JPH10338639A - Filter for leukocyte removal coated with chitosan or modified chitosan - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject filter which shows high efficiency for removing leukocyte without adverse effect on living bodies and is excellent in withdrawing rates of platelets and red blood cells by applying chitosan or modified chitosan on the surface of unwoven cloth. SOLUTION: The objective filter is obtained by immersing unwoven cloth, which is made of synthetic or natural fibers and is preferably 3 μm or less in the space between adjacent fibers, into a solution of chitosan or modified chitosan (a graft polymer of chitosan and a blood affinitive polymer selected from polydimethylaminoethyl methacrylate, polymethyl methacrylate, polyacrylic acid and sodium polyvinyl sulfonic acid), which is contained in a concentration of 0.1-5 wt.% in an organic acid or an inorganic acid and possesses an average molecular weight of preferably 200,000-700,000, for 30-120 min., if necessary, carrying out ultrasonication for 2 hrs. or less during immersing and further irradiating ultraviolet ray to the resultant filter in 10 mJ/cm<2> or less.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a non-woven fabric,
The present invention relates to a leukocyte removal filter coated with a natural polymer chitosan or a modified chitosan. More specifically, the present invention is manufactured by applying a natural polymer chitosan or a modified chitosan having good blood affinity and having no side effects on the human body, that is, a chitosan graft polymer, on a nonwoven fabric having a small distance between adjacent fibers. And a filter for removing leukocytes. The leukocyte removal filter according to the present invention has a high leukocyte removal rate, an excellent platelet and red blood cell recovery rate, and excellent clinical characteristics.

[0002]

BACKGROUND OF THE INVENTION Blood makes up about 6 to 8% by weight of the human body, of which about 40 to 45% by volume is solid and the rest is liquid. The solid cell components of blood include red blood cells, white blood cells and platelets, and plasma, which is a liquid component, has plasma proteins such as fibrinogen, albumin, and γ-globulin, and other organic substances and inorganic salts dissolved in water. In state. As described above, the importance and value of the functional role of not only blood as a component of the human body but also each component of blood is recognized even higher. Therefore, recently, the transfusion pattern has also been switched to an aggressive blood supply pattern instead of the conventional whole blood transfusion. In other words, a component transfusion therapy for transfusing only blood components necessary for a patient is widely used.
The advantage of component transfusion is that besides being able to provide only that component to patients who require a large amount of a specific blood component, one unit of blood to be supplied can benefit more patients. In addition, waste of blood resources can be reduced.

However, when transfecting not only whole blood but also red blood cell concentrates and platelet concentrates, which are blood component preparations, leukocytes mixed in blood products are
Various side effects may occur, such as non-hemolytic febrile transfusion side effects and inappropriate blood transfusion due to leukocyte antibody formation.

[0004] In particular, when continuous administration of a platelet concentrate is required, alloimmunity may occur due to the histocompatibility antigens of the leukocytes contained therein. Elimination can reduce such transfusion side effects.

[0005] As a method of removing leukocytes from blood,
A platelet separation and fractionation method that can reduce the number of blood donors has been recommended, and other methods such as centrifugal sedimentation and saline washing have been commonly used. Recently, a filtration method using a filter has been developed and is being used in place of the centrifugal sedimentation method and the washing method. In the filtration method using a filter, a disposable single-use filter is used.
There is no risk of infection, and since filtration is performed by gravity, there is no need for additional equipment, and the separation time is short, and the leukocyte removal rate is very high compared to other methods. doing.

[0006] Seyfert et al. Performed an experiment of increasing cell adsorption by coating a microscope slide matrix with polyvalent cations, and the cell adsorption was not due to surface tension on the matrix but to electrostatic charge due to surface charge. (S. Seyfert, A. Voigt and D. Kabbeck-Ku
pijai, "Adhesion of Leucocytes to Microscope Slide
s as Influenced by Electrostatic Interaction ", Bio
materials, Vol.16, No.3, pp 201-207, (1995)]. Also, Nishimura et al., When removing leukocytes using a polyester non-woven fabric, the leukocyte removal rate increases as the diameter of the fibers constituting the non-woven fabric increases, and hydroxyethyl methacrylate and diethylaminoethyl methacrylate are added to the surface of the non-woven fabric. It was reported that a random copolymer was applied to give a cationic potential [T. Nishimu
ra, T. Kuroda, Y. Mizoguchi, H. Watanabe, H. Rikum
aruand M. Umegae, "Advanced Method for Leucocyte R
emoval by Blood Filtration "in" The Role of Leucoc
yte Depletion in Blood Transfusion Practice ", Ed.
by B. Brozovic, Blackwell Scientific Publications,
Oxford (1989) pp 35-40]. Meanwhile, Bruil
Et al. Confirmed that leukocytes were adsorbed through selective interaction of amines on the filter surface in a filtration test of a leukocyte removal filter in which polyethylene imine was applied to a polyurethane nonwoven fabric (A. Bruil, HAOosterom, I.
Steneker, BJMA1, T. Beugeling, WG van Aken, a
nd J. Feijen, "Poly (ethyleneimine) Modified Filters
for the Removal of Leucocytes from Blood ", J. Biom
ed. Mat. Res., Vol. 27, pp 1253-1268 (1993)].

[0007] Such a leukocyte removal filter is currently in clinical use, and many patents have disclosed a blood filtration device using a fibrous filter surface-modified with various polymers, and blood using the same. It discloses filtration methods (U.S. Pat. Nos. 4,701,267 and 4,880,54).
No. 8, No. 4,923,620, No. 4,936,9
No. 98, European Patent Publication Nos. 0397403, 0408462, 0406485 and 05
59086). However, in any of the above-mentioned documents, no use example of a blood filter in which a nonwoven fabric is coated with chitosan or a graft polymer of chitosan and a blood affinity polymer cannot be found. Therefore, the present invention is significant in that excellent effects can be obtained by using a natural biocompatible polymer that is not a synthetic polymer or a graft polymer of the polymer as a coating material of the nonwoven fabric.

[0008]

DISCLOSURE OF THE INVENTION The present inventors have conducted intensive studies to develop a blood filtration filter having better biocompatibility. As a result, the nonwoven fabric which has been conventionally used as a filter material is coated with a coating material. It has been found that by applying chitosan, a filter having excellent performance can be obtained. In addition, the present inventors have conducted studies to further increase the blood affinity of chitosan, and as a result, it has been found that a graft polymer of chitosan and various high-molecular substances having good blood affinity is excellently applied to a nonwoven fabric. A filter with good performance was obtained.

The leukocyte-removing filter according to the present invention does not exhibit any adverse biological effects and has satisfactory leukocyte-removing ability and platelet and red blood cell collecting ability. This conforms to the regulations of the American Association Blood Banks for leukocyte removal of 95% or more, platelet recovery of 90% or more, and red blood cell recovery of 90% or more.

[0010]

According to the present invention, there is provided a nonwoven fabric having a surface coated with chitosan or modified chitosan, specifically, a graft polymer of chitosan and a blood affinity polymer.
Provided is a leukocyte removal filter.

The present invention preferably has a degree of deacetylation of 8
Chitosan having a molecular weight of 5 to 95% and an average molecular weight of 200,000 to 700,000, or a blood affinity selected from the group consisting of polydimethylaminoethyl methacrylate, polymethyl methacrylate, polyacrylic acid and sodium salt of polyvinyl sulfonic acid. Provided is a leukocyte removal filter comprising a synthetic or natural fiber nonwoven fabric having a gap between adjacent fibers of 3 μm or less, coated with a polymer grafted with a hydrophilic polymer.

The present invention also provides a method for producing a leukocyte removing filter by applying a chitosan solution or a graft polymer solution of chitosan and a blood affinity polymer to a nonwoven fabric.

[0013] The present invention provides a method of immersing a nonwoven fabric in a 0.1 to 5% chitosan solution, preferably in an organic or inorganic acid, for 30 minutes to 120 minutes, and in some cases, for 2 hours or less during the immersion. Provided is a method for producing a leukocyte removal filter that performs ultrasonic treatment.

The present invention is also directed to immersing the nonwoven fabric in a graft polymer coating solution of a chitosan solution having a concentration of 0.1 to 5% and a blood affinity polymer in an organic or inorganic acid for 30 to 120 minutes. In some cases, the present invention provides a production method in which the solution is subjected to ultrasonic treatment for 2 hours or less during immersion, or the produced filter is further irradiated with ultraviolet rays of 10 mJ / cm ² or less.

The principle of leukocyte removal in the present invention is based on the following two. First, leukocytes of 6 to 20 μm are temporarily removed by the inter-fiber gap of the nonwoven fabric made of ultrafine fibers, and at this time, 2 to 4 μm platelets pass through a 6 to 9 μm red blood cell filter. The secondary filtration mechanism is due to static electricity between the cationic residues on the coated nonwoven surface and the leukocytes. When the present invention is compared with the results of a filtration experiment using a filter using only the nonwoven fabric, the filtration is closely related to the recovery rate of red blood cells and platelets, and the leukocyte removal rate, due to the size of the gap between the fibers of the nonwoven fabric. Found that surface adsorption played a more important role.

Blood cells are regarded as a mixture of a protein, which is a conjugate of amino acids, and fat, and are generally anionic. In the present invention, chitosan or a graft polymer of chitosan and a blood-affinity polymer is used as an adsorption substrate having a cation potential, which can be adsorbed by such an electrostatic interaction with blood cells.

Chitosan is a deacetylated product of chitin, a kind of carbohydrate derivative, derived from fungi, yeast, shrimp, crab and marine invertebrates.
(1 → 4) 2-amino-2-deoxy-β-D-glucosamine, and its chemical structure is represented by the following general formula (1).

[0018]

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On the other hand, blood-affinity polymers that can be graft-polymerized with chitosan include, for example, polydimethylaminoethyl methacrylate, polymethyl methacrylate, polyacrylic acid, and sodium salt of polyvinyl sulfonic acid. And the following general formulas (2) to (5). That is, these polymers act on the amino group at the second carbon position of glucopyranose of chitosan.

[0020]

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As can be seen from the above formula, the graft polymer with chitosan or a blood-affinity polymer has a cationic functional group that adsorbs negative charges existing on the surface of leukocytes,
Since it is a natural biological substance and is harmless and toxic to the human body, it can be effectively used for a leukocyte removal filter through surface modification of a filtration medium.

The chitosan used in the present invention preferably has a degree of deacetylation of 85 to 95%. Also,
Those having an average molecular weight of 200,000 to 700,000 are particularly desirable. The graft polymer of chitosan and the polymer can be produced by a conventional method known in the art, and particularly has a degree of deacetylation of 85 to 95% and an average molecular weight of 200,000 to 700,000.
Is preferably obtained by graft polymerization with chitosan.

According to the present invention, nonwoven fabrics made of various synthetic or natural fibers can be used as nonwoven fabrics that provide a primary filtration mechanism depending on the size of the gap between adjacent fibers. ,
Cellulose and other cellulose derivatives can be used. The non-woven fabric used has a gap between adjacent fibers of 3
μm or less, fiber diameter about 1.8 μm, bulk density about 0.15
g / cm ³ , and particularly a nonwoven fabric of polyester ultrafine yarn having the above properties.

The leukocyte-removing blood filter according to the present invention can be manufactured by immersing a nonwoven fabric in the above-mentioned chitosan solution or chitosan-graft polymer solution, or by spraying the chitosan solution or chitosan-graft polymer solution on the nonwoven fabric. it can. For example, when applying by dipping in a solution, the nonwoven fabric is placed in an organic or inorganic acid such as acetic acid or formic acid, preferably in a 0.1 to 5% concentration chitosan solution or chitosan graft polymer solution, for 30 minutes to 120 minutes. It can be manufactured by immersion for minutes. During immersion, it is desirable to sonicate the solution for up to 2 hours. Further, it is desirable that the filter produced by applying a nonwoven fabric to a graft polymer solution of chitosan and a blood affinity polymer is irradiated with ultraviolet rays of 10 mJ / cm ² or less to further modify the filter.

The filter produced according to the present invention can be used for filtering whole blood or various blood component preparations by a usual method in the art.

[0026]

The following examples serve to illustrate the present invention but do not limit the present invention in any way. In the following Examples and Comparative Examples, the leukocyte removal rate, platelet recovery rate, and red blood cell recovery rate are values obtained by calculating data obtained using a hemacytometer by the following formula.

Leukocyte removal rate (%) = [1−number of total leukocytes after filtration / number of total leukocytes before filtration] × 100 Platelet recovery rate (%) = [number of total platelets after filtration / number of total platelets before filtration] Number of total platelets] × 100 Red blood cell recovery rate (%) = [Number of total red blood cells after filtration / Number of total red blood cells before filtration] × 100

Example 1 Chitosan having an average molecular weight of about 500,000 and a degree of deacetylation of about 92% obtained from shrimp was dissolved in 1% acetic acid and 500 ml of a 1% chitosan solution was obtained.
Was manufactured. In addition to this, a medical-use ultrafine polyester nonwoven fabric (30 mm × 30 mm × 1.8 mm, Lyme) having a gap between adjacent fibers of 3 μm, a fiber diameter of 1.8 μm, and a bulk density of 0.156 g / cm ^3.
dall Co., USA) at 25 ° C. for about 60 minutes. The nonwoven fabric was taken out of the coating solution, dried at 40 ° C. for about 50 minutes, and then dried in a vacuum dryer at 20 to 25 ° C. for about 24 hours. Two units of 600 ml of whole blood blood purchased from the Red Cross Blood Institute were filtered in a room temperature filtration kit containing the above filter at a passage time of about 13 to 15 minutes / 1 unit. Hematology analyzer (Cell-dyn 900, SeQuoia-Turner C
o., USA) was used to determine the number of blood cells before and after filtration. The leukocyte removal rate, platelet recovery rate and red blood cell recovery rate according to the above formula were 99%, 95% and 95%, respectively.

<Example 2> In producing a filter in the same manner as in Example 1, a 3% chitosan solution in 1% acetic acid was used as a coating solution. After filtration of whole blood under the same conditions as in Example 1, the measured leukocyte removal rate, platelet recovery rate and red blood cell recovery rate were 96%, 95% and 9%, respectively.
5%.

<Example 3> In producing a filter in the same manner as in Example 1, a 5% chitosan solution in 1% acetic acid was used as a coating solution. After the blood was filtered under the same conditions as in Example 1, the measured leukocyte removal rate, platelet recovery rate and red blood cell recovery rate were 90%, 80% and 67%, respectively.

Example 4 2 g of chitosan having an average molecular weight of about 500,000 and a degree of deacetylation of about 90% obtained from crab, and 5 g of dimethylaminoethyl methacrylate monomer were placed in a reactor, and 0.5 g of the mixture was added. % Acetic acid (200 ml) was added, and the mixture was stirred under a nitrogen stream to swell. 0.1 as a reaction initiator
M Celic ammonium nitrate (Ce (NO ₃ ) ₄
(4 ml of 2NH ₄ NO ₃ ) solution was added and graft polymerization was carried out at 40 ° C. for 4 hours. The obtained polymer was immersed in 3,000 ml of acetone and stirred, and the product was filtered, dried under reduced pressure at 50 ° C. for 6 hours, and refluxed in methanol using a Soxhlet apparatus for 24 hours to obtain a homogenous polymer. The polymer was extracted.
Furthermore, it dried under reduced pressure at 50 degreeC for 6 hours, and completed polymerization, and obtained polydimethylaminoethyl methacrylate graft chitosan (graft rate 35%).

Example 5 According to a method similar to that of Example 4, the average molecular weight was about 450,000 and the degree of deacetylation was about 8.
Methyl methacrylate was graft-polymerized to 5% of chitosan to obtain polymethyl methacrylate-grafted chitosan (graft ratio: 16%).

Example 6 According to a method similar to that of Example 4, the average molecular weight was about 550,000, and the degree of deacetylation was about 9.
Acrylic acid was graft-polymerized to 5% of chitosan to obtain polyacrylic acid-grafted chitosan (graft ratio: 17%).

Example 7 By a method similar to that of Example 4, the average molecular weight was about 700,000 and the degree of deacetylation was about 9.
Sodium vinyl sulfonate was graft-polymerized to 0% of chitosan to obtain a polyvinyl sulfonate sodium salt grafted chitosan (graft ratio: 90%).

Example 8 Average molecular weight of about 450,00
After obtaining 0, chitosan with a degree of deacetylation of about 85% as a 3% solution in 1% acetic acid, film casting was performed. The cast film was vacuum-dried at 50 ° C. for 24 hours, and then cut into a film having a size of about 10 mm × 10 mm × 0.5 mm. The leukocyte concentrate (Red Cross Blood Institute) was diluted 4-fold with physiological saline, and the film was immersed in the diluted solution. The relative leukocyte adsorption rate, which is a percentage of the number of leukocytes in the leukocyte concentrate before and after immersion, is expressed by the immersion time of 10
Minutes, 30 minutes, 60 minutes, 90 minutes, and 120 minutes, and as a result, 16%, 40%, 70%, 72%, and 8 respectively
9%.

Example 9 Average molecular weight of about 470,00
Example 8 was carried out in the same manner as in Example 8, except that chitosan having a deacetylation degree of about 90% was used. 10
Minutes, 30 minutes, 60 minutes, 90 minutes, and 120 minutes, the leukocyte adsorption rates after immersion were 22%, 41%, 79%, and 82%, respectively.
And 93%.

Example 10 Average molecular weight of about 420,00
Example 8 was carried out in the same manner as in Example 8, except that chitosan having a deacetylation degree of about 0% was used. 10
Min, 30 minutes, 60 minutes, 90 minutes, and 120 minutes after immersion, the leukocyte adsorption rates were 25%, 43%, 81%, and 85%, respectively.
And 99%.

Example 11 An average molecular weight of about 5 obtained from a crab
50,000 chitosan with a degree of deacetylation of about 95%
A filter was prepared as in Example 1 as a 1% solution in 1% acetic acid. After the blood was filtered under the same conditions as in Example 1, the measured leukocyte removal rate and platelet recovery rate were 99% and 97%, respectively. Under the same conditions, when chitosan having an average molecular weight of about 700,000 and a degree of deacetylation of about 90% was used as a 1% solution in 1% acetic acid, the leukocyte removal rate and the platelet recovery rate were 90% and 80%, respectively. Met.

Example 12 A filter was manufactured in the same manner as in Example 1, except that the average molecular weight of chitosan used and the concentration of the coating solution in 1% acetic acid were changed as described below. The leukocyte removal rate and the platelet recovery rate were as shown in Table 1.

[0040]

[Table 1]

Example 13 Average molecular weight of about 500,00
0, chitosan having a deacetylation degree of 90% was dissolved in 1% acetic acid to obtain a 2% coating solution. After the same nonwoven fabric as in Example 1 was immersed therein, ultrasonic treatment at 40 kHz was performed at room temperature for about 60 minutes. After whole blood filtration under the same conditions, the measured leukocyte removal rate was 99%, the platelet recovery rate was 95%, and the red blood cell recovery rate was 95%.

Example 14 Average molecular weight of about 400,00
0, chitosan having a degree of deacetylation of 90% was dissolved in 1% acetic acid to obtain a 5% coating solution. After the same nonwoven fabric as in Example 1 was immersed therein, ultrasonic treatment at 40 kHz was performed at room temperature for about 90 minutes. After whole blood filtration under the same conditions, the measured leukocyte removal rate was 90%, the platelet recovery rate was 95%, and the red blood cell recovery rate was 95%.

Example 15 The polydimethylaminoethyl methacrylate graft chitosan obtained in Example 4 was replaced with 1
And dissolved in 0.5% acetic acid to obtain a 0.5% chitosan coating solution. At room temperature, the gap between adjacent fibers was 3 μm and the fiber diameter was 1.8.
μm, 0.156 g / cm ³ bulk density microfiber polyester nonwoven fabric for medical use (10 mm × 10 mm × 1.85 mm, Lydall C
o., USA) for 60 minutes. The nonwoven fabric was taken out of the solution and dried first at 40 ° C. for 2 hours, and then dried at 50 ° C. in a vacuum oven for 48 hours.

Two units of 600 ml of whole blood blood product purchased from the Red Cross Blood Institute were filtered in a room temperature filtration kit containing the above filter at a passage time of about 13 to 15 minutes / 1 unit. Hematology analyzer (Cell-dyn 900, SeQuoia-Turner
Co., USA) was used to determine the number of blood cells before and after filtration. The leukocyte removal rate, platelet recovery rate, and red blood cell recovery rate according to the above equations were 99%, 96%, and 97%, respectively.

Example 16 Example 15 was repeated except that a 2% chitosan solution in 1% acetic acid was used as a coating solution.
A filter was manufactured in the same manner as described above. After filtering the blood under the same conditions, the measured leukocyte removal rate, platelet recovery rate and red blood cell recovery rate were 90%, 70% and 75%, respectively.

Example 17 In producing a filter in the same manner as in Example 15, the polymethyl methacrylate graft chitosan obtained in Example 5 was used as a graft polymer, and the concentration of the coating solution was 1% in acetic acid. Was immersed in a 1% solution for 30 minutes and then dried. After filtering the blood under the same conditions,
The measured leukocyte removal rate, platelet recovery rate and red blood cell recovery rate were 70%, 92% and 90%, respectively.

Example 18 The same procedure as in Example 17 was carried out except that the concentration of the coating solution of polymethyl methacrylate grafted chitosan as a graft polymer was changed to a 3% solution in acetic acid. After filtering the blood under the same conditions, the measured leukocyte removal rate, platelet recovery rate and red blood cell recovery rate were 60%, 80% and 70%, respectively.

<Example 19> In the same manner as in Example 15, the polyacrylic acid grafted chitosan obtained in Example 6 was used as the graft polymer, and the concentration of the coating solution was 0.1% in acetic acid. It was made into a 5% solution, immersed for 90 minutes, and dried. After filtering the blood under the same conditions, the measured leukocyte removal rate, platelet recovery rate and red blood cell recovery rate were 90%, 95% and 90%, respectively.

Example 20 In carrying out the method in the same manner as in Example 19, the concentration of the polyacrylic acid grafted chitosan coating solution as the graft polymer was changed to a 5% solution in 1% acetic acid. After filtering the blood under the same conditions, the measured leukocyte removal rate, platelet recovery rate and red blood cell recovery rate were 80%, 85% and 80%, respectively.

<Example 21> In the same manner as in Example 15, the graft polymer used was the polyvinyl chitosan sulfonate sodium salt obtained in Example 7 and the concentration of the coating solution was 1%. It was made into a 1% solution in acetic acid, immersed for 30 minutes, and then dried. After filtering the blood under the same conditions, the measured leukocyte removal rate, platelet recovery rate and red blood cell recovery rate were 60%, 85% and 80%, respectively.

<Example 22> A graft polymer, a polyvinyl sulfonate sodium salt grafted chitosan, was prepared in the same manner as in Example 1 except that the concentration was changed to a 0.5% solution in 1% acetic acid.
Performed in the same manner as in Example 21. After filtering the blood under the same conditions, the measured leukocyte removal rate, platelet recovery rate and red blood cell recovery rate were 70%, 90% and 85%, respectively.
%Met.

Example 23 A nonwoven fabric was immersed in a polydimethylaminoethyl methacrylate-grafted chitosan coating solution under the same conditions as in Example 15 except that the nonwoven fabric was treated with ultrasonic waves of about 40 Hz for 60 minutes. The leukocyte removal rate, platelet recovery rate, and red blood cell recovery rate were calculated to be 95%, 95%, and 97%, respectively.

Example 24 The non-woven fabric coated with the polydimethylaminoethyl methacrylate-grafted chitosan solution obtained in Example 15 was subjected to a 3 mJ / cm ² ultraviolet treatment. After filtering the blood under the same conditions, the measured leukocyte removal rate, platelet recovery rate and red blood cell recovery rate were 98% each.
%, 97% and 97%.

<Comparative Example 1> Evaluation was performed by the same method using only the nonwoven fabric itself used in Example 1 above. Leukocyte removal, platelet recovery, and red blood cell recovery were 45%, 70%, and 69%, respectively.

As can be seen from the above results, when only the polyester non-woven fabric itself not treated with the chitosan solution is used,
Not only the leukocyte removal efficiency was very poor, but also the permeation efficiency of fibrin, protein gel, platelets, etc. was poor, indicating that it was not suitable as a filter for removing leukocytes.

[0056]

According to the present invention, a leukocyte-removing filter produced by applying a natural high molecular weight chitosan or a chitosan graft polymer which has good blood affinity and has no adverse effects on the human body on a nonwoven fabric is a chitosan or chitosan graft. By the polymer, based on the secondary filtration by electrostatic attraction between leukocytes and cationic residues provided on the surface of the nonwoven fabric,
The ability to remove leukocytes is high, and the recoveries of platelets and erythrocytes are excellent.

Claims (11)

[Claims] 1. A leukocyte removal filter comprising a nonwoven fabric having chitosan or modified chitosan applied to the surface. 2. The filter according to claim 1, wherein the modified chitosan is a graft polymer of chitosan and a blood affinity polymer. 3. The filter according to claim 2, wherein said blood affinity polymer is selected from polydimethylaminoethyl methacrylate, polymethyl methacrylate, polyacrylic acid and sodium salt of polyvinyl sulfonic acid. 4. The chitosan having a degree of deacetylation of 85
The filter according to claim 1, wherein the ratio is from about 95% to about 95%. 5. The chitosan having an average molecular weight of 200,
The filter according to claim 1, wherein the number is from 000 to 700,000. 6. The filter according to claim 1, wherein the nonwoven fabric is a synthetic or natural fiber nonwoven fabric having a gap between adjacent fibers of 3 μm or less. 7. A method for producing a leukocyte removal filter by applying a chitosan solution or a modified chitosan solution to a nonwoven fabric. 8. The method according to claim 7, wherein the modified chitosan is a graft polymer of chitosan and a blood affinity polymer. 9. 0.1 to 5% in an organic or inorganic acid
9. The nonwoven fabric is immersed in a concentrated or modified chitosan solution for 30 to 120 minutes.
The described method. 10. The method of claim 9, wherein the solution is sonicated for up to 2 hours during the immersion. 11. The method according to claim 7, wherein the filter obtained by applying the modified chitosan solution to the nonwoven fabric is further irradiated with ultraviolet rays of 10 mJ / cm ² or less.