KR101441165B1 - Blood Filter - Google Patents

Abstract

The present invention relates to a method and apparatus for treating a large amount of blood in a short time by having an optimum affinity with blood and having an optimal fiber diameter, pore size and density, The present invention relates to a blood filter which can be used for a removal filter. The blood filter of the present invention has a CWST of 63 to 120 dyne / cm; A maximum pore diameter of 15 to 30 mu m; An average pore diameter of 7 to 15 mu m; And a nonwoven fabric having a lamination density of 0.10 to 0.17 g /..

Description

Blood Filter

The present invention relates to a blood filter, and more particularly, to a blood filter for removing white blood cells.

When blood or red blood cell concentrates containing white blood cells are transfused, side effects such as headache, vomiting, chills, fever, virus infection, and allogeneic antigen sensitization may occur. The need to adequately remove leukocytes from blood has been increasing, as these side effects have been prevented and health awareness has increased.

Methods for removing leukocytes from blood containing leukocytes include centrifugation in which blood is separated by high rotation, filter method in which blood is filtered through a filter to adsorb leukocyte on the filter, And a text method in which a separated white blood cell layer is sucked and removed. Among these, a filter method having excellent leukocyte removal performance, easy operation and low cost is widely used.

A blood filter used in such a filter method uses a substrate having various shapes, and a nonwoven fabric having a high porosity indicating the degree of pore formation, a pore size indicating a pore size, and a relatively easy manufacture is widely used.

These blood filters must meet various requirements. First, the blood filter should be able to treat large volumes of blood in a short time to prevent the blood from clotting. Second, the blood filter should have a high leukocyte removal rate to prevent the above-mentioned side reaction. Third, the blood filter must pass smoothly through the blood without damaging other useful components in the blood, such as red blood cells.

Conventionally, a blood filter having a high blood affinity, a small pore size, and a high lamination density has been used in order to enhance the removal efficiency of leukocytes.

However, such a conventional blood filter has a problem of high erythrocyte damage rate and low erythrocyte recovery rate. That is, the development of a blood filter satisfying both the leukocyte removal performance and the red blood cell recovery rate has not been developed.

Disclosure of Invention Technical Problem [8] The present invention has been made to solve the above-mentioned problems, and it is an object of the present invention to provide a blood- And is excellent in the recovery rate of red blood cells. Therefore, it is an object of the present invention to provide a blood filter which can be effectively used for a filter for removing white blood cells.

In order to achieve the above object, the present invention provides a CWST of 63 to 120 dyne / cm; A maximum pore diameter of 15 to 30 mu m; An average pore diameter of 7 to 15 mu m; And a nonwoven fabric having a lamination density of 0.10 to 0.17 g / cm3.

The present invention has the following effects.

First, since the blood filter according to the present invention has an optimum CWST, damage of red blood cells can be minimized and a large amount of blood can be treated in a short time.

Second, since the blood filter according to the present invention has an optimum fiber diameter, pore size and lamination density, it has not only high leukocyte removal rate but also high red blood cell recovery rate.

A blood filter having such characteristics can be used in a leukocyte removal filter device.

It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the spirit and scope of the invention. Therefore, the present invention encompasses all changes and modifications that come within the scope of the invention as defined in the appended claims and equivalents thereof.

Hereinafter, a blood filter according to an embodiment of the present invention will be described in detail.

The blood filter of the present invention is formed in the form of a nonwoven fabric. The nonwoven fabric is formed by dispersing short fibers of small diameter to form voids, and the short fibers are physically or chemically entangled to form a three-dimensional structure. Since the nonwoven fabric having the three-dimensional structure of the short fibers has a wide surface area, there is an advantage in that the filtration efficiency is excellent.

Such a nonwoven fabric has a maximum pore diameter of 15 to 30 mu m. Preferably, the nonwoven fabric may have a maximum pore size of 20 to 25 [mu] m.

The nonwoven fabric having the maximum pore size in this range selectively adsorbs only leukocytes and smoothly passes red blood cells, platelets, and the like.

The nonwoven fabric has an average pore diameter of 7 to 15 mu m. Preferably, the nonwoven fabric may have an average pore diameter of 8 to 12 [mu] m. That is, the nonwoven fabric has an average attack in the range to selectively adsorb and remove only leukocytes. If the average pore diameter of the nonwoven fabric is less than 7 탆, erythrocytes having a size of 6 to 8 탆 can not pass through the filter smoothly, and the pressure loss is increased, so that the blood flow rate is lowered and the blood can be solidified. On the other hand, when the average pore diameter of the nonwoven fabric exceeds 15 탆, the leukocyte removal rate may be lowered because white blood cells having a size of 12 to 15 탆 easily pass through the filter.

The nonwoven fabric has a lamination density of 0.10 to 0.17 g / cm3. Preferably, the nonwoven fabric may have a lamination density of 0.11 to 0.15 g / cm3. The lamination density is quantified by the mass of the whole nonwoven fabric constituting the filter as a whole volume of the case of the blood filter. If the density of the nonwoven fabric is less than 0.10 g / 백, the leukocyte can easily pass through the filter, so that it can not have the leukocyte removal rate required by the industry. Especially, as the gap between the filter and the case is generated, And the red blood cell recovery rate and the leukocyte removal rate do not show a constant value, that is, the performance may deviate significantly. On the other hand, when the density of the nonwoven fabric exceeds 0.17 g / ㎣, the space between the adjacent nonwoven fabrics becomes dense to less than 5 탆, and the red blood cell recovery rate may drop sharply because the red blood cells can not smoothly pass between the nonwoven fabrics.

The nonwoven fabric may include staple fibers having an average diameter of 1 to 3 mu m. That is, the nonwoven fabric may include staple fibers having an average diameter in the above range in consideration of leukocyte removal performance and economy. If the average diameter of the staple fibers is less than 1 탆, the pressure loss becomes too high when the blood is filtered. Thus, when the average diameter of the staple fibers exceeds 3 탆, the probability of contact between the leukocytes and the staple fibers The leukocyte removal rate may be lowered.

In addition, the nonwoven fabric may include staple fibers having a coefficient of variation (CV%) with respect to the diameter of 30% or less. Accordingly, since the nonwoven fabric includes the monofilaments having a uniform diameter, the nonwoven fabric can have a uniform blood flow over the entire filter, so that the treatment efficiency is excellent and the uniform performance can be exhibited. The coefficient of variation is obtained by dividing the standard deviation of the diameter of the short fibers by the arithmetic mean.

In order to produce such a nonwoven fabric made of short fibers having three densities of uniform diameter, a nonwoven fabric obtained by meltblown process under conditions set at a spinning temperature of 260 to 320 DEG C and an air pressure of 0.7 to 1.5 kgf / . More preferably, the meltblown process may be carried out at a spinning temperature of 280 to 300 DEG C and an air pressure of 0.8 to 1.1 kgf / cm < 2 >.

If the spinning temperature is less than 260 ° C, the spinning temperature is too low to produce a sufficient number of fibers. As a result, short fibers having a fineness of 3.0 μm or less can not be obtained. And thus it may be difficult to obtain smooth filter performance. On the other hand, when the spinning temperature exceeds 320 ° C, due to the high temperature, the bonding force between the laminated short fibers on the collector becomes too strong, so that proper pore size can not be formed and a paper- It may not proceed smoothly.

On the other hand, when the air pressure is less than 0.7 kgf / cm < 2 >, the fibers can not be sufficiently stretched, so that short fibers having three fineness of 3.0 mu m or less can not be obtained. On the other hand, when the air pressure exceeds 1.5 kgf / A phenomenon in which fibers are blown may occur, and it may be difficult to obtain a nonwoven fabric having a uniform shape.

The nonwoven fabric may have a weight of 10 to 50 g / m 2, and more preferably 25 to 30 g / m 2. In addition, the nonwoven fabric may have an average thickness of 0.1 to 0.25 mm, more preferably 0.12 to 0.18 mm. The nonwoven fabric having the weight and the average thickness in the above range can be obtained by suitably adjusting the spinning temperature, the air pressure, the gap between the spinneret and the collector, and the like.

The nonwoven fabric may have a Critical Wetting Surface Tension (CWST) of 63 to 120 dyne / cm. More preferably, the nonwoven fabric may have a CWST of 80 to 120 dyne / cm.

The CWST drops a series of liquids whose surface tension varies in the range of 2 to 4 dyne / cm (mN / m) onto the surface of the sample in the form of droplets, and then observes the respective liquid droplets, . CWST using a unit of dyne / cm is defined as the average of the surface tension of the absorbed liquid and the surface tension of the unabsorbed liquid. If the liquid has a surface tension lower than the CWST of the filter, it will spontaneously wet the filter upon contact with the filter. For example, a filter with a surface tension of 72 dyne / cm and a lower CST is not wetted upon contact with water. Therefore, the CWST of the filter can be regarded as a measure of the hydrophilicity, and the higher the CWST, the higher the hydrophilicity of the filter.

The CWST of these filters can have a reasonable range. In other words, when the affinity with blood is too weak, the blood treatment time is too long to be practical. On the other hand, when affinity with blood is too strong, not only leukocytes but also red blood cells and platelets are adsorbed and removed. If the CWST of the nonwoven fabric is less than 63, affinity with the blood is too low, and the blood treatment time is too long, so that the blood can be coagulated and the collision between the red blood cells and the fibers increases as the blood passes through the filter pores. As the level of LDH (Lactate Dehydrogenas), which indicates the degree of damage, rises, the life of red blood cells can be shortened rapidly. On the other hand, when the CWST of the nonwoven fabric exceeds 120, it is impossible to obtain a blood product having a level of ingredients required in the industry due to adsorption of red blood cells and platelets.

The nonwoven fabric may be produced from various materials such as natural fibers such as cellulose or thermoplastic fibers. Preferably, thermoplastic fibers can be used. The thermoplastic fibers have an advantage that they can be obtained easily and inexpensively with relatively uniform physical properties through the melt spinning method. In particular, the polyethylene terephthalate nonwoven fabric is advantageous in that it is inexpensive, easy to manufacture, and excellent in mechanical properties. In addition, since the polybutylene terephthalate nonwoven fabric has excellent heat resistance, the pore properties and the like are not changed during the sterilization process using heat, so that there is an advantage that the polybutylene terephthalate nonwoven fabric can be regenerated several times.

Such a nonwoven fabric such as polyethylene terephthalate can not have CWST in the above-mentioned range as hydrophilicity is deteriorated. Accordingly, the nonwoven fabric having poor hydrophilicity can have a CWST in the above-mentioned range by modifying its surface.

Accordingly, the nonwoven fabric may include a coating layer having hydrophilicity. Such a coating layer may include a polymer having a nonionic hydrophilic group. The polymer having a nonionic hydrophilic group can be obtained by polymerizing a monomer such as 2-hydroxyethyl methacrylate.

Nonwovens made from polyethylene terephthalate or polybutylene terephthalate may contain up to 10 ppm antimony trioxide. The antimony trioxide is a substance presumed to be a carcinogen and is known as a substance causing skin diseases and the like. Accordingly, the nonwoven fabric containing polyethylene terephthalate or the like may preferably contain 10 ppm or less of antimony trioxide.

In order to obtain a nonwoven fabric including polyethylene terephthalate which is harmless to the human body, the nonwoven fabric may be a polymer produced from a germanium or titanium catalyst, and thus the nonwoven fabric including the polyethylene terephthalate and the like may include germanium or titanium.

The blood filter manufactured in this way has an excellent leukocyte removal rate of 98% or more and an erythrocyte recovery rate of 85% or more. Accordingly, the blood filter can be used for a blood purifying apparatus for blood transfusion and blood donation which require excellent leukocyte removal rate and erythrocyte recovery rate.

Hereinafter, the present invention will be described in detail with reference to examples and comparative examples. It should be noted, however, that the following examples are intended to assist the understanding of the present invention, and the scope of the present invention should not be limited thereby.

Example  One

The polyethylene terephthalate having an intrinsic viscosity of 0.52 and a melting temperature of 257 DEG C manufactured by using a germanium-based catalyst was melted to prepare a spinning solution, and this spinning solution was fed into a conventional meltblown nonwoven fabricating apparatus in such a manner that the air pressure, the discharge amount, , And the collector speed to adjust the meltblown web to have a weight average molecular weight of 30 g / m < 2 > and an average thickness of 0.15 mm, having an average diameter of 2 mu m and a coefficient of variation of 12%.

Subsequently, the above-mentioned web was treated with commercially available blood-affinity agent to obtain a nonwoven fabric having physical properties as shown in Table 1.

Subsequently, the non-woven fabric was cut to a filtration area of 62 cm 2, and a plurality of cut nonwoven fabrics were laminated to obtain a laminated nonwoven fabric having a lamination density of 0.119 g / cm 3.

Then, the laminated nonwoven fabric was inserted into a polycarbonate filter case, and then the case was sealed to prevent blood from leaking to prepare a blood filter.

Example  2

A blood filter was prepared in the same manner as in Example 1 except that the lamination density of the laminated nonwoven fabric was changed to 0.137 g / 에서.

Example  3

A blood filter was prepared in the same manner as in Example 1 except that a nonwoven fabric having a maximum pore diameter of 12.6 탆 and an average pore diameter of 6.9 탆 was prepared by adjusting the conditions for producing the meltblown web in Example 1 described above .

Example  4

A blood filter was prepared in the same manner as in Example 1, except that the non-woven fabric having a CWST of 65 was prepared by adjusting the deposition amount of the blood affinity agent in Example 1 described above.

Comparative Example  1 to 2

A blood filter was prepared in the same manner as in Example 1 except that the lamination density of the laminated nonwoven fabric was changed to 0.09 and 0.174 g / 각각, respectively.

Comparative Example  3

A blood filter was prepared in the same manner as in Example 1, except that a nonwoven fabric having a CWST of 55 was prepared by adjusting the deposition amount of the blood affinity agent in Example 1 described above.

The physical properties of the blood filters manufactured by the examples and comparative examples were measured by the following methods and are shown in Table 2 below.

Leukocyte removal rate and erythrocyte recovery rate of blood filter

The blood filter manufactured by the examples and the comparative examples was installed on a stand of 2.0 m in height and directly connected to a tube through which whole blood was passed to filter the blood. Then, about 15 cc of blood before and after filtration was collected, (Multicolor Flow Cyometric Method) was used to measure the blood cell counts, and the leukocyte removal rate and erythrocyte recovery rate of the blood filter were obtained. The automated blood cell counting apparatus measured the leukocyte removal rate and erythrocyte recovery rate of the blood filter under the conditions shown in Table 1 below.

division Auto CBC Reference RBC Counter 3.80 to 6.5 M / μl WBC Counter 4.0 to 11.0 K / WBC differential counter Lym-: 20-45%, Neutro-: 40-75% Hemoglobin (Hb) 11.5 to 18 g / dL Hematocrit (Hct) 37.0 to 50.0% Platelet 150 to 400 K / μl

Average fiber diameter (탆) and coefficient of variation ( CV %)

The mean diameter and the coefficient of variation of the fibers constituting the nonwoven fabric of the blood filter were measured using a scanning electron microscope (model name) and an image analyzer (using JVC Digital Camera KY-F70B in Image-Pro Plus software) Were measured and the average diameter and the coefficient of variation of the fibers were determined using the measured diameters. At this time, more than 20 measurement specimens were collected and measured, and average diameter and coefficient of variation of the fibers were obtained.

Coefficient of variation (CV%) = standard deviation / arithmetic mean

The average pore diameter (占 퐉) and the maximum pore diameter (占 퐉)

The average pore diameter (탆) and the maximum pore diameter of the nonwoven fabric constituting the blood filter were indirectly measured using an electron microscope image analyzer (Model: JSM6700F, manufacturer: JEOL, measurement magnification: 1.0K). Specifically, the maximum pore size of the nonwoven fabric was calculated from the largest pore size measured, and the average pore size was obtained by electron microscope image analysis and the pore portion of these images, that is, And the number of effective voids B, which is the number of black image pieces that can be seen as actual voids by showing a certain area or more, not defects or shadows on the image among the portions recognized as black in the image A and the electron microscope image, To obtain the cell density, and using the cell density and the constant, the cell density was obtained by the following equation.

Constant = density of raw polymer / density of nonwoven

Cell density = (B / A x 100) ^3/2 x 10 ⁹ x Constant

Average pore diameter = [(constant -1) x 6 / (? X cell density)] ^1/3 × 10 ⁴

Nonwoven CWST ( dynes / Cm)

CWST of the nonwoven fabric constituting the blood filter was applied to the surface of the nonwoven fabric with a series of liquids each having a surface tension of 2 to 4 dynes / cm. After 10 minutes, it was observed whether each liquid was absorbed or absorbed on the nonwoven fabric surface , And the average value of the surface tension of the absorbed liquid and the surface tension of the unabsorbed liquid adjacent thereto was obtained.

Performance of blood filter

The performances of the blood filters manufactured by the examples and the comparative examples were four (⊚: very good, ◯: good, Δ: normal, ×: poor) in consideration of the treatment time, leukocyte removal rate, Respectively.

division CWST (dynes / cm) Maximum pore size (탆) Average pore size (탆) Lamination density (g / ㎣) Red blood cell recovery (%) Leukocyte removal rate (%) Blood filter performance Example 1 110 19.2 10.1 0.119 91.0 99.3 ◎ Example 2 110 19.2 10.1 0.137 91.6 99.9 ◎ Example 3 113 12.6 6.9 0.119 87.9 99.0 ○ Example 4 65 19.2 10.1 0.119 89.1 98.4 ○ Comparative Example 1 109 19.2 10.1 0.09 86.4 58.8 × Comparative Example 2 108 19.2 10.1 0.174 79.9 87.9 △ Comparative Example 3 55 19.2 10.1 0.119 80.0 86.6 △

Claims (5)

63 to 120 dyne / cm CWST;
A maximum pore diameter of 15 to 30 mu m;
An average pore diameter of 8 to 12 占 퐉; And
Wherein the nonwoven fabric has a lamination density of 0.10 to 0.17 g / mm 3. The method according to claim 1,
Wherein the nonwoven fabric comprises staple fibers having an average diameter of 1 to 5 占 퐉 and a diameter variation coefficient (CV%) of 30% or less. The method according to claim 1,
The non-woven fabric is a blood filter comprising antimony trioxide (Sb ₂ O ₃₎ of less than 10 ppm. The method according to claim 1,
Wherein the nonwoven fabric comprises polyethylene terephthalate or polybutylene terephthalate. The method according to claim 1,
Wherein the blood filter has a leukocyte removal rate of 98% or more and an erythrocyte recovery rate of 85% or more.