JP2013095682A - Method for manufacturing hemoadsorption device and apparatus for manufacturing the device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To accurately pack an adsorbent in a predetermined packing amount in a column.SOLUTION: An adsorbent 14 is packed in a column 12 while the inner volume of the column 12 is decreased compared to the maximum value A of the inner volume.

Description

  The present invention relates to a method and apparatus for manufacturing a blood adsorber.

  In recent years, a blood purification technique called “apheresis” has advanced, and in particular, a treatment technique called direct blood perfusion therapy (DHP) has become widespread. Direct blood perfusion therapy is a treatment technique that purifies blood by directly contacting a patient's blood with an adsorbent. The therapy is rapidly spreading in recent years because the apparatus configuration is simpler than other treatment techniques such as plasma separation method in which plasma is separated from blood and adsorbed on an adsorbent.

  A blood adsorber is known as a medical device used for direct blood perfusion therapy. The blood adsorber includes a cylindrical column, an adsorbent filled in the column, and a cap that seals the opening at both ends of the column. Further, the cap is provided with a fluid passage port connected to the extracorporeal circulation blood circuit. Blood is allowed to flow in from one flow port at both ends of the column, and after passing through the column, blood is flowed out from the other flow port. When blood passes through the column, the pathogenic substance in the blood is adsorbed by the adsorbent.

  In order to fill the adsorbent into the column, as shown in FIG. 9, one liquid passing port 108 of the cap 106 that closes the openings at both ends of the column 104 is opened, and the adsorbent is mixed with a liquid such as water. The suspension (slurry) is introduced from the introduction port 102 of the blood adsorber 100. The cap 106 is provided with a filter 110 so as to cover the opening of the column 104, thereby preventing the adsorbent 112 from passing through and discharging the liquid from the liquid passing port 108.

  The amount of adsorbent packed in the column is determined based on the blood flow in the column and the adsorption efficiency. That is, if the column is filled with the adsorbent material, the flow of blood in the column is delayed. On the other hand, if the adsorbent in the column is packed at an excessively low density, the adsorption efficiency is lowered. Therefore, a target value is determined for the filling rate of the adsorbent in order to prevent blood retention and to secure adsorption efficiency. For example, the packing amount of the adsorbent is determined so that the bulk volume of the adsorbent is 60% or more and 99% or less, preferably 80% or more and 95% or less with respect to the internal volume of the column.

  As means for obtaining the filling rate of the adsorbent, for example, a means using pressure loss as in Patent Document 1 is known. That is, as the adsorbent 112 accumulates in the column 104, the pressure loss in the column increases and the liquid discharge amount decreases. Here, the relationship between the change in the flow rate of the liquid relative to the change in the filling rate of the adsorbent 112 is obtained in advance by actual measurement or the like. By using the above relationship and the change in the flow rate of the liquid discharged from the liquid passing port 108, the filling rate of the adsorbent can be estimated.

JP-A-63-160668

  By the way, as shown in FIG. 9, the bubble 114 remaining in the column 104 adheres to the filter 110, thereby obstructing the flow of the liquid, and as a result, the pressure loss may increase. Therefore, in the method of estimating the filling rate of the adsorbent based on the pressure loss, an estimated value different from the actual filling rate is calculated, and there is a possibility that the adsorbent cannot be accurately filled.

  The present invention has been made in view of such circumstances, and a method for manufacturing a blood adsorber capable of accurately filling a column with an adsorbent material in a predetermined predetermined amount. And an apparatus.

  The present invention relates to a method for manufacturing a blood adsorber having a column filled with an adsorbent. In the manufacturing method, the adsorbent is packed into the column in a state where the internal volume of the column is reduced with respect to the maximum value.

  Moreover, in the said invention, it is suitable to fill the said adsorbent in the said column in the state which has arrange | positioned the internal volume adjustment member which occupies the predetermined ratio of the internal volume of the said column in the said column.

  In the above invention, it is preferable that the ratio of the internal volume adjusting member to the internal volume of the column can be changed by making the insertion length into the column variable.

  In the above invention, the internal volume adjusting member includes a nozzle part that discharges the fluid supplied into the column together with the adsorbent, and the column is wider than the discharge pipe part and the discharge pipe part. And a main body. Further, when the adsorbent is filled, the adsorbent is inserted into the column in a state where the nozzle is inserted into the discharge pipe so that the nozzle does not protrude from the boundary between the discharge pipe and the main body. Is preferably filled.

  The present invention also relates to an apparatus for manufacturing a blood adsorber in which a column is filled with an adsorbent. In the manufacturing apparatus, the adsorbent is filled in the column in a state where the internal volume of the column is reduced with respect to the maximum value.

  Moreover, in the said invention, it is suitable to provide the internal volume adjustment member which is arrange | positioned in the said column and occupies the predetermined ratio of the internal volume of the said column.

  In the above invention, it is preferable that the ratio of the internal volume adjusting member to the internal volume of the column can be changed by making the insertion length into the column variable.

  In the above invention, the internal volume adjusting member includes a nozzle part that discharges the fluid supplied into the column together with the adsorbent, and the column is wider than the discharge pipe part and the discharge pipe part. And a main body. Further, when the adsorbent is filled, the adsorbent is inserted into the column in a state where the nozzle is inserted into the discharge pipe so that the nozzle does not protrude from the boundary between the discharge pipe and the main body. Is preferably filled.

  According to the present invention, the adsorbent can be accurately packed in the column with a predetermined packing amount.

It is a figure which illustrates the blood adsorption device concerning this embodiment. It is a figure which illustrates the filling apparatus which concerns on this embodiment. It is a figure explaining a filling process. It is a figure explaining a filling process. It is a figure explaining a filling process. It is a figure explaining a filling process. It is a figure which illustrates the filling apparatus which concerns on this embodiment. It is a figure explaining a filling process. It is a figure explaining the conventional filling process.

  FIG. 1 illustrates a blood adsorber 10 according to this embodiment. The blood adsorber 10 includes a column 12, an adsorbent 14, and a cap 16.

  The column 12 is a member having an internal volume that can accommodate the adsorbent 14. The column 12 can be constituted by a substantially cylindrical member having openings at both ends, for example. Moreover, the column 12 may be comprised from the material provided with the rigidity of the grade which can resist a weight against the weight of the adsorption material 14, for example, can be comprised from a polycarbonate.

  The column 12 preferably includes a supply pipe part 11, a discharge pipe part 13, and a main body part 15. The main body part 15 is a main part filled with the adsorbent 14, and the supply pipe part 11 and the discharge pipe part 13 are tubular parts formed so as to protrude from both ends of the main body part 15. When the adsorbent 14 is filled in the column 12, a supply nozzle 42 described later is inserted into the supply pipe portion 11, and a discharge nozzle 44 described later is inserted into the discharge pipe portion 13. Further, the width of the main body portion 15, the supply pipe portion 11, and the discharge pipe portion 13 changes at the boundary b, and the main body portion 15 is formed wider than the supply pipe portion 11 and the discharge pipe portion 13.

  The adsorbent 14 is a member having an adsorbability for a pathogenic substance in blood. The adsorbent 14 can be made of, for example, a polymer resin mainly composed of a hydrophobic polymer resin. Specifically, at least one selected from the group consisting of polyarylate resin (PAR), polyethersulfone resin (PES), and polysulfone resin (PSF) can be used. Further, the adsorbent 14 has a shape that can be filled in the column 12, and can be formed of, for example, a granular material (bead) having a diameter smaller than the opening diameter of the supply pipe portion 11. At this time, the average particle size of the adsorbent 14 is preferably 200 μm or more and 3000 μm or less.

  The cap 16 includes a filter 24, an O-ring 26, a column fixing ring 28, and a sealing cap 30. The cap 16 is a member for sealing the openings of the supply pipe part 11 and the discharge pipe part 13.

  The filter 24 is a member that allows blood to pass while preventing leakage of the adsorbent 14 in the column 12 during blood purification. For example, the filter 24 may be configured to have the same diameter as or larger than the liquid passage port 34 and to cover the liquid passage port 34. The O-ring 26 is a member for preventing leakage of blood flowing in the column 12. For example, when the column fixing ring 28 is attached to the flange 32 of the supply pipe portion 11 and the discharge pipe portion 13, the O-ring 26 is interposed between the column fixing ring 28 and the flange 32. The sealing cap 30 is a member that closes the liquid passage port 34 of the column fixing ring 28. When blood purification is performed, the sealing cap 30 is removed from the column fixing ring 28, and the liquid passing port 34 and an extracorporeal circulation blood circuit (not shown) are connected for use.

  Next, a filling apparatus for filling the adsorbent 14 in the column 12 will be described with reference to FIG. The filling device 40 includes a supply nozzle 42, a discharge nozzle 44, and a storage tank 46.

  The storage tank 46 stores a suspension 47 in which the adsorbent 14 and a liquid (dispersion medium) such as water are mixed. The suspension 47 is fed from the storage tank 46 toward the column 12 at a predetermined liquid feeding pressure. The liquid feeding pressure is preferably a pressure that does not cause the adsorbent 14 to be crushed, and can be set to a pressure of 10 kPa to 100 kPa, for example.

  The supply nozzle 42 is a member that supplies a suspension to the column 12. The supply nozzle 42 includes a fixed part 50 and an insertion part 52. The fixing unit 50 is a member that fixes the supply nozzle 42 to the supply pipe unit 11. For example, the fixing unit 50 may fix the fixing unit 50 to the flange 32 of the supply pipe unit 11 by means such as screwing. At this time, by sandwiching the O-ring 26 between the fixed portion 50 and the flange 32, leakage of the suspension can be prevented when the adsorbent 14 is filled.

  The insertion portion 52 is a member that is inserted into the supply pipe portion 11. By inserting the insertion portion 52 into the supply pipe portion 11, the internal volume of the column 12 (the volume that can be filled with the adsorbent 14) is reduced. Therefore, the insertion portion 52 has a function as an internal volume adjusting member with respect to the column 12. Moreover, it is suitable that the insertion length to the supply pipe | tube part 11 of the insertion part 52 can be changed. For example, the insertion portion 52 is composed of a plurality of nozzles having different diameters, such as a large diameter nozzle and a small diameter nozzle, and the length of the insertion portion 52 can be expanded and contracted by allowing the small diameter nozzle to be accommodated in the large diameter nozzle. Configure to be By doing in this way, it becomes possible to change the ratio for which the insertion part 52 occupies the internal volume of the column 12. The insertion portion 52 is provided with an opening 52a, and the suspension can be supplied into the column 12 from the opening 52a.

  The discharge nozzle 44 includes a fixed portion 51, an insertion portion 53, a filter 56 and a flow rate sensor 58. The discharge nozzle 44 is a member that discharges a liquid that is a dispersion medium in the suspension supplied into the column 12. Similarly to the fixing part 50 and the insertion part 52 of the supply nozzle 42, the liquid in the column 12 is drained while the insertion part 53 of the discharge nozzle 44 is inserted into the discharge pipe part 13 and fixed to the discharge pipe part 13 by the fixing part 51. Discharge. By inserting the insertion portion 53 into the discharge pipe portion 13, the internal volume of the column 12 (the volume that can be filled with the adsorbent 14) is reduced. Therefore, the insertion portion 53 has a function as an internal volume adjusting member with respect to the column 12. Further, it is preferable that the insertion length of the insertion portion 53 into the discharge pipe portion 13 can be changed. By doing so, it becomes possible to change the ratio of the discharge pipe portion 13 to the internal volume of the column 12.

  The filter 56 is a member that allows the liquid (dispersion medium) supplied during filling of the adsorbent to pass through while preventing leakage of the adsorbent 14 in the column 12. The filter 56 is provided on the path from the insertion portion 53 to the discharge port 60, and is preferably provided so as to cover the opening 55 of the insertion portion 53, for example. As will be described later, in order to facilitate the removal of bubbles in the column 12, it is preferable that the hole diameter (opening size) of the filter 56 is larger than the hole diameter of the filter 24 of the cap 16.

  The flow sensor 58 is a sensor capable of measuring the amount of liquid discharged from the discharge port 60. As the packing ratio of the adsorbent 14 in the column 12 increases, the pressure loss in the column 12 increases. As a result, when the supply pressure of the suspension containing the adsorbent 14 is constant, the discharge amount of the liquid (dispersion medium) decreases as the filling rate of the adsorbent 14 increases.

  Next, the filling process of the adsorbent 14 will be described. As shown in FIG. 3, after inserting the insertion portion 52 of the supply nozzle 42 into the supply pipe portion 11, the fixing portion 50 is fixed to the supply pipe portion 11. Similarly, after the insertion part 53 of the discharge nozzle 44 is inserted into the discharge pipe part 13, the fixing part 51 is fixed to the discharge pipe part 13. In the example shown in FIG. 3, the column 12 is placed in an upright state, and the supply nozzle 42 is disposed on the lower side (floor side) to collect the adsorbent 14 from the lower side to the upper side of the column 12. The nozzle 44 is arranged on the upper side (top side).

  By inserting the insertion portion 52 of the supply nozzle 42 and the insertion portion 53 of the discharge nozzle 44 into the column 12, the internal volume of the column 12 is reduced with respect to the maximum value. In this state, the adsorbent 14 is filled.

  Prior to the filling of the adsorbent 14, the column 12 may be filled with a liquid such as water by supplying a liquid from a filling-side nozzle as shown in FIG. By filling the column 12 with liquid before filling the adsorbent 14, the gas in the column 12 can be efficiently removed.

  Next, as shown in FIG. 5, the suspension in the storage tank 46 is supplied to the column 12. The liquid (dispersion medium) in the suspension is discharged from the filter 56, and the adsorbent 14 in the suspension is blocked by the filter 56 and accumulates in the column 12. Thereby, the adsorbent 14 is filled in the column 12.

  In the present embodiment, the insertion portion 53 of the discharge nozzle 44 and the insertion portion 52 of the supply nozzle 42 are inserted into the column 12, that is, in a state where the internal volume in the column 12 is narrowed by the insertion portions 52 and 53. Filler 14 is filled.

  The occupied volume in the column 12 by the insertion parts 52 and 53 is preferably set according to the maximum internal volume of the column 12 and the filling amount of the adsorbent 14 filled in the column 12. Here, the maximum internal volume of the column 12 refers to the volume in which nothing is packed in the column 12. Further, the filling rate of the adsorbent 14 is determined with respect to the maximum internal volume of the column 12. If the maximum internal volume of the column 12 is A and the target filling rate of the adsorbent is α, the target bulk volume (packing amount) of the adsorbent 14 can be expressed as αA. When the target bulk volume αA is subtracted from the internal volume A of the column 12, an unfilled volume (1-α) A is obtained. It is preferable to allocate at least a part of the unfilled volume as the occupied volume in the column 12 occupied by the insertion portions 52 and 53. If the ratio of the occupied volume to the unfilled volume (1-α) A (hereinafter referred to as the occupied ratio) is β, the occupied volume can be represented by β (1-α) A. For example, when the occupied volume β (1-α) A is evenly distributed to the insertion portion 52 of the supply nozzle 42 and the insertion portion 53 of the discharge nozzle 44, the occupied volumes of the insertion portion 52 and the insertion portion 53 are each β (1-α) A / 2 may be used.

  The bulk volume indicates a volume value of the adsorbent 14 after the suspension is transferred to a liquid measuring instrument such as a measuring cylinder and allowed to stand for a predetermined time (for example, 1 hour).

  Here, if the adsorbent 14 is packed too densely, the blood flow in the column 12 is stagnated. On the other hand, if the density is excessively low, the adsorption efficiency is lowered. The inner volume A is 60% or more and 99% or less, preferably 80% or more and 95% or less. When the adsorbent 14 is packed, the bubbles 62 remaining in the column 12 are driven out of the column 12 through the filter 56 as shown in FIG.

  Suspension is supplied into the column 12 and the filling process is performed until the adsorbent 14 is filled with the desired amount αA based on the change in the flow rate measured by the flow rate sensor 58. For example, in the case of FIG. 6, all of the unfilled volume (1-α) A is allocated as the occupied volume of the insertion portions 52 and 53, and the volume in the column 12 is adsorbed in the state where the adsorbent 14 is filled with αA. It will be occupied by the material 14 and the insertion portions 52 and 53, and the amount of drainage will converge to a certain amount under the above-described liquid feed pressure. Therefore, the filling of the adsorbent 14 is terminated when the measured value of the flow sensor 58 becomes a constant value or near a constant value.

  When the filling of the adsorbent 14 is completed, the top and bottom of the supply nozzle 42 and the discharge nozzle 44 are reversed. Further, the supply nozzle 42 is pulled out from the column 12. Further, the opening of the column 12 on the side from which the supply nozzle 42 is pulled out is sealed with the cap 16.

  Further, the top and bottom of the column 12 is reversed. Subsequently, the discharge nozzle 44 is pulled out from the column 12. Further, the opening of the column 12 on the side from which the discharge nozzle 44 is pulled out is sealed with a cap 16. Thus, the filling process is completed.

  As shown in FIG. 7, if the insertion portion 53 protrudes from the boundary b between the discharge pipe portion 13 and the main body portion 15, a gap between the protruding portion of the discharge pipe portion 13 and the inner wall of the main body portion 15 of the column 12. The air bubbles 62 stay in the air and it becomes difficult to discharge the air bubbles 62 from the opening 55 of the insertion portion 53. Therefore, it is preferable that the insertion portion 53 has a shape that does not protrude from the boundary b between the discharge pipe portion 13 and the main body portion 15 in a state of being inserted into the discharge pipe portion 13. For example, it is preferable that the length L1 of the insertion portion 53 in the column longitudinal direction is equal to or less than the length L2 of the discharge tube portion 13 in the column longitudinal direction. Thereby, the removal of the bubble 62 becomes more reliable.

  In this case, if the cross-sectional area of the insertion portion 53 is S, the occupied volume in the column 12 of the insertion portion 53 is L2 × S or less. Accordingly, a value (β (1-α) A) − (L1 × S) obtained by subtracting the occupied volume L1 × S of the insertion portion 53 from the occupied volume β (1-α) A of the supply nozzle 42 and the discharge nozzle 44 is supplied. It is preferable to determine the occupied volume of the insertion portion 52 of the nozzle 42.

  In the above-described embodiment, the filling of the adsorbent 14 and the draining of the liquid are performed by separate nozzles, but these may be integrated. That is, as illustrated in FIG. 8, the adsorbent 14 may be filled by the supply / discharge nozzle 70 in which the supply nozzle and the discharge nozzle are integrated. In this case, it is preferable that the occupied volume of the insertion portion 71 of the supply / discharge nozzle 70 is β (1-α) A described above. Further, when the supply / discharge nozzle 70 is used, it is preferable that the opening on the side where the supply / discharge nozzle 70 is not inserted among the openings at both ends of the column 12 is sealed with the cap 16. In this way, after the filling of the adsorbent 14, the supply / discharge nozzle 70 is pulled out and the opening of the column 12 exposed by the drawing is sealed with the cap 16, so that the filling process is completed. It becomes possible to shorten. In addition, about the part which contacts the adsorption material 14 in the column 12 among the insertion parts 71, it is suitable to form with elastic members, such as a silicone rubber.

  Furthermore, in the above-described embodiment, the case where the main body 15 is a column wider than the discharge pipe 13 has been described as an example. However, the present invention is not limited to such a shape. For example, in the case of a cylindrical column The present invention is also applicable.

  DESCRIPTION OF SYMBOLS 10 Blood adsorption device, 11 Supply pipe part, 12 Column, 13 Exhaust pipe part, 14 Adsorbent material, 15 Main body part, 16 Cap, 24 Filter, 26 O-ring, 28 Column fixing ring, 30 Sealing cap, 32 Flange, 34 liquid passing port, 40 filling device, 42 supply nozzle, 44 discharge nozzle, 46 storage tank, 47 suspension, 50 supply nozzle fixing part, 51 discharge nozzle fixing part, 52 supply nozzle inserting part, 53 discharge nozzle Insertion part, 55 discharge nozzle opening, 56 filter, 58 flow sensor, 60 discharge port, 62 bubbles, 70 supply / discharge nozzle, 71 supply / discharge nozzle insertion part.

Claims (8)

A method for producing a blood adsorber in which an adsorbent is packed in a column,
A method for producing a blood adsorber, comprising: filling the column with the adsorbent in a state where the internal volume of the column is reduced with respect to a maximum value. It is a manufacturing method of the blood adsorption device according to claim 1,
A method for producing a blood adsorber, comprising: filling the column with the adsorbent in a state where an internal volume adjusting member occupying a predetermined proportion of the internal volume of the column is disposed in the column. It is a manufacturing method of the blood adsorption device according to claim 2,
The method for manufacturing a blood adsorber, wherein the internal volume adjusting member can change the ratio of the internal volume of the column by changing the insertion length into the column. It is a manufacturing method of the blood adsorption device according to claim 3,
The internal volume adjusting member includes a nozzle part that discharges the fluid supplied into the column together with the adsorbent,
The column has a discharge pipe part and a main body part wider than the discharge pipe part,
When the adsorbent is filled, the adsorbent is filled into the column with the nozzle portion inserted into the discharge pipe portion so that the nozzle portion does not protrude from the boundary between the discharge pipe portion and the main body portion. A method for producing a blood adsorber, comprising: An apparatus for producing a blood adsorber in which an adsorbent is packed in a column,
An apparatus for manufacturing a blood adsorber, wherein the adsorbent is filled in the column in a state where the internal volume of the column is reduced with respect to a maximum value. The blood adsorber manufacturing apparatus according to claim 5,
An apparatus for manufacturing a blood adsorber, comprising an internal volume adjusting member disposed in the column and occupying a predetermined proportion of the internal volume of the column. It is a manufacturing apparatus of the blood adsorption device according to claim 6,
The apparatus for manufacturing a blood adsorber, wherein the internal volume adjusting member is capable of changing a ratio of the internal volume of the column by changing an insertion length into the column. It is a manufacturing apparatus of the blood adsorption device according to claim 7,
The internal volume adjusting member includes a nozzle part that discharges the fluid supplied into the column together with the adsorbent,
The column has a discharge pipe part and a main body part wider than the discharge pipe part,
When the adsorbent is filled, the adsorbent is filled into the column with the nozzle portion inserted into the discharge pipe portion so that the nozzle portion does not protrude from the boundary between the discharge pipe portion and the main body portion. An apparatus for producing a blood adsorber, comprising:

Images