes and platelets. Can be. More preferably, the average fiber diameter is made of fibers having 0.1 to 3 μm, and it is preferable to prepare and use a fiber material so that a pore size of 0.5 to 10 μm is formed.

The fiber is not limited but may be a fiber produced using a resin such as polyethylene terephthalate, polybutylene terephthalate, polypropylene, polyethylene, polyurethane, polyamide, and the like. More preferably, polyvinylpyrrolidone, polyvinylalcohol, hydroxyethyl cellulose, hydroxypopylcellulose, hydroxypropylmethylcellulose, (meth) acrylic acid ( (meth) acrylic acid, hydroxyethylmethacrylate, hydroxyethylmethacrylate, carrageenan, silicone rubber, polyethyleneglycol, polyacrylamide, polyhydroxyethylmethacrylate polyhydroxyethylmethacrylate, polydioxolane, polyacrylacetate, polyacrylamide, polyvinylchloride, polyethyleneoxide, methylcellulose, polyacrylic acid, Gelatin, argar, alginine Alginate, chitosan, poly lactic acid, polycaprolactone, polyglycolic acid, poly (L-lactide-co-ε-caprolactone) (Poly (L-lactide-co-ε-caprolactone), a biocompatible polymer comprising any one or a mixture of two or more selected from poly (L-lactide-co-glycolide) It is preferable to reduce human toxicity by using a fibrous filter medium prepared by electrospinning In the present invention, "biocompatible polymer" means a polymer harmless to the human body.

In the present invention, the fibrous filter medium applied to the first filter material may include a fabric form such as a nonwoven fabric and a rod form. The rod form includes a form in which several strands of fiber are twisted, such as a rope.

In the present invention, the second filter material is used to attach a functional group for adsorbing and separating leukocytes to the polymer material by irradiating radiation, the polymer material may be a fibrous filter material or bead filter material.

The functional group for adsorbing and separating the white blood cells in the present invention is not limited as long as the functional group capable of adsorbing and separating white blood cells, the present invention is positively charged and the monomer having a double bond at the terminal by irradiation with the polymer material After grafting, an immunofactor absorber capable of adsorbing and separating leukocytes on part or all of the terminal groups of the grafted monomer can be grafted by irradiation.

As the monomer having a positive charge and having a double bond at the terminal, an acrylic monomer may be preferably used, and for example, acrylic acid, methacrylic acid, or the like may be used. Leukocytes have a large amount of negative charges on the surface compared to platelets or red blood cells, and may act to selectively adsorb white blood cells by electrostatic attraction by grafting a positively charged monomer as described above.

In addition, by grafting an immunofactor absorber that can utilize chemotaxis according to the antigen-antibody reaction of leukocytes to the acrylic monomer, it is first removed by electrostatic attraction and further removed by the antigen-antibody reaction. The efficiency can be further increased. Specific examples of the immunofactor absorber may include alkylcatechols such as vitamin K ₁ , urushiol, and the like.

In addition, the content of the functional group is preferably grafted to 0.05 ~ 5 uM / mg because it can efficiently remove the white blood cells.

In the present invention, when the second filter material is a fibrous filter material, a fibrous filter material may be prepared by electrospinning a biocompatible polymer, and a functional group for adsorbing and separating leukocytes may be used to irradiate and graft the functional filter.

The biocompatible polymers include polyvinylpyrrolidone, polyvinylalcohol, hydroxyethylcellulose, hydroxypopylcellulose, hydroxypropylmethylcellulose, and (meth). Acrylic acid, hydroxyethylmethacrylate, carrageenan, silicone rubber, polyethyleneglycol, polyacrylamide, polyhydroxyethylmethacryl Polyhydroxyethylmethacrylate, polydioxolane, polyacrylacetate, polyacrylamide, polyvinylchloride, polyethyleneoxide, methylcellulose, polyacrylic acid ), Gelatin, agar , Alginate, chitosan, poly lactic acid, polycaprolactone, polyglycolic acid, poly (L-lactide-co-ε-caprolactone) ( Poly (L-lactide-co-ε-caprolactone)), poly (L-lactide-co-glycolide) or any mixture of two or more selected from It is preferable because it is less toxic.

In the method of preparing the fibrous filter medium, the biocompatible polymer may be dissolved in a solvent to prepare a dope solution, followed by electrospinning to prepare a nonwoven fabric or rod-like fibrous filter medium. Thereafter, the fibrous filter medium may be grafted to an acrylic monomer solution to graf the functional group by irradiating radiation. In addition, after the acrylic monomer is grafted, the functional group may be further grafted by supporting radiation in an alkyl catechol solution.

In this case, the radiation is preferably using gamma rays, electron beams, ultraviolet rays or X-rays, the radiation dose is preferably 1 ~ 100 kGy. The graft reaction is not sufficiently achieved at low doses, and economical waste may be caused at high doses, so it is suitable in the above range.

In the present invention, when the second filter material is a bead-like filter material, after producing a bead using a biocompatible polymer, a functional group for adsorbing and separating leukocytes on the surface of the bead may be used by grafting radiation. have.

The biocompatible polymers include polyvinylpyrrolidone, polyvinylalcohol, hydroxyethylcellulose, hydroxypopylcellulose, hydroxypropylmethylcellulose, and (meth). Acrylic acid, hydroxyethylmethacrylate, carrageenan, silicone rubber, polyethyleneglycol, polyacrylamide, polyhydroxyethylmethacryl Polyhydroxyethylmethacrylate, polydioxolane, polyacrylacetate, polyacrylamide, polyvinylchloride, polyethyleneoxide, methylcellulose, polyacrylic acid ), Gelatin, agar , Alginate, chitosan, poly lactic acid, polycaprolactone, polyglycolic acid, poly (L-lactide-co-ε-caprolactone) ( Poly (L-lactide-co-ε-caprolactone)), poly (L-lactide-co-glycolide) or any mixture of two or more selected from It is preferable because it is less toxic.

As a method of preparing the beads, for example, the biocompatible polymer is dissolved in a solvent to prepare a solution, and more preferably, an aqueous solution using water as a solvent.

At this time, the biocompatible polymer aqueous solution preferably contains the biocompatible polymer in a solid content of 5 to 40 wt%, more preferably 15 to 20 wt%. If it is included in less than 5% by weight it may be difficult to form a bead, when containing more than 40% by weight it is preferable to include the content because the size of the bead may be too large.

In the present invention, a solubilizer may be further added if necessary, and any one or a mixture of two or more selected from ethanol and polyhydric alcohols may be used. The content preferably contains 10 to 20% by weight of the biocompatible polymer aqueous solution.

Further, a crosslinking agent such as aluminum hydroxide or magnesium hydroxide may be added for the purpose of controlling the cohesive force and adhesive force of the hydrogel layer, and a softener, a pH adjuster, a preservative, an antioxidant and the like selected from commonly used glycerin, ethylene glycol and propylene glycol Can be further added.

In the present invention, when the biocompatible polymer aqueous solution is prepared, it is preferable to stir until homogeneous to produce a homogeneous particle, and it is preferable to prepare the polymer aqueous solution by heating in an autoclave as necessary. In this case, the heating is preferably performed at 100 to 140 ° C, more preferably at 110 to 120 ° C, and preferably for 10 to 60 minutes.

In the present invention, it is possible to form uniformly sized biocompatible polymer particles by injecting the homogeneously prepared biocompatible polymer aqueous solution into the oily phase and then stirring to produce a water-in-oil type emulsion.

The oily phase is used to control the cohesion and dispersion of the small molecules dissolved, specifically, for example, may be a silicone oil or vegetable oil, the vegetable oil is specifically, for example, soybean oil, olive oil, canola oil, grapeseed oil And the like.

It is preferable to form uniformly sized biocompatible polymer particles by uniformly dispersing at a high speed of 6000 rpm or more using a uniform particle disperser or the like in the production of emulsion of water-in-oil type.

Next, the water-in-oil emulsion is frozen and thawed to prepare physically crosslinked pre-hydrated gel particles.

At this time, the freezing is preferably carried out at -100 ~ -15 ℃, more preferably -70 ~ -40 ℃. The thawing is preferably performed at 5 to 50 캜, more preferably 20 to 30 캜. Freezing at temperatures lower than −100 ° C. has no significant difference in the formation of physical crosslinks, while the hydrogel may not freeze at temperatures higher than −15 ° C. In addition, at a defrosting temperature lower than 5 캜, a proper defrosting time can not be ensured, and at a defrosting temperature higher than 50 캜, physical crosslinking can be weakened.

The time for performing the above-mentioned freezing process can be changed according to the freezing temperature, and it is generally preferably 5 minutes to 1 hour. When the freezing time is less than 5 minutes, effective freezing can not be performed. If the freezing time is more than 1 hour, unnecessary time is wasted in the hydrogel manufacturing process.

The freezing and thawing process can be repeated to ensure stable physical crosslinking. The number of times of execution is preferably 1 to 5 times, and it is preferably 1 to 3 times in order to simplify the process.

Next, the pre-hydrated gel particles physically crosslinked through the freezing and thawing process are irradiated with radiation to perform crosslinking and sterilization. The radiation is preferably gamma ray, electron ray, ultraviolet ray or X-ray.

The radiation is used to crosslink the polymer, and the dose of the radiation is preferably 10 to 100 kGy. If the radiation is irradiated in excess of 100 kGy, the degree of crosslinking of the polyvinyl alcohol is increased and it is difficult to sufficiently express the intended swelling and shrinkage characteristics. If the radiation is less than 10 kGy, crosslinking is insufficient. It may be difficult to maintain shape.

The polymer gel filter medium produced by the production method of the present invention has a spherical bead form, the average particle diameter of 100 ~ 200 ㎛.

A functional group capable of removing leukocytes is attached to the surface of the bead-like filter medium thus prepared, which may be performed in the same manner as the fibrous filter medium of the second filter medium.

In this case, the radiation is preferably using gamma rays, electron beams, ultraviolet rays or X-rays, the radiation dose is preferably 1 ~ 100 kGy. The graft reaction is not sufficiently achieved at low doses, and economical waste may be caused at high doses, so it is suitable in the above range.

In the two-stage filter for leukocyte removal of the present invention, as shown in FIG. 1, the first filter material 10 and the second filter material 20 are sequentially flowed from the inlet portion 11 of the blood to the outlet portion 21. Is connected, the first filter material 10 is inserted into the first filter case 100, the second filter material 20 may be made to be inserted into the second filter case 200, the first filter case The 100 and the second filter case 200 may be connected by the connection part 31 to be a filter in two stages.

2 shows an example of a two-stage filter of the present invention. As shown in FIG. 2, whole blood is introduced from the inlet 11, and the white blood cells are first filtered by the difference in pore size while passing through the first filter case 100 into which the first filter material 10 is inserted. The second filter case 200 is introduced into the second filter case 200 through the connecting portion 31 to adsorb and separate the white blood cells by a functional group for adsorbing and separating the white blood cells, and then through the outlet 21. Leukocytes are drained of blood. In this case, the first filter case 100 into which the first filter material 10 is inserted and the second filter case 200 into which the second filter material 20 is inserted may have a circular shape as shown, and have a diameter L1. ) May be 40 to 60 mm. In addition, the diameter L3 of the inlet part 11, the outlet part 21, and the connection part 31 for introducing the blood into the first filter case 100 may be 2 to 3 mm, and the length L2 may be It can be 6-8mm.

3 shows an example of a two-stage filter of the present invention, in which the first filter case 100 into which the first filter material 10 is inserted and the second filter case 200 into which the second filter material 20 is inserted. ) Is connected by a connection part 31, the connection part 31 may be formed with a step with the inlet 11 and outlet 21 to allow the blood to move. That is, it is preferable to make the movement of blood easier by forming the height of the connection part 31 higher than the inflow part 11 and the outflow part 21. FIG.

1 to 3 are only examples for explaining one embodiment of the present invention, and the present invention is not limited to the drawings.

10: first filter material
20: second filter material
100: first filter case
200: second filter case
11: inlet
21: outlet
31: Connection

Claims (13)

A two-stage filter for leukocyte removal for preventing transfusion side effects in which a first filter material having a pore size through which leukocytes do not pass and a second filter material made of a polymer material grafted with a functional group for adsorbing and separating leukocytes are sequentially connected.
The method of claim 1,
The first filter material is a two-stage filter for leukocyte removal for preventing transfusion side effects, which is a fibrous filter medium having a pore size of 0.5 to 10 μm.
3. The method of claim 2,
The first filter material is a two-stage filter for leukocyte removal for preventing transfusion side effects, which is a fibrous filter material consisting of fibers having an average fiber diameter of 0.1 to 3 μm.
The method of claim 1,
The second filter material is a two-stage filter for leukocyte removal to prevent side effects of blood transfusion that is attached to a functional group for adsorbing and separating leukocytes on the polymer material by irradiation with radiation.
5. The method of claim 4,
The polymer material is a two-stage filter for removing leukocytes for the prevention of side effects of blood transfusion, which is a fibrous filter material, a film filter material, or a bead filter material.
6. The method of claim 5,
The fibrous filter medium may be polyvinylpyrrolidone, polyvinyl alcohol, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, (meth) acrylic acid, hydroxyethyl methacrylate, carrageenan, silicone rubber, polyethylene glycol, Polyacrylamide, polyhydroxyethyl methacrylate, polydioxolane, polyacrylic acetate, polyacrylamide, polyvinylchloride, polyethylene oxide, methylcellulose, polyacrylic acid, gelatin, agar, alginate, chitosan, polylactide, poly A biocompatible polymer comprising one or a mixture of two or more selected from caprolactone, polyglycolic acid, poly (L-lactide-co-ε-caprolactone), and poly (L-lactide-co-glycolide) Spinning to produce a fibrous filter medium, functional groups for adsorbing and separating leukocytes By irradiating a diagonal graft which will prevent transfusion of leukocyte removal for the two-stage filter for the side effects.
6. The method of claim 5,
The bead filter medium is polyvinylpyrrolidone, polyvinyl alcohol, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, (meth) acrylic acid, hydroxyethyl methacrylate, carrageenan, silicone rubber, polyethylene glycol , Polyacrylamide, polyhydroxyethyl methacrylate, polydioxolane, polyacrylic acetate, polyacrylamide, polyvinylchloride, polyethylene oxide, methylcellulose, polyacrylic acid, gelatin, agar, alginate, chitosan, polylactide, From a biocompatible polymer comprising one or a mixture of two or more selected from polycaprolactone, polyglycolic acid, poly (L-lactide-co-ε-caprolactone) and poly (L-lactide-co-glycolide) Irradiated functional group to adsorb and separate white blood cells Leukocyte removal for the prevention of transfusion reactions which will prompt two-stage filter.
5. The method of claim 4,
The functional group for adsorbing and separating the white blood cells is positively charged, and the monomer having a double bond at the end is grafted to the polymer material by radiation, and then the white blood cells are adsorbed to some or all of the terminal groups of the grafted monomer. A two-stage filter for leukocyte removal for preventing transfusion side effects, in which a detachable immunofactor absorber is grafted by irradiation.
5. The method of claim 4,
The functional group for adsorbing and separating the white blood cells is grafted to 0.05 ~ 5 uM / mg two-stage filter for leukocyte removal for the prevention of blood transfusion side effects.
5. The method of claim 4,
The radiation is gamma rays, electron beams, ultraviolet rays or X-rays leukocyte removal step for preventing transfusion side effects.
5. The method of claim 4,
The radiation dose is 1 ~ 100 kGy leukocyte removal step for preventing blood transfusion side effects.
The method of claim 1,
The first filter material and the second filter material is inserted into each filter case is to be connected to the two-stage filter for leukocyte removal for prevention of transfusion side effects.
13. The method of claim 12,
The filter case is a two-stage filter for removing white blood cells for the prevention of side effects of transfusion that is made of a transparent material so that the inside can be observed.

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