FLOW REDUCER FOR A FLEXIBLE PIPE

Description

[0001] The present invention relates to a system comprising a flexible tube and a clamp for reducing the flow of a fluid in said flexible tube, as well as to a device for removing leukocytes from blood or a blood component comprising such a clamp.

[0002] The invention applies to the field of medical devices and in particular to devices intended for the filtration of blood or a blood component.

[0003] Whole blood is made up of two types of components: blood cells including red blood cells, white blood cells, and platelets, and plasma, a pale yellow liquid in which the blood cells are suspended.

[0004] It has been shown that leukocytes have very significant adverse effects, which has led to attempts to eliminate them from blood components intended for transfusion. In particular, leukocytes increase the risk of immune rejection such as graft-versus-host disease and promote the transmission of infectious agents.

[0005] To remove leukocytes from blood components intended for transfusion, filtration units containing a leukocyte-removing medium are available on the market, generally comprising an assembly of several layers of non-woven polyester fibers. This assembly selectively retains leukocytes from the blood by two main retention mechanisms: sieving and adhesion.

[0006] The leukocyte retention performance of these filtration units depends on many parameters not only related to intrinsic characteristics of the filtration units such as the filtration surface, the diameter of the fibers, the density of the fibers, the time of passage in the filter, but also related to extrinsic characteristics such as the composition of the blood to be filtered, the duration and temperature of storage of the blood before filtration or the temperature of the blood at the time of its filtration.

[0007] In particular, it is known that filtering blood at high temperature, i.e. above 24°C, leads to an increase in the residual leukocyte count compared to filtration at room temperature or at 4°C.

[0008] One possible explanation is that as blood temperature increases, its viscosity decreases. Thus, above 24°C, blood flow through the filtration unit will be faster and the contact time of leukocytes with the leukocyte-removal medium will be reduced. In addition, leukocytes also become more deformable as temperature increases, making the sieving action of the leukocyte-removal medium less effective.

[0009] In order to maintain the blood flow rate between 20 and 50 ml / min in a device for removing leukocytes from blood or a low-viscosity blood component, US 6,013,184 proposes a device comprising an inlet port, a filter for removing leukocytes, an outlet port and tubing which connects, in this order, the inlet port, the filter for removing leukocytes and the outlet port. A narrow portion for regulating the blood flow rate in said device is provided in said flexible tubing, on the downstream side of the filter. The narrow portion of the flexible tubing is made either by inserting a hollow tube having a specifically reduced useful cross-section into said flexible tubing, or by compressively deforming the flexible tubing using a sliding clamp.The sliding clamps must be designed so that the narrow portion of the flexible tubing has a useful cross-sectional area of ​​between 0.1 mm 2 and 5.0 m 2 and a ratio of length to useful cross-sectional area of ​​between 3 and 400 mm / mm 2. In the examples, the length of the narrow portion in the flexible tubing is thus between 25 and 240 mm, which would make a clamp with such dimensions unwieldy.

[0010] Also known from document DE 36 31 411 is a clamp for modifying the flow section of a flexible tube. This clamp comprises a plurality of openings of different widths, connected to each other, making it possible to obtain flow sections of different sizes.

[0011] Document US 4,434,963 discloses a sliding clamp of generally flat shape used to close a flexible tube. This clamp is not designed to reduce the flow of fluid in a flexible tube but to completely stop the flow of fluid in said flexible tube.

[0012] Document US 4,248,401 discloses the same type of sliding clamp as the previous document, intended to stop the flow of fluid in a flexible tube. This clamp has a teardrop-shaped slot intended to receive and close the flexible tube. An insert having clamping surfaces parallel to each other and perpendicular to the plane of the clamp is placed in this slot.

[0013] The invention proposes to easily reduce the flow rate of a fluid in a flexible tube using an improved clamp. In particular, this clamp arranged in a device for removing leukocytes from blood or a blood component makes it possible to obtain a leukocyte depletion rate in accordance with European standards when the blood to be filtered has a temperature ranging from 24°C to 30°C.

[0014] For this purpose and according to a first aspect, the invention proposes a system for reducing the flow rate of a fluid in a flexible tube comprising said flexible tube and a clamp, said clamp comprising a body provided with an opening intended to receive said flexible tube, the opening having at least one pinching portion configured to compress said flexible tube without closing it, said pinching portion is defined between a first pinching surface and a second pinching surface which face each other and which approach each other over a height smaller than or equal to the width of the flexible tube when said flexible tube is compressed until it is closed, so as to reduce the flow rate of fluid in said flexible tube.

[0015] According to a second aspect, the invention relates to a device for removing leukocytes from blood or a blood component, comprising on the one hand a filter for removing leukocytes from blood or a blood component and a first flexible tube in fluid communication with said filter and on the other hand a clamp placed or intended to be placed on the first flexible tube in order to reduce the flow rate in said first flexible tube.

[0016] The accompanying drawings illustrate the invention: [ Fig. 1 ] represents a perspective and top view of a clamp according to a first embodiment of the invention. [ Fig.2 ] represents a sectional view of the clamp of the figure 1 with a flexible tube inserted into it. Fig.3 ] represents a perspective and top view of a clamp according to a second embodiment of the invention. [ Fig.4 ] represents a front view of the clamp of the figure 2 . [ Fig.5] represents a perspective and top view of a clamp according to a third embodiment of the invention. [ Fig.6 ] represents a perspective and bottom view of the clamp of the Figure 5 . [ Fig.7 ] represents a sectional view of the clamp of the Figure 5 . [ Fig.8 ] represents a sectional view of a variant of the clamp of the Figure 5 . [ Fig.9 ] represents a sectional view of another variant of the clamp of the Figure 5 . [ Fig. 10 ] represents a schematic view of a device for removing leukocytes comprising a clamp according to the invention.

[0017] In the following description, the terms "upper" and "lower" are defined in relation to the direction of use of the clamp when placed on a vertical flexible tube.

[0018] There figure 1 represents a clamp for reducing the flow of fluid in a flexible tube according to a first embodiment.

[0019] This clamp is designed to compress a flexible tube without completely sealing it. Fluid flows through the flexible tube, including through the portion compressed by the clamp. Compression reduces the cross-sectional area of ​​the flexible tube, thereby reducing the fluid flow rate in the flexible tube compared to uncompressed flexible tube.

[0020] According to a first realization of the Figures 1 and 2 , the clamp 1 comprises a body 2 provided with an opening 3 intended to receive a flexible tube 4. The opening 3 has at least one pinching portion 5 configured to compress said flexible tube 4 without closing it. The pinching portion 5 is defined between a first pinching surface 6 and a second pinching surface 7 which face each other and which approach each other over a height h smaller than or equal to the width of the flexible tube 4 when said flexible tube is compressed until it is closed, so as to reduce the flow rate of fluid in said flexible tube.

[0021] According to the figure 1 , the body 2 of the clamp 1 is substantially flat. Furthermore, the body of the clamp has a substantially U-shape. In the following description and according to the space (x,y,z) referenced on the figure 1 , the length of clamp 1 is in the x-axis, the width in the y-axis and the height or thickness in the z-axis.

[0022] The body 2 of the clamp comprises a first arm 8 and a second arm 9 in the lengthwise direction, said first and second arms 8, 9 being connected to each other by a base 10. The first and second arms 8, 9 comprise the first and second clamping surfaces 6, 7, respectively. The opening 3 of the clamp is located between the first and second arms 8, 9.

[0023] On the figure 1, the opening 3 of the clamp further comprises an insertion portion 11 configured to introduce the flexible tube 4 to be compressed into the opening 3, said insertion portion 11 being in communication with the pinching portion 5.

[0024] The insertion portion 11 is formed at the ends of the first arm 8 and the second arm 9 of the body 2. The distance between the first and second arms 8, 9 at the insertion portion 11 is greater than that at the pinching portion 5. Seen from above, the insertion portion 11 has a substantially V-shape. Thus, the reduction in the cross-section of the tube is progressive in the direction of flow of the fluid in the tube.

[0025] According to the figure 1, one of the first or second arms 8, 9 has a projection 12 at the level of the insertion portion 11 configured to hold the flexible tube 4 in the opening 3 of the body 2 of the clamp and in particular in the pinching portion 5.

[0026] According to the realization of the figure 1 , the first and second pinching surfaces 6,7 are substantially planar.

[0027] The pinching surfaces 6,7 of the clamp approach each other in the height direction, i.e. the distance between said pinching surfaces 6,7 is smaller at the lower face of the clamp than at the upper face. Thus, seen in section, the pinching surfaces 6,7 form a V and the cross-section of the flexible tube inserted into the clamp 1 reduces in the direction of fluid flow ( figure 2 ).

[0028] Furthermore, in order to facilitate the handling of the clamp, the height h of the pinching portion 5 is smaller than or equal to the width of the flexible tube 4 when said flexible tube is compressed until it is closed.

[0029] Furthermore, the length l of the pinching surface is greater than or equal to the width L of the flexible tube 4 when said flexible tube is compressed until it is closed in order to completely engage the flexible tube 4 in the pinching portion 5.

[0030] For example, when the flexible tube has an inner diameter of 3 mm and an outer diameter of 4.1 mm, the width of the flexible tube when compressed to a stop is about 5.1 mm. The pinch portion, for example, has a width of about 1.5 mm at the upper face and a width of about 1.3 mm at the lower face. The height of the pinch portion is about 5 mm. The length of the pinch portion is about 10 mm.

[0031] Clamp 1 for reducing the flow of a fluid in a flexible tube is rigid enough to compress the flexible tube without the clamp deforming. This clamp is made by 3D printing or injection molding. Examples of materials for making the clamp are polypropylene, polycarbonate, polyamide, or an acrylate copolymer.

[0032] THE figures 3 And 4 represent a second embodiment of a clamp according to the invention. This second embodiment differs from the first embodiment in that the clamp 1 comprises a gripping portion 13 allowing the user to easily grasp the clamp. In this second embodiment, the gripping portion 13 essentially consists of the base 10 of the body 2 of the clamp, the latter having dimensions designed so that the user can place his fingers on the upper surface and the lower surface of said base 10 of the body of the clamp.

[0033] Furthermore, the lateral edge of the gripping portion 13 is concave in order to facilitate the insertion of the flexible tube 4 into said clamp 2, the user pushing the clamp 2 at the level of this concavity using one of his fingers or the thumb to insert the flexible tube 4 into said clamp 2.

[0034] In this second embodiment, neither the first arm 8 nor the second arm 9 of the body 2 of the clamp comprises a projection.

[0035] Figures 5 to 9 represent a third embodiment of a clamp according to the invention.

[0036] This third embodiment differs from the first embodiment of the clamp in that the opening 3 of the clamp further comprises a holding portion 14 in which the flexible tube 4 is held without being deformed or compressed. The width of the holding portion 14 is substantially equal to the outside diameter of the flexible tube. This holding portion makes it possible to associate the clamp with a flexible tube, without compressing it.

[0037] As illustrated on the Figures 5 and 6 , the holding portion 14 is in communication with the pinching portion 5 of the opening 3.

[0038] The holding portion 14 is further in communication with the insertion portion 11 of the opening 3 of the clamp. By inserting the flexible tube 4 into the clamp, it first penetrates the insertion portion 11, then the holding portion 14 and finally the pinching portion 5.

[0039] In this third embodiment, each of the first arm 8 and the second arm 9 comprises a projection 12a, 12b configured to hold the flexible tube 4 in the opening 3 of the clamp.

[0040] In addition, as shown on the Figures 5 and 6 , the body 2 of the clamp comprises a central recess 15a, 15b. In particular, the clamp comprises on each of its upper and lower faces a central recess 15a, 15b forming a border on the periphery of the body of the clamp and around the opening 3. This border has a greater thickness than the thickness of the body thus hollowed out. This recess lightens the clamp.

[0041] The pliers further comprise a gripping portion 13 allowing the user to easily manipulate the pliers.

[0042] In this third embodiment, this gripping portion 13 extends the base 10 of the body 2 of the pliers in the lengthwise direction. Advantageously, the gripping portion 13 comprises a plurality of ribs 16a, 16b. The ribs are parallel to each other and prevent the pliers from slipping between the user's fingers. In particular, each of the upper face and the lower face of the gripping portion 13 comprises a plurality of ribs 16a, 16b.

[0043] According to the Figures 5 and 6 , the clamp 2 further comprises a ring 17 consisting of an annular-shaped recess. This ring is intended to hang an identification label for the clamp.

[0044] There figure 7is a front view of the clamp according to this third embodiment. The clamping surfaces 6, 7 move closer to each other so as to gradually reduce the cross-section of the flexible tube inserted in this clamp, but without closing said flexible tube.

[0045] As a variant shown on the figure 8 , the pinching surfaces 6,7 of the gripper body move towards each other before moving away from each other again. In this variant, the pinching surfaces are substantially planar. Thus, the width of the pinching portion at the upper surface and the lower surface is the same, but the width of the pinching portion at about half the height of the pinching portion is reduced.

[0046] This variant is advantageous since the pinching portion is symmetrical with respect to a plane passing through the middle of the pinching portion and perpendicular to the z axis. Thus, whatever the direction of the clamp when the flexible tube is inserted, the cross-section of the compressed flexible tube will be the same with first a cross-section which reduces from upstream to downstream before enlarging again. In this variant, seen in section, the pinching surfaces 6, 7 substantially form an hourglass.

[0047] For example, when the flexible tube has an inner diameter of 3 mm and an outer diameter of 4.1 mm, the width of the flexible tube when compressed to a stop is about 5.1 mm. The height of the pinch portion is about 5 mm. The pinch portion has, for example, a width of about 1.5 mm at the top and bottom faces. The width of the pinch portion at about 2.5 mm in height is about 1.3 mm. The length of the pinch portion is about 10 mm.

[0048] There figure 9 represents a second variant of the third embodiment of the clamp. In this variant, the first and second clamping surfaces are substantially convex. Thus, the clamping surfaces 6, 7 of the clamp body move towards each other before moving away from each other again. This convex shape facilitates the insertion of the flexible tube into the clamp.

[0049] According to one aspect, the invention relates to a system for reducing the flow rate of a fluid in a flexible tube 4 comprising a clamp as described above and said flexible tube 4.

[0050] In particular, the system comprises a flexible tube 4 inserted into the opening 3 of the clamp 1, at the level of the pinching portion 5 or the holding portion 14.

[0051] By sliding the flexible tube from the holding portion 14 to the pinching portion 5 of the clamp 1, the cross-section of the flexible tube decreases, thereby reducing the flow rate of the fluid in the flexible tube.

[0052] According to another aspect, the invention relates to a device for removing leukocytes from blood or a blood component, comprising on the one hand a filter for removing leukocytes from blood or a blood component and a first flexible tube in fluid communication with said filter and on the other hand a clamp according to the first aspect of the invention placed or intended to be placed on the first flexible tube in order to reduce the flow rate in said first flexible tube.

[0053] There figure 10 represents such a device 18 for removing leukocytes from blood or a blood component comprising a clamp 1 according to the invention.

[0054] The device 18 comprises a leukocyte removal filter 19 having an inlet orifice 20 and an outlet orifice 21. Said leukocyte removal filter 19 is in fluid communication with a filtrate collection bag 22 via a first flexible tube 23, one end of which is connected to the outlet orifice 21 of the filter 19 and the other end to an inlet orifice 24 of the filtrate collection bag 22.

[0055] The device 18 further comprises a second flexible tube 25, one end of which is connected to the inlet orifice 20 of the filter to remove the leukocytes 19 and the other end is connected or intended to be connected to an outlet orifice 26 of a collection bag 27 containing or intended to contain the blood or the blood component to be filtered.

[0056] In the realization of the device of the figure 10, the collection bag 27 includes an anticoagulant solution of the CPD type (Citrate, Phosphate, Dextrose).

[0057] The clamp 1 for reducing the flow rate of a fluid is placed or intended to be placed on the first or second flexible tube 23, 25. Advantageously, the clamp is placed on the first flexible tube 23 downstream of the filter 19 to remove leukocytes. For example, the clamp 1 is placed on the first flexible tube 23 approximately 5 cm below the outlet orifice 21 of the filter 19.

[0058] According to the figure 10, the device further comprises a sampling needle 28 in fluid communication via a third flexible tube 29, with an inlet orifice 30 of the collection bag 27 intended to contain the blood to be filtered. The sampling needle 28 is protected by a cap and the third flexible tube 29 comprises a needle protector 31 which slides along the third flexible tube 29 until it covers the needle after blood collection.

[0059] The device 18 further comprises a blood sampling bag 32 in fluid communication with the sampling needle, via a fourth flexible tube 33 connected to the third flexible tube 29. A tube holder 34 is further connected to the sampling bag 32.

[0060] The device 18 also comprises a first satellite bag 35 in fluid communication with the filtrate collection bag 22 via a fifth flexible tube 36. This first satellite bag 35 is intended to receive the plasma separated from the blood after centrifugation of the device.

[0061] A second satellite bag 37 is in fluid communication with the filtrate collection bag 22 via a sixth flexible tube 38 connected to the fifth flexible tube 36. This second satellite bag 37 comprises a SAGM (Sodium, Adenine, Glucose, Mannitol) type red blood cell preservation solution.

[0062] The device 18 further comprises clamps 39a, 39b, 39c for controlling the flow of fluids in the device 18.

[0063] An example of using the device of the figure 10 is described below.

[0064] First, blood is taken from a donor in the collection bag 27 intended to contain the blood to be filtered via the collection needle 28.

[0065] The first flexible tube 23 is compressed using the clamp 1 according to the invention. Alternatively, this compression step is carried out before the blood sample is taken.

[0066] The blood contained in the collection bag 27 containing the blood to be filtered is transferred into the filtrate collection bag 22 by passing it through the filter 19 to remove the leukocytes. The filtrate collection bag 22 then contains the leukocyte-reduced blood.

[0067] The device 18 is placed in a centrifuge so as to separate the leukocyte-depleted blood contained in the filtrate collection bag 22 into a sediment of red blood cell concentrate and a plasma supernatant.

[0068] The plasma is transferred into the first satellite bag 35 and then the red blood cell preservation solution from the second satellite bag 37 into the filtrate collection bag 22 containing the red blood cell concentrate.

[0069] In a particular example, the filter 19 for removing leukocytes is the LXT filter (Macopharma, France). The device 18 is thus capable of removing leukocytes from whole blood having a temperature ranging from 18 to 23°C without use of the clamp and from 24° to 30°C with use of the clamp. Example 1

[0070] Whole blood leukocyte depletion assays were performed using a bag system similar to that of the figure 10 comprising a LXT whole blood leukocyte removal filter (Macopharma, France) and a clamp of the type of that of the figure 1 .

[0071] The clamp has a spacing of 1.5 mm on one side and 1.3 mm on the other and is 5 mm thick. The upstream and downstream flexible tubes of the LXT filter have an outside diameter of 4.1 mm and an inside diameter of 3 mm.

[0072] Whole blood was collected in the bag systems mentioned above. The bags containing whole blood are received one day after collection and contain approximately 475 ml of blood. They are placed for one hour in a water bath at 30°C.

[0073] Whole blood filtration is performed under 3 different conditions: without clamp, with a clamp placed above the filter or with a clamp placed below the filter.

[0074] The results obtained are as follows: [Table 1] Without clamp Clamp above the filter Clamp below the filter Number of filtration 8 7 5 Average filtration time (mm:ss) 19:52 34:34 36:24 Average residual white blood cell count 3,24x10 5< 2,51 x10 5< 1,47 x10 5<

[0075] The presence of a clamp above or below the leukocyte removal filter reduces the blood flow rate through the filter and leads to an improvement in the leukocyte removal rate without impacting blood loss through the filter.

[0076] After filtration, leukocyte-depleted whole blood is separated by centrifugation into red blood cell concentrate and plasma.

[0077] The presence of the clamp does not affect the rate of hemolysis in the red blood cell concentrate or the amount of fibrinogen in the plasma. A slight decrease in the amount of factor VIII and factor XI in the plasma is observed. Example 2

[0078] Leukocyte depletion tests were carried out as in Example 1 using five forceps of the type in figure 8 .

[0079] Each clamp has a 1.5 mm gap on each side and a 1.3 mm gap in the middle. It is 5 mm thick. The upstream and downstream flexible tubes of the LXT filter have an outside diameter of 4.1 mm and an inside diameter of 3 mm.

[0080] The clamp is placed on the flexible tube downstream of the LXT filter.

[0081] The results are as follows: [Table 2] Pliers Filtration time (h:mm:ss) Residual white blood cell count (10 6 < / bag) Hemolysis (%) Hemoglobin (g / bag) Clamp 1 00:25:31 0,10 0,01 51,0 Clamp 2 00:25:48 0,20 0,00 53,4 Clamp 3 00:26:20 0,73 0,15 65,1 Clamp 4 00:23:15 0,30 0,02 59,6 Clamp 5 00:19:28 0,36 0,00 49,3 Clamp 6 00:21:01 0,32 0,00 61,3 Clamp 7 00:20:40 0,09 0,00 40,6

[0082] It is found that the residual white blood cell count is less than 1.106< per bag, the hemoglobin level is greater than 40g per bag, the hemolysis rate is less than 0.8%. The blood product thus complies with European standards.

Claims

1. System for reducing the flow rate of a fluid in a flexible tube (4) comprising said flexible tube (4) and a clamp (1), said clamp (1) comprising a body (2) provided with an opening (3) intended for receiving said flexible tube (4), the opening having at least one pinching portion (5) configured to compress said flexible tube (4) without obstructing it, said pinching portion (5) being defined between a first pinching surface (6) and a second pinching surface (7) which face each other, characterized in that said pinching surfaces (6, 7) of the clamp (1) move closer to each other over a height (h) less than or equal to the width of the flexible tube when said flexible tube is compressed until obstruction thereof, so as to reduce the fluid flow rate in said flexible tube, i.e., the distance between said pinching surfaces (6, 7) is smaller at the lower face of the clamp than at the upper face.

2. System according to claim 1, characterized in that the opening (3) further comprises an insertion portion (11) configured to introduce the flexible tube (4) into said opening (3), said insertion portion (11) being in communication with the pinching portion (5).

3. System according to claim 1 or 2, characterized in that the opening (3) further comprises a holding portion (14) in which the flexible tube (4) is held without being deformed, said holding portion (14) being in communication with the pinching portion (5).

4. System according to any of claims 1 to 3, characterized in that the first and second pinching surfaces (6, 7) are flat.

5. System according to any of claims 1 to 3, characterized in that the first and second pinching surfaces (6, 7) are convex.

6. System according to any of claims 1 to 5, characterized in that the body of the clamp has a first arm (8) and a second arm (9) connected to each other by a base (10).

7. System according to any one of claims 1 to 6, characterized in that the body (2) of the clamp comprises a gripping portion (13) provided with a plurality of ribs (16a, 16b).

8. System according to any of claims 1 to 7, characterized in that the body (2) of the clamp comprises a central recess (15a, 15b).

9. Device (18) for removing leukocytes from blood or a blood component, comprising, on the one hand, a filter (19) for removing leukocytes from blood or a blood component and a first flexible tube (23) in fluid communication with said filter (19) and, on the other hand, a clamp (1) placed or intended to be placed on the first flexible tube in order to reduce the flow rate in said first flexible tube, said first flexible tube (23) and said clamp (1) forming a system according to any of claims 1 to 8.

10. Device according to claim 9, characterized in that one end of the first flexible tube (23) is connected to an outlet port (21) of said filter (19) for removing leukocytes and the other end is connected to an inlet port (24) of a filtrate collection bag (22).