JP2006068618A - Filtering method and filtering system - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a filtering method for enhancing filtering efficiency using centrifugal force, and a filtering system. <P>SOLUTION: The filtering method is constituted so as to filter a liquid containing a physiologically active substance through a filter by using centrifugal force and includes a process (a) for applying pressure directly proportional to centrifugal acceleration to the liquid on the filter in addition to the centrifugal force directly acting on the liquid on the filter and/or a process (b) for making the pressure of a space on the secondary side of the filter more negative than that of a space on the primary side of the filter and applying the suction force to the secondary side of the filter to the liquid by the negative pressure. For example, the pressure directly proportional to the centrifugal acceleration is applied to the liquid as the centrifugal force acting on a loading matter of constant mass. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a method and system for filtering a liquid containing a physiologically active substance. More specifically, the present invention is a method for filtering a liquid containing a physiologically active substance, and includes a step of applying a force other than centrifugal force to the liquid existing inside the centrifugal direction with respect to the filter, The present invention relates to a filtration method that improves the filter permeation rate of a liquid containing the physiologically active substance, and a system for the filtration method. In particular, the method and system of the present invention are suitable for removing minute pathogens such as viruses from blood-derived components, and are particularly preferably used when blood-derived components from which pathogens have been removed are transfused into a patient.

Filtration using centrifugal force is widely performed, and the centrifugal force F at that time is expressed as follows: mass (m) of an object on the filter is m (kg), centrifugal radius is r (m), and angular frequency is ω (rad / s). ), It is represented by the following formula (1).
F = mrω ²
From the above formula (1), since the centrifugal force is proportional to the weight of the object existing on the filter, the permeation speed decreases with the transmission of the object on the filter after the start of the centrifugation. In this phenomenon, the permeation speed at time t (s) is V (kg / s), the filter flux is L (kg / m ² / Pa / s), and the weight of the object on the filter at the start of the filter centrifugation is m _0. If (kg), it will be described by the following equation (2).
V = Lm ₀ ^{rω 2} e ^-Lr ω ^2t
The flux here is an index indicating the filtration characteristics of the filter, and is the amount of permeated liquid per unit time when unit pressure is added to the unit membrane area.

  As is apparent from the above description, the transmission rate decreases exponentially with time. Therefore, conventionally, in order to improve the efficiency of filtration by centrifugation, means for increasing the centrifugal radius or increasing the rotational speed has been adopted, and in order to achieve this means, it is inevitable to increase the size of the apparatus. It was. Even if such means are adopted, it is difficult to improve the permeation rate in the final phase of centrifugal filtration where the weight of the object on the filter is extremely small, especially when the pore diameter or aperture ratio of the filter is small. The problem is even more serious.

On the other hand, as a method of filtering a liquid containing a physiologically active substance while centrifuging, there is a method of filtering plasma separated by centrifuging whole blood using a filter provided in a centrifuge bowl in Patent Document 1. Although described, the direction in which plasma permeates through the filter is opposite to the centrifugal direction, and centrifugal force is not utilized during filtration. In this method, a pump that pumps blood into the bowl is used as the driving force for filtration, but in situations where a filter with a small flux must be used, a large amount of pressure is required to obtain a sufficient permeation rate. Needs to be generated by a liquid feed pump. In addition, there is a drawback that the area of the filter cannot be increased more than a certain amount with respect to the amount of the liquid containing the physiologically active substance to be filtered. Patent Document 2 discloses a centrifuge equipped with an annular filter, but the force acting upon permeation through the filter is only the centrifugal force with respect to the permeated liquid, and a decrease in permeation speed is avoided at the end of filtration. Have the aforementioned problem of not. Thus, conventionally, there has been no known method for easily improving the efficiency of filtration even in the final phase of filtration in a filter having a low permeation rate.
JP 2001-17540 A Special Table 2000-516194

  An object of the present invention is to provide a method for improving the efficiency of filtration using centrifugal force and a system for the method.

  As a result of intensive research in order to solve the above-mentioned problems, the present inventor, in a filtration method using centrifugal force, for a liquid containing a physiologically active substance present on a filter, with respect to the liquid It has been found that the filter permeation speed of the liquid can be improved by applying a force through a weighted material in addition to the direct acting centrifugal force. Moreover, in the filtration method using a centrifugal force, it discovered that the filter permeation | transmission speed | velocity | rate could be improved by making the secondary side of a filter into a negative pressure. The present invention has been completed based on the above findings.

That is, according to the present invention,
In the method of filtering a liquid containing a physiologically active substance through a filter using centrifugal force, in addition to centrifugal force acting directly on the liquid on the filter,
(a) applying a pressure directly proportional to the centrifugal acceleration to the liquid on the filter, and / or
(b) A method including the step of applying a suction force to the filter secondary side by the negative pressure with respect to the liquid by making the secondary side space of the filter more negative than the primary side space is provided.

In the above method, the pressure directly proportional to the centrifugal acceleration is preferably applied to the liquid by a centrifugal force acting on a weight of a constant mass, and more preferably, for example, the following means:
The filter is housed in a sealed housing made of a flexible member, and the housing is partitioned into at least two spaces by the filter, and at least one space (however, this space is A space on the primary side of the filter disposed on the inner side in the centrifugal direction with respect to the filter), and a weighted material on the inner side in the centrifugal direction of the housing forming the space filled with the liquid Can be applied by means of the arrangement.

In the above method, the attraction force is the following means:
The filter is housed in a sealed housing made of a flexible member, and the housing is partitioned into at least two spaces by the filter, and at least one space (however, this space is A space on the primary side of the filter disposed on the inner side in the centrifugal direction with respect to the filter), and at least one of the secondary side spaces of the filter is more negative than the primary side space. It can be applied by means of pressure.
Means for applying a pressure directly proportional to the centrifugal acceleration to the liquid on the filter, and setting the secondary side space of the filter to a negative pressure with respect to the liquid to the secondary side of the filter by the negative pressure. It may be combined with a means for applying the suction force.

  According to a preferred embodiment of these inventions, the above method wherein the filter is a filter that captures health-inhibiting particles; the health-inhibiting particles are viruses, bacteria, fungi, protozoa, parasites, pathogenic prions, leukocytes, and The above method, which is at least one kind of particles selected from the group consisting of cell-derived particles; the above method, wherein the liquid is a biological suspension; and the biological suspension, which is blood or a blood-derived component The above method wherein the blood-derived component is plasma; the above method wherein the plasma is plasma collected by a component blood collection device; and the above method wherein the plasma is plasma separated after whole blood collection Is provided.

  According to a further preferred aspect of the invention, the above method wherein the liquid is supplied continuously or intermittently to the primary space of the filter; the above method wherein the weight is attached to the outside of the housing; The above method wherein the load is detachable from the housing; the method wherein the load is attached to a centrifuge rotor to which the housing is attached; and the centrifugal direction is perpendicular to the filter surface. There is provided the above method of attaching the housing to the rotor; and the above method, wherein each space is provided with connecting means to the outside.

  Furthermore, the present invention provides a filtration system for carrying out the above method. More specifically, the filtration system is a system for filtering a liquid containing a physiologically active substance through a filter using centrifugal force, and the centrifugal force acting directly on the liquid on the filter. In addition, (a) means capable of applying pressure directly proportional to the centrifugal acceleration to the liquid on the filter, and / or (b) the secondary space of the filter is made more negative than the primary space. This is a system provided with means capable of applying a suction force to the secondary side of the filter by the negative pressure to the liquid.

  More specifically, in the means (a), the filter is housed in a sealed housing made of a flexible member, and the housing is partitioned into at least two spaces by the filter. And at least one of these spaces (however, this space is a space on the primary side of the filter disposed in the centrifugal direction with respect to the filter) is filled with the liquid, and the liquid is filled This can be achieved by placing a load on the inner side in the centrifugal direction of the housing forming the space. The means (b) includes the filter housed in a sealed housing made of a flexible member, and the housing is partitioned into at least two spaces by the filter. At least one space (however, this space is a space on the primary side of the filter disposed on the inner side in the centrifugal direction with respect to the filter) is filled with the liquid, and at least one of the secondary side spaces of the filter Can be achieved by making negative pressure more than the primary space. These systems may be equipped with a rotor for centrifugation. The system may be connected to at least one container other than the housing, and the space may be provided with a connection means to the outside. The filter may have a laminated structure of two or more layers.

  According to the method of the present invention, the efficiency of filtration by centrifugation can be improved by simple means. The method of the present invention is useful as a method for easily improving the filter permeation rate of blood-derived components while maintaining the ability to remove minute pathogens when removing pathogens from blood-derived components.

  In the first aspect of the method of the present invention, in the method of filtering a liquid containing a physiologically active substance with a filter using centrifugal force, in addition to the centrifugal force acting directly on the liquid on the filter, the filter The method includes the step of applying a pressure directly proportional to the centrifugal acceleration to the liquid. Further, in the second aspect of the present invention, in the method of filtering a liquid containing a physiologically active substance with a filter using centrifugal force, in addition to the centrifugal force acting directly on the liquid on the filter, the filter And a step of applying a suction force to the secondary side of the filter by the negative pressure with respect to the liquid. Further, a third aspect of the method of the present invention is a combination of the first aspect and the second aspect described above. In the method of filtering a liquid containing a physiologically active substance with a filter using centrifugal force, the filter Applying a pressure directly proportional to the centrifugal acceleration to the liquid on the filter, in addition to the centrifugal force acting directly on the liquid on the filter, and the negative pressure in the secondary space of the filter relative to the primary space And a step of applying a suction force to the secondary side of the filter by the negative pressure with respect to the liquid.

  In the filtration using a filter, means for increasing the filtration rate by centrifugation is known. The primary side of the filter (in this specification, the term “primary side of the filter” means the side in contact with the liquid before filtration in the filter used for filtration. The term “secondary side of the filter” The liquid existing on the opposite side of the primary side receives a force that moves from the primary side to the secondary side of the filter by the direct action of centrifugal force.

  The first aspect of the method of the present invention is characterized in that, in addition to the centrifugal force that directly acts on the liquid, a pressure that is directly proportional to the centrifugal acceleration is applied to the liquid to increase the filtration rate. The means for applying a pressure directly proportional to the centrifugal acceleration to the liquid is not particularly limited, and any means may be used as long as a pressure is generated inside the liquid by a force acting on the liquid and the pressure is directly proportional to the centrifugal acceleration. Can be adopted. For example, the pressure that is directly proportional to the centrifugal acceleration can be applied to the liquid by a centrifugal force that preferably acts on a weight of constant mass. In this specification, the term “directly proportional to centrifugal acceleration” should be interpreted in the broadest sense, not only when there is a mathematically directly proportional relationship but also when there is an approximate directly proportional relationship. In any sense, it should not be interpreted in a limited way.

  More preferably, as means for applying a pressure directly proportional to the centrifugal acceleration to the liquid, for example, the following means: the filter is housed in a sealed housing made of a flexible member, and the housing is contained by the filter. Is divided into at least two spaces, and at least one of the spaces is filled with the liquid (however, this space is the space on the primary side of the filter arranged in the centrifugal direction with respect to the filter). It is possible to adopt a means in which a weight is disposed on the inner side in the centrifugal direction of the housing that forms the space filled with the liquid.

  In the second aspect of the present invention, in addition to the centrifugal force acting directly on the liquid on the filter, the negative side space of the filter is set to a negative pressure rather than the primary side space, and the negative pressure is The filtration speed is increased by applying a suction force to the secondary side of the filter by pressure. The means for setting the secondary space to negative pressure is not particularly limited. For example, a decompression pump may be connected to an outlet provided in a housing that forms the secondary space of the filter to continuously discharge the gas in the secondary space of the filter, or a housing having a restoring force may be used. It is also possible to form a secondary side space, discharge the air in the secondary side space of the filter from the outlet, and make the secondary side space negative pressure by the restoring force of the housing.

Hereinafter, an example of the preferred embodiment will be specifically described with reference to the drawings. However, the present invention is not limited to the specific preferred embodiments described in the accompanying drawings.
FIG. 1 is an example of the filtration system of the present invention. The interior of the housing 2 is partitioned by a filter 1 as shown in FIG. 1 and includes an inlet 4 and an outlet 5 in the partitioned primary space 7 and secondary space 8 in the centrifugal direction 6, respectively. Since the liquid filtered by the filter 1 moves from the primary space 7 in the centrifugal direction 6 to the secondary space 8 by centrifugal force, the primary space 7 in the centrifugal direction 6 is the primary side of the filter 1 and the centrifugal direction. 6 is a secondary side of the filter 1. Centrifugal direction 6 means a direction in which centrifugal force is applied to an object such as a filtration system, and is a direction perpendicular to the rotation axis that generates centrifugal force.

  When the weight 3 is attached to the outside of the housing 2 and inside the centrifugal direction 6 with respect to the filter 1 as shown in FIG. 1 and centrifuged, the weight 3 is moved in the centrifugal direction 6 by centrifugal force. The power to be added. If the housing 2 is made of a member that can be deformed by the force from the weight 3 and the primary side space 7 is filled with a liquid containing a physiologically active substance, centrifugal force is applied to the liquid by the above force. A force different from itself is added. Centrifugal force is already applied to the liquid, but the above-mentioned force different from the centrifugal force is further applied, and these forces are combined to form a force that allows the liquid to pass through the filter. In this way, by applying a force other than the centrifugal force that acts directly on the liquid containing the physiologically active substance to the liquid, the liquid containing the physiologically active substance can efficiently pass through the filter. The filtration rate can be improved. The weight 3 may be integrated with the housing 2, but the weight 3 is preferably attached to the outside of the housing 2 from the viewpoint of freedom of attachment and handling of the housing 2 before and after centrifugation, and is removable from the housing. It is more preferable that

  In the above system, when the outlet 5 is connected to a decompression pump (such as a vacuum pump or a water pump) and the secondary space 8 is set to a negative pressure, the primary space 7 contains a physiologically active substance. If the liquid is filled and the liquid is in contact with the filter 1, a suction force different from the centrifugal force itself is applied to the liquid by the negative pressure. Centrifugal force is already applied to the liquid, but the above suction force different from the centrifugal force is further applied, and these forces are combined to form a force that allows the liquid to pass through the filter. Further, in the above system, when the housing 2 is formed of a flexible member having a restoring force, a pressure reducing means (from a pressure reducing pump such as a vacuum pump or a water flow pump as well as a syringe barrel) is used from the outlet 5. By closing the outlet plug after the housing 2 is atrophically deformed by sucking the gas in the secondary side space by a means for sucking gas), a restoring force is generated in the housing 2 and the secondary side space becomes Negative pressure is reached. Using the restoring force of the housing 2, the secondary space can be set to a negative pressure. As described above, by applying a suction force other than the centrifugal force that directly acts on the liquid containing the physiologically active substance to the liquid, the liquid containing the physiologically active substance can efficiently pass through the filter. Thus, the filtration rate can be improved. In the system that applies the suction force, the presence of the weight 3 is not essential, but as in the system described above, the system that applies the pressure generated by the weight 3 and the suction force due to the negative pressure to the liquid. Is preferable as the system of the present invention.

  In this specification, a filter is a structure made of a porous body, has a large number of fine pores communicating from one surface to the other surface, and can selectively separate and remove specific particles. Or the base material which has surface affinity is meant. The porous body refers to a substrate having a large number of fine pores, and the material, thickness, shape, dimensions, and the like are not limited. The material of the porous body may be, for example, an organic material or an inorganic material, or a composite material composed of an organic material and an inorganic material. Of these, organic materials are preferable, and organic polymer materials are particularly preferable because they have excellent processability such as cutting. Examples of the organic polymer include polycarbonate, polyurethane, polyacrylonitrile, polyvinyl alcohol, polyvinyl acetal, polyester, polyamide, polystyrene, polysulfone, cellulose, cellulose acetate, polyethylene, polypropylene, polyvinyl fluoride, polyvinylidene fluoride, and polytrifluoro. Examples include chlorovinyl, vinylidene fluoride-tetrafluoroethylene copolymer, polyethersulfone, poly (meth) acrylate, butadiene-acrylonitrile copolymer, polyether-polyamide block copolymer, ethylene-vinyl alcohol copolymer. The porous body is not limited to these.

  The shape of the porous body is not particularly limited as long as it has pores capable of capturing particles, and may be any shape such as a flat plate shape, a spherical shape, a rod shape, a fiber shape, or a hollow shape. For example, a mesh, a film, a sheet, a membrane, a board, a nonwoven fabric, a filter paper, a sponge, a woven fabric, a knitted fabric, a lump, a thread, a hollow fiber, or a particle can be used. In capturing particles by filtration by centrifugal force, the size of the holes for capturing particles can be easily controlled so that the operation can be easily performed, and considering the ease and cost of manufacturing filters and housings, mesh, film, The shape of a sheet, filter paper, membrane, plate, nonwoven fabric, sponge or particle is preferred, and the shape of a mesh, film, sheet, filter paper, membrane, nonwoven fabric or sponge is more preferred.

  The pore size of the porous body is not limited, but considering that the particles can be selectively captured, the average pore diameter is preferably 0.05 nm or more and 500 nm or less, preferably 0.10 nm or more. 100 nm or less, more preferably 0.15 nm or more and 80 nm or less. The average pore diameter of the porous body can be measured with, for example, a mercury porosimeter. When measuring with a mercury porosimeter, the pore diameter (diameter) showing the maximum peak in the pore diameter distribution curve can be adopted as the average pore diameter. Accordingly, it should be understood that particles having a diameter larger than the average pore size of the porous body are less likely to enter the pores, but not necessarily into the pores. In order to facilitate selective capture of particles, a plurality of the porous bodies may be used in combination, or a plurality of the same or a plurality of porous bodies may be used in a stacked manner.

  The nonwoven fabric is a cloth-like material in which a collection of fibers or yarns are chemically, thermally, or mechanically bonded regardless of knitting. Even when the fibers are kept in contact with each other, by friction, or entangled with each other, they can be said to be mechanically bonded and are included in the concept of nonwoven fabric. A woven fabric generally means a fabric made by crossing warps and wefts.

  In order to improve the affinity for a liquid containing a physiologically active substance, the porous body may be surface-treated with a hydrophilic compound to such an extent that the pores of the porous body are not blocked. As means, grafting, electron beam irradiation, surface coating with a polymer, or the like can be used. Examples of hydrophilic compounds used for the surface treatment by grafting include acrylic acid, methacrylic acid, glycidyl methacrylate, hydroxypropyl acrylate, hydroxyethyl acrylate, hydroxyethyl methacrylate, methoxyethyl acrylate, methyl methacrylate, ethyl acrylate, ethylhexyl acrylate, and phenoxyethyl. Hydrophilic monomers such as acrylic acid such as acrylate or esters of methacrylic acid and polyhydric alcohols, mixtures of monomers, polyethylene oxide having a crosslinkable vinyl group or allyl group, polyglycidol, polyvinylpyrrolidone, or the like A copolymer or the like is preferably used. The above-mentioned hydrophilic polymer having a crosslinkable vinyl group or allyl group in the main chain or side chain can be coated on the filter surface and crosslinked with heat, radiation, or a crosslinking agent. It is also possible to coat the filter surface with a hydrophilic polymer such as a polymer. Moreover, after adding diacrylate type compounds, such as polyethyleneglycol diacrylate, to a hydrophilic compound, it can react, and the obtained reaction product can also be bridge | crosslinked.

The ability of the filter to transmit a liquid containing a physiologically active substance is preferably a flux of 2 × 10 ⁻⁹ (kg / m ² / Pa / s) or more, more preferably 2 × 10 ⁻⁸ (kg / m ² / Pa / s) or more.

  The liquid containing a physiologically active substance means a liquid containing a natural or artificial substance that has some effect on an organism. Examples of the liquid containing a natural physiologically active substance include individuals, organs and organs derived from animals belonging to, for example, round-mouthed fish, thornfish, plate skin, cartilaginous fish, teleost fish, amphibians, reptiles, birds, or mammals. And fluids contained in tissues, body fluids, or human urine, such as blood, urine, sweat, saliva, gastric juice, bile, pancreatic juice, and the like. Examples of liquids containing artificial physiologically active substances include, for example, solutions or suspensions containing nucleic acids, proteins, sugars, lipids, etc. obtained by gene recombination techniques, or chemically synthesized nucleic acids or polypeptides. A solution or suspension containing Examples of the liquid state containing a physiologically active substance include a pure liquid or a mixture of liquids, a solution, a suspension, a slurry, a sol, and an emulsion. Examples of the liquid containing a physiologically active substance include those obtained by pretreating a liquid containing a physiologically active substance, such as plasma obtained by centrifuging blood, globulin, immune albumin, blood obtained through a purification step, and the like. Plasma fraction preparations such as clotting factors, antithrombin III, fibrin glue, haptoglobin, activated protein C, or C1-inactivator are also included. However, the liquid containing a physiologically active substance is not limited to those specifically exemplified above. Examples of the liquid containing a physiologically active substance that is widely used in the medical field and that is required to improve safety include plasma for blood transfusion or preparation of a fractionated preparation. It is preferable as an object of the method. Examples of plasma for transfusion or fraction preparation preparation include plasma separated from donor blood by a component blood collection device and plasma obtained by centrifugation of blood obtained after whole blood collection. However, it is not limited to these.

  Particles trapped in the filter are trapped in the filter pores by size or affinity. When capturing by size, the pore size of the filter pores is preferably smaller than the particle diameter, but any pore size can be used if it can prevent the particles from flowing out to the secondary side of the filter during the filtration process. can do. By capturing health-inhibiting particles with a filter, for example, the safety of blood for blood transfusion can be increased. Health-inhibiting particles mean particles that can be harmful to health by entering the human body, such as viruses, bacteria, fungi, protozoa, parasites, pathogenic prions, leukocytes, and cell disruption. It is a cell-derived particle like a thing.

  The filter is preferably housed in a housing for easy handling. Examples of the housing material include polyvinyl chloride, polycarbonate, polyurethane, polyacrylonitrile, polyvinyl alcohol, polyvinyl acetal, polyester, polyamide, polystyrene, polysulfone, cellulose, cellulose acetate, polyethylene, polypropylene, polyvinyl fluoride, and polyvinylidene fluoride. , Polytrifluorochlorovinyl, vinylidene fluoride-tetrafluoroethylene copolymer, polyethersulfone, poly (meth) acrylate, butadiene-acrylonitrile copolymer, polyether-polyamide block copolymer, or ethylene-vinyl alcohol copolymer. However, it is not limited to these. In consideration of ease of filtration, freedom of attachment, ease of storage, and the like, the housing is preferably flexible. Since the housing has a structure partitioned by a filter, a liquid containing a physiologically active substance can be processed in a closed system before and after filtration. Therefore, a physiologically active substance particularly required for cleanliness such as blood for blood transfusion. It is preferable when using a liquid that contains.

  The housing may be provided with connecting means to the outside in each space partitioned by the filter, and such connecting means pretreats the liquid containing the physiologically active substance before filtration. In some cases, it is useful for storing a liquid containing a physiologically active substance after filtration in another container. Such connection means is indispensable particularly when the secondary space is set to a negative pressure. For example, when blood is filtered by the filtration method of the present invention, the blood after blood collection is separated by aseptically connecting a blood bag for separating plasma and blood cell components by centrifugation before filtration to the housing. In addition, it is possible to aseptically perform the process until the health-inhibiting particles are filtered.

  When a liquid containing a physiologically active substance is filtered by centrifugal force using the housing, for example, a centrifugal force acting on the load 3 is attached by attaching the load 3 to the outside of the housing 2 as shown in FIG. A new force utilizing the above can be applied to the liquid, thereby facilitating filtration. At this time, it is possible to promote filtration by applying a negative pressure to the secondary side of the filter through a connecting means attached to the secondary side of the filter, which is particularly useful in a system requiring a permeation rate. It is.

  The housing may be connected to at least one container other than the housing by a connection means with the outside provided in the housing. For example, storing the collected whole blood in a connected container is suitable for performing a subsequent centrifugation step. The whole blood stored in the container is subjected to a centrifugation step to separate the plasma, and then the plasma is transferred into the housing in the system of the present invention and filtered by the method of the present invention. It is possible to quickly and easily remove health-inhibiting particles such as plasma from plasma. Plasma prepared in this way has improved safety and is suitable for transfusion.

  When applying a centrifugal force to the housing, in order to obtain a larger centrifugal force, it is desirable to attach and rotate the rotating body such as a rotor. At that time, the centrifugal force can be utilized more efficiently by attaching the housing to the rotor so that the filter surface is perpendicular to the centrifugal direction.

Hereinafter, the present invention will be described more specifically with reference to examples. However, the present invention is not limited to the following examples.
Example 1
FIG. 2 shows one embodiment of the system of the present invention, showing a filter and a housing. A porous polyethylene filter 21 having a width of 22 cm and a length of 10 cm was joined to a polyethylene housing 22 of the same size using a heat sealer, so that the inside of the housing 22 was partitioned into a primary side and a secondary side by the filter 21. At the time of joining, polyethylene tubes 23 (inlet) and 24 (outlet) with wires inserted into the inner holes are inserted at the boundaries between the filter and the primary and secondary sides of the housing, respectively, and the wires are pulled out after heat sealing. Thus, means for connecting to the outside were provided on the primary side and the secondary side of the filter, respectively. In order to heat seal the outer periphery, the membrane area actually used for filtration is 108 cm ² . As shown in FIG. 3, the housing 22 was attached to the side surface of the cylindrical rotor 31 via a rubber spacer 32. At the time of attachment, a lead tape 33 having a width of 18 cm, a length of 6 cm, and a weight of 40 g was affixed to the inside of the housing in the centrifugal direction, and a lead tape not affixed was prepared as a comparative example. The polyethylene used for the housing is flexible, and when the lead tape 33 is affixed to the inside of the housing 22 in the centrifugal direction, a force is applied to the lead tape 33 to push the housing 22 outward in the centrifugal direction by centrifugal force. Purified water was introduced into the primary side of the partitioned space in the housing through the inlet 23, and centrifugal filtration was performed by rotating the rotor at 500 rpm. Centrifugation was stopped at a predetermined time after the start of centrifugal filtration, and the value obtained by dividing the amount of purified water remaining on the primary side by the amount before the start of centrifugal filtration was defined as the residual rate. The residual rate is 1 at the start of centrifugal filtration, and it is desirable that the residual rate approaches 0 in a shorter time.

  FIG. 4 shows the result of centrifugal filtration. In FIG. 4, Δ indicates the result of centrifugal filtration with no lead tape 33 attached (system of comparative example) and ▲ with lead tape 33 attached (system of the present invention). 30 minutes after the start of centrifugal filtration, the residual ratio was 0.72 in the system of the comparative example, whereas it was 0.53 in the system of the present invention. At 60 minutes after the start of centrifugation, the residual rate was 0.60 in the system of the comparative example, whereas it was 0.31 in the system of the present invention. This result shows that the filtration efficiency is improved by applying the lead tape 33 to the inside of the housing 22 in the centrifugal direction.

Example 2
Purified water was introduced into the primary side of the partitioned space in the housing of the system obtained in Example 1 through the tube 23, and centrifugal filtration was performed by rotating the rotor at 1000 rpm. FIG. 5 shows the result of centrifugal filtration. In FIG. 5, □ indicates the result of centrifugal filtration with no lead tape 33 attached (system of comparative example) and ■ with lead tape 33 attached (system of the present invention). 30 minutes after the start of centrifugal filtration, the residual rate was 0.36 in the system of the comparative example, whereas it was 0.19 in the system of the present invention. At 60 minutes after the start of centrifugation, the residual rate was 0.15 in the system of the comparative example, whereas it was 0.093 in the system of the present invention. This result shows that the filtration efficiency is improved by applying the lead tape 33 to the inside of the housing 22 in the centrifugal direction.

Example 3
An aqueous dispersion containing 100 ppm of gold colloid having an average particle diameter of 35 nm is introduced through the tube 23 to the primary side of the partitioned space in the housing of the system obtained in Example 1, and the rotor is rotated at 1000 rpm. Centrifugal filtration was performed. Centrifugation was stopped at 30 minutes or 60 minutes after the start of centrifugal filtration, the absorbance at a wavelength of 524 nm of the filtrate permeated to the secondary side was measured, and the gold colloid removal rate was calculated from the following formula.
Gold colloid removal rate (LRV) = log ₁₀ (absorbance of the stock filtrate) / (absorbance of the filtrate)
The colloidal gold removability test is suitable as a method for confirming the virus removal performance of the filter. The gold colloid removal rate (LRV) at the time of constant pressure filtration of the filter 21 used in the housing 22 was 2 or more. Therefore, it is desirable that the gold colloid removal rate (LRV) is 2 or more also in the above method. FIG. 6 shows the result of centrifugal filtration. The absorbance of the filtered solution at a wavelength of 524 nm was 0.965, whereas it was 0.002 30 minutes after starting centrifugal filtration and 0.004 at 60 minutes. In 30 minutes after the start of centrifugal filtration, the gold colloid removal rate was 2.68 according to the above formula and 2.38 was obtained in 60 minutes, so that the gold colloid removability was maintained even by centrifugal filtration by the above method.

Example 4
Purified water was introduced into the primary side of the partitioned space in the housing 22 of the system obtained in Example 1 through the tube 23, and the internal air was completely extracted by the syringe through the tube 24 on the secondary side. . As a comparative example, a secondary housing was cut and opened. Since the housing is flexible but not a perfect soft body, its restoring force creates a negative pressure on the secondary side during centrifugal filtration. Centrifugal filtration was performed by rotating the rotor at 500 rpm. FIG. 7 shows the result of centrifugal filtration. In FIG. 7, ◇ shows the result of centrifugal filtration with the secondary housing cut out (system of comparative example), and ◆ with the secondary side having negative pressure (system of the present invention). In 30 minutes after the start of centrifugal filtration, the residual rate was 0.72 in the system of the comparative example, whereas the residual rate was 0.41 in the system of the present invention. At 60 minutes after the start of centrifugation, the residual rate was 0.60 in the system of the comparative example, whereas it was 0.30 in the system of the present invention. This result shows that the efficiency of filtration is improved by setting the secondary side of the housing 22 to a negative pressure.

Example 5
Purified water was introduced into the primary side of the partitioned space in the housing 22 of the system obtained in Example 1 through the tube 23, and the internal air was completely extracted by the syringe through the tube 24 on the secondary side. . As a comparative example, a secondary housing was cut and opened. Since the housing is flexible but not a perfect soft body, its restoring force creates a negative pressure on the secondary side during centrifugal filtration. Centrifugal filtration was performed by rotating the rotor at 1000 rpm. FIG. 8 shows the result of centrifugal filtration. In FIG. 8, ◯ indicates the result of centrifugal filtration with the secondary housing cut out (system of comparative example), and ● with the secondary side having negative pressure (system of the present invention). In 30 minutes after the start of centrifugal filtration, the residual rate was 0.36 in the system of the comparative example, whereas the residual rate was 0.18 in the system of the present invention. At 60 minutes after the start of centrifugation, the residual ratio was 0.15 in the system of the comparative example, whereas it was 0.068 in the system of the present invention. This result shows that the efficiency of filtration is improved by setting the secondary side of the housing 22 to a negative pressure.

It is the figure which showed the one aspect | mode of this system. It is the figure which showed the one aspect | mode of the cross section of the housing used by this system. It is the figure which showed the one aspect | mode of the attachment method of the housing used by this system. It is the figure which showed the filtration result in Example 1. It is the figure which showed the filtration result in Example 2. It is the figure which showed the filtration result in Example 3. It is the figure which showed the filtration effect in Example 4. FIG. 10 is a diagram showing a filtration effect in Example 5.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Filter 2 Housing 3 Weighted object 4 Inlet 5 Outlet 6 Centrifugal direction 7 Primary side space 8 Secondary side space 21 Filter 22 Polyethylene housing 23 Polyethylene tube (inlet)
24 Polyethylene tube (Outlet)
31 Rotor 32 Rubber spacer 33 Lead tape

Claims (16)

In the method of filtering a liquid containing a physiologically active substance through a filter using centrifugal force, in addition to the centrifugal force acting directly on the liquid on the filter, (a) the liquid is centrifuged against the liquid on the filter. Applying pressure directly proportional to acceleration, and / or (b) making the secondary space of the filter more negative than the primary space, and applying a negative pressure to the liquid to the secondary side of the filter. A method comprising the step of adding. The method of claim 1, wherein the pressure directly proportional to the centrifugal acceleration is applied to the liquid by a centrifugal force acting on a weight of a constant mass. The pressure directly proportional to the centrifugal acceleration is the following means:
The filter is housed in a sealed housing made of a flexible member, and the housing is partitioned into at least two spaces by the filter, and at least one space (however, this space is Is a space on the primary side of the filter disposed on the inner side in the centrifugal direction with respect to the filter), and is filled with the liquid, and a load is applied on the inner side in the centrifugal direction of the housing forming the space filled with the liquid The method of claim 2, wherein the liquid is applied to the liquid by means of which it is disposed. The suction force is as follows:
The filter is housed in a sealed housing made of a flexible member, and the housing is partitioned into at least two spaces by the filter, and at least one space (however, this space is A space on the primary side of the filter disposed on the inner side in the centrifugal direction with respect to the filter), and at least one of the secondary side spaces of the filter is more negative than the primary side space. 4. The method according to claim 1, wherein the liquid is applied to the liquid by means of pressure. The method according to claim 1, wherein the filter is a filter that captures health-inhibiting particles. The method according to claim 5, wherein the health-inhibiting particles are at least one particle selected from the group consisting of viruses, bacteria, fungi, protozoa, parasites, pathogenic prions, leukocytes, and cell-derived particles. The method according to any one of claims 1 to 6, wherein the liquid is a biological suspension. The method according to claim 7, wherein the biological suspension is blood or a blood-derived component. The method according to claim 8, wherein the blood-derived component is plasma. The method according to claim 9, wherein the plasma is plasma collected by a component blood collecting device. The method according to claim 9 or 10, wherein the plasma is plasma separated after whole blood collection. A filtration system for carrying out the method according to any one of the preceding claims. A system for filtering a liquid containing a physiologically active substance through a filter using centrifugal force, in addition to the centrifugal force acting directly on the liquid on the filter, (a ) Means capable of applying a pressure directly proportional to the centrifugal acceleration to the liquid on the filter, and / or (b) the secondary side space of the filter is made more negative than the primary side space. A system comprising means for applying a suction force to the filter secondary side by the negative pressure. 14. The system of claim 13, comprising means for applying the pressure directly proportional to centrifugal acceleration to the liquid by centrifugal force acting on a weight of constant mass. The filter is housed in a sealed housing made of a flexible member, and the housing is partitioned into at least two spaces by the filter, and at least one space (however, this space is Is a space on the primary side of the filter disposed on the inner side in the centrifugal direction with respect to the filter) and is filled with the liquid, and a weight is placed on the inner side in the centrifugal direction of the housing forming the space filled with the liquid. 15. A system according to claim 14 arranged. The filter is housed in a sealed housing made of a flexible member, and the housing is partitioned into at least two spaces by the filter, and at least one space (however, this space is A space on the primary side of the filter disposed on the inner side in the centrifugal direction with respect to the filter), and at least one of the secondary side spaces of the filter is more negative than the primary side space. 16. A system according to any one of claims 13 to 15 comprising means for applying pressure.

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