JP6231733B2 - Hollow fiber membrane medical device - Google Patents

Description

  The present invention relates to a hollow fiber membrane type medical device.

  Many blood purification therapies using hollow fiber membrane separation techniques such as hemodialysis, blood filtration, and hemofiltration dialysis have been devised. These blood purification therapies are applied not only to chronic renal failure patients but also to acute renal failure patients, congestive heart failure patients, and the like, and in recent years, they have been widely applied in lifesaving emergency, ICU, and the like.

  The hollow fiber membrane module has a cylindrical container and 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. The hollow fiber membrane bundle includes a potting resin portion that is embedded and fixed at both ends of the cylindrical container. Further, opposite to both end surfaces of the hollow fiber membrane, provided at both end portions of the cylindrical container, each provided with a header having a nozzle serving as a fluid inlet / outlet, and provided on a side surface portion of the cylindrical container. And a port serving as a fluid inlet / outlet port.

  The nozzle of the header attached to the hollow fiber membrane bundle is oriented in the axial direction, and the axis of the flow path also passes through the center of the hollow fiber membrane bundle. In general, since the liquid flows in a region having the least resistance, it is known that the liquid does not smoothly reach the outer peripheral portion in the header and blood drifts and stays.

  For example, Patent Document 1 discloses a method in which the liquid is spread to the outer peripheral portion in the header by increasing the taper angle of the header and decreasing the resistance in the header. However, this method increases the capacity in the header and results in a heavy burden on the patient.

  For example, Patent Document 2 discloses a method of reducing the occurrence of drift and retention in the header by narrowing the spread of the root portion of the nozzle inside the header. Patent Document 3 discloses a method of reducing the occurrence of drift and retention in the header by thinning and flattening the inside of the header. However, in the methods described in the cited references 2 and 3, the resistance in the header becomes too high, the liquid does not smoothly reach the outer periphery of the header, blood stagnates in the header, and the dispersibility deteriorates. Result.

JP 04-305229 A JP 09-108338 A Japanese Patent No. 2554958

  In order to prevent blood drift, that is, to improve distribution, generally, the pressure loss in the header may be reduced with respect to the resistance value (pressure loss) on the hollow fiber membrane side. In order to reduce the pressure loss in the header, it is only necessary to widen the space in the header. As a result, a header having a large volume is advantageous. However, a large-volume header has a problem in that the priming volume increases, the priming processing time and unit price increase, and this is disadvantageous for enforcement. Conversely, when a small-volume header is used to reduce the priming volume, the resistance value in the header increases, resulting in poor blood distribution.

  The present invention aims to solve the above-described problems. The hollow fiber membrane having a header shape that solves the above two conflicting problems and can achieve both a reduction in priming volume and an improvement in blood distribution. An object is to provide a type medical device.

  As a result of intensive studies to solve the above-mentioned problems, the present inventors have found the conditions for optimizing the above-mentioned header shape and have come up with the present invention.

That is, the present invention includes 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, and both ends of the cylindrical container. The hollow fiber membrane bundle is surrounded by both ends of the hollow fiber membrane bundle, and both ends of the hollow fiber membrane bundle are embedded and fixed. A hollow fiber membrane-type medical device comprising a header having a nozzle that faces an end face of a yarn membrane and that serves as a fluid inlet / outlet, and a port that is provided on a side surface of the cylindrical container and serves as a fluid inlet / outlet. Assuming that the cross-sectional area when the inner space of the header is cut along the direction perpendicular to the axis of the cylindrical container is the cross-sectional area of the header, the volume of the header per cross-sectional area of the header is the volume of the hollow fiber membrane. 1.0 × is ^{10 -2,} and the hollow fiber membrane With respect to such pressure loss, the header has a height h at which the pressure loss applied to the header is 1.5 to 7.0%, and the inner space of the header includes an opposing surface facing the end surface of the hollow fiber membrane, The side surface is defined by a side surface that surrounds the edge portion, and the side surface is an inclined surface that is inclined outward from the edge portion of the opposing surface when viewed in a cross section along the direction of the axis. It is inclined 15 to 70 ° with respect to the end face. The pressure loss applied to the header with respect to the pressure loss applied to the hollow fiber membrane is more preferably 1.9 to 6.9%, and further preferably 2.0 to 6.0%. Moreover, the inclination angle of the side surface is more preferably 30 to 60 ° with respect to the end surface of the hollow fiber membrane.

Furthermore, the radius of the inner diameter of the header is a, the height h _{1 of} the header at a position a / 3 away from the center of the header in the direction orthogonal to the axis of the cylindrical container, and the axis of the cylindrical container from the center of the header If the header height h ₂ is 2a / 3 away in the direction orthogonal to the header height h, the header height h is 0.9 to 1.0 h ₁ = h ₂ , or h ₁ = 0.9 to It is preferable that 1.0 h ₂ is satisfied.

  Further, it is preferable that the nozzle is disposed at the central portion of the header along the axis of the cylindrical container, and the radius of curvature of the base portion of the nozzle is 3 mm or less. At this time, the radius of curvature is more preferably 2.5 mm or less, and further preferably 2.0 mm or less.

  Furthermore, the bundle of hollow fiber membranes preferably has a filling rate of 55 to 70% with respect to the volume of the inner space of the cylindrical container.

  Moreover, this invention is a header which comprises said hollow fiber medical device.

  According to the present invention, as a result of optimizing the height of the header, it is possible to achieve both reduction in the priming volume and improvement in the distribution of blood in the header.

It is a longitudinal section showing an outline of a hollow fiber membrane type medical device concerning an embodiment of the present invention. FIG. 2 is a transverse cross-sectional view taken along the line II-II in FIG. 1, and particularly shows a cross-section of the inner space that is the basis for calculating the cross-sectional area of the header. It is sectional drawing which expands and shows a header. It is sectional drawing which shows the structure of the header shown in FIG. 3 in detail. It is a perspective view which shows the header shown in FIG. It is sectional drawing which expands and shows the header which concerns on another form. It is a perspective view which shows the header shown in FIG. It is a graph which shows the ideal residence time distribution of the fluid in a header. It is a graph which shows the residence time distribution of the blood filter which concerns on 1st Example. It is a graph which shows the residence time distribution of the blood filter which concerns on 2nd Example. It is a graph which shows the residence time distribution of the blood filter which concerns on 3rd Example. It is a graph which shows the residence time distribution of the blood filter which concerns on 4th Example. It is a graph which shows residence time distribution of the blood filter which concerns on 5th Example. 5 is a graph showing a residence time distribution of a blood filter according to Comparative Example 1. 10 is a graph showing a residence time distribution of a blood filter according to Comparative Example 2. 10 is a graph showing a residence time distribution of a blood filter according to Comparative Example 3.

  Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. Note that the embodiments described below do not limit the present invention. In addition, this invention is not limited to the following description, In the range of the summary, various deformation | transformation can be implemented.

[Hollow fiber membrane medical device]
As shown in FIG. 1, a hollow fiber membrane medical device 1 according to this embodiment is loaded along a substantially cylindrical tubular container 3 and the longitudinal direction of the tubular container 3, and both ends 5 a and 5 b. Are bundles of hollow fiber membranes 4 (hereinafter referred to as “hollow fiber membrane bundles”) 5 fixed to both end portions 3a and 3b of the cylindrical container 3, and inside the both end portions 3a and 3b of the cylindrical container 3. A potting resin portion 7 is provided that surrounds both end portions 5a and 5b of the hollow fiber membrane bundle 5 and in which both end portions 5a and 5b of the hollow fiber membrane bundle 5 are embedded and fixed.

  Further, a port 9 serving as a fluid inlet / outlet is provided on the side surface portion 3 c of the cylindrical container 3, and headers 10 are attached to both end portions 3 a and 3 b of the cylindrical container 3, respectively.

  In this embodiment, since the header 10 attached to each of both end portions 3a and 3b of the cylindrical container 3 has the same configuration, the header 10 at one end portion 3a (upper end portion shown in FIG. 1) is used. This will be explained as a representative.

  As shown in FIGS. 1 and 3 to 5, the header 10 is a circular cap-like member disposed so as to face one end surface 4 c (upper side shown in FIG. 1) of the hollow fiber membrane 4. The header 10 is provided in a cylindrical shape along the peripheral edge of the cover portion 10 a and a substantially circular cover portion 10 a that covers the opening of the one end portion 3 a of the cylindrical container 3, and circumscribes the one end portion 3 a of the cylindrical container 3. And the fixing | fixed part 10b fixed to the cylindrical container 3 is provided.

  The cover portion 10a has a facing surface S1 that faces the end surface 4c of the hollow fiber membrane 4, and a peripheral side surface S2 that surrounds the peripheral portion of the facing surface S1. The facing surface S1 and the peripheral side surface S2 define an inner space A of the header 10. The peripheral side surface S2 is an inclined surface that linearly inclines toward the end surface 4c side of the hollow fiber membrane 4 outward from the peripheral edge of the opposed surface S1 with respect to the end surface 4c (opposing surface S1) of the hollow fiber membrane 4. . That is, the opposing surface S1 and the peripheral side surface S2 form a predetermined angle of 90 ° or more. A nozzle 11 serving as a liquid inlet / outlet is provided in the central portion of the cover portion 10a (the central portion of the header 10). The nozzle 11 extends along the axis CS of the cylindrical container 3. In addition, an annular sealing material 13 for securing airtightness is sandwiched between the end surface of the potting resin portion 7 on the cover portion 10a side and the periphery of the cover portion 10a. As for the header 10 and the cylindrical container 3, the screw part formed in the inner peripheral surface of the fixing | fixed part 10b and the screw part formed in the outer peripheral surface of the one side edge parts 3a and 3b of the cylindrical container 3 are screwed together. It is fixed by.

  Next, each element of the hollow fiber membrane medical device 1 will be described in more detail, and a method for manufacturing the hollow fiber membrane medical device 1 will be described.

  The hollow fiber membrane 4 which concerns on this embodiment is not specifically limited regarding a shape, a dimension, and a fractionation characteristic, It can select suitably in light of the intended purpose.

  Examples of the material of the hollow fiber membrane 4 include cellulose polymers, polysulfone polymers, polyacrylonitrile polymers, polymethyl methacrylate polymers, polyvinyl polymers including ethylene vinyl alcohol copolymers, polyamide polymers Examples include molecules, polyester polymers, polyolefin polymers, and the like.

  The hollow fiber membrane 4 can be manufactured by a conventionally known technique.

  Moreover, when using a hydrophobic polymer for the base material of the hollow fiber membrane 4, 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 hole diameter of the target hollow fiber membrane 4, an additive such as water may be added to the spinning dope.

  When the hollow fiber membrane 4 is formed, 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 the composition and the like may be determined according to the permeation performance of the target hollow fiber membrane 4. 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 the wet hollow fiber membrane winder, the hollow fiber membrane bundle 5 is obtained, and a drying process is performed after that. Alternatively, the hollow fiber membrane bundle 5 may be obtained by performing drying in a dryer after the washing step.

  The hollow fiber membrane bundle 5 is loaded along the longitudinal direction of the cylindrical container 3, and both end portions 5 a and 5 b are fixed to the both end portions 3 a and 3 b of the cylindrical container 3.

  For example, the hollow fiber membrane bundle 5 is inserted into a cylindrical container 3 having a port 9 serving as a fluid inlet / outlet port, and potting resin is injected into both end portions 5a and 5b of the hollow fiber membrane bundle 5 to thereby form the cylindrical container 3 Can be fixed by forming a potting layer (potting resin portion) 7 at both ends 5a and 5b of the hollow fiber membrane bundle 5 and sealing the both ends.

  In addition, after fixing the hollow fiber membrane bundle 5, the excess potting resin is cut and removed, the end surface 4c of the hollow fiber membrane 4 is opened, and the header 10 having the port 9 is attached. The hollow fiber membrane type medical device 1 filled in the cylindrical container 3 can be manufactured.

  Examples of the material of the potting resin that seals both ends 5a and 5b of the hollow fiber membrane bundle 5 include polyurethane resin, epoxy resin, and silicon resin, but are not particularly limited thereto.

  Examples of the material of the cylindrical container 3 and the header 10 include polypropylene resin, polystyrene resin, polymethyl methacrylate resin, polyethylene terephthalate resin, nylon 6 resin, polysulfone resin, polyacrylonitrile resin, polycarbonate resin, ABS resin, and styrene / butadiene. Polymer resin etc. are mentioned.

  In particular, polypropylene resin, polystyrene resin, polyacrylonitrile resin, and styrene / butadiene copolymer resin are preferable because the resin cost is low, the versatility in the field of medical members is high, and high safety is confirmed. A styrene / butadiene copolymer resin is particularly preferred, but it is not particularly limited thereto.

  The nozzle 11 of the header 10 is, for example, JIS T 3250: 2005 (hemodialyzer, hemodiafiltration filter, blood filtration filter and blood concentrator) 44.3 (hemodialyzer). , Hemodiafiltration filter and blood side connection part of blood filter).

  The hollow fiber membrane bundle 5 has a filling rate of 55 to 70% with respect to the volume of the inner space B of the cylindrical container 3.

[Conditions for optimizing header shape]
Next, a condition for optimizing the header shape in order to achieve both reduction in the priming volume and improvement in blood distribution, that is, to define the optimum height (h) and shape of the header 10 The first condition, the second condition, and the third condition will be described.

The first condition is that the volume per cross-sectional area of the header 10 is 1.0 × 10 ⁻² or less of the volume of the hollow fiber membrane 4. Here, regarding the cross-sectional area of the header 10 (see FIG. 2 and FIG. 3), the cross-section when the inner space A of the header 10 is cut along the direction perpendicular to the axis CS of the cylindrical container 3 (transverse cross-section). And the cross-sectional area is assumed as the cross-sectional area of the header 10.

  The second condition is that the pressure loss applied to the header 10 with respect to the pressure loss applied to the hollow fiber membrane 4 is 1.5 to 7.0%. In this case, the ratio of the pressure loss applied to the header 10 to the pressure loss applied to the hollow fiber membrane 4 is preferably 1.9 to 6.9%, more preferably 2.0 to 6.0%. .

  Further, the third condition is that the peripheral side surface S2 of the cover portion 10a of the header 10 is an inclined surface, and the inclined angle of the peripheral side surface S2 is 15 to 70 °. The inclination angle of the peripheral side surface S2 is more preferably 30 to 60 °.

  Hereinafter, the meaning of terms and calculation methods under each condition will be described in more detail.

[Volume per header cross-sectional area]
The volume (mL / cm ² ) per header cross-sectional area is obtained by the following equation (1).

(1) Header capacity Header capacity, Ru can be obtained from the weight of the water injected into the header (first calculating how). The first calculation method is, for example, a case where the hollow fiber membrane bundle 5 is filled in the cylindrical container 3, and the weight when the hollow fiber module in which the headers 10 are attached to both ends 3a and 3b of the cylindrical container 3 is filled with water. The volume of the entire hollow fiber module is measured, and 1/2 of the difference from the volume of the hollow fiber membrane 4 obtained by the following equation (3) is calculated.

(2) Cross-sectional area of the header The cross-sectional area of the header 10 refers to the inner diameter of the header 10 on the cylindrical container 3 side, for example, the inner surface of the cover portion 10a is the end surface of the hollow fiber membrane 4 and the potting resin portion 7 (hereinafter referred to as “ The area (cm ² ) determined by the following equation (2), where D (see FIGS. 2 and 3) is the inner diameter of the portion adjacent to the “urethane surface”) .

(3) Volume of Hollow Fiber Membrane The volume of the hollow fiber membrane 4 refers to the inner diameter of the hollow fiber membrane 4 as d, the length of the hollow fiber membrane 4 as L, and the number of the hollow fiber membranes 4 in the hollow fiber membrane bundle 5 as N. It is a volume (mL) calculated | required by the following formula | equation.

[Pressure loss on the header against pressure loss on the hollow fiber membrane]
The ratio (%) of the pressure loss applied to the header 10 to the pressure loss applied to the hollow fiber membrane 4 can be obtained by the following equation (4).

(1) Pressure loss applied to the hollow fiber membrane The pressure loss applied to the hollow fiber membrane 4 means that the inner diameter of the hollow fiber membrane 4 is d, the length of the hollow fiber membrane 4 is L, the number of the hollow fiber membranes 4 is N, liquid When the flow rate of the liquid is 100 (mL / min) and the viscosity of the liquid is 0.0033 (Pa · s), the following Hagen-Poiseuille theoretical formula (Formula (5)) is obtained (kPa).

(2) Pressure loss applied to the header The pressure loss applied to the header 10 is determined by the following equation (6) (kPa).

Note that the pressure loss applied to the entire hollow fiber membrane medical device in Formula (6) is, for example, the hollow fiber when a PVP aqueous solution adjusted to a viscosity of 0.0033 (Pa · s) is passed through the hollow fiber module. It can be obtained by measuring the difference in pressure loss before and after the module (kPa). Alternatively, in the model in which the header 10 is attached to both ends 5a and 5b of the hollow fiber membrane bundle 5, the hollow fiber bundle 5 is a porous body having a pressure loss applied to the hollow fiber bundle 5 and has a viscosity of 0.0033 (Pa · s), a general fluid analysis software Star-CCM + is used to calculate the pressure loss between the inlet and outlet of the model when a liquid having a density of 1.055 (g / cm ³ ) is passed at a flow rate of 100 (mL / min). It can be obtained by using and simulating.

[Inclination angle of the peripheral side surface of the header cover]
The inclination angle of the peripheral side surface S2 of the cover portion 10a of the header 10 is set as an angle with respect to the end surface 4a (inflow surface) of the hollow fiber membrane 4. In the present embodiment, the circumferential side surface S2 is inclined at an inclination angle of 45 ° with respect to the end surface 4c (urethane surface) of the hollow fiber membrane 4. Specifically, when viewed in a section (longitudinal section) when the header 10 is cut along the axis CS of the cylindrical container 3, a straight line along the inclination of the peripheral side surface S2 of the cover portion 10a of the header 10 The angle formed by the end surface 4c of the hollow fiber membrane 4 is the inclination angle of the peripheral side surface S2. The inclination angle of the peripheral side surface S2 is 15 to 70 °, and more preferably 30 to 60 °.

[Header height]
The height (h) of the header 10 is intended to be the distance (dimension) from the urethane surface to the inner surface (opposing surface S1) of the cover portion 10a in the state where the header 10 is attached to both end portions 3a, 3b of the cylindrical container 3. doing. It is preferable that the height (h) of the header 10 is substantially the same height in the entire range of the cover portion 10a, and this substantially the same is not only the case where it is completely the same, but also the following height. A case where (h ₁ ) and height (h ₂ ) satisfy predetermined conditions is also included.

(1) Height (h ₁ )
When the radius of the header 10 on the cylindrical container 3 side, specifically, 1/2 of the inner diameter D of the portion where the inner surface of the cover portion 10a is close to the urethane surface is a, the central axis of the header 10 (tubular container 3 is a distance from the urethane surface at a position a / 3 away from the third axis CS) to the facing surface S1 of the cover portion 10a of the header 10.

(2) Height (h ₂ )
This is the distance from the urethane surface at a position 2a / 3 away from the central axis of the header 10 (axis CS of the cylindrical container 3) to the facing surface S1 of the cover portion 10a of the header 10.

(3) Height (h ₁ ) and conditions to be satisfied by height (h ₂ ) 0.9 to 1.0 h ₁ = h ₂ , or h ₁ = 0.9 to 1.0 h ₂

[Curve radius of nozzle base]
The radius of curvature is obtained as the radius of a circle when the arc is assumed to be part of the circle. The radius of curvature of the base portion 11a of the nozzle 11 according to this embodiment is 3 mm or less. Specifically, when a cross section (longitudinal cross section) when the header 10 is cut along the axis CS of the cylindrical container 3 is viewed, the inner surface of the nozzle 11 and the cover portion 10a are formed on the inner space A side of the header 10. The radius of curvature of the portion that is bent and communicated with the inner surface is the radius of curvature of the base portion 11a of the nozzle 11, and the radius of curvature is 3 mm or less. At this time, the radius of curvature is more preferably 2.5 mm or less, and further preferably 2.0 mm or less. A radius of curvature of less than 0.01 mm is practically difficult to manufacture and means a substantially right angle.

  As mentioned above, according to the hollow fiber membrane type medical device 1 which concerns on this embodiment, since the height (h) and shape of the header 10 can be optimized in consideration of the blood distribution, the height of the header 10 ( h) can be kept as low as possible, and the priming volume can be reduced. As a result, according to the hollow fiber membrane medical device 1, it is possible to achieve both a reduction in the priming volume and an improvement in the distribution of blood in the header 10.

  In addition, the fixing method of the header 10 and the cylindrical container 3 is not limited to the form which screws together with a screw part. As shown in FIGS. 6 and 7, the header 10A includes a cover portion 10Aa and a fixing portion 10Ab, and the fixing portion 10Ab of the header 10A and the cylindrical container 3A may be fixed by welding. . In the case of this configuration, since airtightness is secured by welding the header 10A and the cylindrical container 3A, the airtightness is between the end surface of the potting resin portion 7 on the cover portion 10a side and the peripheral edge of the cover portion 10a. It is not necessary to provide the annular sealing material 13 for ensuring the above.

  Hereinafter, although a specific example (blood filter) and a comparative example with this will be described, the present invention is not limited to the following example.

[About the evaluation test]
An aqueous solution obtained by dissolving polyvinyl pyrrolidone K90 (manufactured by Wako Co., Ltd.) so as to have a viscosity of 3.3 mPa · s was used as a pool and allowed to flow at room temperature at a flow rate of 100 mL / min. 2.5 mL of red ink (manufactured by Non-Easy Paste Industry Co., Ltd.) diluted 100 times before the blood filter was injected instantaneously, and 5 mL of the liquid discharged from the blood filter was sampled. The absorbance at 485 nm of the obtained sampling solution was measured, and the residence time distribution through which the red ink passed through the blood filter was plotted. If there is no stagnation and drift, a waveform as shown in FIG. 8 is drawn.

[Example 1]
6300 hollow fiber membranes were inserted into a cylindrical container and potted to mold a module having an effective membrane area of 0.7 m ² . Headers having the following specifications were attached to both ends of the cylindrical container, and irradiation sterilization with γ rays (25 kGy) was performed to obtain a blood filter (blood filter 1).

In Example 1, the capacity of the attached header was 1.8 mL, the cross-sectional area of the header was 9.0 cm ² , and the volume of the hollow fiber membrane (hereinafter referred to as “hollow fiber capacity”) was 44 mL. The volume per cross-sectional area was set to 9.1 × 10 ⁻³ of the hollow fiber capacity. The pressure loss applied to the hollow fiber membrane is 2.41 kPa, the pressure loss applied to the entire hollow fiber membrane medical device is 2.48 kPa, and the ratio of the pressure loss applied to the header to the pressure loss applied to the hollow fiber membrane is 2.9. %.

At this time, the height in the header was h ₁ = 1.8 mm, h ₂ = 1.8 mm, and the inclination angle of the peripheral side surface was 45 °. Moreover, the curvature radius of the base part of the nozzle was 1.2 mm. Using this blood filter 1, the residence time distribution was evaluated. As a result, the plot was as shown in FIG. 9, and the residence time distribution was close to an ideal curve, and it was found that the blood flowed in the blood filter 1 without any drift or residence.

[Example 2]
9100 hollow fiber membranes were inserted into a cylindrical container and potted to mold a module having an effective membrane area of 1.0 m ² . Headers having the following specifications were attached to both ends of the cylindrical container, and irradiation sterilization with γ rays (25 kGy) was performed to obtain a blood filter (blood filter 2).

In Example 2, the volume of the attached header is 2.5 mL, the cross-sectional area of the header is 12.9 cm ² , and the hollow fiber capacity is 63 mL, so that the volume per cross-sectional area of the header is the volume of the hollow fiber membrane. It was set to 6.2 × 10 ⁻³ . The pressure loss applied to the hollow fiber membrane is 1.67 kPa, the pressure loss applied to the entire hollow fiber membrane medical device is 1.73 kPa, and the ratio of the pressure loss applied to the header to the pressure loss applied to the hollow fiber membrane is 3.6. %.

At this time, the height in the header was h ₁ = 1.8 mm, h ₂ = 1.8 mm, and the inclination angle of the peripheral side surface was 45 °. Moreover, the curvature radius of the base part of the nozzle was 1.2 mm. Using this blood filter 2, the residence time distribution was evaluated. As a result, the plot was as shown in FIG. 10, and the residence time distribution was close to an ideal curve, and it was found that it flowed through the hemofilter without causing drift or residence.

[Example 3]
9100 hollow fiber membranes were inserted into a cylindrical container and potted to mold a module having an effective membrane area of 1.0 m ² . Headers having the following specifications were attached to both ends of the cylindrical container, and irradiation sterilization with γ rays (25 kGy) was performed to obtain a blood filter (blood filter 3).

In Example 3, the capacity of the attached header is 1.2 mL, the cross-sectional area of the header is 12.9 cm ² , and the hollow fiber capacity is 63 mL, so that the volume per cross-sectional area of the header is the volume of the hollow fiber membrane. It was set to 3.0 × 10 ⁻³ . The pressure loss applied to the hollow fiber membrane is 1.67 kPa, the pressure loss applied to the entire hollow fiber membrane medical device is 1.77 kPa, and the ratio of the pressure loss applied to the header to the pressure loss applied to the hollow fiber membrane is 6.0. %.

At this time, the height in the header was h ₁ = 0.7 mm, h ₂ = 0.7 mm, and the inclination angle of the peripheral side surface was 30 °. Moreover, the curvature radius of the nozzle root part was 1.2 mm. Using the blood filter 3, the residence time distribution was evaluated. As a result, the plot was as shown in FIG. 11, and the residence time distribution was close to an ideal curve, and it was found that the sample flowed through the hemofilter without causing drift or residence.

[Example 4]
8200 hollow fiber membranes were inserted into a cylindrical container and potted to mold a module having an effective membrane area of 1.0 m ² . Headers having the following specifications were attached to both ends of the cylindrical container, and sterilization by irradiation with γ rays (25 kGy) was performed to obtain a blood filter (blood filter 4).

In Example 4, the volume of the attached header is 3.1 mL, the cross-sectional area of the header is 10.8 cm ² , and the hollow fiber capacity is 55 mL, so that the volume per cross-sectional area of the header is the volume of the hollow fiber membrane. 1.0 × 10 ⁻² Further, the pressure loss applied to the hollow fiber membrane is 3.67 kPa, the pressure loss applied to the entire hollow fiber membrane medical device is 3.74 kPa, and the ratio of the pressure loss applied to the header to the pressure loss applied to the hollow fiber membrane is 1.9. %.

At this time, the height in the header was h ₁ = 2.7 mm, h ₂ = 2.7 mm, and the inclination angle of the peripheral side surface was 60 °. Moreover, the curvature radius of the nozzle root part was 2.5 mm. The blood filter 4 was used to evaluate the residence time distribution. As a result, the plot was as shown in FIG. 12, and the residence time distribution was close to an ideal curve, and it was found that the sample flowed through the hemofilter without causing drift or residence.

[Example 5]
11700 hollow fiber membranes were inserted into a cylindrical container and potted to mold a module having an effective membrane area of 1.3 m ² . Headers having the following specifications were attached to both ends of the cylindrical container, and irradiation sterilization with γ rays (25 kGy) was performed to obtain a blood filter (blood filter 5).

In Example 5, the capacity of the attached header is 2.7 mL, the cross-sectional area of the header is 16.6 cm ² , and the hollow fiber capacity is 81 mL, so that the volume per cross-sectional area of the header is the volume of the hollow fiber membrane. It was set to 4.0 × 10 ⁻³ . The pressure loss applied to the hollow fiber membrane is 1.30 kPa, the pressure loss applied to the entire hollow fiber membrane medical device is 1.39 kPa, and the ratio of the pressure loss applied to the header to the pressure loss applied to the hollow fiber membrane is 6.9. %.

At this time, the height in the header was h ₁ = 1.7 mm, h ₂ = 1.7 mm, and the inclination angle of the peripheral side surface was 45 °. Further, the radius of curvature of the nozzle root portion was 0.5 mm. The blood filter 5 was used to evaluate the residence time distribution. As a result, the plot was as shown in FIG. 13, and the residence time distribution was close to an ideal curve, and it was found that the sample flowed through the hemofilter without causing drift or residence.

[Comparative Example 1]
6300 hollow fiber membranes were inserted into a cylindrical container and potted to mold a module having an effective membrane area of 0.7 m ² . Headers having the following specifications were attached to both ends of the cylindrical container, and irradiation sterilization with γ rays (25 kGy) was performed to obtain a blood filter (blood filter 6).

In Comparative Example 1, the volume of the attached header is 3.6 mL, the header cross-sectional area is 9.0 cm ² , and the hollow fiber capacity is 44 mL, so that the volume per cross-sectional area of the header is the volume of the hollow fiber membrane. It was set to 1.8 × 10 ⁻² . The pressure loss applied to the hollow fiber membrane is 2.41 kPa, the pressure loss applied to the entire hollow fiber membrane medical device is 2.47 kPa, and the ratio of the pressure loss applied to the header to the pressure loss applied to the hollow fiber membrane is 2.5. %.

At this time, the height in the header was h ₁ = 3.7 mm, h ₂ = 3.7 mm, and the inclination angle of the peripheral side surface was 60 °. In addition, the radius of curvature of the base portion of the nozzle was 3.0 mm. Using the blood filter 6, the residence time distribution was evaluated. As a result, the plot was as shown in FIG. 14, and the residence time distribution was different from an ideal curve, and peak cracking was observed, causing drift and residence.

[Comparative Example 2]
9100 hollow fiber membranes were inserted into a cylindrical container and potted to mold a module having an effective membrane area of 1.0 m ² . Headers having the following specifications were attached to both ends of the cylindrical container, and irradiation sterilization with γ rays (25 kGy) was performed to obtain a blood filter (blood filter 7).

In Comparative Example 2, the capacity of the attached header is 5.1 mL, the cross-sectional area of the header is 12.9 cm ² , the hollow fiber capacity is 63 mL, and the volume per cross-sectional area of the header is 1.3 of the volume of the hollow fiber membrane. ^X10-2 . The pressure loss applied to the hollow fiber membrane is 1.67 kPa, the pressure loss applied to the entire hollow fiber membrane medical device is 1.72 kPa, and the ratio of the pressure loss applied to the header to the pressure loss applied to the hollow fiber membrane is 3.0. %.

At this time, the height in the header was h ₁ = 3.7 mm, h ₂ = 3.7 mm, and the inclination angle of the peripheral side surface was 60 °. In addition, the radius of curvature of the base portion of the nozzle was 3.0 mm. Using this blood filter 7, the residence time distribution was evaluated. As a result, the plot was as shown in FIG. 15, and the residence time distribution was different from an ideal curve, and peak cracking was observed, causing drift and residence.

[Comparative Example 3]
9100 hollow fiber membranes were inserted into a cylindrical container and potted to mold a module having an effective membrane area of 1.0 m ² . Headers having the following specifications were attached to both ends of the cylindrical container, and irradiation sterilization with γ rays (25 kGy) was performed to obtain a blood filter (blood filter 8).

In Comparative Example 3, the capacity of the attached header is 0.7 mL, the cross-sectional area of the header is 12.9 cm ² , the hollow fiber capacity is 63 mL, and the volume per cross-sectional area of the header is 1.7 times the volume of the hollow fiber membrane. ^X10-3 . The pressure loss applied to the hollow fiber membrane is 1.67 kPa, the pressure loss applied to the entire hollow fiber membrane medical device is 1.81 kPa, and the ratio of the pressure loss applied to the header to the pressure loss applied to the hollow fiber membrane is 8.4. %.

At this time, the height in the header was h ₁ = 0.3 mm, h ₂ = 0.3 mm, and the inclination angle of the peripheral side surface was 90 °. Moreover, the curvature radius of the base part of the nozzle was 1.2 mm. The blood filter 8 was used to evaluate the residence time distribution. As a result, the plot was as shown in FIG. 16, and the residence time distribution was different from an ideal curve. Peak cracking was observed, and drift and residence occurred.

  In Table 1, for Examples 1 to 5 and Comparative Examples 1 to 3, the volume per cross-sectional area of the header relative to the hollow fiber capacity, the ratio of the pressure loss applied to the header to the pressure loss applied to the hollow fiber membrane, and the radius of curvature , And the inclination angle of the peripheral side surface are shown together.

  The hollow fiber membrane type medical device of the present invention 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 include concentrators, plasma concentrators, ascites filters, ascites concentrators, etc. Filtration characteristics and selective adsorption characteristics of hollow fiber membranes (ligands that interact with adsorbed substances are fixed to the hollow fiber membranes) Can be used for various medical devices.

DESCRIPTION OF SYMBOLS 1 ... Hollow fiber membrane type medical device, 3 ... Cylindrical container, 3a, 3b ... End part of cylindrical container, 3c ... Side surface part of cylindrical container, 4 ... Hollow fiber membrane, 4c ... End surface of hollow fiber membrane, 5 ... bundle of hollow fiber membranes, 5a, 5b ... end of hollow fiber membrane bundle, 7 ... potting resin part, 9 ... port, 10 ... header, 11 ... nozzle, 11a ... base part of nozzle, A ... inner space of header , B: inner space of the cylindrical container, CS: axis of the cylindrical container, h, h ₁ , h ₂ ... height of the header, S1: facing surface, S2: peripheral side surface.

Claims (4)

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 portion that surrounds both ends of the bundle of hollow fiber membranes inside the both ends of the cylindrical container, and is embedded and fixed at both ends of the bundle of hollow fiber membranes;
A header having nozzles that are provided at both ends of the cylindrical container, face the end face of the hollow fiber membrane, and serve as a fluid inlet and outlet;
A hollow fiber membrane-type medical device provided on a side surface of the cylindrical container and having a port serving as a fluid inlet and outlet;
When assuming the cross-sectional area when cutting the internal space of the header along the direction orthogonal to the axis of the cylindrical container as the cross-sectional area of the header,
The header has a volume per sectional area of the header of 1.0 × 10 ⁻² / cm ² or less of the volume of the hollow fiber membrane, and a pressure applied to the header with respect to a pressure loss applied to the hollow fiber membrane. loss Ri is Do the 1.5 to 7.0 percent,
The inner space of the header is defined by a facing surface facing the end surface of the hollow fiber membrane and a side surface surrounding an edge of the facing surface,
The side surface is an inclined surface that is inclined outward from the edge of the facing surface when viewed in a cross section along the direction of the axis, and is inclined by 15 to 70 ° with respect to the end surface of the hollow fiber membrane. and it is,
A radius of the inner diameter of the header, a height of the header, which is a distance between the end surface and the opposing surface at a position a / 3 away from the central portion of the header in a direction orthogonal to the axis of the cylindrical container. h ₁ , where h ₂ is the height of the header, which is the distance between the end surface and the facing surface at a position 2a / 3 away from the central portion of the header in a direction orthogonal to the axis of the cylindrical container ,
The height (h) of the header, which is the distance between the end surface and the opposing surface,
0.9 to 1.0 h ₁ = h ₂ , or
h ₁ = 0.9 to 1.0 h ₂ ,
A hollow fiber membrane medical device that meets the requirements . The nozzles in the central portion of the header, are positioned along the axis of the tubular container, and the radius of curvature of the root portion of the nozzle is less than 3mm, the hollow fiber membrane type medical device according to claim 1 Symbol placement. The hollow fiber membrane type medical device according to claim 1 or 2 , wherein the bundle of hollow fiber membranes has a filling rate of 55 to 70% with respect to the volume of the inner space of the cylindrical container. The header which comprises the hollow fiber medical device of any one of Claims 1-3 .

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