JPH02286172A - Leucocyte separating filter in platelet preparation - Google Patents

Abstract

PURPOSE:To efficiently and completely remove the leucocyte incorporated into platelet preparations, such as concd. platelet and plasma by packing fibers having the average fiber diameter of a specific value into the filter in such a manner that the average circle corresponding diameter of inter-fiber spacings attains a specific value. CONSTITUTION:Hydrophobic polypropylene and polyester stock or the like which have the good removability of the leucocyte and has the less correction activity and excellent bioadaptability are used for the filter stock. A melt blow spinning method is particularly preferable as the method of obtaining the extremely fine non-woven fabric to be used for the filter from this filter stock. This filter is packed with the fibers having 2.0 to 10.0mum average fiber diameter in such a manner that the average circle corresponding diameter DH of the inter-fiber spading defined by equation I attains 16.0 to 35.0mum.

Description

Detailed Description of the Invention (Field of Industrial Application) The present invention provides a body plate treatment filter for blood transfusion as L1, and more specifically, a platelet preparation exclusively for concentrated platelet plasma transfused to patients with bleeding tendency. This invention relates to a filter for efficiently and safely removing contaminated white blood cells.

(Prior art) In recent years, the trend towards blood transfusions has been to replace conventional whole blood transfusions with component transfusions in which only the face plate component of the patient is transfused, reducing bleeding tendency. Some patients often receive repeated transfusions of platelet products, such as platelet plasma concentrate, which have a high hemostasis effect.

However, since platelet preparations are made by centrifugation, the difference in density between platelets and white blood cells is small.
Platelet preparations contain large amounts of white blood cells. The type of white blood cells is related to histocompatibility antigens, and it is extremely rare for the type of leukocytes to match between the donor and the recipient. The white blood cells produced by the patient produce blood cell antibodies, which can cause side effects such as fever, chills, headache, nausea, and allergic reactions. Furthermore, it has been reported that the survival rate of transfused platelets within a patient's body is better as the number of contaminated leukocytes decreases. (Takayuki Iwanaga et al., Journal of the Society of Blood Transfusion 27, 197-198. (+98
1)) For the following reasons, there are concerns regarding platelet transfusions.
The necessity of removing 1-contaminated leukocytes is strongly advocated.

One method for removing leukocytes from platelet preparations is by centrifugation, but this method requires expensive equipment, low leukocyte removal rate and low platelet recovery rate, and is complicated to operate. There are problems such as the inability to process blood transfusions online.

-Recently, leukocyte removal devices using ultrafine fiber nonwoven filters have been developed and are used to remove leukocytes from red blood cell preparations. (For example, Japanese Patent Application Laid-Open No. 61-276584) These leukocyte removal devices can efficiently remove leukocytes from red blood cell preparations, and are small and easy to operate, but platelets are also separated and removed at the same time. It cannot be used to remove white blood cells inside.

(Problems to be Solved by the Invention) The conventional method of removing 1 u cell from platelet preparations has problems such as low leukocyte removal efficiency, or that platelet recovery decreases when leukocyte removal efficiency is increased. There is.

An object of the present invention is to provide a filter for efficiently and safely removing contaminated leukocytes from platelet preparations such as platelet concentrates and plasma.

(L stage for solving the problem) Conventional leukocyte removal filters using nonwoven fabrics have fiber diameters of 1 to 21 m, and have a high leukocyte removal efficiency, but also remove platelets at the same time. Therefore, the present inventors conducted extensive studies on the relationship between filter fiber diameter and leukocyte and platelet removal properties, and found that by adjusting the fiber diameter, fiber gap, filter surface area, processing speed, and processing temperature,
We found that scales control the selectivity of leukocytes and platelets.

In other words, using a filter with a larger fiber diameter than the fibers of conventional non-woven leukocyte removal filters,
The present inventors have discovered that adsorption of platelets to the filter can be suppressed while maintaining leukocyte removal efficiency by performing treatment at a treatment temperature close to body temperature at a relatively slow rate, leading to the present invention.

That is, in the filter of the present invention, fibers having a diameter in the y direction of 2.0 to 10.07 m have an average circular equivalent diameter of 16.0 to 35.0 m in the fiber gaps defined by the following formula. It is characterized by being a filter filled with

γ 1),: Average circular equivalent diameter (ptm) of fiber gaps γ
: Uniform diameter of the fiber (unit) ρ : Density of the fiber (g/c product) γIm = Bulk density of the filter (g/cJ) Equivalent to the average circle of the 1-1 fiber gap when the fiber diameter is 2.0 pm or more diameter to 18
．． Platelet permeability can be increased by setting it to 0/ffl or more to 14. On the other hand, if the fiber diameter is 10.0 mm or more, the filter becomes bulky and the device becomes large.
If the average equivalent circle diameter is less than 35.0/i#I, the leukocyte removal rate will decrease, which is not preferable. A more preferable range is a fiber diameter of 3.0 to 8. OIJIm fiber gap .l/uniform equivalent diameter is 16 to 3.0.0.

Furthermore, in the present invention, the surface area of the filter fiber is 0.1 to 0.5 per n20 treated with platelet preparation. / is desirable. If the fiber surface area is less than 20 o, trj per Q, the area for adsorbing leukocytes becomes narrower, and the area for adsorbing leukocytes becomes smaller (0.5 r/or more than 1-
If so, the adsorption area becomes too large and the platelet removal property increases, which is not preferable.

The shape of the filter is preferably non-woven fabric.

In the leukocyte separation filter in platelet preparations of the present invention, it is preferable to use platelet preparations per [-11th area of the device]. t11th processing speed per area 0.51
By setting aQ/mln/(T11 or higher, good leukocyte removal rate and platelet permeability can be obtained. 0, 5 m
Q/mtn/c+a to -L, leukocyte removal rate,
This is unfavorable because it causes a decrease in platelet permeability and an increase in pressure loss.

Furthermore, the method for separating leukocytes in platelet preparations of the present invention is characterized in that the processing temperature is 20°C or higher and 37°C or lower. At a treatment temperature of 20° C. or lower, platelets will non-specifically adsorb to the fibers, and at a treatment temperature of 37° C. or higher, platelets and plasma will be damaged by heat, which is not preferable.

The filter material of the present invention is not necessarily limited, but hydrophobic polypropylene or polyester materials, which have good leukocyte removal ability of 41°, low complement activity and excellent biocompatibility, are desirable.

As a method for obtaining ultrafine fiber nonwoven fabrics that can be used in the apparatus of the present invention from such materials, melt blow spinning is particularly preferred.

Hereinafter, the effects of the present invention and more detailed explanation will be added by way of Examples.

Examples In both the Examples and Comparative Examples of the present invention, nonwoven fabrics of polyethylene terephthalate obtained by a melt blowing method were used. Concentrated platelet plasma was prepared using fresh bovine blood using ACDM as an anticoagulant at 1500 rpm, 151
It was obtained by centrifugation and collecting the clarified water. In the experiment, concentrated platelet plasma was pumped at a constant rate of 200.
1! The leukocyte removal rate, platelet permeability, pressure loss between the apparatus and the output were measured. The number of white blood cells and platelets were measured using a Coulter counter.

Further, the thread diameter of the non-woven ultrafine fibers was determined by taking photographs with a scanning electron microscope and measuring 50 points for one type of sample.

Note that the average equivalent circle diameter of the fiber gaps was calculated using 1.38 g/cJ as the specific gravity of the polyethylene terephthalate fibers.

[Example 1] 3.4 g of ultrafine fiber nonwoven fabric with an average thread diameter of 3.5 mm was collected,
Filter area 20cJ1 Bulk density 0.20g/cJ
was filled. According to the method described in the examples, treatment temperature 3
Constant rate treatment was performed at 7° C. and 1f&10 J/+in. The average equivalent circle diameter of the fiber gaps at this time was 24 mm, and the surface area of the nonwoven filter fibers per platelet preparation treatment was 0.28♂.

The processing speed per tit area is O-5yaQ/1n/
It is cJ. As shown in Table 1, the leukocyte removal rate and platelet permeability were both 90% or higher, indicating good performance with little pressure loss.

[Example 2] Using the same module as in Example 1, only the processing temperature was 20
The temperature was 1 t, and the other conditions were the same as in Example 1. As shown in Table 1, the leukocyte removal rate and platelet permeability were both over 90%. 1-, and the pressure loss was small (showing good performance).

[Comparative Example 1] Using the same module as in Example 1, only the processing temperature was 10
℃ and the other conditions were the same as in Example 1. The results, as shown in Table 1, alleviated the problem of low platelet permeability.

[Comparative Example 2] Using the same module as in Example 1, only the amount of liquid sent was 25□
(j/m!n, and other conditions were the same as in Example 1.The results are as shown in Table 1.
Problems such as a decrease in the removal rate of 11 spheres and an increase in pressure loss were shown. At this time, the processing speed per tltl surface position is 1,
2+mQ/sin/cT11.

[Comparative Example 3] The same ultrafine fiber nonwoven fabric as in Example 1 (''-17 yarn diameter 3.
5 households) was collected, and the bulk density was 0.30 g/cri.
The experiment was carried out under the same conditions as in Example 1. As shown in Table I, the results showed a problem of low platelet permeability. In addition, %I of the fiber gap at this time
/, the equivalent circle diameter was as narrow as 12.6-.

[Comparative Example 4] Ultrafine fiber nonwoven fabric similar to Example 1 (average thread diameter 3.5 s)
3.4g of the sample was collected and filled to a bulk density of 0.11g/cIil, and an experiment was conducted under the same conditions as in Example 1. The result is Ta
As shown in ble 1, the problem was that the leukocyte removal rate was low. The equivalent circle diameter of the fiber gap at this time is 40.4
The μ layer was wide.

[Example 3] Average yarn diameter: 8. An experiment was conducted under the same conditions as in Example 1, with 7.8 g of O/Jj microfiber nonwoven fabric taken and filled to a bulk density of 0.40 g/cnl. The average circular equivalent diameter of the fiber gaps at this time was 19.67 J, and the platelet preparation throughput was 2.
The surface area of nonwoven filter fibers per 0 mQ is 0.2
He is 8 years old. As shown in Table I, both the leukocyte removal rate and the platelet permeability were 90% or higher -1-, indicating good performance with little pressure loss.

[Comparative Example 5] - 1.9 g of ultrafine fiber nonwoven fabric with a V-leveled yarn diameter of 2.0 μm was collected and filled to a bulk density of 0.15 g/cri, and an experiment was conducted under the same conditions as in Example 1. The equivalent diameter of the fiber gap at this time was 1B, 4s, and the platelet preparation treatment;
The surface area of nonwoven filter fibers per 0.0 - 0.281
/ is. As shown in Table 1, the results showed the problem of low platelet permeability.

[Comparative Example 6] Ultrafine fiber nonwoven fabric similar to Experimental Example 1 (average yarn diameter 3.5/j
1.0 g of J1) was collected, and the bulk density was 0.20 g/cTi.
The experiment was carried out under the same conditions as in Example 1. The average circular equivalent diameter of the fiber gaps at this time was 24/jj, and the surface area of the nonwoven filter fibers per 20 mQ of platelet preparation treatment was 0.081/.

As shown in Table 1, the results showed a problem in which the leukocyte removal rate decreased.

[Comparative Example 7] Ultrafine fiber nonwoven fabric similar to Experimental Example 1 (average thread diameter 3.51I
11.2g of II) was collected, and the bulk density was 0.20g/c.
The experiment was conducted under the same conditions as in Example 1.

The average equivalent circle diameter of the fiber gaps at this time was 241i11, and the surface area of the nonwoven filter fibers per 20 - of platelet preparation treated acid was 0.92. / is.

As shown in Table I, the results showed a problem of low platelet permeability.

Margin (Effects of the Invention) According to the present invention, it is possible to efficiently and safely remove contaminated leukocytes from platelet preparations such as platelet concentrates and plasma.
It is considered as a skill.

Claims (1)

[Claims] (1) Fibers with an average fiber diameter of 2.0 to 10.0 μm have an average circular equivalent diameter of the fiber gap defined by the following formula of 16.0
A leukocyte separation filter in a platelet preparation filled to a thickness of ~35.0 μm. D_H=γ×(ρ-γ_m)/γ_m D_H: Average circular equivalent diameter of fiber gap (μm) γ: Average diameter of fiber (μm) ρ: Density of fiber (g/cm^3) γ_m: Bulk density of filter (g/cm^3)