JPH11267200A - Sterilizing method using ozone gas - Google Patents

Abstract

PROBLEM TO BE SOLVED: To downsize a device and secure a stable blood channel by holding the aspect ratio within a specified range when sides where partial planes are adjacent to each other are laid down in a blood processing device using a filter. SOLUTION: The first partial plane 18 and the second partial plane 19 are formed by folding longitudinally a sheet into an inverted chevron state, and then the third partial plane 20 is formed by folding into a chevron state. Thus by repeating folding, a pleated filter sheet is obtained. This filter sheet is stored in housing having top and bottom faces of the size of the partial plane 18. The size of the partial plane 18 formed by folding a filter sheet is specified as d for the vertical length and w for the horizontal length. If the length ratio w/d is more than 2 and 10 or less, the blood processing device can be downsized. A stable blood channel can be secured for many hours because the filter sheet is protected against clogging.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a structure of a blood processing apparatus using a filter.

[0002]

2. Description of the Related Art Taking plasma separation by filtration as an example of a blood processing technique as an example, many plasma separation apparatuses require a large number of hollow sections in order to secure a membrane area for plasma separation while miniaturizing the apparatus. Most are hollow fiber types that use yarn as a filter. In an apparatus using a flat membrane type filter as opposed to a hollow fiber type, it was essential that the apparatus be large in size to secure a necessary membrane area. In order to solve this problem, a flat film is processed into a pleated shape to secure a film area. In many cases, the filter sheet is processed into a pleated shape, wound into a cylindrical shape, and then placed in a case. In addition, it has been practiced to make a piece of the pleat into a rectangular shape in a rectangular parallelepiped housing and compress and store many pleats.

[0003]

However, the conventional blood processing apparatus using a filter has the following problems. The hollow fiber type is expensive in equipment. In a device in which a filter sheet is processed into a pleated shape, wound into a cylindrical shape and placed in a case, there is a limit in downsizing the device because the filter is cylindrical. From the viewpoint of blood loss, the cylindrical device has a problem that the priming volume is large and blood loss is large. In a device having a pleated membrane structure in which a piece of pleat is made rectangular and a large number of pleats are folded and stored in a rectangular container, the price can be suppressed and the priming volume is small but there are many pleats. To secure a stable blood flow path for a long time,
There were problems that it was difficult to perform blood treatment such as plasma separation and selective adsorption, and that the membrane was not effectively used due to channeling.

[0004]

SUMMARY OF THE INVENTION It is an object of the present invention to provide a blood processing apparatus using a filter, in which the size of the apparatus can be reduced and a stable blood flow path can be secured. It is in. More specifically, it is an object of the present invention to provide a blood processing apparatus used for processing blood or blood components with a filter in blood purification, blood cell separation, plasma separation, and the like.

That is, according to the present invention, a rectangular filter sheet is folded in the longitudinal direction, a mountain-fold and a valley-fold are repeated to form a partial plane of the same shape continuously, and It is stored in a rectangular parallelepiped housing having an inner surface having substantially the same dimensions as a plane, and a space in the housing is divided into two by the filter sheet. A first space is provided with a blood inlet and a blood outlet, and a second space is provided. In a device provided with a filtrate outlet, the length ratio (w / d) of length (d) to width (w) is more than 2 and 10 or less when the side where the partial planes are adjacent to each other is horizontal. Characteristic blood processing device. Here, assuming that the distance at which the partial planes are continuous is c, the dimension of c is preferably 0.5 to 2% of the longitudinal dimension F of the developed filter sheet. Also,
It is preferable that the filter sheet is at least two or more multilayer materials selected from a mesh material, a porous material, and a nonwoven fabric. Preferably, the filter sheet has a selective adsorption function. Preferably, a polyamine compound is immobilized on the filter sheet.

The present invention will be described below with reference to preferred examples shown in FIGS. 1 to 3, but the present invention is not limited to these examples. The blood processing apparatus of the present invention shown in FIG. 1 has a front surface 8, a rear surface 9, a right side surface 10, a left side surface 11, an upper surface 12, and a lower surface 13.
This is a blood processing apparatus including a filter sheet 22 in a housing 15 having a filter sheet 22. A blood inlet 2 and a blood outlet 4 are provided on a front surface 8 of the housing 15, and a filtrate outlet 6 is provided on a rear surface 9. These blood inlet, blood outlet, and filtrate outlet may be provided on any plane in any positional relationship as needed.

The filter sheet 22 has a rectangular shape as a whole and, as shown in FIG. 2, comprises one surface 23 as a front surface and the other surface 24 as a back surface thereof. FIG. 2 schematically shows the left side view of FIG. 1, and the outline of FIG. 2 shows the housing 15, and one flat surface 23 of the filter sheet and the front surface 8 of the housing 15 are a blood entry side space. Is formed as the first space 34. The other flat surface 24 of the filter sheet and the back surface 9 of the housing 15 form a second space 36 which is a blood outlet side space. The blood inlet 2 and the blood outlet 4 provided in the housing 15 communicate with a first space 34, and the blood outlet 6 communicates with a second space 36.

As shown in FIG. 3, the filter sheet 22 is valley-folded in the longitudinal direction to form a first partial plane 18 and a second partial plane 19, and then is mountain-folded to form a third partial plane 20.
To form Conversely, the mountain fold may be performed first, and the pleated filter sheet 22 is obtained by repeating the fold of the peak / valley in this manner. The pleated filter sheet 22 is housed in a housing 15 having an upper surface 12 and a lower surface 13 having substantially the same size as the partial plane 18. The ridges formed on the front surface and the back surface of the filter sheet 22 may be fixed in the housing 15 by a support material such as a net, for example. In FIG. 32 are shown. The present invention is characterized by the dimensions of the partial plane formed by folding the filter sheet 22, and the length (d) of the partial plane.
When the length of w and the width (w) is defined as shown in FIG. 3, the length ratio w / d is more than 2 and 10 or less, preferably 3 to 7. When the length ratio w / d is more than 2 and not more than 10, the entire blood processing apparatus 1 can be downsized, and a stable blood flow path without clogging of the filter sheet 22 can be secured for a long time.

The vertical length d of the partial plane of the filter sheet is 1
It is 0 mm to 60 mm, preferably 20 mm to 40 mm. The width w is 30 mm to 400 mm, preferably 100 mm to 200 mm. Further, when the distance at which the partial planes are continuous is represented by c, the dimension of c is preferably 0.5 to 2% of the longitudinal dimension F of the developed filter sheet, and c is 5 to 400 mm, more preferably 5 to 400 mm.
２００200 mm. Within this range, the device can be downsized and a blood flow path can be stably secured for a long time.

The material of the filter sheet 22 is not particularly limited, and examples thereof include a porous membrane, a nonwoven fabric, and a woven fabric. Examples of the porous membrane include a porous flat membrane substrate having pores having an average pore diameter of 0.1 or more and 10 microns or less, and the material thereof is not limited, but cellulose, cellulose acetate, polypropylene, polyethylene, poly PVC, polysulfone, polytetrafluoroethylene,
Examples thereof include polyester and nylon. When the blood processing apparatus of the present invention is a processing apparatus that performs plasma separation, the average pore size of the porous material may be any pore size that allows plasma separation.
1 to 0.5 μm is preferred. The thickness of the filter sheet depends on the size of the device, but is preferably 1 mm or less. A more preferable ratio of w, d, and c is w: d: c = 20.
~ 60: 2 to 6: 3 to 50, most preferably w,
The ratio of d and c is w: d: c = 24: 5: 12.

The housing 15 has a shape capable of accommodating the folded filter sheet 22, and further has a first space formed by one surface 23 of the folded filter sheet and the front surface 8 of the housing on the blood inflow side. The space is designed so that the second space formed by the other surface 24 of the filter sheet and the back surface 9 of the housing can be used as the space on the filtrate outflow side. The housing 15 may also have holding means for fixing the filter sheet 22 in a folded state and properly securing the first space and the second space, and the holding means may be provided with a groove provided in the housing. Alternatively, the support rod may be a protrusion, or one or more support rods extending in the continuous direction of the folded partial plane. By providing the inflow side net 30 and the filtrate side net 32, it is possible to fix the filter sheet 22 and remove coarse components in blood components.

The material of the housing 15 is not particularly limited, and examples thereof include polypropylene, polyethylene, polyvinyl chloride, polysulfone, polytetrafluoroethylene, polyester, nylon, and polycarbonate.
Polycarbonate is preferred for reasons of heat and sterilization resistance.

In particular, when the blood processing apparatus of the present invention is a processing apparatus for performing plasma separation for separating whole blood into a blood cell component and a plasma component, a mesh material may be laminated on the whole blood inflow side of the filter sheet 22. Preferably, this mesh material is not limited, but has a thickness of 100 μm to 400 μm and a basis weight of 10 to 45 g /
It is preferable that the mesh has an m ² and a filament count of 21 or less in the roll direction and 13 or less in the cross direction. 2 A mesh material whose material is polypropylene, polyethylene, polyvinyl chloride, polysulfone, polytetrafluoroethylene, polyester, or nylon is preferable. Here, the roll direction indicates the number of filaments per inch in the roll winding direction, and the cross direction indicates the number of filaments per inch in the direction perpendicular to the roll winding direction. The above-mentioned mesh material is laminated on the whole blood inflow side of the filter sheet and folded into a predetermined shape, whereby the specific processing ability of the device of the present invention can be improved.

In the case where the present invention is a processing apparatus for separating blood cells and plasma, a nonwoven fabric may be laminated on the filtrate side of the filter sheet 22.
0 μm to 400 μm, nonwoven fabric with a basis weight of 5 to 50 g / m ² , and 2 materials are polypropylene, polyethylene, polyvinyl chloride, polysulfone, polytetrafluoroethylene,
Non-woven fabrics such as polyester and nylon are exemplified.
It is not limited to these.

When the blood processing apparatus of the present invention is a blood processing apparatus for purifying blood by removing a specific virus or the like in blood, the blood inflow side of the filter sheet 22 and / or
Alternatively, a nonwoven fabric may be laminated on the filtrate side. Preferably, the non-woven fabric-porous membrane-non-woven fabric, mesh material-porous membrane-non-woven fabric may be multilayered from the blood inflow side to the filtrate side, and the non-woven fabric has a thickness of 100 μm to 400 μm and a basis weight of 5 to 50 g / m ² . The nonwoven fabric is a nonwoven fabric whose material is polypropylene, polyethylene, polyvinyl chloride, polysulfone, polytetrafluoroethylene, polyester, or nylon, but is not limited thereto.

[0016] The blood processing apparatus of the present invention can be used for HIV in blood.
Blood purification system that purifies blood by removing specific viruses such as blood cells, blood cell separation system that separates blood cells and plasma from whole blood, and blood cell separation system that removes white blood cells from blood transfusion components. It can be used as a device or the like.

Further, the filter sheet 22 of the present invention comprises:
It may have a selective adsorption function. The selective adsorption function in the present invention refers to a function of adsorbing or inactivating a specific component or substance by treating a filter surface, and the treatment method may be any known method. More specifically, it refers to the function of adsorbing or inactivating pathogenic substances such as viruses such as HIV, HCV, and HBV, and endotoxins and LDL in blood. As a method for treating the surface of a filter sheet, see JP-A-7-136257. JP-A No. 2000-209, as a working example, a method of modifying the surface by plasma polymerization or coating and fixing polyethyleneimine.

The surface of the filter sheet may have a free amino group not forming a salt with the anticoagulant active substance and an amino group forming a salt with the anticoagulant active substance. Preferably, polyamine compounds such as polyethyleneimine and polypropyleneimine are used as free amino groups as measured by non-aqueous reverse titration as more than 0.1 × 10 ⁻⁴ eq / g, more preferably more than 0.1 × 10 ^{−4 to} 3 ×. By immobilizing 10 ^-4 eq / g on the surface of the filter sheet and further forming a salt with an anticoagulant active substance such as heparin, the infectious titer of blood collected from an HIV-positive patient can be below the detection limit. .

[0019]

DESCRIPTION OF THE PREFERRED EMBODIMENTS Here, an embodiment of the apparatus of the present invention will be described with reference to a plasma separating apparatus and a leukocyte removing apparatus for the purpose of separating plasma, but the present invention is not limited to these.

(Examples 1 to 6 and Comparative Examples 1 to 3) A porous polypropylene flat membrane having an average pore diameter of 0.45 μm and a film thickness of 80 μm subjected to a hydrophilization treatment was prepared to a thickness of 200 μm and a basis weight of 2
7 g / m ² , a polypropylene mesh material having a filament count roll direction of 21 and a cross direction of 13, a thickness of 150 μm, and a basis weight of 15 g / m ²
was processed into a pleated by pleating machine so as to be sandwiched between m ² polypropylene nonwoven. The processed membrane was cut so that c = 9 mm, d, and w each had the predetermined dimensions shown in Table 1, arranged so that the blood inflow side became a mesh material, and housed in the case of the plasma separation device. Using this apparatus, the performance of separating plasma from bovine fresh blood was evaluated. Blood flow rate 7 ml / min, blood sampling rate 1.7
When plasma separation was performed under the condition of 5 ml / min, in Example 1, TMP (transmembra
ne pressure) was as small as 50 mmHg or less, and stable plasma separation was performed. FIG. 4 shows the change over time of the TMP of Example 1 in comparison with Comparative Example 1. The rapid increase in TMP in Comparative Example 1 indicates that clogging occurs in the plasma separation device, or that the flow path is blocked, and the pressure in the device increases.

Table 1 d (mm) w (mm) w / d Plasma Separable Time (h) Example 1 25 120 4.8 6 Example 2 20 140 7.0 3 Example 3 20 120 6.0 3 Example 4 20 60 3.0 3 Example 5 50 160 3.2 3 Comparative Example 1 20 200 10 1 Comparative Example 2 20 40 21 Comparative Example 3 40 80 21

The flat membrane used in Example 1 was pleated at a pleated height of 25 mm to obtain 25 × 9 × 120 m.
m. Therefore, the blood processing apparatus (plasma separation apparatus) of Example 1 could be such a small apparatus. On the other hand, the flat membrane of Example 1 had a size of 120 mm × 700 mm unless pleating was performed, so that if the apparatus of the present invention was not pleated at a predetermined size, the plane had a large size of this size. Equipment needed.

(Embodiment 6) Under the same conditions as in Embodiment 1, d
= 25 mm, w = 120 mm, w / d = 4.8, and c was changed to the following conditions to perform plasma separation.
A plasma separation of time -6 hours was performed. c (mm) Longitudinal dimension F (mm) of expanded filter sheet c / F (%) 9 700 1.3 60 8000 0.75 25 1480 1.7

(Comparative Example 4) The flat membrane processed into a pleated shape used in Example 1 was formed into a cylindrical shape.
m, and must be stored in a cylindrical case having a length of 120 mm. Thus, plasma separation was performed using the same filter sheet as in Example 1 using the prepared cylindrical module under the conditions of Example 1, but immediately after the start of the experiment, plasma could not be separated.

(Embodiment 7) JP-A-7-136257
Of the blood flow path forming body described in Example 1 of the report
Pore diameter obtained by cationizing the surface of the base material
Example 1 A 0.45 μm-thick polypropylene porous membrane was prepared in Example 1.
The thickness is 150 μm and the basis weight is 15 g / m ^TwoPolypro
Pleated by sandwiching between pyrene nonwoven fabrics
It was processed into a pleated shape by a grease machine. The processed membrane is
Film area 0.07m^TwoAnd cut it into a case
Was. Using the present blood processing apparatus to convert HI from plasma containing HIV
V removal was performed. HIV-containing human plasma is HIV-1
RP containing (HTLV-IIIB) 1 μg / ml PHA
37 ° C, 5% in MI1640 (containing 20% FCS)
CO_TwoCulture in an incubator and ultracentrifuge for HIV
After purification, it was added to human plasma. This HIV-containing human plasma
Through the device to determine the amount of p24 antigen before and after passing through the device.
-Products HIV-1 p24 Antigen
 Measured by ELISA kit, the following results were obtained.
Was. Before passing through the device (p24 Ag pg / ml) After passing through the device (p24 Ag pg / ml) 1,200 10.5

(Example 8) A polyurethane porous membrane having an average pore diameter of 5 µm and having a cationized surface of the substrate as in Example 7 was sandwiched between nonwoven fabrics made of polypropylene with a thickness of 150 µm and a basis weight of 15 g / m ^2. It was processed into a pleated shape by a pleating machine. The processed membrane is
The membrane was cut so as to have a membrane area of 0.07 m ² and housed in a case so that the nonwoven fabric was arranged on the blood inlet side. Red blood cell concentrate (white blood cells:
3.0 × 10 ^{3 to} 5.0 × 10 ³ / μl, platelets:
0 × 10 ^{5 to} 3.0 × 10 ⁵ / μl, erythrocytes: 3.0 ×
(10 ^{6 to} 5.0 × 10 ⁶ / μl) was passed through the apparatus, and the number of white blood cells and the number of platelets before and after passing through the apparatus were measured by an automatic hemocytometer. As a result, a high removal performance shown below was obtained even when processed into a pleated shape. Leukocyte removal rate (%) Platelet removal rate (%) 99.9 99.2 Leukocyte removal rate (%) = (1- (number of leukocytes at apparatus exit / number of leukocytes at apparatus entrance)) x 100 Platelet removal rate (%) = ( 1- (Number of platelets at device exit / number of platelets at device entrance)) × 100

[0027]

According to the present invention, a blood processing apparatus capable of maintaining stable blood processing performance for a long period of time can be realized by setting a dimension when processing a pleated membrane to a specific range. Further, the device of the present invention can realize excellent effects on blood purification, plasma separation and blood cell separation, and is economically effective because the device can be downsized.

[Brief description of the drawings]

FIG. 1 is a perspective view showing an example of the blood processing apparatus of the present invention.

FIG. 2 is a schematic diagram illustrating a side surface of the apparatus of FIG.

FIG. 3 is a perspective view showing a filter sheet.

FIG. 4 is a graph showing the results of Example 1 # and Comparative Example 1 #.

[Explanation of symbols]

 Reference Signs List 1 blood processing apparatus 2 blood inlet 4 blood outlet 6 filtrate outlet 8 front 9 back 10 right side 11 left side 12 upper surface 13 lower surface 15 housing 18 partial plane 19 second partial plane 20 third partial plane 22 filter sheet 23 Surface 24 The other surface 30 Inlet side net 32 Filtrate side net 34 First space (inlet side) 36 Second space (filtrate side)

Claims (5)

[Claims] 1. A rectangular filter sheet is folded in its longitudinal direction, a mountain plane and a valley path are repeated to form a partial plane of the same shape continuously, and the folded filter sheet is substantially identical to the partial plane. Housed in a rectangular parallelepiped housing having an inner surface of dimensions, the space in the housing is bisected by the filter sheet, a first space has a blood inlet and a blood outlet, and a second space has a filtrate outlet. Wherein the length ratio (w / d) of length (d) to width (w) is more than 2 and not more than 10 when the side where the partial planes are adjacent to each other is horizontal. Processing equipment. 2. The blood processing apparatus according to claim 1, wherein a distance c is 0.5 to 2% of a longitudinal dimension F of the developed filter sheet, where c is a distance at which the partial planes are continuous. . 3. The blood processing apparatus according to claim 1, wherein the filter sheet is at least two or more multilayer materials selected from a mesh material, a porous material, and a nonwoven fabric. 4. The blood processing apparatus according to claim 1, wherein said filter sheet has a selective adsorption function. 5. The blood processing apparatus according to claim 1, wherein a polyamine compound is immobilized on the filter sheet.