JP2007061329A - White blood cell removal filter with high pressure steam sterilization resistance - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a white blood cell removal filter using a flat hard plastic container of excellent handleability which does not have a failure such as sticking to the other members due to high pressure steam sterilization. <P>SOLUTION: In the white blood cell removal filter, the average surface roughness of the outer surface parts which can contact with the other members such as a sterilization bag, the blood bag of the container, especially, that of the outer surface parts in the direction of the face of the container is made to be ≥1μm. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a leukocyte removal filter that removes leukocytes from a blood product for transfusion. More particularly, the present invention relates to a leukocyte removal filter that uses a flat hard plastic container that is resistant to high-pressure steam sterilization and has uneven surfaces.

The leukocyte removal filter is used for the purpose of removing leukocytes contained in blood products for blood transfusion in order to reduce side effects caused by leukocytes.
A commercially available leukocyte removal filter has a container made of hard plastic such as polycarbonate or a container made of soft plastic such as vinyl chloride filled with a filtration medium such as nonwoven fabric. In addition, there is a so-called closed system that can prepare a blood component preparation from which white blood cells are aseptically removed, comprising a blood bag, a filter, a bag for each blood component preparation that is adjusted after centrifugation, and a circuit that connects these members. Attention has been focused on the use of such systems (Patent Documents 1 and 2).

  Since the closed system is integrated with a bag containing liquid components such as an anticoagulant and an erythrocyte preservative, generally, high-pressure steam sterilization is performed. On the other hand, since the flat surface of the leukocyte removal filter made of hard plastic that is available on the market is smooth, this sterilization process causes sticking to the blood bag or sterilization bag, and the bag label is not easily peeled off or removed from the bag. There was a risk of causing a malfunction. In order to avoid this, a device such as wrapping the filter with an appropriate protective material so that it does not come into direct contact with other members, or a device such as arranging the filter in a position where it does not come into contact with a bag or the like has been made ( Patent Document 3). However, there is a possibility that the expected effect may not be obtained if there is a shift in the protective material or the filter position, and there is a problem that the introduction of the protective material increases the cost, and there are still problems to be improved. The current situation is.

In recent years, a leukocyte removal filter for a soft container has also been developed. For example, a filter having an inner surface of a container with an uneven surface of 0.2 to 2 mm is disclosed (Patent Document 4). However, this is intended to avoid adhesion between the soft container and the filter medium filled in the container, and is not intended to improve the handleability after sterilization as described above.
JP-A-1-320064 JP-A-1-320065 JP 2001-70443 A JP-A-11-216179

  An object of the present invention is to provide a leukocyte removal filter using a flat hard plastic container that is resistant to high-pressure steam sterilization and does not cause operability problems such as label peeling and difficulty of removal without using a protective material. The purpose is to do.

As a result of intensive studies by the present inventors, it has been found that the above-described problems can be achieved by using a filter as shown below. That is, the present invention
(1) A leukocyte removal filter using a flat hard plastic container that has an inlet and an outlet for blood and is resistant to high-pressure steam sterilization, and has an average surface roughness of 1 μm or more in the surface direction of the container (2) The leukocyte removal filter according to (1), wherein the coefficient of variation of the surface roughness is 80% or less, (3) the hard plastic is polycarbonate, (1) or (2) The present invention relates to the leukocyte removal filter.

  The leukocyte removal filter of the present invention does not change in dimensions due to high-pressure steam sterilization, and has an appropriate surface roughness, so that it can exhibit an excellent effect without causing problems such as sticking to other members.

Hereinafter, the leukocyte removal filter container of the present invention will be described in detail.
The term “resistant to high-pressure steam sterilization” as used in the present invention means that significant container size deformation is not caused by high-pressure steam sterilization. More specifically, it is said to be resistant to high-pressure steam sterilization when the deformation of the filter dimensions (for example, the length of the vertical and horizontal sides, the nozzle diameter, etc.) before and after treatment by high-pressure steam sterilization is 1% or less. High-pressure steam sterilization is a method in which microorganisms are killed by placing a specimen to be sterilized in a sealed device and heating it with saturated steam at an appropriate temperature and pressure. As normal conditions, the pressure is 1.0 kg / cm ^{2 to} 2.0 kg / cm ² , the temperature is 110 to 130 ° C., and the time is 10 to 30 minutes.

  Examples of the hard plastic material include polycarbonate, polyethylene, polypropylene, polyethylene terephthalate, and acrylic. Polycarbonate is preferable from the viewpoint of heat resistance and impact resistance.

  The surface direction of the container referred to in the present invention means a direction perpendicular to the blood flow direction. More specifically, when the filtration medium is filled in the container, when the thickness direction of the filtration medium is the blood flow direction, the direction perpendicular thereto, that is, the same direction as the surface of the filtration medium is the surface direction of the container. To tell. The outer surface refers to a surface that can be in direct contact with another member such as a blood bag or a sterilized bag. The average surface roughness of the outer surface in the planar direction is preferably 1 μm or more, more preferably 2 μm or more and 200 μm or less, and most preferably 10 μm or more and 100 μm or less. The average surface roughness is an index of surface unevenness, and the larger this number, the rougher the surface. Since the container with the rough outer surface can be prevented from coming into contact with other members, the members can be easily separated or stuck even if high-pressure steam sterilization is performed. Can be prevented. On the other hand, although there is no upper limit to the average surface roughness, it is recommended that the average surface roughness be 200 μm or less in consideration of the molding or workability of the container.

In addition, the average surface roughness said here can be calculated | required with the following procedures. First, a grid-like transparent sheet with lines drawn at equal intervals is placed on the outer surface in the container surface direction so as to cover the entire surface of the container. The number of grid points is 1 point / cm ² or more per area of the outer surface in the surface direction of the container, and an address is assigned to each grid point in advance. Next, addresses of 30 points or more, preferably 50 points or more are randomly selected by a method such as using a random number table. The arithmetic average roughness of the outer surface located immediately below the selected address (grid point) is obtained. Here, the arithmetic average roughness (Ra) of the outer surface means that only the reference length (L) is extracted from the outer surface roughness curve in the direction of the average line, and the X-axis is extracted in the direction of the average line of the extracted portion. When the Y-axis is taken in the direction of the vertical magnification and the roughness curve is expressed by y = f (x), the value obtained by the integral formula from 0 to L is expressed in micrometers (μm) as follows. (JISB0601: 2001).
Ra = 1 / L × ∫ | f (x) | dx

  In addition, Ra can be measured using various commercially available devices of contact type or non-contact type. Thus, Ra values of 30 points or more, preferably 50 points or more are obtained, and the arithmetic average of these is defined as the average surface roughness referred to in the present invention. In addition, when the grid point of the selected address corresponds to a stepped portion of the container and is an unsuitable or difficult location for Ra measurement, the address is selected again without performing measurement at this location.

  Further, when the average surface roughness is determined by the above-described method, the coefficient of variation (CV) is preferably 80% or less, and more preferably 40% or less. The coefficient of variation referred to here is an average value of surface roughness (average surface roughness) and its standard deviation from all measured addresses, and is a value obtained by dividing the standard deviation by the average value and multiplying by 100. It means that the unevenness | corrugation of the surface property of an outer surface is so uniform that this figure is small. If the coefficient of variation exceeds 80%, a rough surface and a relatively smooth surface will be mixed on the outer surface. As a result, there is an increased risk that sticking will be insufficient in a relatively smooth part. It is preferable to have the shape on the outer surface. That is, a leukocyte removal filter in which the variation coefficient of the surface roughness of the outer surface in the surface direction is 80% or less is preferable.

  A filter using a hard plastic container having such an outer surface in the surface direction significantly reduces the probability of occurrence of defects such as sticking even if it is sterilized by contacting with other members such as blood bags and sterilization bags. be able to.

  In order to obtain a container made of hard plastic having the above-mentioned suitable surface roughness, various known methods can be used. The surface of the mold (mold) of the container may be roughened by sandblasting, file, laser, etc., and the container may be molded by pouring resin into it, or a suitable surface by applying the same processing to the molded container The roughness may be controlled.

[Example]
EXAMPLES Hereinafter, although this invention is demonstrated further in detail based on an Example, the scope of the present invention is not limited only to these Examples.

The outer surface was roughened by laser etching on a polycarbonate rigid container having an outer surface length of 78 mm × 78 mm. This container was covered with a transparent sheet with grid lines drawn at intervals of 0.5 mm, 30 points were arbitrarily selected using a random number table, and Ra at that location was measured (ultra-depth shape measuring microscope VK-8500, KEYENCE). Company-made). When the average surface roughness of the container was determined from all the Ra values obtained, it was 25 μm and the coefficient of variation was 17% (the following Examples and Comparative Examples were also measured in the same manner).
A filter was prepared by filling the container with a nonwoven fabric and performing ultrasonic welding.
A soft PVC circuit was connected to the created filter, and a commercially available blood bag was connected to both ends of the filter to create a system in which the filter and the circuit were integrated. The filter and the bag were stacked and placed in a polypropylene sterilization bag so that the outer surface of the filter was in contact with the sterilization bag. After the sterilization bag was sealed with a heat sealer, it was placed in a high-pressure sterilization pot and treated at a pressure of ² kg / cm ² and a temperature of 115 ° C. for 30 minutes. After completion of autoclaving, the system was removed from the sterilization bag, but the filter could be easily removed without sticking to the sterilization bag. Moreover, when the length of the outer surface of a filter was measured, it was 78 mm, and the dimensional change by sterilization was not recognized.

  A filter was prepared in the same manner as in Example 1 except that the average surface roughness of the outer surface of the container was 80 μm and the coefficient of variation was 24%, and the same experiment was performed. As a result, removal of the system was equally easy, and no change in the dimensions of the container was observed.

  A filter was prepared in the same manner as in Example 1 except that the average surface roughness of the outer surface of the container was 7 μm and the coefficient of variation was 14%, and the same experiment was performed. As a result, removal of the system was equally easy, and no change in the dimensions of the container was observed.

[Comparative Example 1]
A filter was prepared in the same manner as in Example 1 except that the average surface roughness of the outer surface of the container was 0.2 μm and the coefficient of variation was 5%, and the same experiment was performed. As a result, no change in the dimensions of the container was observed, but the container stuck to the sterilization bag and was difficult to remove.

  A similar experiment was performed using the same members as in Example 1 except that the container was placed between the bags and the bag label was in contact with the outer surface of the container. There was no sticking of the bag label to the container, and no defects in appearance were observed.

[Comparative Example 2]
The container of Comparative Example 1 was placed between bags in the same manner as in Example 3 to conduct an experiment. As a result, the bag label stuck to the container, and the label peeled off when the container and the bag were separated.

  The container was sandblasted to produce a container having an outer surface with an average surface roughness of 42 μm and a coefficient of variation of 35%. When it was connected to a blood bag in the same manner as in Example 1 and sterilized under high pressure steam, no change in the dimensions of the container was observed, and removal from the bag of the system was easy.

  The container mold (mold) was sandblasted, and the container was molded using this mold. The average surface roughness of the outer surface of the molded container was 17 μm, and the coefficient of variation was 8%. When connected to a blood bag in the same manner as in Example 1 and sterilized under high pressure steam, no change in the dimensions of the container was observed, and removal from the system bag was easy.

  The leukocyte removal filter of the present invention can be used for removing leukocytes contained in blood products for blood transfusion. In particular, it can be used as a leukocyte removal filter that can be suitably incorporated into a closed system sterilized by autoclaving.

Claims (3)

  A leukocyte removal filter using a flat hard plastic container that has an inlet and an outlet for blood and is resistant to high-pressure steam sterilization, and the average surface roughness of the outer surface in the surface direction of the container is 1 μm or more Leukocyte removal filter characterized by   The leukocyte removal filter according to claim 1, wherein the coefficient of variation of the surface roughness is 80% or less.   The leukocyte removal filter according to claim 1 or 2, wherein the hard plastic is polycarbonate.