FR2954694A1 - PROCESS FOR MANUFACTURING A FLEXIBLE CONTAINER FOR MEDICAL USE - Google Patents

Abstract

The invention relates to a method of manufacturing a flexible container for medical use and a flexible container for medical use having a sealed internal volume for receiving a liquid. According to this method, at least the following steps are carried out: a) a single flexible plate is folded on itself without generating a fold to form two plate portions at least partially placed one above the other, said parts of plate being connected together by a curved portion intended to form an end of said internal volume, b) a minimum radius of curvature Rc of said curved portion is ensured during the assembly of said plate parts preventing the appearance of a defect at said curved portion, c) said plate portions are assembled along at least two connecting lines, said connecting lines being spaced from each other, at least two of said connecting lines laterally delimiting the internal volume of said container passing through said curved portion to form the edges of said container.

Description

Method of manufacturing a flexible container for medical use

The present invention relates to a method of manufacturing a flexible container for medical use. It also relates to an administration set comprising such a flexible container, in particular for the administration for medical purposes of a liquid contained in this container.

Long-term storage systems for biological materials are known. Such systems are used in storage, for example, red blood cells extracted from blood or stem cells stored in biobanks. It is known, for example, to preserve stem cells by placing them in a storage bag with a cryoprotectant and then freezing this bag at a very low temperature, typically at -190 ° C. When the contents of the bag are required by a patient, the corresponding storage bag is released. The stem cells are then delivered to the patient by intravenous route.

Now, after defrosting the contents of the storage bag, a significant mortality of the living cells thus conserved is observed. This mortality is caused in the first place by the existence of stress zones in the storage pocket. These stress zones result from the assembly at their periphery of flat sheets of plastic to form the internal volume of the pocket. This mortality is also the consequence of a non-uniform freezing / thawing rate over the entire internal volume of the storage bag. During freezing, the stressed cells die and therefore, it can not be guaranteed that a sufficient amount of live cells will be delivered to the patient.

It therefore quickly became necessary to increase the storage volume of the bag for a given size to ensure a sufficient amount of live cells after thawing. So-called three-dimensional pockets formed of two flat sheets of plastic material are known which are connected on their periphery to define an internal volume, the walls being deformed during the assembling step of these walls to define a uniform and increased internal volume. on a large part of the storage pocket. This ensures a uniform freezing rate in this internal volume and, consequently, a decrease in the mortality of living cells. However, it has been found that these so-called three-dimensional pockets are weakened by the deformation caused to the walls of the pocket delimiting the internal storage volume. These walls, which in fact have ridges, may have tears during cryopreservation of the storage bag, which will cause leaks after thawing of this bag. In addition, the storage pockets of the state of the art are generally made of plasticized polyvinyl chloride (S-PVC) or ethylene-vinyl acetate or EVA. These materials have the advantage of offering some elasticity to ensure optimal filling of the internal volume of the pocket. However, these flexible S-PVC or EVA storage pockets include additives known as plasticisers, which can migrate into the liquid contained in the internal volume of these bags. However, it is not desirable that these chemical elements pass into the blood of the patient during the administration of the contents of the storage bag because some of them are listed as carcinogenic. It would therefore be important to address these various disadvantages by providing a storage pocket whose original design allows to solve the technical problems posed by the storage pockets of the prior art. The objective of the present invention is therefore to propose a storage bag which is simple in its design and in its operating mode, economic and inert, offering an optimization of the storage volume for a given bulk without weakening thereof, this which results in the formation of a volume storage pocket.

To this end, the invention relates to a method for forming a flexible container for medical use comprising a sealed internal volume for receiving a liquid. According to the invention, at least the following steps are carried out: S a) a single flexible plate is folded on itself without generating folds to form two plate portions at least partially placed one above the other, said plate portions being interconnected by a curved portion for forming an end of said internal volume; b) providing a minimum radius of curvature Rc of said curved portion 10 during assembly of said plate portions preventing the appearance of a defect at said curved portion; c) joining said plate portions along at least two joining lines, said connecting lines being spaced from one another, at least two of said joining lines laterally delimiting the internal volume of said container passing through said curved portion to form the edges of said container. Preferably, after forming the internal volume of the pocket, this internal volume is closed by assembling the still free ends of the two plate portions at least partially placed one above the other, while maintaining a path or channel access to this internal volume to allow access to the content. This can be achieved, for example, by inserting between the plate portions of an access member to said internal volume of said container, and then assembling these portions and the access member. This assembly can be achieved by welding. The access element 25 may be, for illustrative purposes, a chimney. The term "flexible plate", a single flexible sheet of an inert material or on the contrary, a superposition of several sheets, at least one designed to define the inner wall of the container is inert material, this assembly being flexible. By "defect" is meant a scratch, a fold, a stitch or a stretch constituting an embrittlement of the flexible container and likely to lead to the cryogenization of this container to a rupture thereof. Preferably, in step a), an edge of the plate is folded on the opposite edge thereof so as to duplicate this plate without generating fold.

Advantageously, in step c), the plate parts are assembled by welding. The applicant has developed an experimental method for determining the minimum radius of curvature Rc. According to this test, a flexible plate identical to that used to manufacture the flexible containers is first taken. This flexible plate is folded on itself without generating a fold to form two superposed plate parts and possibly placed edge to edge. A rod is placed on the outer surface of the upper plate portion. The rod is moved from its free end to the other end having the curved portion until the appearance of a fold on this curved portion. From the appearance of this fold, the operator knows that the minimum radius of curvature of the curved portion has been exceeded. The position of the end of the rod relative to the curved portion allows the operator to determine the value of this minimum radius of curvature Rc. In various particular embodiments of this manufacturing method, each having its particular advantages and capable of many possible technical combinations: in step b), a conformation piece 20 is inserted between said plate parts to guarantee a radius of minimum curvature Rc of said curved portion during assembly, Preferably, the conformation piece is inserted between the plate parts so that the end of this conformation piece is placed at a distance from this curved portion. This distance is, for example, of the order of 1/4 of the height of the internal volume of the flexible container. In fact, it is sought to avoid the appearance of scratches likely to weaken the flexible container, the sensitive area being constituted by the bottom or curved portion of this container. said conformation piece is a rigid sheet or a rigid U-shaped portion whose branches move away from each other while moving away from the bottom of the U, in step b) is inserted between said plate portions an inflatable balloon, said balloon being in its inflated state to ensure said minimum radius of curvature Rc, - in step b), a pressurized fluid is introduced between said plate portions to ensure said beam radius. minimum curvature Rc, before step c), it ensures the positioning edge of said plate portions, It seeks to ensure the parallelism of the superimposed portions of flexible plate and folded for assembly to manufacture flexible containers whose dimensions are regular. For this, the conformation piece may include stops for ensuring the parallelism of said plate portions. Preferably, these plate portions are placed edge to edge after step a). after step c), said conformation piece, or said inflatable balloon, is removed from the internal volume thus defined, and then said conformation piece, or said inflatable balloon, is introduced again between said plate portions but at the same time; outside said internal volume and in that said plate portions are assembled along at least one new junction line passing through said curved portion to delimit an internal volume portion of another container, these steps are optionally repeated to to form as many internal volumes, and consequently of receptacles, as necessary. - said conformation piece, or said inflatable balloon, being fixed, a tension is applied on an edge of said plate thus folded to maintain the radius of curvature Rc of at least the portion of the plate thus folded between said conformation piece , or said inflatable balloon, and said edge, - the plate thus folded is guided with guide means to hold the folded ends of the plate, - in step c), at least one additional junction line is made to split said internal volume, - is made on at least one of said junction lines, a weakening line. By way of example, this line of weakness is a pre-cut line consisting of perforations. The invention also relates to a flexible container for medical use comprising a sealed internal volume for receiving a liquid, an upper portion and a lower portion of said container, said internal volume being placed between said upper and lower portions of said container, said container comprising more than one access element to said internal volume. According to the invention, this internal volume is delimited by a single flexible plate folded on itself and of which only the lateral edges and the upper part are assembled at least on their periphery. For purely illustrative purposes, this assembly can be achieved by welding or gluing. In various particular embodiments of this flexible container, each having its particular advantages and capable of many possible technical combinations: the plate comprises a single sheet of an inert material or a superposition of sheets, at least one for defining the wall; internal of the container is inert material, said plate being such that once released after being folded back on itself without generating a fold, it is able to return to its initial state without presenting a defect so that said plate is intended to give a volume effect to said container, it is also said that the plate has structural characteristics giving it a "loop effect", that is to say an ability to return to its original unfolded state without presenting deformation after to have been folded back on itself. the plate is made of polypropylene, polyolefin, polyamide, plasticized or flexible PVC, ethylene-vinyl acetate (EVA) or EVA derivatives, EVO (ethylene vinylolefin), ethylene-vinyl alcohol copolymer (EVOH), thin layer of oxide or a combination of at least two of these elements, - the plate further comprises on at least a portion of its outer surface a layer blocking or absorbing UV rays, - the internal volume of this container may comprise one or more compartments. The invention also relates to an administration set comprising a container obtained by the manufacturing method as described above and a transfer set connected to an access element to said internal volume of said container.

The invention will be described in more detail with reference to the accompanying drawings in which: - Figure 1 schematically shows a folded sheet on itself, a conformation piece being inserted between the parts of the sheet thus folded in a manner of embodiment of the invention; - Figure 2 schematically shows a flexible container according to a preferred embodiment of the invention; - Figure 3 is a sectional view along the axis A-A of the flexible container of Figure 2; Figure 1 shows one of the steps of manufacturing a flexible container according to a particular embodiment of the invention. Take a single sheet of inert material such as a polyolefin film or EVA or EVA derivatives in accordance with the prescriptions of the pharmacopoeia. One edge of this sheet is folded on the opposite edge thereof so as to duplicate this sheet. Care is taken during this step not to generate folds that could lead to embrittlement of the container and therefore a subsequent tear of the container during cryopreservation. This sheet being initially rectangular, it forms a band after folding.

Two pieces of sheet 1, 2 placed one above the other are thus obtained, these parts being connected to each other by a curved portion 3. Then, a piece of conformation is inserted between these parts of sheet 1, 2. 4 to ensure a minimum radius of curvature Rc of the curved portion 3 during assembly of these parts of sheet 1, 2 to prevent the occurrence of a defect. As shown in Figure 1, this shaping piece 4 is inserted so that its end 5 is placed at a distance, here about a quarter of the height of the internal volume, the end of the internal volume defined by the top of the portion curve 3 so as not to weaken this curved portion when assembling the sheet portions 1, 2. An edge of the thus folded sheet is inserted between two drive shafts to scroll this sheet relative to the workpiece of conformation 4 whose position is fixed. These drive axes which are here rollers, also allow to exert tension on this edge of the sheet to maintain the radius of curvature Rc of the portion of the sheet thus folded between the shaping piece 4 and this edge. These sheet portions are welded along two connecting lines 6, 7 passing through the curved portion 3, these connecting lines being spaced from each other to define the edges laterally delimiting the internal volume of the container. Optionally and purely for illustrative purposes, an additional junction line is made to divide this internal volume. However, this additional junction line does not pass through the curved portion 3. The liquid received in the internal volume of the container can therefore pass from one compartment to another of the internal volume thus divided. This additional junction line will separate the internal volume into two separate compartments by a weld subsequently made to fill the flexible container. After forming this initial internal volume, the sheet thus folded is advanced relative to the shaping piece 4, then a new junction line is formed to define the internal volume of another container. These steps are repeated to form as many flexible containers as necessary. Figures 2 and 3 show a flexible and flexible container obtained by the method of manufacturing a flexible container as described above.

This container therefore comprises a single sheet of an inert material whose edge has been folded on the opposite edge of this sheet so as to duplicate it. The superposed parts of this sheet thus folded were welded to define the side edges 6, 7 of the flexible container thus delimiting the internal volume.

This internal volume which is intended to receive a liquid, the medical solution, is therefore delimited by an upper portion 8, a lower portion 3 and side edges 6, 7. While the lower portion 3 can receive a liquid, the upper portion 8 and the side edges 6, 7 are not adapted to receive a liquid and are, in this sense, distinct from the internal volume. They each have a part in contact with the internal volume delimiting the upper end and the lateral edges of the latter. The upper part 8 of the container comprises a port 9 allowing access to the internal volume of the container. This access port 9 is, in known manner, taken between the thus connected walls of the container. It is here placed in the upper portion 8 of the flexible container. This access port 9 comprises a lower orifice 10 intended to be placed in contact with the medical solution contained in the internal volume of the container and an upper portion 11 protruding from the container and intended to allow the attachment temporarily or permanently a coupling member of a transfer set or an intravenous line. For purely illustrative purposes and in a particular embodiment of the present invention, flexible bags having a side weld of 90 mm in length with a weld width of 3 mm were made. The compartment thus formed had a width of 90 mm inside thus defining the interior volume of the flexible pouch. The shaping part used was a 2 mm thick U-shaped sheet with a diverging U-bar. The length of the inserted portion of this sheet between the plate portions was 2/3 of the depth of the pocket produced. The soft pouch material was 18% EVA manufactured by Renolit.

Claims (12)

REVENDICATIONS1. Process for the formation of one or more flexible containers for medical use each having a sealed internal volume for receiving a liquid, characterized in that at least the following steps are carried out: a) a single flexible plate is folded over it; even without generating folds to form two plate portions at least partially placed one above the other, said plate portions being interconnected by a curved portion for forming an end of said internal volume, b) ensuring a minimum radius of curvature Rc of said curved portion when assembling said plate portions preventing the appearance of a defect at said curved portion, c) assembling said plate portions along at least two lines junction, said connecting lines being spaced from each other, at least two of said junction lines laterally delimiting the internal volume of a container passing through ladit curved portion to form the edges of said container. 2. Method according to claim 1, characterized in that in step b) is inserted between said plate portions a shaping piece for ensuring a minimum radius of curvature Rc of said curved portion during assembly. 3. Process according to claim 2, characterized in that said conformation piece is inserted between said plate parts, so that the end of said conformation piece is placed at a distance from said curved portion. 4. Method according to claim 2 or 3, characterized in that said conformation piece is a rigid sheet or a U-shaped rigid portion whose branches deviate from each other away from the bottom of the U. 5. Method according to claim 1, characterized in that in step b) is inserted between said plate portions an inflatable balloon, said balloon being in its inflated state to ensure said minimum radius of curvature Rc. 6. Method according to any one of claims 1 to 5, characterized in that before step c), it ensures the positioning edge of said plate portions. 7. Method according to one of claims 2 to 4 and claim 6, characterized in that said shaping piece comprises stops to ensure the parallelism of said plate portions. 8. Method according to any one of claims 2 to 4 or 5, characterized in that after step c), said conformation piece, or said inflatable balloon, is removed from the internal volume thus defined, and then Again said conformation piece, or said inflatable balloon, between said plate portions but outside said inner volume and in that said plate portions are assembled along at least one new junction line passing through said curved portion for delimiting an internal volume portion of another container. 15 9. A method according to any one of claims 1 to 4 or 5, characterized in that said conformation piece, or said inflatable balloon, being fixed, a tension is applied on an edge of said plate and folded to maintain the radius of curvature Rc of at least the portion of the plate thus folded between said conformation piece, or said inflatable balloon, and said edge. 10. Method according to any one of claims 1 to 9, characterized in that in step c), at least one additional junction line is made to split said internal volume. 11. Method according to any one of claims 1 to 10, characterized in that one carries on at least one of said junction lines, a weakening line. 12. Administration set comprising a container obtained by the manufacturing method according to any one of claims 1 to 11 and a transfer set connected to an access element to said internal volume of said container.