JP2013034600A - Stopper body, blood treatment medical implement including the same, and electron beam sterilization method to the blood treatment medical implement - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a stopper body for a blood treatment medical implement, the blood treatment medical implement, and a hollow fiber membrane type medical implement, allowing effective prevention of a dielectric breakdown in electron beam sterilization treatment.SOLUTION: This stopper body sealing an outlet and/or an inlet of the blood treatment medical implement 1 includes a portion wherein surface resistivity is 1×10Ω or below, and is performed with the sterilization treatment by electron beam irradiation including the blood medial implement in a state that the inside of the blood treatment medical implement is airtightly and/or liquid-tightly sealed.

Description

  The present invention relates to a plug, a blood processing medical device including the plug, and an electron beam sterilization method for the blood processing medical device.

  In recent years, blood treatment medical technology, particularly hollow fiber membrane technology, has been applied to medicine. For example, artificial kidneys used in hemodialysis therapy for patients with chronic renal failure, patient plasma discarded, fresh frozen plasma and albumin Various blood processing medical devices are used in plasma separators used in plasma exchange therapy to replace solutions, plasma fractionators used in double filtration plasma exchange therapy to remove high molecular weight substances in patient plasma, etc. Yes.

Various blood processing medical devices such as hollow fiber membrane medical devices are medical devices that come into contact with a patient's body fluid, such as blood, and therefore need to be sterilized during use.
Conventionally, heat sterilization, chemical sterilization, irradiation sterilization, and the like are known as sterilization methods for blood processing medical devices, and are selected in consideration of the thermal and chemical properties of medical devices.
In particular, the electron beam irradiation sterilization of the above-mentioned irradiation sterilization does not cause the medical device to be exposed to a high temperature as in the case of heat sterilization, and the drug does not remain in the medical device as in the case of chemical sterilization. It is known as a highly useful and promising sterilization method because there is no need to incur high costs due to the use of expensive radioisotopes such as irradiation sterilization or to select special disposal means (for example, , See Patent Document 1).

JP 2000-325434 A

  However, when a blood treatment medical device is sterilized by electron beam irradiation, it has the following problems.

An electron beam has a smaller transmission power to an object than a γ-ray, and its transmission distance depends on the apparent specific gravity, the density of the material, and the thickness of the irradiation object in the irradiation direction.
The blood treatment medical device has a high apparent specific gravity as a whole module, including a tube material and a hollow fiber membrane or a non-woven fabric housed in the tube body, and the constituent material is also highly insulating such as polyolefin resin. Since the density itself is high, the electron beam is not easily transmitted. Moreover, since the shape is complicated, it is difficult to perform uniform electron beam irradiation as a whole, and electrons that could not be transmitted accumulate inside the blood processing medical device, and the blood processing medical device When a potential difference is generated between the inside and the outside, a dielectric breakdown will eventually occur at the top plate portion of the plug body, a spark may be generated, and a through hole or a burnt mark may be generated in the plug body, resulting in damage.
Furthermore, since the blood processing medical device needs to be kept in a sterilized state until just before use, the tubular body is sealed with a predetermined stopper, for example, in the case of a hollow fiber membrane type medical device, a nozzle plug. The electron beam irradiation is performed in a state where the inside of the module is liquid-tight and / or air-tight. For this reason, when the electric charge accumulated inside is not released to the outside and continuous electron beam irradiation is performed in the sterilization process, the electric charge is further accumulated, resulting in dielectric breakdown.
If dielectric breakdown occurs in a part of the blood processing medical device, not only there is a risk of loss of sterility, but there is a risk of causing great harm to the patient.

  Conventionally, as an electron beam irradiation method for an object having a complicated shape and a large density difference depending on a part, a method of increasing an accelerating voltage to increase a transmission power, or irradiating an electron beam from three or more directions However, these irradiation methods are difficult to control, and there is a concern of promoting the accumulation of electric charges on a part of the irradiated object including the insulating component or on the entire irradiated object.

  Therefore, in the present invention, in view of the problems of the prior art as described above, a blood processing medical device and its plug that can realize uniform irradiation in electron beam sterilization and can effectively prevent the occurrence of dielectric breakdown. An object of the present invention is to provide an electron beam sterilization method for the blood processing medical device.

As a result of intensive studies to solve the above problems, the present inventors have identified the surface resistivity of at least a part of a component constituting a blood processing medical device, particularly a plug body, thereby causing dielectric breakdown. The inventors have found that this can be prevented, and have completed the present invention.
That is, the present invention is as follows.

[1]
A plug for sealing the outlet and / or the inlet of the blood processing medical device,
A portion having a surface resistivity of 1 × 10 ¹⁰ Ω or less,
A plug body that is sterilized by electron beam irradiation including the blood medical device in a state where the inside of the blood processing medical device is gas and / or liquid tightly sealed.
[2]
The plug according to [1], wherein the plug is a molded body of a polymer material having a surface resistivity of 1 × 10 ¹⁰ Ω or less.
[3]
The plug according to [1], wherein the surface is coated with a polymer material having a surface resistivity of 1 × 10 ¹⁰ Ω or less.
[4]
The plug according to any one of [1] to [3], wherein the blood processing medical device is a hollow fiber membrane type medical device.
[5]
A stopper having a portion having a surface resistivity of 1 × 10 ¹⁰ Ω or less;
A blood processing medical device that is sterilized by electron beam irradiation in an airtight and / or liquid tightly sealed state by the stopper.
[6]
The blood processing medical device according to [5], which is a hollow fiber membrane type medical device.
[7]
A cylindrical container;
A bundle of hollow fiber membranes loaded along the longitudinal direction of the cylindrical container and having both ends fixed to both ends of the cylindrical container;
A potting resin in which the bundle of hollow fiber membranes is embedded and fixed at both ends of the cylindrical container;
Opposing both end surfaces of the hollow fiber membrane, provided at both end portions of the cylindrical container, and headers each having a nozzle serving as a fluid inlet / outlet,
Provided on the side surface of the cylindrical container, and a port serving as a fluid inlet and outlet;
A nozzle plug detachable from the nozzle;
A port plug detachable from the port;
Comprising
The blood processing medical device according to [5] or [6], wherein the port plug body is a hollow fiber membrane medical device having a portion having a surface resistivity of 1 × 10 ¹⁰ Ω or less.
[8]
The blood processing medical device according to [7], wherein the port plug is made of a polymer material having a surface resistivity of 1 × 10 ¹⁰ Ω or less.
[9]
The blood processing medical device according to [7] or [8], wherein the nozzle plug has a portion made of a polymer material having a surface resistivity of 1 × 10 ¹⁰ Ω or less.
[10]
The blood treatment medical device according to any one of [7] to [9], wherein the nozzle plug is made of a polymer material having a surface resistivity of 1 × 10 ¹⁰ Ω or less.
[11]
A blood processing medical device that irradiates the blood processing medical device according to any one of [5] to [10] with electron beam irradiation in a state in which the inside is hermetically and / or liquid tightly sealed by the stopper. Electron beam sterilization method.

  According to the present invention, there is provided a highly reliable blood processing medical device and its stopper, and an electron beam sterilization method for the blood processing medical device, which can effectively prevent the occurrence of charging spark and dielectric breakdown in the electron beam sterilization step. Can be provided.

The schematic for demonstrating the structure of an example of a hollow fiber membrane type medical device is shown. The schematic block diagram of the port which comprises a hollow fiber membrane type medical device is shown. (A) The schematic sectional drawing of an example of the plug for ports is shown. (B) The schematic sectional drawing of the state which attached the plug for ports to the port is shown. The schematic sectional drawing of the nozzle which comprises a hollow fiber membrane type medical device is shown. An outline sectional view of an example of a plug for nozzles is shown. (A) The schematic sectional drawing of another example of the plug for ports is shown. (B) The schematic sectional drawing of the state which attached the plug for ports of another example to the port is shown. (A)-(j) The schematic sectional drawing of the specific example of the plug for ports is shown.

Hereinafter, a mode for carrying out the present invention (hereinafter referred to as “the present embodiment”) will be described with reference to the drawings.
The present invention is not limited to the following description, and various modifications can be made within the scope of the gist thereof.
In the drawings, the same elements are denoted by the same reference numerals, and redundant description is omitted. Further, the positional relationship such as up, down, left, and right is based on the positional relationship shown in the drawings unless otherwise specified, and the dimensional ratio in the drawing is not limited to the illustrated ratio.

[Blood treatment tools and plugs]
As the blood processing medical device of this embodiment, for example, a non-woven fabric that separates blood components, a separation membrane, and the like are loaded in a predetermined cylindrical container, and the liquid is passed from the inlet to the outlet of the cylindrical container. A device having a form that can be made airtight and / or liquid-tight with a predetermined plug is applied.

<Cylindrical container>
The cylindrical container constituting the blood processing medical device may be cylindrical or rectangular parallelepiped, and is not limited at all.
In addition, as a constituent material of the cylindrical container, glass, other resin materials such as polyethylene resin, polypropylene resin, polystyrene resin, polymethyl methacrylate resin, polyethylene terephthalate resin, nylon 6 resin, polysulfone resin, polyacrylonitrile resin, polycarbonate Resins, ABS resins, styrene / butadiene copolymer resins and the like.
In particular, polyethylene resin, polypropylene resin, polystyrene resin, polyacrylonitrile resin, and styrene / butadiene copolymer resin have low resin cost, high versatility in the field of medical materials, and high safety has been confirmed. The styrene-butadiene copolymer resin is particularly preferable, but is not limited thereto.

<Plug body>
The blood processing medical device of this embodiment has a configuration in which the inside is sealed in an airtight and / or liquid-tight state by a plug, and is performed in a state of being sealed with a plug during electron beam sterilization. .
The plug of the blood processing medical device of the present embodiment is particularly limited in shape as long as it has a function of sealing the inside of the blood processing medical device in an airtight and / or liquid tight state. It may be anything, not something.
Examples of the material of the plug of the blood processing medical device of the present embodiment include polyethylene resin, polypropylene resin, polycarbonate resin, polystyrene resin, polyamide resin, polyacetal resin, and silicon resin, but are not limited thereto. Absent.
In particular, polyethylene resin and polypropylene resin are preferable because they have adhesiveness and plugging properties based on moderate hardness, and are widely used as a plug-type or push-type plug.

The plug of the blood processing medical device of the present embodiment has a portion having a surface resistivity of 1 × 10 ¹⁰ Ω or less. The surface resistivity of the portion is preferably 1 × 10 ⁸ Ω or less, and more preferably 1 × 10 ⁶ Ω or less.
When the surface resistivity exceeds 1 × 10 ¹⁰ Ω, the charge accumulated in the main body of the hollow fiber membrane type medical device cannot be sufficiently dissipated by the electron beam irradiation performed in the sterilization process described later, and accumulated. The electric breakdown easily causes dielectric breakdown in the hollow fiber membrane type medical device.
Further, the smaller the surface resistivity, the easier it is to dissipate the charge accumulated in the main body of the hollow fiber membrane type medical device, and it becomes easier to obtain a dielectric breakdown prevention effect, so the hollow fiber membrane type of this embodiment It is preferable that the plug constituting the medical device has at least a portion made of an individual molecular material having a surface resistivity as low as possible.
The portion having a surface resistivity of 1 × 10 ¹⁰ Ω or less may be a part of the plug body or the whole.
The part whose surface resistivity is 1 × 10 ¹⁰ Ω or less may be constituted by a single part or may be constituted by a plurality of parts. Alternatively, the surface resistivity of the portion may be 1 × 10 ¹⁰ Ω or less by coating a predetermined coating material on the surface.
If a polymer material having a surface resistivity of 1 × 10 ¹⁰ Ω or less can be obtained by combining a single resin or a combination of two or more resins as the plug forming material, it can be used as a plug material. However, by combining an antistatic agent and a conductive polymer material, it is possible to obtain a plug material that meets the object of the present invention more easily.

When the part having a surface resistivity of 1 × 10 ¹⁰ Ω or less is a part of the plug, the part needs to be in contact with the space inside the blood processing medical device and communicate with the outside.
Thereby, the electric charge accumulate | stored in the blood processing medical device can be discharge | released outside.

[Hollow fiber membrane medical device and plug]
As a typical example of the blood processing medical device described above, there is a hollow fiber membrane type medical device.
A specific example of the hollow fiber membrane type medical device will be described with reference to FIG.
In FIG. 1, the right side of the alternate long and short dash line A shows a schematic cross-sectional view of the hollow fiber membrane type medical device 1, and the left side of the alternate long and short dash line shows a schematic side view of the hollow fiber membrane type medical device.

<Overall structure>
A hollow fiber membrane type medical device 1 shown in FIG. 1 is opposed to a cylindrical container 9, a hollow fiber membrane 3 loaded in the cylindrical container 9, and both end faces of the hollow fiber membrane 3. Headers 2, 2 ′ having nozzles 4, 5 serving as blood inlets / outlets, respectively, and ports 6, 7 serving as blood inlets / outlets provided on the side surface of the cylindrical container 9. And have.
The nozzles 4 and 5 and the ports 6 and 7 are each provided with a plug body (not shown) that can be attached and detached.
The hollow fiber membranes 3 are filled in a bundle along the longitudinal direction of the cylindrical container 9, and both ends of the bundle of hollow fiber membranes 3 are separated from the inside and the outside of the hollow fiber membrane 3, It is embedded in the potting resin 8 and fixed to both ends of the cylindrical container 9, and the inner surface of the hollow fiber membrane 3 is open at the end surface of the potting resin 8.
A first space 11 is provided between the inner side of the hollow fiber membrane 3 and the inner surface of the header 2, 2 ′, and between the outer side of the hollow fiber membrane 3 and the inner surface of the cylindrical container 9. Has a second space 12.

In FIG. 2, the schematic side view of the ports 6 and 7 provided in the side surface of the cylindrical container 9 which comprises the hollow fiber membrane type medical device 1 is shown.
As the structure of the ports 6 and 7, for example, JIS T 3250: 2005 (hemodialyzer, hemodiafiltration filter, blood filter and blood concentrator) 4.4.4 (blood The structure described in the dialysate side connection part of a dialyzer and a hemodialysis filter (filter) filter) is mentioned.
The broken line in FIG. 2 represents the hollow part of the ports 6 and 7, and the said hollow part is connected with the inside of the cylindrical container 9 in FIG. The ports 6 and 7 can be opened and closed by attaching and detaching a port plug, which will be described later.
3A shows a schematic cross-sectional view of the port plug body 20 that can be attached to and detached from the ports 6 and 7 and can be opened and closed by this, and FIG. 3B shows the port plug body 20 connected to the port 6, 7 is a schematic cross-sectional view of the state attached to 7.
For example, as shown in FIG. 3A, the port plug body 20 includes a cylindrical projection 21 that matches the outer surface of the ports 6 and 7 and a cylindrical projection that matches the hollow portion of the ports 6 and 7. The part 22 may be provided.
When the port plug 20 is attached to the ports 6 and 7, as shown in FIG. 3B, the port plug 20 covers almost the roots of the ports 6 and 7.
In this embodiment, when performing sterilization treatment by electron beam irradiation, the ports 6 and 7 are sealed by the above-described port plug body 20 so that the inside is airtight and / or liquid tight. Thereby, the sterilization state of the second space 12 can be maintained until just before using the hollow fiber membrane medical device.

FIG. 4 shows a schematic cross-sectional view of the nozzles 4 and 5 of the headers 2 and 2 ′.
The structure of the nozzles 4 and 5 is, for example, JIS T 3250: 2005 (hemodialyzer, hemodiafiltration filter, blood filtration filter and blood concentrator) 4.4.3 (blood Examples thereof include a structure described in a dialyzer, a hemodialysis filter, and a blood side connection portion of the blood filter.
FIG. 5 shows a schematic cross-sectional view of a nozzle plug 30 that can be attached to and detached from the nozzles 4 and 5 and can be opened and closed. The nozzle plug 30 may include a cylindrical protrusion 31 that matches the hollow portion of the nozzles 4 and 5.
In the present embodiment, when performing sterilization by electron beam irradiation, the nozzles 4 and 5 are sealed by the nozzle plug 30 described above to make the inside airtight and / or liquid tight. Thereby, the sterilization state of the first space 11 can be maintained until just before using the hollow fiber membrane medical device.

Examples of the material of the cylindrical container 9, the ports 6 and 7, and the headers 2 and 2 'include polyethylene resin, polypropylene resin, polystyrene resin, polymethyl methacrylate resin, polyethylene terephthalate resin, nylon 6 resin, polysulfone resin, and polyacrylonitrile. Resins, polycarbonate resins, ABS resins, styrene / butadiene copolymer resins, and the like.
In particular, polyethylene resin, polypropylene resin, polystyrene resin, polyacrylonitrile resin, and styrene / butadiene copolymer resin have low resin cost, high versatility in the field of medical materials, and high safety has been confirmed. The styrene-butadiene copolymer resin is particularly preferable, but is not particularly limited thereto.

<Plug body>
The shapes of the port plug 20 and the nozzle plug 30 of the hollow fiber membrane medical device are not particularly limited.
For example, the port plug 20 will be described as an example. As shown in FIG. 3 (a), the plug 6 having a shape for wrapping the entire ports 6 and 7 and the plug 200 of FIGS. 6 (a) and 6 (b) are provided. As shown in the figure, there is a push-in plug having a shape that achieves hermeticity by bringing a part of the port plug body 200 into contact with the inner wall surface of the internal space (second space 12) of the ports 6 and 7.
As shown in FIG. 3 (a), the shape of the wrapping plug that wraps the entire ports 6 and 7 is superior as a function of maintaining a sterilized state, but the ports 6 and 7 of the hollow fiber membrane medical device, Each plug attached to the nozzles 4 and 5 of the headers 2 and 2 ′ may be any type, and other types of plugs may be used.

Examples of the material for forming the port plugs 20 and 200 and the nozzle plug 30 include, but are not limited to, polyethylene resin, polypropylene resin, polycarbonate resin, polystyrene resin, polyamide resin, polyacetal resin, and silicon resin. It is not something.
In particular, polyethylene resin and polypropylene resin are preferable because they have adhesiveness and plugging properties based on appropriate hardness and are already widely used as wrapping plug-type and push-in plug-type plug bodies.

At least one of the port plugs 20 and 200 and the nozzle plug 30 described above has a portion having a surface resistivity of 1 × 10 ¹⁰ Ω or less.
The “part” may be a part or the whole.
The part whose surface resistivity is 1 × 10 ¹⁰ Ω or less may be constituted by a single part or may be constituted by a plurality of parts. Alternatively, the surface resistivity of the portion may be 1 × 10 ¹⁰ Ω or less by coating a predetermined coating material on the surface.
If a polymer material having a surface resistivity of 1 × 10 ¹⁰ Ω or less can be obtained by combining the resin that is a material for forming the port plugs 20 and 200 and the nozzle plug 30 described above alone or in combination, Although it can be used as a plug body material, a combination of an antistatic agent and a conductive polymer material makes it possible to obtain a plug body material more suitable for the purpose of the present invention.

When the part having a surface resistivity of 1 × 10 ¹⁰ Ω or less is a part of the port plugs 20 and 200 and the nozzle plug 30, the part includes the space inside the hollow fiber membrane medical device and the outside. And communicate with.
Thereby, the electric charge accumulate | stored in the hollow fiber membrane type medical device can be discharge | released outside.

A portion where the surface resistivity constituting the plug body is 1 × 10 ¹⁰ Ω or less will be described with reference to specific examples shown in FIGS.
7A to 7J, the port plug body 20 of the hollow fiber membrane type medical device will be described as an example. However, the present invention is not limited to the specific example, and the nozzle plug The same applies to the case of a body.
7A to 7J, reference numerals 21 and 210 indicate portions where the surface resistivity is 1 × 10 ¹⁰ Ω or less, and reference numerals 22 and 220 indicate portions where the surface resistivity is 1. A portion larger than × 10 ¹⁰ Ω is shown.
Any of them may be composed of only a single part, or may be composed of a plurality of parts.
For example, in FIG. 7A, the entire plug is formed of a single component having a surface resistivity of 1 × 10 ¹⁰ Ω or less, and FIGS. 7B to 7D, 7F, and 7F are shown. In h) to (j), a part of the plug is formed of a part having a surface resistivity of 1 × 10 ¹⁰ Ω or less.
FIGS. 7E and 7G are obtained by coating the surface of the plug with a predetermined material for controlling the surface resistivity to 1 × 10 ¹⁰ Ω or less.

In the hollow fiber membrane type medical device of the present embodiment, the electric charge accumulated in the main body by the electron beam irradiation is released to the outside, so that the dielectric breakdown is effectively prevented.
Therefore, among the parts constituting the plug, the part having a surface resistivity of 1 × 10 ¹⁰ Ω or less is the first space 11 or the second space constituting the hollow fiber membrane medical device 1 shown in FIG. 12 and is in contact with the space outside the main body without interruption.
As a result, the charge accumulated in the main body of the hollow fiber membrane medical device passes only through the portion having a surface resistivity of 1 × 10 ¹⁰ Ω or less and is dissipated to the space outside the main body of the hollow fiber membrane medical device. Can be made.

In order to prevent the dielectric breakdown, at least a part of the plug constituting the hollow fiber membrane medical device has a surface resistivity of 1 × 10 ¹⁰ Ω or less, preferably 1 × 10 ⁸ Ω or less, more preferably 1 × 10 ⁶ Ω or less.
Examples of a method of setting the surface resistivity to 1 × 10 ¹⁰ Ω or less include a method using a resin itself having a surface resistivity of 1 × 10 ¹⁰ Ω or less, and a method of applying a commercially available antistatic agent to the surface of a component. Alternatively, a method of blending a commercially available antistatic agent or a conductive polymer material with a thermoplastic resin is mentioned as a relatively simple method, and a desired surface resistivity can be easily obtained.

  Examples of the antistatic agent include an antistatic agent having a polyoxyalkylene chain (for example, JP-A Nos. 03-255161 and 03-258850), a polyether having an oxyethylene group and an oxyethylene group. A polyether copolymer, an antistatic agent having a crystallinity of the oxyethylene group portion in a specific range (for example, JP-A-2009-108259), and a block polymer having a polyether as a hydrophilic segment. And polymer type antistatic agents such as antistatic agents (commercially available products), surfactant type antistatic agents, conductive fillers (carbon black and the like), conductive ABS resins and the like.

When the surface resistivity exceeds 1 × 10 ¹⁰ Ω, the charge accumulated in the main body of the hollow fiber membrane type medical device cannot be sufficiently dissipated by the electron beam irradiation performed in the sterilization process described later, and accumulated. The electric breakdown easily causes dielectric breakdown in the hollow fiber membrane type medical device.
Further, the smaller the surface resistivity, the easier it is to dissipate the charge accumulated in the main body of the hollow fiber membrane type medical device, and it becomes easier to obtain a dielectric breakdown prevention effect, so the hollow fiber membrane type of this embodiment It is preferable that the plug constituting the medical device has at least a portion made of a polymer material having a surface resistivity as low as possible.
In addition, polymer materials with sufficiently low surface resistivity are usually expensive to manufacture and may cause problems such as poor mechanical strength and difficulty in mounting on ports. It is preferable to carry out.

The constituent members other than the plug body constituting the hollow fiber membrane type medical device of the present embodiment may have a surface resistivity of 1 × 10 ¹⁰ Ω or less using the above-described plug body material.
In this case, the surface resistivity can be relatively easily reduced to 1 × 10 ¹⁰ Ω or less by combining commercially available antistatic agents and conductive polymer materials as necessary.

  Regarding the surface resistivity of the plug body and other parts constituting the hollow fiber membrane type medical device of this embodiment, according to the double ring electrode method (IEC60093, ASTM D257, JIS K6911, JIS K6271) The electrical resistance can be measured with an insulation resistance meter, and the surface resistivity can be determined from the electrode shape.

<Hollow fiber membrane>
The hollow fiber membrane 3 constituting the hollow fiber membrane-type medical device 1 is not particularly limited with respect to the shape, dimensions, and fractionation characteristics, and can be appropriately selected according to the purpose of use.
Examples of the material of the hollow fiber membrane 3 include cellulose polymers, polysulfone polymers, polyacrylonitrile polymers, polymethyl methacrylate polymers, polyvinyl polymers including ethylene vinyl alcohol copolymers, polyamide polymers, Examples thereof include polyester polymers and polyolefin polymers.
Among them, the polysulfone polymer is an aromatic compound, so that it is particularly excellent in radiation resistance, is extremely resistant to heat and chemical treatment, and is excellent in safety.
Accordingly, various film forming conditions can be adopted and electron beam sterilization can be performed, which is particularly preferable as a material of the hollow fiber membrane used in the hollow fiber membrane type medical device, but is not particularly limited thereto.

The hollow fiber membrane 3 can be manufactured by a conventionally known technique.
Moreover, when using a hydrophobic polymer for the base material of the hollow fiber membrane 3, it is common to form a film by blending a hydrophilic polymer in order to impart hydrophilicity to the membrane.
Examples of the hydrophilic polymer include polyvinyl pyrrolidone (PVP), polyethylene glycol, polyvinyl alcohol, and polypropylene glycol.
In particular, polyvinylpyrrolidone is preferable from the viewpoint of hydrophilization effect and safety, but is not particularly limited thereto.
First, a polymer material for a base material and a hydrophilic polymer are dissolved in a common solvent to prepare a spinning dope.
As such a common solvent, when the hydrophilic polymer is PVP, for example, a solvent such as dimethylacetamide (hereinafter referred to as DMAC), dimethyl sulfoxide, N-methyl-2-pyrrolidone, dimethylformamide, sulfolane, dioxane and the like. Or the solvent etc. which mixed 2 or more types of the said solvent are mentioned. In order to control the pore diameter of the target hollow fiber membrane, an additive such as water may be added to the spinning dope.
When forming the hollow fiber membrane, a tube-in-orifice type spinneret is used, and the spinning stock solution is discharged from the spinneret orifice into the air simultaneously with the hollow inner solution for coagulating the spinning stock solution.
As the hollow inner liquid, water or a coagulating liquid mainly composed of water can be used, and its composition or the like may be determined according to the permeation performance of the target hollow fiber membrane. In general, a mixed solution of a solvent and water used for the spinning dope is preferably used. For example, a 0-65 mass% DMAC aqueous solution etc. are used.
The spinning dope discharged from the spinneret together with the hollow inner liquid travels through the idle running part and is introduced into the coagulation bath mainly composed of water installed at the bottom of the spinneret to complete the coagulation. Then, it winds up with a wet hollow fiber membrane winder to obtain a bundle of hollow fiber membranes, and then performs a drying treatment. Alternatively, after passing through the washing step, drying may be performed in a dryer to obtain a bundle of hollow fiber membranes.

<Method for producing hollow fiber membrane medical device>
In the hollow fiber membrane medical device 1, the bundle of hollow fiber membranes 3 is loaded along the longitudinal direction of the cylindrical container 9, and both end portions are fixed to both end portions of the cylindrical container 9.
For example, a bundle of hollow fiber membranes 3 is inserted into a cylindrical container 9 having a fluid inlet / outlet, and potting resin is injected into both ends of the bundle of hollow fiber membranes 3 so that the longitudinal center of the cylindrical container 9 is centered. It can be fixed by forming a potting layer at both ends of the bundle of hollow fiber membranes 3 and sealing both ends by centrifugal rotation as a shaft.
After fixing the bundle of hollow fiber membranes 3, excess potting resin is cut and removed, the end surfaces of the hollow fiber membranes 3 are opened, and the headers 2, 2 ′ having a fluid inlet / outlet port are attached, so that the hollow fibers A bundle of membranes 3 is loaded into a cylindrical container 9, and a first space 11 formed between the inner side of the hollow fiber membrane 3 and the inner surface of the header, and between the outer side of the hollow fiber and the inner surface of the cylindrical container 9. A hollow fiber membrane type medical device including the second space 12 can be manufactured.

  Examples of the material of the potting resin 8 that seals both ends of the bundle of the hollow fiber membranes 3 include, but are not limited to, polyurethane resin, epoxy resin, and silicon resin.

  In general, hollow fiber membrane type medical devices are roughly classified into a wet type in which the hollow interior of the hollow fiber membrane and the gap between the container and the container are filled with an aqueous medium, and a non-wet type that is not filled with the aqueous medium. Are further classified into a dry type in which the moisture content of the membrane is as low as several percent, and a semi-dry type in which the membrane is moderately wetted by moisture, a humectant or the like (sometimes referred to as a half-wet type). However, in the present embodiment, any type of hollow fiber membrane medical device can be used depending on the purpose.

When the hollow fiber membrane medical device is a wet type, an aqueous medium in which an antioxidant or a buffer solution is mixed with pure water or a solvent can be generally used.
Antioxidants include sodium pyrosulfite, acetone sodium bisulfite, sodium formaldehyde sulfoxylate, sodium hydrosulfite, 1-ascorbic acid, etc. Buffers include phosphate buffer, trishydroxy Examples include, but are not limited to, methylaminomethane buffer, acetate buffer, citrate buffer, and borate buffer.
Examples of the solvent include methanol, ethanol, glycerin, propylene glycol, isopropanol and the like, but are not particularly limited thereto.
When the hollow fiber membrane type medical device is a semi-dry type, the moisturizing agent has a function of protecting the deterioration of the hydrophilic polymer and has an appropriate viscosity and is easily held on the membrane surface. A polymer that does not form a strong chemical bond with a polymer and that simultaneously satisfies the requirement of being easily washed with a physiological aqueous solution can be preferably used.
Examples thereof include polyhydric alcohols such as glycerin, mannitol, glycols (for example, ethylene glycol, diethylene glycol, propylene glycol, tetraethylene glycol), and polyglycols (for example, polyethylene glycol).
In particular, an aqueous solution of glycerin or polyethylene glycol is more preferable, and an aqueous solution of glycerin is particularly preferable because it has a track record as a pore diameter retaining agent or a surface modifier for a blood purification hollow fiber membrane, but it is not particularly limited thereto.

[Sterilization treatment for blood treatment medical devices (hollow fiber membrane type medical devices)]
In the electron beam sterilization method of this embodiment, sterilization is performed by irradiating the above-described blood processing medical device, for example, a hollow fiber membrane medical device, with an electron beam.
At this time, as described above, the stopper is closed and the inside is sealed in an airtight and / or liquid tight state.

<Electron beam irradiation device>
As an electron beam irradiation apparatus for performing electron beam sterilization, a conventionally known electron beam irradiation apparatus can be used. For example, a microwave acceleration type electron beam irradiation apparatus that employs a method of accelerating an electron beam to a predetermined energy using a linac type acceleration tube and a microwave electric field is preferably used. According to this method, the electron beam can be controlled by turning on / off the accelerator, and the electron beam can be generated or stopped immediately at a desired timing.

<Control of electron beam absorbed dose>
In the electron beam sterilization method of the present embodiment, the cumulative electron beam absorbed dose of the blood processing medical device is preferably 5 to 60 kGy, more preferably 15 to 50 kGy, and still more preferably 15 to 45 kGy. Thereby, practically sufficient sterilization processing is performed.

Moreover, in the electron beam sterilization method in this embodiment, it is preferable to carry out in the state which packed the blood processing medical device in the predetermined sterilization bag at the electron beam irradiation process. Thereby, the blood processing medical device can be held in a sterilized state until just before use, and can be used immediately in the medical field.
Examples of the material of the sterilization bag include polyvinylidene chloride film, polyvinyl alcohol film, biaxially stretched polyvinyl alcohol film, polyvinylidene chloride coated biaxially stretched polyalcohol film, polyester / aluminum / polyethylene laminate sheet, aluminum Examples thereof include a foil and a polyethylene / nylon two-layer structure film.
In particular, a method of sealing a polyethylene / nylon two-layer structure film by laminating is preferable from the viewpoint of bag-making property and cost, but is not particularly limited thereto.

Furthermore, when sterilization is performed by electron beam irradiation, the sterilization atmosphere may be in the air, but sterilization with oxygen removed is preferable for reducing the amount of eluate.
The oxygen scavenger is not limited as long as it has a oxygen scavenging function. For example, sulfite, bisulfite, dithionite, hydroquinone, catechol, resorcin, pyrogallol, gallic acid, longalit, ascorbic acid and / or its salt, sorbose, glucose, lignin, dibutylhydroxytoluene, dibutylhydroxyanisole, Examples thereof include oxygen scavengers using metal powders such as ferrous salts and iron powders as oxygen absorbing main agents.
In addition, oxygen scavengers for metal powders are used as an oxidation catalyst, if necessary, such as sodium chloride, potassium chloride, magnesium chloride, calcium chloride, aluminum chloride, ferrous chloride, ferric chloride, sodium bromide, odor. One or two kinds of metal halides such as potassium iodide, magnesium bromide, calcium bromide, iron bromide, nickel bromide, sodium iodide, potassium iodide, magnesium iodide, calcium iodide, iron iodide, etc. The above may be added.

(Use)
The blood processing medical device of the present embodiment can be widely used for various medical devices.
For example, hemodialyzer, hemodialyzer, hemofilter, continuous hemodialyzer, continuous hemofilter, plasma separator, plasma component fractionator, plasma component adsorber, virus remover, virus adsorber, blood Examples thereof include a concentrator, a plasma concentrator, an ascites filter, and an ascites concentrator.

Hereinafter, although a specific Example and a comparative example with this are given and demonstrated, this invention is not limited to a following example.
First, various measurement methods used in Examples will be described.

[Measurement of dielectric breakdown rate]
(Visual observation)
When dielectric breakdown occurred due to electron beam irradiation, the presence or absence of a dark burnt mark was visually confirmed at the dielectric breakdown occurrence location of the hollow fiber membrane medical device.
(Positive water pressure test)
By submerging the entire hollow fiber membrane type medical device in water, sending air into it and holding it under a pressure of 150 kPa for 30 seconds, we observed the generation of bubbles from the location where dielectric breakdown occurred and confirmed the occurrence of dielectric breakdown did.
This positive underwater pressure test was performed in each of the first space and the second space of the hollow fiber membrane medical device.
When the occurrence of dielectric breakdown is confirmed by any of the above methods (visual observation) or (positive underwater pressure test), it is determined that dielectric breakdown has occurred, and the total number of hollow fiber membrane type medical devices produced The percentage of the number of dielectric breakdowns is shown as a percentage.

[Measurement of electron beam irradiation control and electron beam absorbed dose]
The hollow fiber membrane type medical devices of Examples 1 to 4 and Comparative Examples 1 and 2 described later were irradiated with an electron beam, sterilized, and each electron beam absorbed dose was measured.

[Measurement method of surface resistivity of plug]
The port plug material of Examples 1 to 4 and Comparative Examples 1 and 2 which will be described later is processed into a 100 × 100 mm test piece, and conforms to JIS K6911 and is made by ADVANTEST “ULTRA HIGH RESISTANCE METER R8340A, TEST FIXTURE R12702A. ”In an atmosphere of 22 ° C. and humidity 60% RH.

[Example 1]
Polysulfone (manufactured by Solvay Advanced Polymers, P-1700): 17 parts by mass PVP (manufactured by ISP, K-90): 4 parts by mass Dimethylacetamide (hereinafter referred to as DMAC): uniform consisting of 79 parts by mass A spinning stock solution was prepared.
A 42% aqueous solution of DMAC was used as the hollow inner solution, and was discharged from the spinneret together with the spinning stock solution.
At that time, the discharge amounts of the spinning solution and the hollow inner solution were adjusted so that the film thickness after drying was adjusted to 35 μm and the inner diameter was adjusted to 185 μm.
The discharged stock solution for spinning is immersed in a 60 ° C. coagulation bath made of water provided below 50 cm, passed through the coagulation step and the water washing step at a speed of 30 m / min, introduced into a dryer, and dried at 160 ° C. The crimped polysulfone-based hollow fiber membrane was wound up.
Next, a bundle of 16000 wound hollow fiber membranes wound up was a styrene-butadiene copolymer (registered trademark, manufactured by Asahi Kasei Chemicals Corporation) designed so that the effective membrane area of the hollow fiber membrane was 2.5 m ^2. Asaflex was loaded into a cylindrical container, and both ends thereof were bonded and fixed with urethane resin (manufactured by Sanyo Kasei Kogyo Co., Ltd.), and both ends were cut to form an open end of a hollow fiber membrane.
A 63% concentration glycerin aqueous solution (special grade, manufactured by Wako Pure Chemical Industries, Ltd.) is injected from the open end into the hollow fiber membrane for 5 seconds, flushed with 0.2 MPa air for 10 seconds, and then styrene-butadiene at both ends. A header cap made of a copolymer (manufactured by Asahi Kasei Chemical Co., Ltd., registered trademark Asaflex) was attached.
A nozzle plug made of polyethylene (manufactured by Prime Polymer Co., Ltd., registered trademark Hi-Zex) is attached to the blood inflow / outlet nozzle, and a body made of polyethylene (manufactured by Prime Polymer Co., Ltd., registered trademark of Hi-Zex) is attached to the body port Then, a port plug having a surface resistivity of 8.5 × 10 ⁹ Ω, coated with polypyrrole (ST poly), a conductive resin, was applied.

  Then, it wrapped with the sterilization bag of polyethylene / nylon two-layer structure, and it irradiated so that an electron beam absorbed dose might be set to 35 kGy. The surface resistivity and dielectric breakdown occurrence rate of the port plug body of Example 1 are shown in Table 1 below.

[Example 2]
A port plug having a surface resistivity of 9.0 × 10 ⁷ Ω was attached to the port of the main body.
Other conditions were the same as in Example 1, and a hollow fiber membrane type medical device was obtained.
This hollow fiber membrane type medical device was packaged in a sterilization bag having a polyethylene / nylon two-layer structure, and irradiation was performed while controlling the electron beam absorbed dose to be 35 kGy.
The surface resistivity and dielectric breakdown occurrence rate of the port plug body of Example 2 are shown in Table 1 below.

Example 3
A port plug having a surface resistivity of 2.4 × 10 ⁵ Ω was attached to the port of the main body.
Other conditions were the same as in Example 1, and a hollow fiber membrane type medical device was obtained.
This hollow fiber membrane blood purifier was packaged in a polyethylene / nylon two-layer structure sterilization bag, and irradiation was performed while controlling the electron beam absorbed dose to be 35 kGy.
The surface resistivity and dielectric breakdown occurrence rate of the port plug of Example 3 are shown in Table 1 below.

Example 4
A port plug having a surface resistivity of 2.4 × 10 ⁵ Ω was attached to the port of the main body.
Other conditions were the same as in Example 1, and a hollow fiber membrane type medical device was obtained.
This hollow fiber membrane type medical device was packaged in a sterilized bag having a polyethylene / nylon two-layer structure, and irradiation was performed while controlling the electron beam absorbed dose to be 57 kGy.
The surface resistivity and dielectric breakdown occurrence rate of the port plug of Example 4 are shown in Table 1 below.

[Comparative Example 1]
A port plug having a surface resistivity of 7.9 × 10 ¹⁰ Ω was attached to the port of the main body.
Other conditions were the same as in Example 1, and a hollow fiber membrane type medical device was obtained.
This hollow fiber membrane type medical device was packaged in a sterilization bag having a polyethylene / nylon two-layer structure, and irradiation was performed while controlling the electron beam absorbed dose to be 35 kGy.
The surface resistivity and dielectric breakdown occurrence rate of the port plug of Comparative Example 1 are shown in Table 1 below.

[Comparative Example 2]
A port plug made of polyethylene (manufactured by Prime Polymer Co., Ltd., registered trademark Hi-Zex) and having a surface resistivity of 4.5 × 10 ¹⁷ Ω was attached to the port of the main body.
Other conditions were the same as in Example 1, and a hollow fiber membrane type medical device was obtained.
This hollow fiber membrane type medical device was packaged in a sterilization bag having a polyethylene / nylon two-layer structure, and irradiation was performed while controlling the electron beam absorbed dose to be 35 kGy.
The surface resistivity and dielectric breakdown occurrence rate of the port plug of Comparative Example 2 are shown in Table 1 below.

As shown in Table 1, in the hollow fiber membrane medical devices of Examples 1 to 4 in which the port plug is formed of a polymer material having a surface resistivity of 1 × 10 ¹⁰ Ω or less, all of them are dielectric breakdown. Generation was effectively prevented.

  The blood treatment medical device of the present invention is used in medical practice in hemodialysis, hemodiafiltration, hemofiltration, continuous hemodiafiltration, continuous hemofiltration, plasma exchange, double filtration plasma exchange, virus removal, blood concentration, ascites It has industrial applicability for various medical uses such as filtration / concentration and adsorption.

DESCRIPTION OF SYMBOLS 1 Hollow fiber membrane type medical device 2, 2 'Header 3 Hollow fiber membrane 4, 5 Nozzle 6, 7 Port 8 Potting resin 9 Cylindrical container 11 First space 12 Second space 20, 200 Port plug 21 210 Among the parts constituting the plug attached to the port, the part 22 made of a polymer material having a surface resistivity of 1 × 10 ¹⁰ Ω or less, 220 Among the parts constituting the plug attached to the port, the surface resistance Portion made of a polymer material having a rate of less than 1 × 10 ¹⁰ Ω or less 30 Nozzle plug

Claims (11)

A plug for sealing the outlet and / or the inlet of the blood processing medical device,
A portion having a surface resistivity of 1 × 10 ¹⁰ Ω or less,
A plug body that is sterilized by electron beam irradiation including the blood medical device in a state where the inside of the blood processing medical device is gas and / or liquid tightly sealed. The plug according to claim 1, wherein the plug is a molded body of a polymer material having a surface resistivity of 1 × 10 ¹⁰ Ω or less. The plug according to claim 1, wherein the surface of the plug is coated with a polymer material having a surface resistivity of 1 × 10 ¹⁰ Ω or less.   The plug according to any one of claims 1 to 3, wherein the blood processing medical device is a hollow fiber membrane type medical device. A stopper having a portion having a surface resistivity of 1 × 10 ¹⁰ Ω or less;
A blood processing medical device that is sterilized by electron beam irradiation in an airtight and / or liquid tightly sealed state by the stopper.   The blood processing medical device according to claim 5, which is a hollow fiber membrane type medical device. A cylindrical container;
A bundle of hollow fiber membranes loaded along the longitudinal direction of the cylindrical container and having both ends fixed to both ends of the cylindrical container;
A potting resin in which the bundle of hollow fiber membranes is embedded and fixed at both ends of the cylindrical container;
Opposing both end surfaces of the hollow fiber membrane, provided at both end portions of the cylindrical container, and headers each having a nozzle serving as a fluid inlet / outlet,
Provided on the side surface of the cylindrical container, and a port serving as a fluid inlet and outlet;
A nozzle plug detachable from the nozzle;
A port plug detachable from the port;
Comprising
The blood processing medical device according to claim 5 or 6, wherein the port plug is a hollow fiber membrane type medical device having a portion having a surface resistivity of 1 x 10 ¹⁰ Ω or less. The blood processing medical device according to claim 7, wherein the port plug is made of a polymer material having a surface resistivity of 1 × 10 ¹⁰ Ω or less. 9. The blood processing medical device according to claim 7, wherein the nozzle plug has a portion made of a polymer material having a surface resistivity of 1 × 10 ¹⁰ Ω or less. The blood processing medical device according to any one of claims 7 to 9, wherein the nozzle plug is made of a polymer material having a surface resistivity of 1 x 10 ¹⁰ Ω or less.   The blood processing medical device according to any one of claims 5 to 10, wherein the blood processing medical device is irradiated with an electron beam in an airtight and / or liquid tightly sealed state by the stopper. Wire sterilization method.

Images