JP2555722C - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTIONTechnical field   The present invention relates to whole blood and preparations derived therefrom, especially their allowed shelf-life before transfusion.
From packed human red blood cells, including blood cells stored for any period of time until
The present invention relates to a method for lowering blood cell content, and an apparatus for performing the same.Background of the Invention   Transfusing whole blood from one or more donors to another has been more than 50 years.
In recent years, blood components have been transfused. Passage of time
And with the accumulation of research and clinical data, transfusion techniques have improved significantly. Present
In view of current practice, whole blood is rarely administered; rather, red blood cells are required.
Patients in need are given packed red blood cells (PRC) and need platelets
Some patients receive platelet concentrates. These components are separated from whole blood by centrifugation.
This method provides plasma as a third product from which various other useful
Components are obtained.   In addition to the above three components, whole blood can be various types of white blood cells (collectively known as white blood cells).
), The most important of which are granulocytes and lymphocytes. White blood cells
Provides protection against bacterial and viral infections.   From the mid to late 1970s, many researchers separated granulocytes from blood donations,
Patients who lack them, for example their own blood cells Suggested that patients transfused by infection should be transfused. Done as a result
In some studies, this method was found to be generally harmful. This transport
Patients who have blood develop high fever or other untoward reactions and generally reject transfused blood cells.
Because it was extinct. In addition, the transfer of packed or whole blood containing donor white blood cells
Blood can be harmful to recipients in other ways. Triggered by transfusion therapy
Certain viral diseases, such as fatal infections for newborns and debilitated adults
Cytomegalovirus inclusion body disease is mediated by allogeneic leukocyte transfusion
. Another lethal phenomenon for immunocompromised patients is the debris-host reaction (GVH).
Yes; this means that the transfused white blood cells are used in organs including the recipient's skin,
It is a disease that causes irreversible damage to government officials. Normal red blood cell transfusions also
He was accused of adversely affecting the survival of patients undergoing surgery for the disease. This
The beneficial effect is the transfusion of substances other than the donor's red blood cells, including the donor's white blood cells.
It is thought to be mediated.   Particularly desirable in packed erythrocytes, including those stored for relatively long periods.
It is an object of the present invention to remove leukocytes to a level low enough to prevent unwanted reactions.
Is the purpose.   Separates blood into three basic fractions (packed red blood cells, platelet concentrate, and plasma)
In the case of centrifugation methods currently used for
Substantial amounts of leukocytes are present in both fractions of the concentrate. These blood components are leukocyte concentrated
It is now generally accepted that it is highly desirable to reduce
Have been. There is no clear standard, but leukocyte content Many of the undesirable effects of blood transfusion are reduced if they are reduced by about 1/100 before administration.
It is generally accepted that the temperature decreases. This is one unit of PRC (one blood donation
The total leukocyte content in the amount of PRC obtained by⁹Lower to
Almost comparable toDefinition of 1 unit of blood and 1 unit of packed red blood cells:   Blood banks in the United States typically collect approximately 450 ml of blood from donors to prevent blood clotting.
It is usually placed in a bag containing an anticoagulant for cleaning. Here, when collecting this blood donation,
The amount of blood drawn is defined as one unit of whole blood.   Whole blood is rarely used as is; most units are centrifuged separately
Alternatively, the erythrocyte concentrate in plasma, which is treated by gravity sedimentation, here PRC (
Give 1 unit of packed red blood cells). The volume of one unit of PRC is the hematoma of blood at the time of blood collection.
Crit (% erythrocyte volume)-usually 37-54%-; and PRC hematocrit
G, usually 70-80%. Most PRC units are 250-300 ml
However, fluctuations in these figures up and down are not uncommon.   Alternatively, the collected whole blood is processed by separating red blood cells from plasma,
It can also be resuspended in a physical solution. Various physiological solutions are used. like this
Processed red blood cells can be stored for longer periods of time before use,
It seems that removing plasma has some advantages. “Adsol
) "Is the trade name of an example of such a system. In Europe and other countries,
A similar formulation is used.   As used herein, the term "blood product" refers to anticoagulated whole blood, packed form obtained from it.
Red blood cells and red blood cells separated from plasma and resuspended in physiological fluid.   In countries other than the United States, blood banks and hospitals collect about 450 ml or less of blood
However, here, "one unit" is defined by U.S.
The red blood cells in the PRC, or physiological fluid, are quantities derived from one unit of whole blood.   The PRC used herein can be obtained by the above blood products, and other means,
A similar blood product with properties is meant.To remove leukocytes from PRC Conventional method   The spin filter system for obtaining packed red blood cells from which leukocytes have been
Labisini, Rubra, Apzo, Wentz and Shilhia (Parravicini, Rebulla, A
puzzo, Wenz and Sirchia), Transfusion 1984; 24: 508-510.
Other Critical Reviews in Clinical Laboratory Sciences 198
6; 24: 1-20. This method is simple and relatively inexpensive to implement.
It is still widely used because it is unnecessary. However, leukocyte removal efficiency is generally 90
% Or more, but in some patients is sufficient to prevent adverse reactions
Not high.   There are centrifugation methods that lower the level of white blood cells in red blood cells, but these are
Method, very expensive to operate, sterility of the formulation used within 24 hours
That's what you have to do.   Other leukocyte removal methods, such as saline washing of frozen red blood cells or deglycerin
They have been used in the past or now, but these are related to economical and reliable services.
It is disadvantageous and cannot be adopted at the bedside.   Fill the container with fibers to remove microaggregates and some of the contained leukocytes,
Many devices for conducting whole blood have been proposed. All of these devices must be
It is necessary to apply saline solution either before or after use, or both before and after use
There is. In addition, these devices are not very suitable for use in PRC,
0.1 × 10 5 per unit of PRC or whole blood, often or always⁹Less than
Inability to remove leukocytes down to the bottom. Both are suitable for bedside use
Not imaginative.Desirable durability for leukocyte depletion device   The ideal device for leukocyte removal is inexpensive, relatively small,
Blood can be supplied within about 30 seconds after being connected to the bag and the patient's vein.
You. At this time, the apparatus was used to obtain a leukocyte content of 1 × 10⁹Good enough to not exceed
Preferably 0.1 × 10⁹At least 1 unit reduced to the individual level (one blood donation formulation
) Red blood cells must be supplied to the patient. High efficiency for leukocyte removal
It is also desirable to be able to supply a complete second unit of packed red blood cells while maintaining it.
In addition, because red blood cells are expensive and have limited availability, this ideal device
Will supply as much of the red blood cells that were originally present in the bag as possible
. This device can be used to store blood for a very long time, including the date until the end of its useful life.
It will also work for liquid formulations. Such an apparatus is the object of the present invention.   Conventionally, devices developed to meet this purpose are based on the use of filled fibers.
Yes, commonly called a filter. However, filtration based on separation by size is employed.
It will be clear that the method used cannot be successful for two reasons. First, various
Leukocytes of type 5 to 7 μm and above from granulocytes and large red blood cells of 15 μm and above
It extends to a limp ball. Granulocytes and lymphocytes are combined with all leukocytes in normal blood.
Occupy a major proportion. Red blood cells are about 7μm in diameter, ie
It is the size between the two major components that must be avoided. Second, all these blood cells
Will deform to pass through openings much smaller than their normal size.
Therefore, the adsorption of leukocytes to various surfaces can be observed by microscopy.
It is widely accepted that blood cell removal is achieved by adsorption rather than filtration
.   Attempts have been made to reduce leukocyte concentration in blood by treating it with various surfaces.
, Which include polyamides, polyesters, acrylics, and cellulosic materials (such as
For example, cotton), cellulose acetate and siliconized glass wool. now
The available fiber-based equipment is only partially successful at most for the following reasons:
Absent. In describing the problems associated with conventional devices, the devices and methods of the present invention are described.
It will be clear how the law is superior.Blood cell component recovery rate   In the above section, it is important to collect a high percentage of packed red blood cells supplied to the separation device.
He stated what was desirable. Red blood cell recovery rate There are several causes for the decline:   (a) loss due to retention in the connecting tube and drip chamber;   (b) loss of fluid remaining inside the device itself at the end of the transfusion; and   (c) Loss due to adsorption on the device surface or mechanical confinement within the device.   (d) The filter may become clogged before one or two units of blood have passed.
And due to loss.   The loss due to (a) is due to the entrance to the blood bag for bedside use.
And a device with only an outlet to the drip chamber that connects to the patient's vein.
The use of side connections, which is necessary, for example, when using saline solution for starting
Can be minimized by avoiding Equipment design is relatively small
If a drip chamber is used, the loss can be further reduced.
it can. Loss due to cause (b) is commonly referred to as "hold-up volume" (
(Represented in milliliters). Loss due to cause (c)
If so, this would be reported as due to adsorption. Cause (d)
With respect to loss, one of the objects of the present invention is that the
Even if nearby, it is not clogged during administration of 2 units of PRC or
This device is rarely clogged. More generally, the object of the invention is possible
It is a leukocyte removal device with the highest red blood cell recovery rate. capacity   If separated from whole blood by the current blood cell bank method, packed red blood cells are
Not only the percentage of leukocytes present in the blood as collected, but also some platelets (
Very prone to stickiness), fibrinogen, fibrin strand, microscopic
It also contains large fat globules, and a number of other components that are normally present in small amounts. Also, when collecting blood
Factors added to prevent coagulation during storage and nutrients that help preserve red blood cells during storage
Nutrients are also included.   During centrifugation to concentrate red blood cells and partially separate them from the remaining components
Thus, microaggregates tend to form in the PRC. These are some red blood cells, and
Both are thought to consist of leukocytes, platelets, fibrinogen, fibrin and other components.
Will be The gel formed by fibrinogen and / or fibrin is blood silver
Often found in PRCs prepared by rows.   The gel is slightly viscous and forms a separate gel phase in the plasma although it is liquid. Get
Once separated by filtration, it can be removed when operated under a microscope at 30-50x magnification.
They are identified in used filters by showing a tendency to aggregate in strings.
You.   Packed red blood cells within 21-42 days or longer, depending on additive system used
Can be refrigerated for use. CPDA-1 anticoagulant-treated PRC
Thus, the allowed shelf life in the United States is 35 days. Number of microaggregates during storage
And the size increases over time. In addition, gels generally form, which are
Likely consisting of brinogen, denatured protein and denatured nucleic acid, and often
It is thought to be an aggregate of leukocytes during microscopy. Including what is done. In some cases, fat globules present in the blood at the time of blood collection fuse,
Form a larger sphere.   If the leukocyte removal device consists of a porous structure, microaggregates, gels and
More fat globules collect on or within the pores, causing blockages, which obstruct flow.
Indicates the direction.   Leukocyte removal from storage bags for bedside transfusions during hospital work
Usually 0.1 to 0.14 kg / cm to guide the flow through the device to the patient^TwoBeyond
Utilize no gravity. For this reason, a particularly important property of the separation device is the
Be resistant.   Because the combination of clogging factors is unusual and very diverse,
Expert experience in the technical field of printer design has shown the removal of these undesirable components from PRC.
Unsuitable when applied to remove, especially when the PRC is stored for a relatively long time
In some cases, new and inventive methods are needed to design effective prefilters.
It was important.   The best equipment marketed during the development of the present invention was CPR by the manufacturer.
A-1 Anticoagulant-treated PRC With a capacity for 1 unit, blood holding volume is about 64cc
Was evaluated. The same device is centrifuged and then resuspended in a physiological solution
Thus, it was evaluated for use in two units of blood products from which plasma was removed. To the same trader
The earlier device had a blood holding volume of about 52 cc, but this device was clogged.
Is no longer on the market because of the frequency of
Was.   The device according to the invention has an average removal efficiency of about 99.5% or more, preferably It can be designed to supply an arbitrary number of PRC while maintaining about 99.9% or more.
it can. But evaluated to process such units, for example 4 units of PRC
What is used can be 30-50% when used to process one unit of PRC.
Red blood cells will have an internal volume that is lost by retention in the device. 1 or 2
Most commonly, a unit of PRC is required for the patient. Therefore, one unit of P
Processes RC with efficiency of 99.9% or more, but with the second unit maintaining high efficiency
A device that can be conducted is considered to be extremely useful and economical in size.
Selected as the main object of the invention. As discussed below, unless stated otherwise
The thing is a device of this size (this is called the "adult" size).   The devices described here are intended in principle for the above main purpose,
Suitable for larger or smaller PRCs by changing
Device can be manufactured. "Child" size is displayed and about¹/_TwoThe area of
And therefore the adult device¹/_TwoAn embodiment of the device of the present invention having a capacity of
During the development, due to the economics of whole blood and PRC used for testing, and to work in hospitals
Because such units are required, they have been widely used.   Microaggregates that cause clogging vary in size below about 200 μm,
The distribution varies randomly with age and in units of packed red blood cells. Get
The level varies both in hardness and quantity. Large fat globules are small but
It is found in a significant percentage of erythrocyte samples. Hematocrit (red blood cell volume %) And the viscosity each vary greatly. The variability of this characteristic is a source of clogging
Factors and onset vary significantly from blood unit to blood unit. In such a situation,
Luther development is in part close to the general science and experience of experts in the field of filtration.
But fate and intuition are key factors in achieving an effective pre-filter
Becomes   One pack of fresh or old blood
Little or no clogging in erythrocytes and in most cases 2
An effective small particle that conducts all the positions and contributes to the purpose of achieving high leukocyte removal efficiency
The design of a pre-filter system for volume gels is an object of the present invention.   An important group of patients, i.e. rely on regular repeated transfusions to sustain life
For patients with thalassemia, such as
We recognize that the use of fresh PRC is particularly necessary. PRC less than 5 days old
Transfusion requires thalassemia patients require 2 or 3 units of PRC every 3 weeks
However, older PRCs require more frequent transfusions. Own
Some doctors whose patients include thalassemia patients do not use blood older than 5 days.
Would be. For such applications, filter gel and micro-aggregate removal
Less important, the filter has less retention of the PRC and is manufactured at a lower price
Can be designed to be   A very high percentage of PRCs have been stored for more than 15-35 days before use.
For most common applications, the filter increases its defined capacity almost 100% of the time,
High efficiency and low holding capacity It is important to supply products reliably while maintaining the product. Complete the second unit
The inability to conduct is in terms of PRC loss and also nurse-technical and
Expensive in terms of physician time and can be harmful to patients
.   The method of the invention is therefore intended for the use of both fresh and old PRCs.Easy and quick start-up   Ease of use is an important property for any leukocyte removal system. The above
As described above, the ease of starting is a particularly important factor in the leukocyte removal device. “Priming
) "Means that the PRC flows from the bag through the filter to the drip chamber
Means to start. The purpose of the present invention is to keep this time under about 30 seconds.
is there. A short start-up period is always desirable to save nurse / technician time.
However, when rapid dosing is required, for example, unexpectedly significant bleeding may occur during surgery, for example.
If it does, it could save lives.Pre-adjustment of the leukocyte removal device before starting   Before many of the devices currently in use conduct blood, they usually use saline solution.
Pretreatment consisting of continuity—may or may not be supplied to the patient's vein
Need management.   The necessity of such an operation is clearly apparent for the reasons described in the previous section.
It is not desirable.   There are various reasons for employing such a pretreatment. These are cellulose acetate fibers.
Removal of acid hydrolyzate generated during steam sterilization of equipment containing fibers, present in natural fibers
Of foreign matter that may Removal and prevention of hemolysis if the fibers are hygroscopic (loss of red blood cell integrity)
And concomitant loss of its contents to the external environment).   It is an object of the present invention to provide a leukocyte depletion device that does not require pre-adjustment prior to bedside use.
It is a leaving device.Definition of pore diameter   For 25 μm or less, “pore diameter” is described in the section entitled Examples
Measured according to the modified OSU F2 test method. Porous if over 25μm
Microscopy is employed to estimate the approximate diameter of the spherical particles retained in the medium
Was.Definition of element and integrated element   In the above and generally as used herein, the term "element" refers to an element.
Part of the whole assembly, one or more layers (even if adhered to each other)
A porous web in the form of a filter assembly
-That fulfills the functions defined within. Each layer usually has a controlled density and
By hot pressing to a single layer or one or the other
Preformed in combination with two or more layers.   The expression “integral element” is part of the overall assembly.
Thus, one layer or two or more layers of the porous web are included, and each layer (when two or more layers are included)
Represents what is adhered to each other. The monolithic element has its own integrity and is self-contained
Is a single complete structure that is independent of other components until assembled.
You. Wetting of fibrous base material   When a liquid is brought into contact with the upstream surface of a porous substrate and a slight pressure difference is applied,
Inflow to the quality substrate occurs or does not occur. Conditions that do not allow inflow are porous
The liquid does not wet the material forming the porous structure.   A series of liquids each exhibiting about 3 dynes / cm higher surface tension compared to the previous one
Prepare. Then each drop is placed on the porous surface and it is absorbed quickly or
Observationally determine whether it remains on the surface. For example, this method can be applied to a 0.2 μm porous poly
Surface tension when applied to tetrafluoroethylene (PTFE) filter sheet
Rapid wetting was observed for the 26 dynes / cm liquid. But surface tension 29 dies
When the liquid was applied at a pressure of 1 cm / cm, the structure was kept wet.   Similar behavior was observed for other synthetic resin porous substrates.
The non-wetting numerical values are, firstly, the surface characteristics of the material forming the porous substrate, and secondly, the porous substrate.
Depends on the pore size characteristics of the For example, a fiber with a pore diameter of about 20μm or less
Polyester (more specifically, polybutylene terephthalate (hereinafter “PBT”))
G) was wet by a liquid with a surface tension of 50 dynes / cm,
Not wet by liquid.   To elucidate this behavior of a porous substrate, a critical wett surface tension (critical wett
ing surface tension) ”(CWST) is defined as follows.
WST applies a series of liquids having different surface tensions by 2-4 dynes / cm on its surface.
Apply separately, preferably in droplet form, and observe the absorption or non-absorption of each liquid. Is determined by CWST (unit dynes / cm) of porous substrate is absorbed
Defined as the average of the surface tension of the liquid to be absorbed and the surface tension of the adjacent unabsorbed liquid
. Therefore, in section 2 above, the CWSTs were 27.5 and 52 dynes / cm, respectively.
Was.   When measuring CWST, a series of 2 to 4 dynes / cm surface tension
Prepare a standard solution for the test. Standard solution with at least two continuous surface tensions
Place at least 10 drops separately on a typical portion of the porous substrate and let stand for 10 minutes. 10 minutes
Observe later. Wetting: at least 9 out of 10 drops are absorbed by the porous substrate within 10 minutes
Are defined as those that do or obviously wet it. Non-wetting within 10 minutes
Defined as at least 9 out of 10 drops are not absorbed or wet
. One pair with the closest surface tension, one wet and the other non-wet
Test sequentially with liquids of higher or lower surface tension until identified.
to continue. The CWST is within this range, and for convenience, the average of these two surface tensions is CWS
Used as a single numerical value representing T.   Suitable solutions with different surface tensions can be prepared in various ways,
The methods used in the development of the products described here were:                                         surface tension     Solution or fluid Dyne / cm     Sodium hydroxide in water 94-110     Calcium chloride in water 90-94     Sodium nitrate in water 75-87     Pure water 72.4     Acetic acid 38-69 in water     Ethanol in water 22-35     n-hexane 18.4     FC77 (3M) 15     FC84 (3M) 13Wetting of fibrous substrates by blood   In both packed red blood cells and whole blood, red blood cells are suspended in plasma.
Has a surface tension of 73 dynes / cm. Therefore, packed red blood cells or whole blood
If the porous substrate has a CWST of 73 dynes / cm or more when it comes into contact with the material,
Wetting will occur   Hematocrit is the volume percent occupied by red blood cells. Hematocrit of packed red blood cells
The cost is usually 70-80%. Therefore, 70 to 80% of the volume of packed red blood cells
Consists of itself, so that the surface properties of the red blood cells influence the wetting behavior of the PRC.
This is also true for whole blood with a standard hematocrit of 37-54%. Red blood cell surface
Has a surface tension of 64.5 dynes / cm in the literature. ("Measurement of surface tension of blood cells and proteins", AW Neumann Annals N.
. Y. A. S., 1983, pp. 276-297.)   By preconditioning the fiber to a higher CWST value than the natural CWST of the synthetic fiber
The benefits obtained include:   (a) 0.2 kg / cm starting was used for this study for any reason^TwoLower pressure, even if
If done by gravity, the time to start is significantly reduced. However
0.2kg / cm^TwoIn, this shortening is so small that it is difficult to measure.   (b) An important aspect of the present invention is that the fiber surface is treated to convert it to a specific area CWST.
Fibrous base material reduces start-up time, efficiency, and resistance to clogging
It is known that fibers having a CWST value outside this range perform better.
It is a look.   (c) Synthetic fiber base material whose CWST value has been increased by grafting is an excellent fiber.
It has improved fiber-to-fiber adhesion and is therefore intended for the manufacture of preformed elements used in the present invention.
Preferred.   (d) Some of the unmodified filters remain wet, thus eliminating these areas.
Flow through is obstructed.   (e) Devices made with unmodified synthetic fibers are flushed with saline before use
Is recommended by the manufacturer. This operation arranges the required complexity
Blood loss due to on-holding, cost, operating time, and operational complexity
Increase the probability of bacterial loss.   (f) Blood is observed to coagulate when exposed to unmodified synthetic fibers.Disclosure of the invention   According to the present invention, there is provided an apparatus and method for reducing the leukocyte content of a blood product.
Provided.   The present invention relates to an apparatus for reducing the leukocyte content of a blood product, wherein at least the first
, A second and a third preformed porous element, wherein the second element is
Inserted between the second element, each successive element having a smaller point than the one preceding it.
The first element includes means for removing the gel, and the second element includes microaggregates.
Providing a device comprising means for removing leukocytes, wherein the third element comprises means for removing leukocytes.
.   The first device can include a third element having a pore diameter of about 4 to about 8 μm. Was
For example, the third element has a pore diameter of about 4 to about 5.5 μm, where the first device is about 2 μm.
Suitable for treating blood products about 5 to 10 days old, or a third element
Has a pore diameter of about 6 to about 8 μm, in which case the first device can be used for less than about 10 or 15 days.
Suitable for treating older blood products.   The first device may include a first element comprising a needle fiber structure. This first element
It can be hot pressed to a controlled thickness. The average pore diameter of the first element is
0.5 Ccm / sec velocity through the first element when pre-moistened with soprovir alcohol
May require a differential pressure of 4 to 7 cm water column to induce the air flow.   The first device has at least three stages of span in which the pore diameter is approximately geometrically progressive.
At least two insertion elements consisting of a porous substrate ranging from about 25 μm to about 10 μm
(Intervening element).   The first device has a gradually decreasing pore diameter ranging from about 25 μm to about 10 μm.
At least two insertion elements made of a porous substrate having a diameter can be included.   The first device can include a single insertion element, which has a stepped pore diameter of approximately
It varies from 25 μm to a pore diameter of about 10 to about 15 μm.   The first device may contain a surfactant added to one or more devices.
The surfactant has a surface tension of about 55-45 dynes / cm in the blood product to which it is conducted.
May be provided.   The first device has at least one device modified to a CWST of 53 dynes / cm or more.
Can be included. For example, at least one of the elements should be at least about 59 dynes / cm
Modified to CWST, or at least one of the elements has a C of 63 dynes / cm or more.
It may be modified to WST. Or at least one of the elements is from about 55 to about
It may be modified to 75 dynes / cm CWST. Or even fewer of the elements
At least one depends on at least one hydroxyl moiety and an energy source
A monomer comprising one variable moiety, and at least one hydrophobic resident moiety and
In contact with a monomer containing one moiety that can be activated by an energy source,
The surface can be modified by exposure to an energy source.   The first device is 54cm each^TwoFirst, second, and third elements having the above effective cross-sectional areas
May include children. Further, the total pore volume of all elements may be less than 28 ml. First
The total internal pore volume of the device may be less than 37 ml.   The first device may include a third element wherein the means for removing leukocytes includes a filtering means.   The present invention relates to an apparatus for reducing the leukocyte content of a blood product, comprising:
And a third porous element, wherein the second element is inserted between the first and second elements,
Each successive element exhibits a smaller pore diameter than its predecessor, and the first element
Comprises means for removing gel, the second element comprises means for removing microaggregates,
The three elements include means for removing leukocytes and at least one of these elements
Provides a device that has been modified to a CWST of greater than 53 dynes / cm.   This second device has all components compressed to a reduced thickness before assembly.
Is also good.   Before the second device is clogged, one of the human body's acceptable limits has passed
At least 2 units of blood product can be supplied consistently. Less
Both components may be compressed to a controlled thickness before assembly. You
The total pore volume of all elements may be 28 ml or less, and the total internal pore volume of the second device.
May be 37 ml or less. The porous element is fibrous and the entire surface of all fibers
The product is 4m^TwoIt may be as follows. Total surface area of all fibers is 4m^TwoThe following
The pore diameter of the three elements may be 4 to 8 μm. Or a complete table of all fibers
Area is 3.5m^TwoIt may be as follows. 3.5m total surface area of all fibers^TwoBelow
, The pore diameter of the third element may be about 4 to about 8 μm.   The second device is such that at least one element is compressed to a controlled thickness before assembly.
May be.   The device according to the present invention includes the first and second devices described above. May include a first element having two or more means for removing the tool.   The present invention further provides an apparatus for reducing the leukocyte content of a blood product, comprising the steps of:
At least one integral element pre-formed from
An apparatus having a modified CWST of at least dynes / cm is provided.   This third device allows synthetic fibers to increase their CWST by more than 2 dynes / cm.
The surface may be modified.   The third device may be a CWST of 59 dynes / cm or more. For example, CWST
It may be 63 dynes / cm or more.   The third device is powered by at least one hydroxyl moiety and an energy source.
A monomer comprising one moiety capable of being converted, and at least one hydrophobic moiety and
In contact with a monomer containing one moiety that can be activated by an energy source,
It may include fibers that have been surface modified by exposure to a source of energy.   The present invention further provides an apparatus for removing leukocytes from a blood product, wherein the fibrous base material comprises
Radiation grafted to achieve a critical wetting surface tension of dyne / cm or greater, then non-brittle
An apparatus comprising at least one element that is hot-pressed to form a friable aggregate is provided.
Offer.   The fourth device includes a device modified to about 55-75 dynes / cm CWST.
Is also good.   The fourth device is powered by at least one hydroxyl moiety and an energy source.
A monomer comprising one moiety capable of being converted, and at least one hydrophobic moiety and
Active by energy source Exposure to an energy source in contact with a monomer containing one susceptible moiety
May be included.   The present invention further provides a device for reducing the leukocyte content of a blood product, the method comprising:
Apparatus comprising at least one integral preformed element of synthetic fiber, including means for removing
I will provide a.   The fifth device may include a synthetic fiber that has been improved to a CWST of about 55-75 dynes / cm.
You.   This fifth device is powered by at least one hydroxyl moiety and an energy source.
A monomer containing one moiety that can be activated by
In contact with a monomer containing one moiety that can be activated by an energy source
May include fibers that have been surface modified by exposure to an energy source.   The present invention reduces the gel content of the liquid phase prior to filtration, thereby reducing the filter assembly.
At least a first and second porous element in an apparatus for increasing the capacity of a cell
Wherein the first element is at least partially comprised of a needled fiber web;
An apparatus is provided wherein two elements exhibit a smaller pore size than the first element.   This sixth device can reduce the gel content of the liquid phase which is a blood product. No.
The average pore diameter of one element is the average pore diameter when pre-wetted with isopropyl alcohol.
Differential pressure of 4-7cm water column to induce air flow at 0.5cm / sec velocity through one element
It may be what you need. Some of the effective channels are preformed before assembly,
54cm each^TwoIt may be composed of three or more elements having the above-mentioned flow path cross-sectional area.
The total pore volume of all elements was less than 28 ml and the total internal pore volume was less than 37 ml.
You may.   The sixth device may include a second element comprising at least one planar parallel nonwoven component.
Good. The third element is included with the second element disposed between the first element and the third element.
At least one of the second and third elements has a surface tension of the liquid phase of about 2 to 20 dynes.
/ CmW or less. This allows people to
At least 2 units of any blood product that has passed any of the limits acceptable for physical use
Capacity is supplied consistently. The total pore volume of all elements is 28 ml or less,
The total pore volume of the device may be 37 ml or less. At least one of the second and third elements
One may be modified to about 55 to about 75 dynes / cm CWST.   The sixth device compresses at least one component to a controlled thickness before assembly.
It may be. For example, all components can be controlled to a controlled thickness before assembly.
It may be compressed.   The sixth device is powered by at least one hydroxyl moiety and an energy source.
A monomer comprising one moiety capable of being converted, and at least one hydrophobic moiety and
In contact with a monomer containing one moiety that can be activated by an energy source,
A second element that has been surface modified by exposure to an energy source may be included.   The present invention relates to a device for reducing the leukocyte content of a blood product, wherein an inlet and an outlet are provided.
Housing, including, upstream and porous defining a fluid flow path between these inlets and outlets
An element, at least one intermediate porous element, and a downstream porous element;
The flow element includes means for removing the gel, and the intermediate element includes means for removing the microaggregates.
Only, the downstream element includes means for removing leukocytes, The middle and downstream elements provide a device that is secured in the housing by interference fit.
Offer.   The invention further provides for separating one or more substances from a fluid to be administered to a patient.
Apparatus including an inlet and an outlet and a fluid flow between the inlet and the outlet.
A housing that defines a passageway, and whether it is located across the fluid flow path within the housing
With a separation element including one downstream surface, with an inlet near the bottom of the housing and for separation
Communicating upstream from the means with the housing, the housing being further fluid-to-fluid
A passage means for separating the air, the passage means being located downstream from the separating element.
And providing a device in communication with the outlet near the top of the housing.   The eighth device includes a wall facing the downstream surface of the separating element and defining a plenum.
A housing may be included and is located on this wall and connects the plenum to the outlet.
Can include a passage means including a tangling slot, which slot is defined by a plenum.
deep. The wall may include a plurality of concentric grooves communicating with the slots. This
Slot may extend from the bottom to the top of the housing and the depth of the slot
May increase from the bottom to the top of the housing. The length of the slot is housing
50% to 80% of the internal diameter of the housing and the slot may extend to the top of the housing
No. The depth of the slot may increase toward the top of the housing. House
The housing has a generally circular shape and the slot extends from the top of the housing to the housing.
It may extend along at least a portion of the vertical inner diameter.   The invention relates to one or more fluids to be administered to a patient. In a device for separating quality, the device generally comprises an inlet and an outlet and
A housing defining a fluid flow path between an inlet and an outlet, and disposed within the housing;
And a disc-shaped separating element having an upstream surface and a downstream surface,
Further includes: facing the upstream surface of the separating element, forming an inlet plenum.
Entry section (the entrance is a lip that extends vertically along the outside of the entry section)
Opening at the top of the entrance ridge, extending through the entrance ridge, and
At the bottom of the housing communicating with the inlet plenum) and under the separating element
Facing the flow surface, defining an outlet plenum, and a slot (deeper than the outlet plenum,
An exit section (exiting between the exit plenum and the exit)
A ridge extending vertically along the outside of the ridge, and an opening at the bottom of this exit ridge,
A passage extending through the exit ridge and communicating with the slot near the top of the housing
Including a road).   The ninth device extends a plurality of concentric grooves, and between the inlet passage and each circular groove.
These concentric shapes can include an entrance section with access
Grooves and access collectively define an inlet plenum, which is located at the bottom of the housing
It has the maximum depth near the entrance passage.   The ninth device includes an outlet section with a plurality of concentric grooves communicating with the slots.
This slot extends from near the bottom of the housing to the top of the housing.
The depth is greater at the top of the housing than at the bottom.   In the ninth device, the housing further includes a disk-shaped separating element. May be provided with a cylindrical collar arranged around the disc-shaped separating element.
The cylindrical collar is sealed by an interference fit between them.   The present invention further provides a gel content of a liquid phase for reducing the leukocyte content of a blood product.
One or more substances from the fluid to be reduced or to be administered to the patient
In a method for separating quality, a blood product, a liquid phase or a fluid is applied to a suitable device as described above.
Providing a method comprising conducting to a device.   The present invention relates to a method for reducing the gel content of a liquid, comprising the steps of:
There is also provided a method comprising conducting to the web. The preferred liquid for this method is blood
Formulations, especially PRC.   The present invention further provides a method for measuring the wettability of a porous
At least one drop of at least two liquids each exhibiting close surface tension or
Two or more drops are applied at different locations on the porous substrate and exhibit adjacent surface tension.
Required until one of the seed liquids is absorbed by the substrate and the other is not.
A method consisting of repeating this operation in accordance with   Achieve high efficiency and volume for leukocyte removal and reduce blood loss in the device
Significant novel features of the present invention that contribute to minimization are:   (a) The conventional device uses a relatively small cross-sectional area perpendicular to the flow path,
Thus, the liquid flow path in the filter substrate is relatively long. A preferred device according to the invention is
Larger cross-sectional area perpendicular to the channel, and therefore shorter channels in the filter substrate
. Like this Relatively large due to the large filter area on the upstream surface
Prevent clogging by PRC or blood containing small amounts of gels and microaggregates
Granted.   (b) Make this larger cross-section economically and practically, and
In order to carry out the filtration, the porous parts of the preferred device according to the invention must be rigorously assembled before assembly.
Preformed to a controlled size and density, fully or partially integrated
And other elements until self-contained and incorporated into the device according to the invention.
Independent from.   Previously used equipment was created by filling into equipment using filled fibers.
The product of the present invention had a smaller cross-section and greater depth
. Housing inlet face and outlet, unique to filled fiber systems by preforming
The pressure at the surface is relieved and the preform is used to remove certain elements, for example, assembled equipment.
The first stage pre-filter is somewhat compressible, and the subsequent
Lower or higher densities can also be provided. This style extends the useful life.
Contribute to the length.   Compared to devices that use a fibrous web filled in the housing during assembly,
The use of a thin-walled injection-molded housing results in a longer service life and the same
Sometimes equivalent or usually better leukocyte removal efficiency, equivalent or better red blood
Larger cross-section leukocyte depletion devices with higher cell recovery and lower retention
The adoption was made practical by preforming. Pre-forming is filter assembly
Reduces brie volume to reduce blood loss due to retention in the filter assembly
Reducing, excluding Greater removal efficiency and greater ability to handle larger volumes of PRC before clogging
Contributed.   Pre-filter made of various commercially available woven or non-woven fabrics, made of fibrous mat
All together with the final filter of finer pores, the plastic
A device that was filled and incorporated into the jing was reported and manufactured.
  These devices provide effective pre-filtration and filtration enabled by pre-forming.
I don't know. None of these use preformed elements, and consequently hot preforming and
Nor did they use equivalent means. Effective at higher densities by preforming
A pore diameter is achieved, thus occupying less space and retaining equivalent results.
Less blood is retained. This is the closest commercially available product to the product of the present invention.
Is reflected in the comparative performance of the existing devices. The device is out of the machine
And therefore easily confirmed that they have not been preformed in any way.
Using a melt-blown fiber web. The product is compared with the product of the present invention.
About twice the holding volume, with significantly lower efficiency,
It is estimated to conduct only one unit of PRC per position.   (c) a preformed element located upstream of the preformed fiber element assembly
(Hereinafter referred to as “gel pre-filter”) has its main function as
The gel present in a substantial proportion of the supplied PRC units. This markedly
Effective gel pre-filter with smaller internal volume and internal retention
It is possible to employ a device with less blood loss.   Although it is difficult to quantify the gel content of a particular PRC unit, Nevertheless, PRC stored for more than 10-15 days, PRC stored for less than 5 days
It will be obvious to those skilled in the art that the gel content will be substantially higher than in the case of. Gel included
Higher volume, gel pre-filter provided to remove and enclose the gel
The volume of the key must also be large. In the present invention, two kinds of gel prefills
Was prepared. The first consists of a single layer for use with relatively fresh PRC
The second being composed of two or more layers for use with relatively old PRCs
It is. Use filter assembly with a single layer per fresh PRC
If not, always supply one unit of PRC and not supply the second unit before clogging
Is very rare. Prefilters for multi-layer gels are about to expire
Shows similar performance with relatively old blood of the day. Pref for these gels
Filters form an important aspect of the present invention.   (d) Gel pre-filter removes gel at very slight increase in pressure drop
Micro-aggregates, which are often in suspension in gels
But only a small fraction of microaggregates not included in the gel
It only removes minutes.   Removal of these free-suspended microaggregates is accomplished by sequentially removing smaller pore diameter filter bases.
This is achieved by one, two or three layers of filtration through the material, followed by its main purpose.
Is a leukocyte removal layer (herein, sometimes described as "adsorption element").
The product fluid supplied to this downstream element is substantially free of gels and micro-aggregates
, Some of the white blood cells have been removed.   (e) The unexpected finding is that downstream (adsorption, or “final” for simplicity) elements
Was to remove leukocytes from suspension by two mechanisms operating simultaneously
. The first mechanism is the adsorption of leukocytes to the fiber surface; the second is by filtration
. This first mechanism is effective depending on the amount of the fiber surface. The second mechanism is mainly
Relies on maintaining the pore diameter of the luter substrate within or below a certain range
You.   (f) Modification of fiber surface to promote friability by PRC. Of the filter
Starting, that is, guiding the flow of the PRC through it, is more complicated than it seems at first glance
And difficult.   If the CWST on the fiber surface is too low (eg, for unmodified synthetic fibers), the PR
A relatively high pressure is required to allow C to flow through. If more pronounced, filter
The surface of the substrate tends to be uneven, which impedes the flow of the PRC. further
Clogging, especially for relatively thin, high surface area fibers and relatively old blood
Can happen.   Although the reason is not always fully understood, a CWST of about 90 dynes / cm or more
Certain filters have been found to exhibit relatively long start-up periods. H
The CWST of the filter substrate greatly exceeds the surface tension of water (73 dynes / cm).
It seems that there is no theoretical reason to do so,
Slightly higher than WST (52 dynes / cm) and kept within about 75 dynes / cm or less
That seems desirable. Nevertheless, reaching 90 dynes / cm, this
The filter showing a CWST of more than 0.2 worked well.   (g) The housing enclosing the element assembly is easy to use, quick start-up, and
Uniquely designed to achieve effective air exclusion, which ultimately improves efficiency,
This results in an extended useful life and a further reduction in PRC retention.   (h) The lateral dimensions of each element shall be greater than the corresponding inside diameter of the housing in which they are incorporated.
large. For example, if these elements are in the form of a disk, the outer diameter of the disk
It is made 0.1-1% larger than the jing inner diameter. This means that there is no loss in the effective area of the device.
The formation of an interference fit results in a very effective seal and also in the compression area.
Compared to the compression seal around the perimeter of the filter element assembly
Of the blood retention volume of the assembly of the present invention as compared with the assembly of the present invention.
Give.

[Brief description of the drawings]   FIG. 1 is a sectional view of an example of a removing apparatus according to the present invention.   FIG. 2 is an elevational view of the inside of the inlet section of the removal apparatus shown in FIG.   FIG. 3 is an elevational view of the inside of the outlet section of the removal apparatus shown in FIG.   FIG. 4 is a cross-sectional view of the outlet section shown in FIG.BEST MODE FOR CARRYING OUT THE INVENTION :Materials used for construction of leukocyte removal equipment   Various raw materials other than fibers are also considered; for example, a porous substrate is formed from a resin solution into a porous film.
Or a sintered powder substrate can be used. But price
Fiber is preferred because of its simplicity, flexibility, and ease of processing and control.
New raw materials It is pointed out that   Absence of surfactants deliberately added to reduce surface tension of blood products
In order to achieve good start-up with a sufficiently wet fiber substrate underneath, the relevant physical
At first glance, from the basic considerations of chemistry, the blood component device is almost equal to the surface tension of water.
Should be made of a material with a surface tension in the range of 70-75 dynes / cm or more, for example.
It appears to be. Practical considerations dictate the use of commercial fibers. Fiber is manufactured
The synthetic resins that can be used include commercially available polyvinylidene fluoride, polyethylene,
Polypropylene, cellulose acetate, nylon 6 and 66, polyester, polya
Includes acrylonitrile as well as polyaramid. The important properties of resins are their
Critical surface tension (Ziaman, "contact angle, wettability and adhesion",A
dv. Chem. Ser.43, 1-51, 1964). These resins range from less than 25 dynes / cm to 45 dynes.
Critical surface tension (γ_c). Empirically, the products of the invention
The CWST of the filter substrate in the required pore size range should be a solid plastic.
Γ_cIt is expected to be about 10 dynes / cm or less higher than the value. For example, polytetra
For fluoroethylene, γ_cIs 18 and CWST is 27.5. On the other hand
Γ for polyester PBT fiber mat_cIs 45 and CWST is 52.
No suitable commercially available synthetic fiber with a CWST of about 52 dynes / cm or higher is found.   For actual bedside transfusions in the United States, the PRC is 2 units for 1.5 to 4 hours
It is administered at a rate that transfuses blood. The present inventors have developed an unmodified melt blown poly
Use ester as a filter When used, PRC coagulation occurs within 2-3 hours and the filter is completely closed.
Admitted to block.   Some natural fibers have a CWST of 52 or more, but natural fibers with a diameter of about 15 μm or less
Generally not commercially available. Synthetic fibers less than 5μm in diameter
Can be made, this kind of fiber is equal for leukocyte adsorption compared to natural fiber
The mass required to obtain the fiber surface area is less than one-third, and
When processed into a diameter filter, it occupies a smaller volume. For this reason, natural fibers
Weir is not suitable for producing a suitable low retention volume leukocyte depletion device. And
For example, the commercially available filled cotton fiber device currently used for leukocyte removal is started with 75 ml or more.
Capacity, which is more than twice the same capacity of the preferred adult device described in the present invention.
You. In addition, the manufacturer of the device may conduct saline solution before and after PRC conduction.
This device is unsuitable for bedside use. Further processing
The processed blood must be used within 24 hours.   Surface grafting technology has been the subject of extensive research for over 25 years. In scientific literature
Numerous reports and numerous patent specifications have described various ways to perform surface modification by this means.
Methods and procedures are described. One method of this kind, together with the acrylic part, is hydrophilic
Groups (eg, -COOH or -OH) to hydrophobic groups (eg, saturated chains, eg, -CH_TwoC
H_TwoCH_Three), And various monomers containing a second group selected from
These are used in the method of the present invention. Heat, UV light to initiate and complete the reaction
Other reaction initiation methods may be employed. However, cobalt source irradiation grafting is the simplest method For improving the CWST of the fiber mat in the present invention.
Can be. By experimental selection, CWST will be measured from 52 by the above method
Of polybutylene terephthalate enhanced to any desired value
It is possible to find monomer mixtures or monomers that give the fiber mat. upper limit
Is set by a small number of liquids with a surface tension of more than about 110 dynes / cm at room temperature
.   During the development of this invention, ethylenically unsaturated groups, such as acrylic moieties
(Eg, 2-hydroxyethyl methacrylate, ie,
An apparatus was manufactured using a substrate grafted by “HEMA”). The second action
Ryl monomers such as methyl acrylate (MA) or methyl methacrylate
(MMA), which tend to lower the CWST of the grafted porous web
In combination with HEMA and varying the ratio, from 35 to 45 to 110 dynes / c
Any CWST of m or more can be obtained. Devices manufactured in this way are
A distinction is made between devices manufactured using components treated with surfactants in the following respects. sand
That is, the surfactant is removed by passing a liquid through the device, but is removed by grafting.
The resulting surface properties are permanent, no matter how much liquid is passed through the device.
Changing the physical properties of the liquid does not remove or change it, especially the surface tension
It does not change.   A liquid having a surface tension lower than the CWST of a porous substrate wets the substrate,
If the substrate contains through pores, it will easily flow through the substrate. From this CWST
Liquids with high surface tension Does not flow at all at low pressure differentials, but will flow at sufficiently high pressures
. If the surface tension of the liquid is only slightly higher than the CWST, the required pressure is small.
There will be. Conversely, when the difference between CWST and the surface tension of the liquid is large,
The required pressure will be higher.   A liquid mat having a CWST of 15 to 20 dynes / cm lower than the surface tension of the liquid
Forcing the body under pressure tends to cause flow through in an uneven manner,
It was found that some areas of the mat remained dry. This is a white blood cell
It is highly undesirable in a removal apparatus for the following reasons. First is the pressure drop
And this causes premature clogging and, secondly, that all flows are
Passing only a small part, this also increases the probability of clogging, and FIG.
Only a portion of the filter surface area available for adsorption or filtration retention is used for that purpose
As a result, the efficiency of leukocyte removal decreases.Solutions to the problem of poor wettability of synthetic fibers and consequent start-up delays   Fiber surface properties can be measured in a number of ways, for example by chemical, including wet or dry oxidation.
Reaction, by surface coating by depositing a polymer on it, and
Energy sources such as heat, van der Graaff, ultraviolet light or other forms of radiation
(Of which γ-rays are particularly useful).
Wear.   Examples of these various methods include the use of stainless steel fibers at about 370 ° C in air.
Oxidation forms a thin oxide surface film Water wettability, that is, γ of 72 dyne / cm or more._cGrant
can do. Synthetic organic fiber and glass fiber at one end or near
Coated with a polymer containing a reactive (eg, epoxide) moiety and the other containing a hydrophilic group.
Can be Use these and other methods known to surface modification experts.
Can be used, but radiation grafting can be modified if performed under appropriate conditions.
Surface type, the range of reactants used for modification, and the required reactions
Considerable flexibility in the system used to
Is advantageous. In the present invention, the γ-ray grafting method is performed from 50 dynes / cm to 75 dynes / cm.
to produce synthetic organic substrates with a wide range of CWSTs, much larger than
It is noticed. The product is extremely stable, with no detectable levels of water-extractable components
So low, when used in a preformed pre-filtration or adsorption element,
Improved interfiber adhesion is obtained.   Another means of addressing the poor wettability of synthetic fibers is the suspension of red blood cells.
Altering the surface tension of plasma or altering the surface properties of red blood cells
Is included. This reduces, for example, the surface tension of the red blood cell suspension in the leukocyte depletion device.
This is achieved by providing a surfactant or soluble substance to be applied.   Prefilter element for gel used for manufacturing test devices of Examples 1 to 106
Is impregnated with a non-ionic surfactant solution, which allows the PRC flowing through it to
A surface tension of 51.5 dynes / cm was induced. Example 107 and below without using a surfactant
It was conducted.Selection of fiber diameter used for leukocyte removal device   As mentioned in the section entitled “Desirable properties of leukocyte depletion device”,
Leukocyte adsorption is widely accepted as a leukocyte removal mechanism. Constant weight fiber
Surface area is inversely proportional to the fiber diameter, and leukocyte removal by adsorption to the fiber surface is
Since it is an important groove for ball removal, the thinner fiber has higher capacity and the desired efficiency
The amount of fiber (measured by weight) required to achieve
It will be less.   For this reason, there has been a tendency to use finer fibers for leukocyte removal. Historically
Indeed, as technology for producing finer diameter fibers advances,
It has been proposed that the housing be later filled and / or used for leukocyte depletion.
Was.Selection of fiber material used for leukocyte removal device   Numerous commonly used fibers including polyester, polyamide and acrylic
Are suitable for radiation grafting. They are separated by gamma radiation at the level required for grafting.
Have adequate resistance to the solution and they are effective monomers during or after irradiation.
Is a group containing a reactive group.   As mentioned above, the fiber diameter must be as small as possible. Normal spinneret
Fibers produced by gold extrusion and drawing are now smaller than about 6 μm in diameter.
I can't get anything.   The molten resin is made finer by high-speed airflow into fibers, and the molten resin is collected as a nonwoven web.
The melt-blowing process entered production in the 1960s and 1970s, producing fibers that form a web every year
The lower limit of the diameter was gradually widening. Within the last few years, fiber diameters of 3 μm or less
Webs have been achieved, and more recently, of good quality with an average fiber diameter of 2 μm or less. The web was manufactured.   Certain resins are more suitable than others for melt blowing fine fibers. Suitable resin
Are polypropylene, polymethylpentene, nylon 6, polyester PET (
Polyethylene terephthalate) and polyester PBT (polybutylene terephthalate)
Phthalate). The possibility of finding something that has not been tested yet
is there. Among the above resins, polyester PBT is useful for radiation grafting and subsequent heat transfer.
It is also suitable for converting controlled pore size into preformed elements by cold compression
Is a preferred material.   Polyester PBT is the main resin used in the development of the product of the present invention,
It is a resin used for the specific example except the pre-filter for use. However, the fiberized diameter
Others that can be collected as a mat or web containing fine fibers of about 1.5 μm
May be found, and their CWS if necessary
Products with T adjusted to the optimal range are equally effective and smaller leukocyte depletion
It should be noted that it may be suitable for the manufacture of a removing device. Similarly, process appropriately
Glass fibers that have been used may also produce devices with very low blood retention.   Critical surface tension of PBT (γ_c) Is reported to be 45 dynes / cm
Its CWST in cut form has been measured at 52 dynes / cm.Use of Needled Web in Gel Prefilter   Nonwoven webs are manufactured by various means. Fiber extruded from molten plastic
Float in air as it is Collected in a still flexible state on a moving belt or drum or after the fibers have hardened
You. In another mode, the fibers are extruded and drawn as continuous filaments, then
Cut or cut into pieces about 2-6 cm long, float in air,
Collect on moving belt or drum. The surface for collecting fibers is generally about 10 ~
Moving at a speed of 1000 m / min; as a result of this linear motion, the fibers in the web
Also tend to be parallel to each other, very generally parallel to the plane of the web.
They are therefore classified as "planar parallel".   "Needled" webs are also known as "needle punched" webs.
Introduces a plane parallel web to a machine equipped with a large number of rapidly reciprocating multi-layer barbed needles.
Manufactured by further processing by passing through, which randomizes the fibers
And pull or push them through the entire thickness of the web, thereby
Fibers are drawn from one side to the other, where they are combined with the fibers on that side.
Entangle.   Multiple jets are also used to interlace the fibers throughout the thickness of the web,
And if there are other methods, or if they have been developed)
It is called "needleed."   Needle webs are made of very low density and are therefore bulky (often
Porosity ranges from about 95 to about 99%) and is relatively thick (often greater than about 3-5 mm). So
These structures show, by microscopic examination, the appearance of a combination of coils of random diameter.
Many of them are oriented with the coil axis parallel to the web and tend to be spherical
Blood gel seems to be able to easily reach inside the web You. This is in stark contrast to the orientation of a plane parallel nonwoven web, in which the fibers are
A spherical gel parallel to the plane of the web and even in very rough
Or tend to be held near it.   Therefore, the blood gel will not enter into the extremely open surface of the needled nonwoven coil.
Although it can be easily penetrated, the penetration into the nonwoven fabric in which the fiber is oriented parallel to the web is
Seems more difficult. In addition, once the gel enters the needled web
It seems that they are effectively retained in relatively small pores,
The presence is easily recognized by In fact, curled fibrous structures can easily progress.
And is well retained, but can enter relatively straight fibers easily.
And thus rapidly clog as the gels collect on their upstream surfaces.   As the blood containing the gel flows through the needled filter substrate, the smaller
The pores are randomly encountered, and these numbers are based on all or almost all gels.
Sufficient to show the mesh effect collected in the wood. The resulting increase in pressure drop
The size is very small. Relatively large pores remain open and suspended in plasma.
It provides a free passage for turbid red blood cells to flow.   Regardless of whether these filtration concept concepts are effective, needled nonwovens
Exhibiting a unique (and unexpected) effect of allowing gels to enter and then retaining them,
Blood or PRC, on the other hand, causes negligible or negligible pressure drop.
Has been found experimentally to be able to flow through them.   In the development of the present invention, the needled web Before using for the first time, 2 units of P at a blood holding volume comparable to that of the example
Hundreds of tests were performed with the goal of consistently achieving RC. For these tests
Is different in graded pore size in 7 to 10 steps from 50 μm or more to 5 to 10 μm
The base material layer 15 or more was used. For these tests, a plane-parallel nonwoven substrate was used.
Did not succeed.   The use of a needled web allows the development of the filter of the invention,
They hold relatively old blood with high efficiency and without clogging, with a holding volume of 30-35cc or less.
Can be consistently processed.   Same as the needled base material used in the present invention at the time of microscopy other than needling
Although there may be or may be developed methods for producing
It should be understood that products manufactured using these substrates are also included in the scope of the present invention.   A wide variety of fibers, fiber combinations, and / or
Can use a binder. These are all (a) they are hot pressed or
Facilitates subsequent controlled compression by other means, and (b) they are human blood
Can be used if manufactured under materials and conditions suitable for use in processing equipment
.   The web used for the gel pre-filter in the examples of the present invention is a non-ionic lubricant.
Needle-punched fiber (Freindenberg Non-Ubun)
Partners grade P14, nominal weight 80g / m^Two), Resulting in
32cm in 300ml of deionized water^Two48 dynes / cm The surface tension was measured. Use a gel pre-filter made from these fibers
And processing the PRC, the surface tension of the plasma in the PRC effluent from the device is approximately 73 dynes.
/ Cm to 48.5-51.5 dynes / cm. Similar surface tension data is
Tween 80 and BASF-Pluronic
ic) also obtained with other surfactants including L101 and Pluronic F68
. These are all physiologically acceptable for use as parenteral. Example 10
7 Before use, detergents present in the needlepunched substrate must be
Rinsing and rinsing with water.Element for micro-aggregate   The primary function of the device following the gel prefilter is to remove microaggregates. auxiliary
A typical function is to remove a part of leukocytes by adsorption.   For these purposes, this is preferably a melting block of two, three or more layers.
Combine raw web. The layers that make up the device are separately pre-formed and
Or they may be preformed into a single element,
Alternatively, they may be combined with an adsorption element to form a single integrated element.Suction element   The main function of this device is to provide the largest fiber surface to remove leukocytes by adsorption.
Is Rukoto. This is a method of preforming a large number of relatively small diameter fiber web layers into an integrated element.
It is very simple to produce by forming
Combined with a micro-aggregate element, it consists of an adsorption element and a micro-aggregate element A single integral element may be formed.Filter-adsorbent assembly   Gel pre-filter in the proper order with micro-aggregate element and adsorption element
When assembled, a "filter-adsorber assembly" is obtained. All parts
Preform separately or combine them in any convenient combination
It can also be formed in an assembly.Description of an example of the removal device   As shown in FIGS. 1-4, the illustrated removal device 10 generally comprises a housing 11 and a fan.
Consists of a filter-adsorber assembly 12. Housing 11 has inlet 13 and outlet 14
And a fluid flow path is defined between the inlet 13 and the outlet 14. Filter-adsorber assembly
The lee 12 is disposed across the fluid flow path within the housing 11 and flows through the housing 11
Undesired substances, such as gels, from fluids such as suspensions of packed red blood cells
Acts to separate fat globules, aggregates and leukocytes.   Removal of two different sizes that differ only in the area through which the packed red blood cell suspension passes
The device was tested. Smaller child size is effective area 32cm^TwoAlso
In addition, large person defined as adult size is effective area 62cm^Twoshowed that. Both are de
The disk-shaped filter-adsorber assembly 12 was housed in a cylindrical housing.   The housing is designed to accommodate various shapes of filter-adsorber assemblies.
It is. One is, for example, square. As long as the appropriate flow area is obtained,
And other possible shapes are original As a rule, they all function.   Square filter-adsorber assembly theoretically uses material more economically
But compatible with disc-shaped filter-adsorbent assembly-
If the housing uses a tight fit seal as described below,
Will be low. If sealing is obtained by edge compression around the perimeter,
New effective area is lost at the seal. For these reasons, interference seals
Cylindrical housing with preassembled disk-shaped filter-adsorber assembly
Zing is preferred, but other shapes may be employed. Effective area 32 and 62cm^TwoRound
A housing was used in the development of the present invention.   The housing can be made from a reasonably impermeable material,
Thermoplastic materials are included. For example, the housing may be a transparent or translucent polymer,
Manufactured by injection molding, for example, from acrylic or polycarbonate resin
Is preferred. This kind of housing is easy and economical to process
Instead, fluid can be observed to pass through the housing. housing
Is normal overuse in use, and about 0.2kg / cm^Two(3 psi)
Measured. This allows for a lightweight construction, which is a pre-formed filter-adsorber
This is a desirable feature of the present invention made possible by the use of assemblies. How to fiber
Filter-Adsorber Assemblies Effectively Designed by Filling Into Zing
The force required to compress Lee's fibers is 62cm^Two68kg per disc, or about 1
.1kg / cm^TwoHeavier, bulkier and more expensive housing Requires a switching structure.   Although the housing may be formed in various shapes, the housing 11 of the illustrated separation device 10
Preferably has two sections, an inlet section 15 and an outlet section.
16 are formed. The inlet section 15 includes a circular inlet plate 20,
The inner surface of the shaped plate 20 is a wall facing the upstream surface of the filter-adsorber assembly 12.
Surface 21 is defined.   Inlet 13 allows fluid to enter between wall 21 and the upstream surface of filter-adsorber assembly 12.
Send to mouth plenum 22. According to one aspect of the present invention, as shown in FIGS.
The inlet 13 directs fluid to an inlet plenum 22 at or near the bottom of the housing 11.
Send in.   The inlet can be formed in various shapes. However, the inlet 13 of the separation device 10 illustrated is
Includes entrance ridge 23. The entrance ridge 23 has a circular entrance parallel to the diameter axis A of the housing 11.
It extends along the outer surface of the mouth plate 20, which in use has its diameter axis A generally oriented vertically.
Placed. Upstream of the inlet ridge 23 is a bag containing fluid, such as a blood bag.
Socket for receiving a hollow spike 24 used to pierce the bottom of the
It may be formed as follows. The inlet 13 further includes an inlet passage 25, which is a hollow spa
Opening at the upper end of the inlet 24, extending through the hollow spike 24 and the inlet
It communicates with the inlet plenum 22 at the bottom of section 15.   The wall 21 of the circular entrance plate 20 includes a plurality of generally concentric ridges 26,
Defines a concentric groove 27. These ridges 26 are a filter-adsorber assembly
Adjacent to 12 upstream surfaces. As shown in FIG. 2, the ridge 26 is
At the bottom Terminate and define a passage or access 30. Access 30 has entrance passage 25 and each circle
It extends between the grooves 27 and allows fluid to flow from the inlet passage 25 into the cylindrical groove 27. Circular groove 27
And access 30 assemble to define an inlet plenum 22, which is fed through an inlet passage 25.
The collected fluid is distributed over the entire upstream surface of the filter-adsorber assembly 12. Aggregation
Body or other large obstacles may flow at or near the junction of the entrance passage 25 and the entrance plenum 22.
Blockage and at the same time minimize the holding volume in the housing 11
For this reason, the depth of the inlet plenum 22 is greatest at the bottom of the housing 11 and on the vertical axis A
Along the horizontal axis of the housing 11 and has a minimum value.   The outlet section 16 of the housing 11 has a circular outlet plate 31 and a cylindrical collar
32, the latter ranging from around the circular exit plate 31 to around the circular entrance plate 20.
It is growing. The cylindrical collar 32 is preferably integrally formed with the circular outlet plate 31
And in any suitable manner, for example by glue or by sonic welding
It is connected to a circular entrance plate 20.   The inner surface of the circular outlet plate 31 is located on the downstream surface of the filter-adsorbent assembly 12.
The facing wall surface 33 is defined. The wall 33 includes a plurality of generally concentric ridges 34, which
A concentric groove 35 is defined. These ridges 34 are attached to the filter-adsorber assembly 12
Adjacent to the downstream surface of The circular grooves 35 collectively define an exit plenum 36, which is
Collect the fluid that has passed through the Luter-Adsorber assembly. The depth of exit plenum 36 is
Minimal retention volume in housing 11 without unduly restricting fluid flow
To limit the possibilities Smaller.   According to another aspect of the invention, the wall 33 may further be at the top or at the exit section 16.
Include a passage, eg, slot 40, in communication with the outlet 14 near. 35 circular grooves
Slots 40 that collect fluid from each and carry fluid to outlet 14 generally have a vertical axis A
Preferably, the outlet section 16 extends from the bottom to the top. Illustrated separation
In the device 10, the width of the slot 40 is constant, but is greater than the depth of the exit plenum 36.
The depth of the deep slot 40 increases along the vertical axis A from the bottom to the top of the exit section
doing. Or if the height is less than the diameter of the housing, the width varies, or
Alternatively, the depth may be constant. For example, Scott is vertical from the top of the housing
Along axis A, it may extend a distance in the range of about 80% of the inside diameter of the housing.   The outlet 14 can take various shapes. However, the illustrated removal device 10 is parallel to the vertical axis A.
A longitudinal exit ridge 41 extending along the outer surface of the exit plate 31. Exit ridge
The lower end of 41 is used as a tube connector or as a tube connector or other device.
It may be formed as a socket for receiving the device. Exit 14
Communicates with slot 40 at or near the top of the housing 11 and through exit ridge 41
Includes an outlet passage 42 that extends and opens at the lower end of the outlet ridge 41.   As blood flows through the device, filling it from the bottom and draining from the top
Thus, the air is removed and flows toward the outlet passage 42, from which it is discharged. Illustrate
Careful design of the installed equipment ensures that all air is
From inside Reduces the situation where some liquid reaches the area 43 adjacent to the exit passage 42 before being scavenged
It was possible, but not completely eliminated. Slot 40
In the absence of this delayed air flow, some erythrocyte-containing suspension may enter the outlet tube 42.
Will carry in. Slot 40 allows blood carried in this manner to flow into the slot.
Where the air is safely separated from the suspension. Then the air is slot 40
Rises to the outlet 14 without any trouble before the rising liquid level in the
It is almost completely extruded before reaching the top of the mouth passage. Thus an example according to the present invention
The air is removed very effectively from the housing 11 of the removed removal device 10. for example
It has an inner diameter of 8.9cm, an initial air volume of 36cc, a height of 8cm, a width of 0.73cm, and a depth of 0.2c at the bottom.
1 or 2 cc in a stripper with a slot of 0.33 cm deep and 0.33 cm deep
After the blood has passed through the outlet, the residual volume of air passing through the outlet should be 0.1 cc or less.
It is estimated that.   To understand the importance of slot and channel geometry, an equivalent regular leukocyte depletion
The operation of the previous unit will be described.   In a typical unit, fluid enters at the top of the housing and at the bottom
Is discharged. The housing of this type of unit is generally above the normal housing
Between the blood bag and the clear drip chamber downstream of the normal housing
It is connected by a plastic tube and from here to the patient. During the starting period
Reverses the housing with the drip chamber and replaces this normal housing
Forcing blood through the drip chamber through the drip chamber. It loses some pressure head
Disadvantage But in more severe cases 1-2 cc or more of air is still normal
With the fluid trapped in the housing, the fluid reaches the normal housing outlet and
Enter the bar. Once 3-4 cc of fluid has collected in the drip chamber,
Return the housing to their normal position. At that time, the fluid is stored at the bottom of the drip chamber,
And a space is left above the fluid reservoir.   The transparent drip chamber allows the observation of droplets through the space and thus the flow regulation
Performs the task of providing guidance. This is the delayed air entering from the normal housing
Also plays a second role in preventing the patient from reaching the patient. Sky instead
Qi displaces an equal volume of fluid in the reservoir of the drip chamber. However, the reservoir is slow air
Must be large enough to ensure that all fluids are not excluded.
Otherwise, air can enter the patient's veins.   Significant amounts of air, for example 1-2 cc of air, returned the drip chamber to its original position
Systems that can reach there tend to do this without reproducibility.
Therefore, the larger the volume of delayed air, the more it must be collected in the drip chamber reservoir.
No fluid volume will be large. At the end of dosing, the bulk of this volume is
And is therefore discarded. Many of the fluids administered to the patient, such as red blood cells
Fluids containing blood components such as are often difficult to obtain and are extremely expensive
Thus, the fluid that is discarded can be very expensive. Highest air displacement
This allows the use of smaller reservoirs in the drip chamber
Thereby, the removal device according to the invention can be administered This significantly reduces the amount of fluid that is discarded.   The filter-adsorber assembly 12 is described below under the heading Fabrication of fiber elements.
Consisting of a plurality of separately preformed layers. At the development stage,
Although an internal structure is employed, the thickness of the filter-adsorber assembly is
A different housing was constructed. In this way, filters with different total thickness-adsorption
The body assembly could be tested. In each case, the entrance section and
The distance between the tips of the ridges 26 and 34 in the outlet and outlet sections is determined by the filter-adsorbent assembly
Adjusted to be equal to Lee's nominal total thickness.   Obtain an interference fit of the filter-adsorber assembly 12 within the housing 11
For this purpose, the filter-adsorber element is moved from a large pre-compressed slab
It was cut to a diameter of 0.1-1% larger than the inner diameter. Filter-adsorber elements are
The outer edge was cut off to maintain a true right cylindrical shape. This and a slight oversizing
The filter is composed of various filter-adsorbent elements
A good seal between the outer edge of the body assembly 12 and the inner edge of the housing 11, i.e.
A tight fit is obtained and the entire area and volume of the filter-adsorber assembly 12 is reduced.
100% utilization, which minimizes the holding volume.   The end seal obtained by interference fit has been shown to be adequate by itself, but
Since it is important to have high reliability in knit production,
Sounds good. This seal is a pair of inward facing flanges 1-1.5 mm wide.
These can be used to connect the filter substrate to these peripheral flanges. Has dimensions to compress between 20-60% between. Assemblies and assemblies that include this auxiliary seal
The same assembly was used in the development of the present invention.Manufacture of fiber elements   The fiber element incorporated into the housing consists of a number of independent individual elements.
, Each perform one or more functions. The leukocyte removal device of the present invention
In a preferred form, these layers consist of the following in the order in which the fluids flow:   1. The first element is called a gel prefilter. High percentage of whole blood and PRC
The specimen contains a gel, which has a significant effect of clogging the filter substrate. this
These gels form a separate phase with the plasma in which they are suspended, are immiscible, and
Perceived to have a higher viscosity. To deal with filter clogging
State-of-the-art methods of increasing the size of the pores upstream of the filter and subsequently
The pores are gradually or gradually reduced. But this method is good enough
Although it is not known, it was used before the gel prefilter of the present invention was developed.
Had no effect.   We have average fibers, 10-40 μm in diameter, preferably 15-30 μm, more preferred.
The raw material is a non-woven web produced by the needle punching method,
That a very effective gel removal filter can be produced by using
I found it. Needled webs are manufactured using a number of multiple barbed needles,
The thorns are oriented both up and down, causing the fibers to become irregular loops, circles and
Take the shape of a spiral, various other irregular Various shapes are scattered in this. In general, most fibers have irregular shapes,
Is negligible. The gel was of this type, as evidenced by post-test microscopy.
It appears to easily penetrate into the web and be effectively retained within the web.   Needle webs with these properties are generally thicker than desired for gel removal.
Must be compressed to a smaller controlled thickness for optimal results.
I have to. Fabrics made in this way are particularly effective at retaining gels
This is done in a relatively small space within the filter housing.
Was found. The smaller housing achieved in this way is not
Less blood retention and less than 50% reduction in PRC compared to overly suitable filters
Down.   Gel prefilters do not capture microaggregates directly by filtration
However, the gels that they carry often have substantially large numbers of microaggregates of varying sizes.
Included, which are effectively retained with the gel.   Gel prefilters are manufactured at low density to provide extremely high porosity.
It is easily compressed when manufactured with fibers up to 30-50 μm in diameter
. Webs made with fibers much smaller than 10-20 μm have
An inch pressure head compresses the partially gel-filled web, thereby
Can be overly compressible to a state that reduces its pore diameter to an invalid range
There is a potential. Equal pores when manufactured with fibers significantly larger than 30-50 μm
-Open area in size is better than webs made with finer fibers.
Small No.   The preferred material used to make the gel prefilter is polyethylene terephthalate.
(PET) and polybutylene terephthalate (PBT). PET is
Weight 7-9mg / cm^TwoUsed in the form of a web with an average fiber diameter of 23 μm, while
(PBT web) has a fiber diameter of 20 μm and a weight of about 8 mg / cm^TwoMelt blown web
Met.   The PET substrate is too low in density as purchased and the pore diameter is the target
It was big. To improve this, the web is hot-pressed to a smaller thickness
I made it. Since the web is extremely compressible, the thickness control is controlled by the drop test (f
all-out test) ”:   Hold a 6.41 cm diameter disc on the caliper jaws and point the jaws vertically down
Was. The jaws were then gradually opened. The position of the caliper where the disc fell
Is the "falling" thickness.   For example, in Examples 1-106, the surfactant-lubricant was retained on the fibers.
A single layer of a PET substrate was used. This is hot-tested to a value of 0.18 to 0.22 cm by drop test.
Compressed. 0.9mm clear on assembly inserted into filter housing
Lance was allocated. Examples 107-168 are similar, but before hot pressing.
The surfactant was removed.   Example 169 et seq. Were prepared using the following.   (a) One layer of PET upstream, hot compressed to a nominal drop of 0.075 cm.   (b) Downstream, in the following order, one layer of PET and one layer of PBT substrate, both of which are hot
Compressed, with a nominal drop of 0.10cm Form a layer.   (c) When assembled into the filter housing, fill the assembly (a) and (b)
The space allocated was 0.15 cm.   2. The second element is a micro-aggregate removing element, the function of which is particularly a relatively old PRC.
The purpose is to remove aggregates formed therein.   The preferred material for making this device is a melt blown PET web.   To be used in Examples 1 to 168 except where indicated, this element is
It consisted of the following:   Produced using three layers of web with average fiber diameters of 15, 10, and 7 μm respectively
Preformed layer.   Single preformed layer of web with an average fiber diameter of 4.5 μm.   Single preformed layer with an average fiber diameter of 4.5 μm with a higher density than the preceding layer.   Example 169 When used below, do the microaggregate removal elements in the order of flow:
Had become.   First, second and third layers with average fiber values of 3.5, 3.0 and 2.6 μm respectively, assembled
Sometimes, it is hot-pressed with the following adsorption element to form an integrated element. Example of density after compression
Smaller than 1 to 168.   3. The main function of the third (adsorption) element is mainly by adsorption and secondary filtration
Is the removal of white blood cells.   For Examples 1 to 168, the elements were bonded together by hot compression 2.6 or 4.
Manufactured using multiple layers of 5 μm fibers. For example 169 and below, this device is 2.4μ
m fibrous web bonded together with a micro-agglomerate removal layer to form a seven-layer integrated assembly
It was manufactured using what formed.   The numerical values in the above and examples are changed within a certain range as long as they conform to the purpose of the present invention.
be able to. Whether any particular change will result in a completely equal product
A test is required to determine Therefore, the exact fiber diameter, weight and density of the layer
Equal, or perhaps even better, results with minor changes in degrees, thicknesses and numbers
However, what is shown here is a design that meets the objectives of the present invention.
The device manufactured by such a change is a guideline for the present invention.
Should be understood to be included in the range.   All elements, except the gel prefilter, are preferably about 55 dynes / cm or less.
Above, but surface treated to CWST not exceeding 75-80 dynes / cm.Improving adhesion by grafting during hot pressing   A melt-blown fiber mat that has been surface treated to increase the CWST value by 5 dynes / cm or more.
The hot-pressed element preform manufactured using the
For robustness and fraying compared to discs manufactured by raft
It is clearly better with respect to resistance. For this reason, graft before hot pressing
It is preferable to use a hot-pressing device after grafting.
Therefore, it can be manufactured.   In the example of the present invention, an integrated element combining pre-filtration, gel removal and adsorption is formed.
Although hot compression was adopted for this purpose, other means such as resin bonding
It is also possible to form an apparatus using this or a similar method.
In range.   It is preferred to use meltblown fibers in all but the first layer of these devices.
Good. Finer meltblown fibers or other finer fibers (for example,
Fiber produced by mechanically fibrillating fibers)
If they do, it is within the scope of the present invention to use them for the elements of the leukocyte removal device.
You.Sealing the preformed element into the housing   The housing is generally disc-shaped, or more precisely partly in the form of a cylindrical element
It is preferred that Preformed element is also 0.1 to 1% of the dimensions shown in the inner table of the housing.
It is formed in a large regular cylindrical shape. Good seal is obtained when assembled and detected during use
There is no appreciable bypass formation.CWST of device   Pre-filter element for gel (1st) has no problem even if it has low CWST
In fact, that condition will work better. Clogged or near clogged
Conduct sufficient PRC to the device to produce the material, then cut and reduce the pressure drop of each layer.
Examination of the results below showed that increasing the CWST of this layer resulted in little improvement.
Not shown. Microaggregate filters and adsorption sections are preferred
Is CWST 55-80 dynes / cm, more preferably 59-73 dynes / cm, even more
Preferably it is modified to 62-68 dynes / cm.Red blood cell collection   Hematocrit for PRC in bag effluent from device according to the invention
Significant change in hematocrit when compared to No conversion was observed.   Some of the incoming blood or PRC is lost due to retention in the removal device. this
Losses are reported as retained volumes.Judgment of characteristics of porous substrate by physical characteristics   An equation for predicting the pore diameter is provided. These equations are generally
The fiber diameter, bulk (apparent) density and fiber density are used. For example, one is between fibers
Is calculated. But the average distance between fibers is important for predicting performance
Not a factor. Controlling performance in any liquid flow path is the largest that exists
Pores (one or more) that can be deformed into "particles" such as leukocytes
This is especially true for Fiber mat manufactured by melt blow method
In this case, the fibers are parallel to the plane of the surface, but are otherwise randomly arranged and
The distribution of the earth size is extremely wide. Other means for producing fiber mats,
For example, air deposition or formation on a Ford Linier screen
Produces a noise distribution. In these situations, the average distance between fibers is clearly predictable for performance.
Is a poor factor. Pore from data on fiber diameter, fiber density and bulk density
-Various other formulas that can calculate the diameter have been proposed, but the applicant has
For more than 40 years to devise means of manufacture and use,
Find no useful formula for calculating a priori the effective pore diameter of a filter
Was.   For example, measurement of fiber surface area by gas adsorption-commonly called "BET" measurement-
Is a useful technique. Surface area is white by adsorption This is because the amount of fiber surface effective for removing blood cells is a direct indicator. Melting blow
-The average fiber diameter can be calculated using the surface area of the PBT web: (1.38 in the formula is the fiber density of PBT, g / cc)   The area of the fiber is πdL = A_f(2  L in the formula, the total length of the fiber per 1 g,         d = average fiber diameter, cm,   And A_f= Fiber surface area, cm^Two/ G.   When the unit of d is μm, A_fIs in M^Two/ G (square meter / gram)
Yes, hereafter.   The second property required to properly represent a porous substrate so that it can be reproduced is po
Arc diameter (Dp). To this end we used the improved OSU-F2 test method.
This test method and its use are described in the section entitled Examples below.   Other properties that describe the porous substrate include apparent (bulk) density (ρ), (g / cc), fiber density
Degree (same as g / cc), base element thickness (t) cm, effective for filter element flow through
Cross section (Ac), cm^Two〔all, 32 or 62cm per example^Two] And CWST, dyne / cm. these
Behavior can be predicted when used for leukocyte depletion by specifying the parameters of
The filter of the adsorbent element is defined as:   (a) A_f(Fiber surface area / g) multiplied by filter weight (Ac × t × ρ)
The fiber surface area is effective for removing leukocytes by adsorption in the filter.   (b) An object of the present invention is to provide a filter that allows two units of PRC to pass through without clogging.
is there. As the cross-sectional area Ac increases, the flow rate per unit area decreases. Obedience
Therefore, the tendency of clogging is reduced.   (b) Dp and t define the efficiency with which leukocytes are removed by filtration.   The fiber filter-adsorbent element used for leukocyte depletion depends on the density of the fibers that make it.
Degree, and Ac, A_f  Dp, ρ, t and CWST are assigned to each part or part
It is specified by specifying the subassembly.   The present inventors have found that leukocyte removal is partially absorbed by the leukocyte removal fiber filter.
It has been found that this is achieved by dressing and in part by filtration. Important views of the invention
The point is to carefully define and control Dp and to pre-filter in a new and well-defined manner.
By performing the filtration, substantially compared with the filter which mainly depends on the adsorption,
A lower volume filter is obtained. This allows PRC or blood
The liquid holding volume is reduced (which is economically important when using PRC),
Conventionally used for Higher efficiency and better capacity are obtained compared to the best similar devices that have been.   Previously used equipment relied almost entirely or largely on adsorption,
Although relatively large, the device of the present invention employs Dp as a basic design guide,
It is substantially more dependent on filtration and therefore smaller.   The following examples are provided for illustration.Example   The PRC and whole blood used in these examples are blood that meets American Blood Bank Association standards.
Obtained from a bank. Those using CPDA-1 anticoagulants are Greater New
From the York Blood Program (Melville, NY)
Red blood cells suspended in saline using the Adsol anticoagulant system
Red Cross Brand Services, Rochester, New York
Rochester). Unless otherwise indicated, the tests in the Examples
Made with   Blood products, including PRC, were not obtained from the blood bank within two days after blood collection.
This is the minimum time required to check for the presence of an infectious agent.   All white blood cell counts should be performed by a
Performed and reported data is an average of at least two times by different technicians.
When testing adult-sized devices, use two consecutive bags of PRC or whole blood.
Blood weight (or volume) is reported as the sum of two
Pre and post leukocyte counts are reported separately for each bag. It is. For child size units, use one PRC or whole blood bag and process
Pre and post leukocyte counts represent the first half of the bag contents and the back half of the bag.
Reported separately for a second sample.   Inaccurate when using automatic counter on leukocyte-depleted filter effluent
Results were obtained. This is because the auto-counter is normal blood and normal white blood cells of normal PRC.
This is because it is designed to operate within the content range. Therefore the normal of the automatic counter
The operating range is 10 to 1000 times the level achieved in the example shown here. Therefore these low
Automatic counter data at high levels is not reliable. Therefore, counting is a normal
Performed manually by bar counting.   Bag (ie, influent) counts were measured using a ZM Coulter counter.
Was. The usual centrifugation method was used for the measurement of hematocrit.   In the example of the present invention, the start-up time is about 0.2 kg / cm for a bag of blood or PRC.^TwoPressure
The force was measured manually or with a pressure cuff applied. About 0.2kg / cm^Twoof
Pressure is generated when three randomly selected laboratory technicians press the blood bag by hand.
It was determined that it was within the range of the fogging pressure.   The start-up time is such that the test housing is filled with fluid and the inverted drip chamber is filled with fluid.
To¹/_Three(Approximately 3 ml) is defined as the time required to fill.   For Examples 1-168, the pressure head during the test was for adults (62 cm^Two4) For equipment
cc / min, for children (32cm^Two) Equipment required to maintain 2 cc / min flow rate
Was adjusted. During the test The pressure required to maintain this flow rate of 4 or 2 cc / min is a fluid pressure head of 100 cm,
That is, about 0.1 kg / cm^TwoThe flow rate is below 1 or 0.5 c / min respectively
The pressure was maintained until lowered, at which point the test was terminated. Therefore, adult
Luter final flow exceeds 1 cc / min or 0 for child sized units.
If more than 5 cc / min is reported, all blood is removed from the bag and repacked.
The installation did not clog. If the flow rate during the test drops below the above limit, the device
It is considered clogged and the amount remaining in the bag is reported.   For Examples 169-210, the pressure head during the test was required to maintain a flow rate of 6 cc / min.
It has been adjusted to the essential ones. The pressure required to maintain a flow rate of 6 cc / min during the test
Body pressure head 115cm, ie about 0.11kg / cm^TwoIf it reaches to 1cc / min
This pressure was maintained until the flow decreased, at which point the test was terminated. In the bag
If the volume of the remaining PRC is less than 30 cc, the filter has that PRC unit.
We thought that it had effectively conducted. Testing has shown that this can occur during bedside use.
This is because it was determined that the result was possible.   Approximately 5 ml of a minimum sample is taken from each bag of blood or PRC and measured for influent characteristics.
Used for determination. If two or more units of blood or PRC are used, send them sequentially
, Sampled separately and assayed.   The white blood cell (WBC) count is expressed in μl of fluid (1 μl = 1 mm^Three) Reported as per hit. Total
Dilution for the number is from 1 count for relatively fresh blood = 100 WBC to 10
Test using blood from day 14 About 1 count = 50 WBC.   Unless otherwise indicated, the elements used in each example were disc-shaped and child-sized devices.
64.1 mm in diameter for use in devices, and during assembly for use in adult-size devices.
The diameter was 88.9 mm. A laminated element with a total thickness of te is assembled into the housing,
As shown in FIG. 1, the ridges 26 of the two plenums,
Between the tip of the ridge 34 of the exit plate 31 and the tip of the ridge 34 of the exit plate 31 is t_hMet
. After puncturing the blood bag, by hand pressure applied to the bag, or about 0.2 kg / c
m^TwoThe filter was started by a blood pressure cuff pressurized to. After that, whole blood
Indicates that packed red blood cells are conducted by gravity and product assays are described above in this chapter.
Was performed in the manner described in (1).   Red blood cell loss due to adsorption was too small to be detected unless otherwise indicated.
For Examples 169-210, the loss on hold is (47t_h+ Calculated as 12) cc.   The pore diameter of the filter substrate was measured by the modified OSU F2 method and the
99.9% are reported as the diameter of the hard particles removed. For pore size measurement
The F2 test was developed at Oklahoma State University (OSU) in the 1970s.
This is an improved method for two tests. In the OSU test, artificial contaminants in the appropriate test solution
The suspension is passed through the test filter, during which the upstream and downstream
Sample fluid continuously. The sample is selected in advance by an automatic particle counter.
Measured for the content of five or more particle diameters, and
The ratio is automatically recorded. This ratio is beta in the filter industry Also known as the ratio.   The beta ratio for each of the five or more diameters examined is the vertical axis, and the horizontal axis is
Usually, the vertical axis is a logarithmic scale, and the horizontal axis is log^TwoA graph that is a scale
To plot. Then a smooth curve is drawn between each point. Then within the range tested
The beta ratio can be read from this curve for any diameter of. specific
The efficiency at the particle diameter can be calculated from the beta ratio by the following equation.   Efficiency (%) = 100 (1-1 / beta)   For example, if beta = 1000, then efficiency = 99.9%.   Unless otherwise indicated, the removal rates quoted in the examples shown here are beta = 1,000
And therefore the efficiency at the quoted rejection is 99.9%.   Efficiency in the range from 1 to 20 to 25 μm is required for the improved F2 test, and the AC fine test dust
A natural siliceous material supplied by AC Spark Plug Company
Aqueous suspensions of dust were measured using as subject contaminants. Underwater dust suspension
The suspension was mixed until the dispersion was stable before use. Test flow rate about 474-1076 l /
Min / m^Two(Filter area) (44-100 l / min / ft^Two), That is, do not affect the result.
Range.   The data applied to Examples 1 to 168 are shown below:   a) The formulas for the examples and the data on the absorption capacity and filtration capacity are shown in Table A.
It is.   b) The behavior observed when processing blood products with filters is shown in Tables 1-16.
Is shown.   The data in Table A is shown below:   Column A lists example numbers and table numbers where blood data is shown.   Column B lists the order of the individual filtration elements used for each of the assemblies tested.
I can. An upstream gel pre-filter element (number 1) is indicated in Examples 1-168
Unless otherwise described, it is made of needle-punched PET bonded with acrylic. All other elements are
It is made of melt blown PBT. The micro-aggregate removing element is composed of layers 2a, 2b, 2c, 3 and 4
And 2a, 2b and 2c are hot pressed together to form a subassembly,
Layers 3 and 4 are separately hot pressed. Layer 5 is formed as a single layer by hot pressing
It is the formed adsorption element.   Column C shows the fiber surface area (m^Two/ G unit). In column D, the apparent (bulk) density (
g / cc unit). Column E lists the thickness (cm) of the element. Each element in the F column
Per fiber surface area (m^Two) (A_t= A_f× ρ × t × 62). G is the surface area BE
Fiber diameter calculated from T measurement value (fiber diameter = (0.345 A_f)^-1μm). Was
Exclude the gel prefilter estimated by microscopy. OSU F2 in the H column
List the pore size (μm) measured by the test. In this case, it is estimated by microscopy.
Exclude the pore diameter of the gel prefilter. Column I shows the CW for each layer.
The ST value is listed.   Examples 1-18 were prepared according to the instructions in Table A. The listed CWST values change the surface.
It is a base material that has not been converted.   Examples 19 to 34 shown in Table 2 were also performed using five layers. The first of these is
Equivalent to Examples 1 to 18; Equivalent to that of Examples 1-18 except that radiation grafted CWS of 59 dynes / cm
Had been T. The fifth preform is equal to that of Examples 1-18, except that
Had been radiation grafted to a 65 dynes / cm CWST.   Prepared in a manner similar to Examples 35-38-Examples 19-34 shown in Table 3, except that the third layer and
The four layers were radiation grafted to a CWST of 75 instead of 59-CPDA-1
Tested with whole blood containing additives. The average efficiency for the second unit is in Examples 19-34
Substantially lower than the results obtained (since whole blood is a diluted form of PRC)
It is meaningful to compare the results obtained with whole blood with those obtained with PRC).   Examples 39 to 42 shown in Table 4 were tested using packed erythrocytes.
This shows the effect of increasing the CWST of the child. The micro-aggregate removal element is 81 dynes / cm CWS
T, while the adsorption element exhibited a CWST of 75 dynes / cm. Compare with Examples 19-34
As a result, both capacity and efficiency were reduced.   Examples 43 and 44 shown in Table 5 correspond to the microaggregate removing element and the adsorption of the apparatus of Examples 19 to 34.
The effect of increasing the CWST of the device is further shown. Examples 43 and 44 are equal to Examples 19-34 but
However, the CWST of the second layer is 81 dynes / cm, and the third and fourth layers are 77 dynes.
/ CWST, and the adsorption element shows a CWST of 81 dynes / cm. Second unit
This shows that the efficiency for PRC is greatly reduced.   Examples 45-48 shown in Table 6 were performed using the structures of Examples 19-34, except that
3, 4, and 5 layers of the fiber surface had been modified to a CWST of 94 dynes / cm or more.
These data are from Examples 19 to Indicates that both efficiency and capacity were lower than those reported in Table 2 for 34
.   Examples 1 to 18 in Table 1, Examples 19 to 34 in Table 2, Examples 35 to 38 in Table 3, Examples 39 to 42 in Table 4
Examples 43 to 44 in Table 5 and Examples 45 to 48 in Table 6 all have the same basic structure,
Manufactured using WST ranging from 52 dynes / cm (unmodified) to 94 dynes / cm or more
Was done.   The results obtained range from suboptimal at 52 dynes / cm to 59-65 dynes / cm.
Optimal, for CWST values in the range of 65-75 to 95 dyne / cm or more,
It varies to a slightly lower potency in both efficiency and capacity. Examples 19 to 34
Shows a light preferred shape.   Nevertheless, all of these examples are now available for bedside red blood cell administration.
It should be noted that it is superior to all devices available.   Examples 49 to 52 shown in Table 7 are the same as Examples 19 to 34 for child size, except for the following:
Manufactured: In Example 49, the gel pre-filter element was omitted. Example 50 also has a second layer
Omitted. In Example 51, the third layer was omitted in addition to the above two layers. Example 52 uses only the adsorption element
Was. As can be seen in Table 7, the volume passed before clogging
The average was reduced from 308 ml to 116, 46, 35 and 34 ml, respectively. Therefore
The excellence of the light step-pore pre-filtration system is clearly shown.   Examples 53 to 56 shown in Table 8 show the preferred thickness range of the gel pre-filter element.
This device is part of a study to determine the function of gels and very large aggregates.
Is suspended in the gel Removal together with small aggregates. These examples use about 23μm fibers
Needle-punched nonwoven fabric of high bulkiness manufactured by
Pre-compressed to a small thickness, and then further compressed to the specified thickness during assembly.
Was. The data in Table 8 are produced in the same way except for the thickness of the pre-filter element
This can be compared with Examples 19 to 34 described above. These data are less than 0.56mm thick
Indicates a decrease in capacity.   Examples 19-34 show a gel pre-filter element thickness of 0.90 mm. 0.65mm and 1.14
Numerous tests performed in mm show very close results. Based on these data
And the preferred range is about 0.6 mm or more.   The upper end of the range was not examined beyond the 1.14mm test. Based on post-test microscopy
Good results would be obtained with a rather thick first layer, ranging from 2 to 3 mm.
Believe. However, such a relatively large thickness results in an increase in the amount of storage.
It is not desirable because it seems. For example, the adult-sized Howe used in these studies
Jing (effective area 62cm^TwoIn the case of), when the thickness increases by 1 mm, the reserved volume increases by 6.2 cc.
I do. Any increase is undesirable.   The configurations of Examples 19 to 34 were adopted, and the gel pre-filter elements
Initial weight 11mg / cm^TwoAnd then 8.8 mg / cm^TwoElement and mirror after test
The test was compared. 11mg element (25% thick) is more space than necessary for collecting gel
And based on this, the preferred weight with 23 μm PET fiber is 8
.8mg / cm^TwoIt is. Use less weight However, the object of the present invention is to pass two units of PRC without clogging.
May not provide sufficient capacity.   As long as the average pore diameter is within the target range, gel diameters other than 23 μm
Can be used for pre-filters. Fiber with average diameter different from about 23μm
When used, the weight per unit area W, which gives approximately equal pore diameters, is
The fiber can be calculated with appropriate accuracy by the following equation.     And 20 <d <26   It is easy to measure the pore diameter in the area where the gel pre-filter is effective.
Cannot be obtained. The specific material compressed to 0.9 mm thickness is a gel preform according to the invention.
Satisfaction to prove that the filter has a pore diameter within the preferred range
The means to be performed is to use the following operation.   Weight 8.8mg / cm^TwoTest material manufactured in immersion in isopropyl alcohol solution
The material is then tested to a thickness of 0.075 cm,
While monitoring, air pressure can be applied and inserted into the holder. Within the above parameters
To function, the pressure generated at an air flow rate of 0.5 cm / sec should be about 3.5 to about 8.5 cm water column,
More preferably, it must be within the range of about 4 to about 6.5 cm water column.   Example 57 describes a means of further increasing the resistance of the device according to the invention to clogging.
Target. This means that the pore size of the microparticle agglomeration
It is achieved by changing the target.   Examples 58-65 were prepared as shown in Table A and their behavior during PRC processing
Are shown in Table 9. The first four layers are equal to the first four layers of Examples 19-34. The adsorption element
Consists of 5 layers of 4.5 μm PBT fibers, which were radiation grafted to 59 dynes / cm
CWST and then hot pre-compressed to a single density of 0.252 g / cc, 0.251 cm thick
Form one preform, BET fiber surface area is 1.77m for adult size^Two, F2 Po
The average pore size or average pore diameter was 6.9 μm. The total fiber surface of the five layers is 4.
07m^TwoMet. The total volume of the five layers was 33.3 cc.   Similarly, Examples 66 to 73 shown in Table 9 are the same as Examples 53 to 65, except that the third preliminary
Shaped layer made from 4.5μm fibers compressed to 0.069cm thickness and 0.18 / cc density
The F2 pore diameter value was estimated to be 15 μm, the fourth layer was 0.061 cm thick and
Manufactured using 4.5 μm fiber pre-compressed to a density of 0.21 g / cc and estimated F2 pore
-It had a diameter of 12 μm. Radiation grafted 59 dynes / cm CWST
The adsorbing element consisting of 5 layers of 4.5 μm diameter web was compressed to a thickness of 0.277 cm.
, A single preform with a density of 0.229 g / cc and an F2 pore diameter of 7.4 μm.
Table 9 shows the obtained data.   The data for Examples 58-65 and 66-73 are given in Table 10 for Examples 19-34 and 96-97.
Data. The performance with respect to leukocyte removal efficiency of Examples 19-34 is clearly
Better than that of Examples 66-73. Example 58-65 group and 66-
The effective surface area for leukocyte removal by adsorption in group 73 is equal, i.e. both
Fiber surface area 4.07m^TwoThis is unexpected because The significant difference between the examples of these two groups is that the pore diameter (6.9 μm) of the fifth element of Examples 58 to 65 is equal to that of Example 6.
6 to 73 (7.4 μm). Therefore, the smaller the pore diameter,
Efficiency is expected to improve. This conclusion compared the groups of Examples 19-34 with the groups of Examples 58-65
If confirmed. The surface area of Examples 19-34 was 3.29 m according to the BET surface area measurement method.^TwoIn
, I.e. smaller than those of groups 58-65 (4.07 m^Two). Moreover, Examples 19 to 34 are better
With high efficiency. Also in this case, the pore size (6.1 μm) of the downstream elements of Examples 19 to 34 was set to Example 66.
It is smaller than that of the 7373 group (6.9 μm). Therefore the pore size of the adsorption elements of Examples 19-34
Factors That Smaller Contributes to Superior Performance Compared to Larger Pore Diameter Devices
Can be drawn.   Examples 96 and 97, shown in both Tables 10 and 15, further illustrate the pore size of the downstream element.
Prove the effect. Explanation for Tables A and 10 and Table 15
As described in the section below, the structures of Examples 96 and 97 differ from Examples 58-65 only in the following respects:
Is different from:   (a) The adsorption element contains less fiber and the element assembly has a total surface area of 3.13m^TwoTo
Have.   (b) The average pore diameter of the adsorption element is 6.6 μm.   Examples 96 and 97 show that the effective fiber surface area for adsorption is substantially smaller and their thickness
Is significantly better than Examples 58-65 despite the smaller (0.145-0.251 cm)
Is shown. This improvement is due solely to the smaller pore diameter of Examples 96 and 97
I think that the.   Examples 103 to 106 shown in Table 13 are the same as Examples 19 to 34 in Table 2. Manufactured, but with adsorber elements of higher density and smaller Dp (pore diameter)
Compressed. Using PRC derived from blood collected two to four days before the test,
, Four tests of each density were performed. This relatively fresh PRC is older blood,
For example, they are more clogged than those used at least in part in tests reported elsewhere.
Is less likely to occur.   The data in Table 13 shows that when used for fresh blood, a small pore
Can be used, passing 2 units of PRC before clogging
The goal can be achieved. In addition, this series of tests is 100% leukocyte recovery rate.
showed that.   Within 4 days before blood transfusion Use for PRC derived from collected blood
Therefore, a lower limit of 4 μm is preferred, and a lower limit of 4.2 μm is more preferred.   Thus, the pore diameter may have a strong effect on leukocyte removal efficiency. This
This is in contrast to the idea that leukocyte removal by fiber substrates is a function of surface area only.
Therefore, it was unexpected knowledge. As mentioned earlier, granulocytes are larger than red blood cells,
Limbocytes, which make up 20-40% of white blood cells in normal whole blood, are comparable in size to red blood cells.   Utilizing this finding, the blood retention volume was about 8% compared to Examples 58 to 65, and compared to Examples 66 to 73.
A total reduction of 16% was achieved. This is a significant decrease, and in fact
Approximately US $ 3-6 for transfusion of 1 unit based on hospital and blood bank prices
Decrease.   Examples 74 to 78 shown in Table 11 show that the PRC flow rate was 4 cc / min. Effective flow area 32cm^TwoIn the housing of -equivalent to a child-sized device in this respect-
However, the flow rate and flow rate are the same as in the case of adult size units of Examples 19 to 34 (preferred shape).
And a total amount of fibrous substrate equal to that contained in it, this was
With the use of eight layers as follows: the first and second layers were Examples 19-34, respectively.
Equal to the first tier of the group. The third layer was similar to the second layer in Examples 19-34, except that the fibers
Substrates with diameters of 15, 10 and 7 μm are each 15 mg / cm^TwoUse, these are deposited, heat
During compression to form a 0.15 cm thick disk. 4th, 5th, 6th and 7th layers
Similar to layers 3 and 4 of Examples 19-34, except that they are compressed and
Preforms having densities of 0.18, 0.20, 0.22 and 0.23 g / cc were formed. 8th
The layers and final layers had fiber diameters and densities equal to those of Examples 19-34, but double weight
Amount of fiber was compressed into a preform that doubled in thickness, or 0.304 cm
. The data obtained from testing these assemblies is shown in Table 11. Capacity is fresh
Appropriate for surrounding blood, but unsuitable for blood older than several days
It is. Comparing these data with those of Examples 19-34, the same total amount and type of
The advantage of using each fiber substrate for larger cross-section devices becomes apparent.   Examples 79 to 85 shown in Table 12 show the data obtained when "Adsol blood" was used.
Show. Except for the examples in this group, all whole blood and packed red blood cells
Was performed using CPDA-1 treated blood. CPDA-1 is transfused into the patient
Anticoagulants designed to extend the time period during which red blood cells are effectively maintained And nutrients. COPA-1 whole blood or CPDA-1 PRC
Red blood cells are suspended in the plasma; the PRC red blood cell concentration is higher (hema
Tocrit is generally in the range of 70-80%) and its viscosity is very high,
The volume for C is for whole blood with lower hematocrit and much lower viscosity
Capacity tends to be lower.   In recent years, a new group of blood products has been developed, in which centrifugation
After concentrating erythrocytes to almost 100%, compared to CPDA-1 system, erythrocytes
Resuspend them in saline solution containing preservatives to extend the useful life of the spheres. these
Family of blood products is defined as "a product in which red blood cells are suspended in a physiological fluid medium"
. The Adsol system is one of this type of system currently used to some extent in the United States.
It is considered to be representative of others in the country, Europe and Japan.   This type of blood product contains only a small percentage of the original plasma and low red blood cells.
Viscosity is lower than that of whole blood because it is resuspended in a viscous physiological fluid
. Examples 79-85 use devices of the shapes used in Examples 66-73, and all devices are child-sized.
It was carried out. The devices of Examples 79-85 and 66-73 are highly preferred forms of the invention
Despite the fact that these data are not
Shows performance without any hindrance.   Examples 19-34, 58-65, 66-73 Other configurations of the device include CPDA-1 anticoagulant.
Was manipulated using whole blood. Behavior with respect to capacity and efficiency is generally
Similar to the data reported for   Examples 86-95 are shown in Table 14. Example 90 was not actually performed;
The data is the average of Examples 19-34. Examples 86-89 and 91-95 were performed and were similar to Example 90.
However, the density and thickness of the adsorption element change with the weight kept constant.
I let you. As can be seen in Table 14, pore diameter is an important efficiency determinant,
For the PRC of the first unit, from 87% at a pore diameter of 7 μm to 6.2 μm.
At 99.2%, and at 100% at 6.1 μm. About the 2nd unit PRC
The leukocyte removal efficiency also varied in parallel, from about 70% at 6.7-7 μm to 6.1%.
It varies up to 99.6% at μm and 100% at 6.0 μm. These data
From, 25mg / cm of 2.6μm diameter fiber^TwoAbout the adsorption element manufactured using
-A preferred upper limit for the diameter is about 6.7 μm, and a more preferred upper limit is 6.3 μm.
Is allowed.   For pore diameters of about 6.1 μm or less, all examples in this group are based on 2 units of PRC.
100% leukocyte removal efficiency qualitatively, with slight clogging at a low level of about 5.5 μm
There are some satisfactory data. Thus, the preferred pore diameter range is about
It is 5.5-6.7 μm, and a more preferred range is about 5.8-6.3 μm.   Examples 96-101 are shown in Table 15 and described in Table A. These examples are the same as Examples 58-73.
Except that the downstream layer has 3 layers of 4.5μm fiber instead of 5 layers
And densified using hot pre-compression. Child size 5 used
The total surface area of the element is 1.51m^TwoFor comparison (see Table 10)
3.13m^TwoConvert to As can be seen in Table 15, the pore size is about 6.6 μm or less.
And both the first and second units A removal efficiency of 100% was obtained for each of Examples 58-65 in Table 10
Lower efficiency occurred at .255 g / cc and pore diameter of 6.9 μm, and
Even lower efficiency at a density of 0.229 g / cc and a pore diameter of 7.4 μm for Examples 66-73
Is compared to the occurrence of From these data, the upper limit of the pore diameter
A preferred value is about 7.5-8 μm, with a more preferred value appearing to be 6.6 μm.
If it is less than 6.6 μm, the efficiency is maintained at 100%, but the frequency of clogging will increase.
As a result, a preferred lower limit is about 5 to 5.5 μm, and a more preferred lower limit is 6 to 6.5 μm.
It is.   Examples 19-34, 58-65, 66-73. 86-95, and 96-101 together, preferred
An F2 pore diameter range of 5.0-8 μm, more preferably 6-6.7 μm, is shown. this
These preferred ranges will be described in detail below.Preferred range of pore diameter   As we consider the data of Examples 1-107, we determine the preferred range of pore diameters.
A number of conclusions are drawn.   (a) Based on Examples 102-106 in Table 13 tested using only fresh PRC, 4 μm
The lower limit of m was preferred, and 4.2 μm was more preferred.   (b) Based on Examples 86 to 95 in Table 14, the upper limit is preferably 6.7 μm, more preferably 6.3 μm.
I thought it was good. The lower limit is preferably 5.5 μm, more preferably 5.8 μm.
Was.   (c) The data shown in Table 10 is very preferred and is narrower than 6.1-6.6 μm.
The results for Examples 66-73 in Table 9 are also relevant to this specification.
Whatever product you get Is much better, so a lower limit of 7.4μm is justified.
Be transformed into   (d) Finally, consider the discussion of Examples 19-34, 58-65, 66-73, 86-95, and 96-100.
In this case, a preferable range of 5 to 8 μm and a more preferable range of 6 to 6.7 μm are shown.   Regarding the lower limit, some doctors are fresh for patients with disability, such as thalassemia.
The preferred lower limit of pore diameter should be 4 μm, as we prefer to use only blood
.   In consideration of the above other considerations, a preferable range is 4 to 8 μm. Recently collected blood
The lower part of this range is preferred for use in mixed PRC, while the upper part
Preferred for use in RC.   The devices used for Examples 107-168 (see Table 16) were prepared analogously to Examples 19-34, except that
The substrate used in the production of the gel prefilter was rubbed and rinsed,
No sexual agent was included. Examples 107-119 were made without surface modification and had a 52 dynes / cm
It had a CWST. In Examples 120 to 168, radiation
(HEMA and MA and t-butyl alcohol to aid wetting)
(Using a small amount of mixture), their CWST values ranged from 63 to 109 dynes / cm.
It is composed of a modified element. No surfactant present in gel prefilter
Except that their CWST values fluctuated, Examples 120-168 were equivalent to the structures of Examples 19-34
.   Examples 107-168 are all 100% leukocyte depletion for the first PRC unit conducted.
In the second unit, the average efficiency in each group listed in Table 16 is 96%.
Crossed.   In Table 16, when the CWST of the filter substrate is 75 dynes / cm or less,
Clogging occurs relatively frequently before conducting the two units. This is the surface of PRC
It is related to tension, which is 73 dynes / cm for plasma and for red blood cells as described above.
It is reported to be 64.5 dynes / cm.   Based on the data in Table 16, the preferred values for the CWST of the filter substrate are
63 dynes / cm or more; more preferred value is 70 dynes / cm or more;
A good value is 75 dynes / cm or more. But data on all examples is currently
It should be noted that it is better than any of the products on the market.   CWST54 dynes / cm filter assembly for the manufacture of Examples 1-210
Produced satisfactory results; however, only 2 units differed from untreated PBT fibers.
CWST values are considered to be marginal for maintaining consistent performance, and
Dyne / cm is a less preferred CWST value.   The needled web used in Example 169 and below was removed before use to remove fiber lubricant.
Rinsed, rinsed with water, and then dried. The melt blown web used is especially
Radiation grafting was performed unless otherwise indicated to give a CWST of 64 dynes / cm.   Preform thickness is 4.3 g / cm using an anvil with a diameter of 7.7 cm.^TwoAt
Measured.   The filter assembly used in Examples 169-186 consisted of three layers of preforms
Was.   For the first preform, the aforementioned 23 μm needle non-woven fabric The web was hot calendered to a thickness of .076 cm. About the second preform
Average fiber diameter of 23 μm, 0.0077 g / cm^TwoA layer of needled nonwoven web
Average fiber diameter of m, 0.0081 g / cm^TwoOn a non-grafted melt-blown web of
The assembly was hot calendered to a thickness of 0.102 cm. The above two types
Combine the preforms in the above order, pre-wet with isopropyl alcohol,
It ventilated at 0.5 cm / sec. The pressure drop for 10 of these assemblies is 5-7 c
m water column.   For the third preform, seven layers of melt blown web were used. These are in order
The following were: one layer of 3.5 μm diameter fibers, .0069 g / cm^Two; One layer diameter 3.0μm
Fiber, .0052g / cm^TwoOne layer of 2.6 μm diameter fibers, 0.0063 g / cm^Two; And 4 layers straight
2.4 μm diameter layers, .0061 g / cm for each layer^Two, All seven layers are curled as an assembly
It has a thickness of 0.296 cm and an average density of 0.145 g / cc.   In the above structure, the first and second preforms together form a first element;
Represented as a gel pre-filter element. The first three layers of the third preform are microscopic
Constructs an aggregate removal element, which also contributes to leukocyte removal by adsorption
. The last four layers of the third preform constitute the adsorption element.   The pore diameter of the three layers constituting the element for micro-aggregate and the pore diameter of the adsorption element
Open before hot pressing under each of the three layers for microaggregates to allow measurement of
A layer of non-grafting release disc with release pores was placed. These minutes of thickness .004cm
The release disk has an average pore diameter of about 100 μm or more, thus increasing the thickness Other than 3 × .004 = .012 cm does not significantly affect the performance of the assembly. like this
The filter assembly produced was used for all of Examples 169-210. This way
And each layer is easily separated for measuring pore diameter by OSU-F2 test
Was. Layer numbers 1, 2, and 3 of the third preform are about 19, 16, and 13 μm, respectively.
The remaining four layers have a pore diameter of 6.5 μm to 8.
It changed to 2 μm. Assembling three types of preforms gives a total thickness of t_eHold 0.474cm
Put them into the housing ridge-ridge-clearance t_hBuilt in at 0.444cm
As a result, the element assembly was compressed to 0.444 cm.   Examples 169-174 shown in Table 17 were performed using day 24 PRC. 6 tests
All conformed to the above criteria (ie, a pressure head of 115 cm water column and flow rate
<30 cc residue at 1 cc / min).   Examples 175-180 were performed using an average 34.5 day PRC; 5 out of 6 trials
Meets completion criteria.   Examples 181-186 performed using day 2 PRC meet the completion criteria and are more important
In particular, 100% leukocyte removal efficiency for the first unit and
The average efficiency is 98.8%.   Examples 1 to 168 describe devices used in removing leukocytes from PRC,
These examples are primarily intended for use with relatively fresh (recently collected) PRCs.
Thus, it is more suitable for applications using fresh PRC. Also used in Examples 1-168
Of the 100 units or more listed above, only 6 of the 20th day or more of the present invention
Was used for the type of filter that was the subject of. this Two of the six using PRC on days 29 and 30 before the complete supply of two units
Was clogged.   In US hospital practice, PRC anticoagulated with CPDA-1 is stored for 35 days
Use is allowed until later. For those who know the US hospital business, CP after 15-20 days
They questioned the proportion of DA-1 PRC used; their estimates averaged 40%.
Was. The same expert uses 2 units of PRC for 80% of all transfusions and 1 unit for the rest
It was estimated that only A relatively fresh PRC for most hospitals
Owns two types of leukocyte depletion devices, and other types for relatively old PRCs
Impractical. So in order to be practically more useful, bedside at the hospital
The device for use should be at or near the expiration date that can be used for transfusion.
Experience clogging of the device before supplying even 2 units of whole blood
Examples must be at most negligible. This device can be used for any number of days
High removal efficiency per PRC, preferably 99.5-99.9% per first unit conducted
As mentioned above, the second unit conducted must have 95-99% or more.
.   The test articles used in Examples 1 to 168 were needled nonwoven fabrics having the same fiber diameter and weight.
Is used for the production of pre-filters for gels, and the melt blown parts have a pore size range
And CWST are generally the same, but
And similar to the test articles of Examples 169-210.   The prefilters of Examples 1 to 168 use a single layer of needled nonwoven fabric,
The parts of the gel prefilter according to 0 are 2 A layer of needled nonwoven is used in addition to the third blown melt web. Further examples
The density of the gel prefilter according to 169-210 is substantially greater than that of Examples 1-168.
Crisp, the pore diameter is smaller.   In Examples 187 to 199 shown in Table 18, the gel prefilters of Examples 1 to 168
It was tested in combination with 69-186 microaggregate prefilters and adsorption elements.
This combination is called t_h= 0.372 cm housing for gel pref
The filter element was compressed to .09 cm as in Examples 1-168.   Therefore, Examples 187 to 198 show the structure of the pre-filter element and the adsorption element for micro-aggregates.
As in Examples 169-186, differing only in their gel pre-filters.
You. The average number of days of PRC used in the study was essentially equal for both, 29
.2 days and 29.3 days. The gel prefilters of Examples 169 to 186 are only 1 out of 12 cases.
Showed clogging with a 92% success rate. Prefilter for gel of Examples 1 to 168
Examples 187 to 198 combined with 5 showed clogging in 5 out of 12 cases, with a 58% success rate
. Thus, for the use of old PRCs, the gel prefilter table of Examples 169-186 was used.
Transcendence is clearly proven.   The pore diameter of the adsorption element of Examples 169 to 198 is larger than that of Examples 1 to 168, and 6.5 μm
The preferred pore diameters above are shown; Examples 1 to 168 are 4, 5 and 5.5 μm or less, respectively.
The above preferred range of pore diameters is shown.   The use of adsorption elements with smaller pore diameters has the effect of two units of older PRC
The effect on electrical conduction is shown in Table 19 Represented by examples 199-210. These are made in the same way as Examples 169-186, but only
The preform consisting of micro-aggregates and adsorption elements is hot to an average density of 0.192 g / cc
Compressed, the adsorber has pore diameters of 5.1, 5.2 and 5.2 μm in three tests.
Shown, this is the preferred range for relatively new PRCs derived from Examples 1-168
Is within.   T of the housing used in Examples 199-210_hThe setting is made with a pre-filter element for gel.
It was compressed to the same thickness as in Examples 169 to 186 when standing.   The average number of days of PRC used in Examples 199-210 was 29.2 days. These data are 12
Nine of the examples were clogged, indicating a 25% success rate. This is in Examples 169-186
Compared to the 92% rate, which is greater for the larger example 169-186 pore diameter.
Show good things. In conclusion, the preferred pore diameter range of the present invention is at least 5.2 μm.
is there.   Regarding the upper limit of this range, the pore diameter of the adsorption element is significantly larger than 10 μm.
Is expected to maintain substantially the same efficiency; however, for very old blood
In addition, instead of the advantage (if any) that the cases of clogging are further reduced
In addition, because of the disadvantage that the storage volume increases, the present inventors
A range of diameters was not selected. Nevertheless, 8.2μm or more, or 10μ
It is to be understood that devices including pore openings of m or more are also within the scope of the present invention.   Human blood, under certain conditions, both inside and outside the body, "roleaux"
Will form. This is 7.5μm diameter x thickness 2-3 μm red blood cells adhere to each other and exhibit a geometric shape resembling a series of coins
It is a word given to a state. Renny is a virus in the human body.
Tend to form as a result of flu or cold
Lack of passage through relatively thin capillaries contributes to muscle discomfort associated with these infections
There are some ideas to do it. Hair with a diameter of 7.5 μm or less under normal conditions in the human body
The tubules allow red blood cells to pass freely. This is because individual blood cells are easily deformed. ratio
If relatively old blood shows a tendency to form coins, this phenomenon is due to old blood
Requires larger pore diameter to prevent clogging of bright adsorption element
And seems to be involved in   At the beginning of this document, it is widely accepted that "leukocyte removal is achieved by adsorption rather than filtration.
It has been well received. "   According to the disclosure of the present invention, it has been confirmed that leukocytes are removed by adsorption.
Was also obtained. That is, especially for the relatively recently collected PRC,
The pore size of the final element is within the preferred diameter range and the PRC is
Gels, microaggregates and other components present in the PRC as obtained from
Leukocytes are equal or better as long as appropriate pre-filtration is performed to prevent
High efficiency and low blood loss due to retention, combined with adsorption and filtration
Therefore, leukocytes can be removed.

Claims (1)

[Claims] [1. An apparatus for reducing the leukocyte content of a blood product, comprising at least a first and a second
And a third synthetic polymer porous element, wherein the second element is interposed between the first and third elements, each successive element having a smaller pore diameter (pore diameter) than the preceding one. Wherein the first element comprises means for removing gels, the second element comprises means for removing microaggregates, the third element comprises means for removing leukocytes,
The above device, wherein at least one element is modified to exhibit a CWST of greater than or equal to 53 dynes / cm and less than 90 dynes / cm. 2. The apparatus of claim 1, wherein the third element has a pore size in a range from about 4 to about 8 microns. 3. 3. Apparatus according to claim 1 or claim 2 wherein the pore size of the single interposer gradually changes from about 25 µm to a pore size in the range of about 9 to about 15 µm. 4. Apparatus according to any of claims 1 to 3, wherein the apparatus consistently supplies at least 2 units of volume of blood product before clogging. 5. The porous element is the fibrous Apparatus according to claim 4 total surface of all the fibers is less than 4m ^2. 6. Apparatus according to any of claims 1 to 5, wherein at least one element is preformed to a controlled thickness before being assembled. 7. A housing including an inlet and an outlet and defining a fluid flow path between the inlet and the outlet, an upstream porous element, at least one intermediate porous element, and a downstream porous element, wherein the upstream element replaces the first element. Claim 1 wherein the intermediate element includes a second element, the downstream element includes a third element, and the upstream, intermediate and downstream elements are secured within the housing by an interference fit. Item 7. An apparatus for reducing the leukocyte content of a blood product according to any one of Items 6 to 6. 8. An apparatus for reducing the leukocyte content from blood products to be administered to a patient, the top
A housing having a bottom and a bottom , including an inlet and an outlet and defining a fluid flow path between the inlet and the outlet, and disposed within the housing across the fluid flow path and having an upstream surface and a downstream surface. A leukocyte-removing element comprising a porous substrate, the inlet communicating with the housing upstream from the leukocyte-removing element near the bottom of the housing, the housing facing the downstream surface of the leukocyte-removing element. And a wall defining the plenum, and a slot disposed on the wall and communicating between the plenum and the outlet to separate air in the blood product from the blood product,
The outlet is located near the top of the housing and the slot depth is
The apparatus as described above , wherein the depth is greater than the depth of the system. 9 . 9. The apparatus of claim 8 , wherein the housing has a generally circular shape and the slot extends from a top of the housing along at least a portion of a vertical inner diameter of the housing. 10 ． A disk-like element having a leukocyte removal element disposed within the housing and having an upstream surface and a downstream surface, the housing further comprising an inlet section facing the upstream surface of the element and defining an inlet plenum; and An inlet section including a wall facing the downstream surface and an outlet section including a slot, the inlet extending vertically along the outside of the inlet section, and opening at the top of the inlet ridge and extending through the inlet ridge. A ridge extending vertically along the outside of the exit section and including a passage communicating with the inlet plenum at the bottom of the housing, and a ridge opening at the bottom of the exit ridge and extending through the outlet ridge, Claim 9 or Claim 9 including a passage communicating with the slot near the top of the
The device according to item . 11 ． The inlet section includes a plurality of concentric grooves and an access extending between the inlet passage and each of the circular grooves, the circular grooves and the access collectively defining an inlet plenum, wherein the inlet plenum is located at the bottom of the housing. 11. The device according to claim 10 , wherein the device has a maximum depth near the entrance passage. 12 ． Includes a plurality of concentric grooves outlet section communicates with the slot, slots, extending from the bottom of the housing to the housing top, the range 10 of claims having a depth greater than the bottom at the top of the housing or Item 12. The apparatus according to Item 11 . 13 ． Housing further includes a cylindrical collar disposed about the disk-shaped leukocyte removal device, the sealing disc-shaped leukocyte removal device, the cylindrical collar, by being clamped or Ri fit fit between them The apparatus according to any one of claims 10 to 12, wherein : 14 ． An apparatus for reducing the leukocyte content of a blood product, comprising at least one element preformed from synthetic polymer fibers, wherein the surface of the fibers has a CWST of at least 53 dynes / cm and less than 90 dynes / cm. 15 ． An apparatus for reducing the leukocyte content of a blood product, comprising at least a first and a second
And a third synthetic polymer porous element, wherein the element is preformed to tightly controlled dimensions, density and pore size, with a second element interposed between the first and third elements. Wherein each successive element has a smaller pore size than that preceding it, the first element comprises means for removing gel, the second element comprises means for removing microaggregates, The above device wherein the third element comprises means for removing leukocytes. 16 ． Placed in the housing, prior to this placement, tightly controlled physical dimensions,
Density and saw including at least one synthetic polymeric nonwoven fibrous elements are preformed hole diameter, the at least one synthetic polymeric nonwoven fibrous element 53 dynes / cm or less
A device for reducing the leukocyte content of a blood product, wherein the device exhibits a CWST of less than 90 dynes / cm . 17 ． Apparatus according to any one of claims 14, wherein to paragraph 16 according performing the preformed by thermocompression. 19 . At least one device has a first monomer having at least one hydroxyl moiety and one moiety that can be activated by an energy source, and a second monomer having at least one hydrophobic moiety and one moiety that can be activated by an energy source. ranging first term in contact with a monomer claims are surface modified by exposure to an energy source, according to Section 14 or Section 16. 19 . A CWST of 53 dynes / cm or more and less than 90 dynes / cm has a ratio of 2-hydroxyethyl methacrylate which is a first monomer which increases CWST to methyl acrylate or methyl methacrylate which is a second monomer which lowers CWST. 19. The device according to claim 18 , wherein the device is made by: 20 . 20. Apparatus according to any of claims 1 to 7, 14 and 16 to 19 , wherein the CWST is in the range of 55 to 80 dynes / cm. 21 . 21. The device of claim 20 , wherein the CWST is in the range of 59-73 dynes / cm. 22 . 21. The device of claim 20 , wherein the CWST is greater than the surface tension of the blood product suspension medium fluid minus 15 dynes / cm. 23 . 15. The apparatus of claim 14 , further comprising a housing including an inlet and an outlet and defining a fluid flow path between the inlet and the outlet, wherein a leukocyte removal element is disposed in the housing across the fluid flow path. Or the apparatus according to paragraph 16 . 24 . 24. The device of claim 23 , wherein the outer edge of the element is cylindrical and the element is secured within the housing by an interference fit. 25 . Apparatus according to any pending volume 37 cm ³ paragraph 1 range of less that according to paragraph 24. 26 . Pending volume 20 cm ³ or less devices range 25 claim of claim is. 27 . The blood product comprising at least one preformed leukocyte removal means,
A method for reducing the leukocyte content of a blood product, comprising passing through a synthetic polymer element having a CWST of at least 53 dynes / cm and less than 90 dynes / cm. 28 . Passing the blood product through a device containing the porous element to reduce the leukocyte content of the blood product, and then passing a slot connecting the downstream surface of the device to an outlet located near the top of the device; In this slot, separating the air from the blood product , the porous element has a CW of not less than 53 dynes / cm and less than 90 dynes / cm.
A method for reducing leukocyte content of a blood product, the method comprising having ST . 29 . A CWST of 53 dynes / cm or more and less than 90 dynes / cm has a ratio of 2-hydroxyethyl methacrylate which is a first monomer which increases CWST to methyl acrylate or methyl methacrylate which is a second monomer which lowers CWST. 29. The method according to claim 27 or claim 28 , wherein the method is controlled by: 30 . 27. A method for reducing the leukocyte content of a blood product, comprising passing the blood product through a device according to any of claims 1 to 26 .