AU2003202448A1

AU2003202448A1 - Defibrination bag and method using a textile element

Info

Publication number: AU2003202448A1
Application number: AU2003202448A
Authority: AU
Inventors: Francis Goudaliez; Thierry Verpoort
Original assignee: Maco Pharma SAS
Current assignee: Maco Pharma SAS
Priority date: 2002-03-26
Filing date: 2003-03-25
Publication date: 2003-10-23
Anticipated expiration: 2023-03-25
Also published as: FR2837713A1; EP1348456A1; ATE409501T1; EP1348456B1; NZ524919A; DE60323776D1; AU2003202448B2; FR2837713B1

Abstract

Pouch (1) designed for defibrination of a biological fluid such as blood or blood plasma, comprises an external envelope (2) forming an internal volume (6) for the fluid. The envelope has an inlet (7) and an outlet (8) for the fluid. A textile element (9) designed to fix fibres in the fluid is placed in the internal volume without subdividing it. Pouch (1) designed for defibrination of a biological fluid such as blood or blood plasma, comprises an external envelope (2) forming an internal volume (6) for the fluid. The envelope has an inlet (7) and an outlet (8) for the fluid. A textile element (9) designed to fix fibres in the fluid is placed in the internal volume without subdividing it. The textile element includes at least one knitted, woven or non-woven layer and is made from a polymer or copolymer based on polyethylene, polypropylene, polyester, polyamide, polyurethane and their derivatives. The external envelope is made of two leaves (3, 3') of supple plastic material which are assembled around their periphery. The textile element is fixed on one part of the periphery of the internal volume. Independent claims are also included for the following: (1) a system of pouches designed for the sampling and defibrination of a biological fluid such as blood or blood plasma, containing a primary fluid receiving pouch with a textile element as described above. A second fluid receiving pouch is connected to the outlet from the primary fluid receiving pouch by a second pipe which contains a filter which can retain microclots; and (2) a defibrination process using a pouch containing a textile element as described above, with the pouch agitated for a period allowing the elimination of effectively all the fibre in the fluid. The defibrinated fluid may be transferred to a second pouch which is connected to the first by sealed and sterile means. The agitation is stopped to allow the defibrinated blood to be decanted to separate the blood serum and the blood cells.

Description

-1-

AUSTRALIA

PATENTS ACT 1990 COMPLETE SPECIFICATION FOR A STANDARD PATENT

ORIGINAL

Name of Applicant: Actual Inventors: Address for Service:

CCN:

Maco Pharma Francis Goudaliez and Thierry Verpoort Baldwin Shelston Waters MARGARET STREET SYDNEY NSW 2000 3710000352 Invention Title: DEFIBRINATION BAG AND METHOD USING A TEXTILE ELEMENT The following statement is a full description of this invention, including the best method of performing it known to us:- File: 38449AUP00 500135731_1.DOCJ5844 DEFIBRINATION BAG AND METHOD USING A TEXTILE ELEMENT Field of the Invention The invention relates to a bag intended for defibrination of a biological fluid, a bag system comprising such a bag, and defibrination methods.

The invention applies typically to the elimination of fibrin from the blood or plasma of an animal or a human being, so as to obtain a so-called incoagulable blood or a blood serum, that is to say a defibrinated plasma.

Background to the Invention During extraction of blood, the addition of chemical substances or anticoagulants to the blood is known in order to avoid its coagulation. Such anticoagulants, contained in the bag intended to collect the extracted blood, are for example Citrate Phosphate Dextrose (CPD) or Acid Citrate Dextrose

(ACD).

This is because such anticoagulants make it possible, by complexing the calcium ions, to block the blood coagulation cascade from the start of the chain. But the addition of anticoagulant is sometimes undesirable. This is the case in particular for the preparation, from incoagulable blood or blood serum, of biological reagents used in the field of cell culture or in the medical field.

One solution for avoiding coagulation of the blood without addition of anticoagulant is defibrination, that is to say the elimination of fibrin from the blood or blood plasma.

This is because, during coagulation of the blood, fibrinogen, which is a soluble protein present in blood plasma, polymerises, under the action of thrombin, into insoluble fibrin. The result of this reaction is coagulation, that is to say the formation of blood clots which comprise in particular red corpuscles, possibly other blood cells and fibrin.

Consequently, fibrin is the last element in the coagulation cascade, and its elimination therefore makes it possible to obtain an incoagulable blood or a blood serum.

Defibrination of the blood is usually achieved by naturally letting the blood coagulate and separating the serum from the clots by settlement and/or centrifuging.

But this method does allow incoagulable blood to be obtained. Moreover, the clots formed contain a non-negligible quantity of serum, so that the volume of serum obtained and therefore the quantity of components useful for the subsequent preparation of reagents are reduced non-negligibly. Finally, this method can be difficult to envisage in high production rates.

Another solution for the defibrination of blood is "beating" of the blood so as to obtain fibrin while avoiding the formation of clots. Such a method is for example described in the document US-4 129 131 in which rigid balls or a reticulated material are used.

Such a solution has the drawback, during agitation, of highly stressing the receptacle in which the balls or the reticulated material are placed. This is why, in order to avoid possible breaking of the casing of the receptacle, it must be conveyed into a rigid extraction device, which makes it not very practical to use. Moreover, the reticulated material has a fibrin retention capacity which is small, which necessitates subsequent carrying out of a filtration step in order to separate the fibrin and the blood.

It is an object of the present invention to overcome or ameliorate at least one of the disadvantages of the prior art, or to provide a useful alternative.

Unless the context clearly requires otherwise, throughout the description and the claims, the words 'comprise', 'comprising,' and the like are to be construed in an inclusive sense as opposed to an exclusive or exhaustive sense; that is to say, in the sense of "including, but not limited to".

In order to overcome these drawbacks, the invention proposes in particular a method of defibrination in a single step which makes it possible to obtain simply and efficiently an incoagulable blood or a blood serum, the method being capable of being implemented in a bag structure conventionally used in the field of blood extraction and processing.

SUMMARY OF THE INVENTION To that end, and according to a first aspect, the invention proposes a bag intended for the defibrination of a.biological fluid such as blood or blood plasma, of the type comprising an outer envelope forming an internal volume for said fluid, said envelope being provided with at least one input and/or output orifice for the fluid, in which at least one textile element able to fix the fibrin in the fluid is disposed in the internal volume, without partitioning said intemrnal volume.

According to a second aspect, the invention proposes a bag system intended for the extraction and defibrination of a biological fluid such as blood or blood plasma, of the type comprising a primary bag for collecting the fluid comprising an outer envelope forming an internal volume for said fluid, said envelope being provided with at least one input orifice to which means of extracting the fluid are connected by means of a first tube, in which at least one textile element able to fix the fibrin in the fluid is disposed in the internal volume.

According to a third aspect, the invention proposes a method of defibrination of a biological fluid such as blood or blood plasma, in which the fluid is collected in the internal volume of a bag inside which at least one textile element able to fix the fibrin in the fluid is disposed, said bag being agitated for a duration making it possible to eliminate substantially all the fibrin from the fluid.

According to a fourth aspect, the invention proposes a method of extraction and defibrination of a biological fluid such as blood or blood plasma, in which the fluid is extracted and collected in the internal volume of a bag inside which at least one textile element able to fix the fibrin in the fluid is disposed, said volume not containing any anticoagulant solution and said bag being agitated for a duration making it possible to eliminate substantially all the fibrin from the fluid.

BRIEF DESCRIPTION OF THE DRAWINGS Other objects and advantages of the invention will emerge in the course of the following description, given with reference to the accompanying drawings in which: Figure 1: depicts a front view of a bag according to a first embodiment of the invention; Figure 2: depicts a view in perspective and cross-section along the line II-Il of Figure 1; Figure 3: depicts a front view of a bag according to a second embodiment of the invention; and Figure 4: depicts, in a schematic front view, a bag system intended for the extraction and defibrination of blood.

DESCRIPTION OF A PREFERRED EXAMPLE Figures 1 to 3 depict a bag 1 intended for the defibrination of blood or blood plasma. In one particular example, the blood is animal blood such as the blood of bovines, ovines, swine, felines, canines and horses. In particular, the blood is sheep's blood. In another particular example, the blood is human blood.

In the embodiments depicted, the bag 1 is flexible and comprises an outer envelope 2 formed from two sheets of weldable and sterilisable flexible plastic material 3 and For example, the sheets 3 and 3' can be made of PVC, polyolefin, ethylene vinyl acetate (EVA), polyurethane or polyester.

These two sheets are assembled on their periphery 4, for example by a weld seam 5, so as to define an internal volume 6 for the blood.

The flexible bag 1 comprises an input orifice 7 and an output.orifice 8 for the blood. These orifices 7 and 8 are intended to be connected to flexible tubes, typically made from plastic material, intended to allow respectively the introduction and the recovery of the fluid in the bag 1.

According to another embodiment, not depicted, the input and the output of the fluid can be carried out by one and the same orifice.

The bag 1 also comprises a textile element 9 disposed in the internal volume 6, without partitioning it.

In Figures 1 and 2 (first embodiment), the textile element 9 moves freely in the bag 1. Thus, when the bag 1 contains the biological fluid, the textile element 9 "floats" in the bag 1.

The textile element 9 is inserted between the two sheets 3 and 3' during manufacture of the bag 1, before carrying out the welding for example.

In Figure 3 (second embodiment), the textile element 9 is fixed locally inside the bag 1. Typically, at least one of the edges of the textile element 9 is held in part of the weld seam 5. Thus, the textile element 9 is prevented from folding back on itself and/or hindering the flow of the fluid by blocking the input orifice 7 and/or the output orifice 8 of the bag 1.

In the embodiments depicted in Figures 1 to 3, the textile element 9 comprises a sheet formed from at least one layer of knitted fabric, woven material or non-woven material.

The material forming the textile element 9 is chosen from amongst the polymers or copolymers based on polyethylene, polypropylene, polyester, polyamide, polyurethane and their derivatives or any other polymer compatible with-blood. The textile element 9 is able to retain the fibrin. During extraction, fibrinogen is converted into fibrin under the action of thrombin. This fibrin is in filament form. When the fibrin filaments come into contact with the textile element 9, they become entangled in the threads and/or fibres of the element 9 and thus remain locked in the textile element 9. Moreover, the porosity and wettability of the textile element 9 make it possible to improve the penetration and retention of the fibrin therein.

In the embodiments depicted, the textile element 9 is formed from a sheet placed inside the bag 1 so that the surface of the sheet is parallel with the surface of the sheets 3 and Thus, the thickness and volume of the bag 1 containing the textile element 9 are substantially unchanged compared with the thickness and volume of the same bag with no textile element 9.

The flat configuration of the sheet provides a large surface of contact between the fibrin in the blood and the textile element 9, without substantially modifying the internal volume 6 of the bag 1.

The surface area of the textile element 9 is for example smaller than the surface area of the sheets 3 and 3' which formn the envelope 2. However, the textile element 9 can also be pleated or undulating, for example in the case where its surface area is greater than that of the sheets 3 and 3'.

In order to increase the probability of meeting between the textile element 9 and the fluid, the surface area of this element can represent more than 50% of the surface area of the sheets 3 and 3'.

By way of example, the textile element 9 consists of a rectangular polyester sheet in the form of a layer of non-woven material with a thickness of around 400 p.m and having a mean pore size of around 40 pm.

In a variant, another shape and/or a different number of textile elements 9 can be provided depending in particular on the shape of the bag and/or the quantity of fluid to be defibrinated.

A description is now given, in connection with Figure 4, of one particular embodiment of a bag system intended for the extraction and defibrination of blood in closed circuit, this system comprising a flexible bag 1 as described above.

The bag 1, referred to as the primary collection bag, is connected by means of a first tube 10 and at one of its input orifices 7 to extraction means 11. The system also comprises a bag 12, referred to as the secondary bag, intended to receive the defibrinated blood, which is connected to the bag 1 by means of a second tube 13 and at one of its output orifices 8.

The secondary bag 12 is made from weldable and sterilisable flexible plastic material.

In one particular embodiment, the extraction means 11 are an extraction needle.

The bag system also comprises a filter capable of retaining micro-clots 14 disposed between the primary bag 1 and the secondary bag 12 on the second tube 13. This filter 14 consists of a drip chamber 15 made from a plastic material comprising a porous element 16 having a pore diameter of around 200 pm, the porous element 16 being for example made from nylon.

This filter 14 makes it possible to eliminate the last fibrin filaments and any micro-clots present in the blood or serum.

In another embodiment, not depicted, the bag system does not contain a filter capable of retaining micro-clots.

In these two embodiments of the bag system, other bags, referred to as satellite bags (not depicted), can optionally be connected in a sterile manner to the primary bag 1 and/or secondary bag 2. This is the case, for example, when the defibrinated blood or the serum has to undergo other processing such as centrifuging.

The bag system of the invention is sterilisable and closed, so that the risk of bacterial contamination is limited.

A description is now given of two extraction and defibrination methods using the bag system depicted in Figure 4.

In a first step of the two methods, the fluid is extracted and collected in the internal volume 6 of the bag 1, said volume not containing any anticoagulant solution and said bag 1 being agitated for a duration sufficient to eliminate substantially all the fibrin from the fluid.

In the second step of the first method, the defibrinated blood is transferred into the secondary bag 12.

The transfer of the defibrinated blood is carried out via the filter 14 capable of retaining micro-clots.

The bag 12 containing defibrinated blood can next be processed conventionally by settlement and/or centrifuging in order to prepare blood serum.

Typically, the defibrinated blood contained in the bag 12 is left to settle so as toobtain an upper layer containing the serum and a lower layer containing the blood minus serum. The serum is next separated from the blood, and then, optionally, the serum is centrifuged again so as to obtain a supernatant of serum which is substantially pure, that is to say devoid of cellular components.

In a variant, the defibrinated blood contained in the secondary bag 12 is centrifuged immediately so as to obtain an upper layer containing practically pure serum and a lower layer containing the blood minus serum.

It is then advantageous to use a bag system according to Figure 4 which has in addition at least one satellite bag in fluidic communication with the secondary bag 12 for collecting the blood serum.

In the second step of the second method, after defibrination of the blood, the agitation of the bag is interrupted so as to let the defibrinated blood in said bag 1 settle until separation of the blood serum and the cellular elements of the blood.

Next the serum is transferred in closed circuit into the second bag 12.

The transfer of the serum is carried out via a filter 14 capable of retaining micro-clots, preferentially by means of a press.

The bag 12 then contains blood serum which can optionally be centrifuged so as to obtain a substantially pure acellular serum.

It is then advantageous to use a bag system according to Figure 4 which has in addition at least one satellite bag in fluidic communication with the secondary bag 12 for collecting the pure blood serum.

During the blood collection step, the bag 1 is agitated in order to improve the contact between the fibrin filaments and the textile element 9. The bag is in a horizontal position and the agitation can be carried out manually or by means of an automatic agitator. In one particular example, the bag is laid flat on the platform of the automatic agitator during operation.

During this agitation, the textile element 9, on account of its flexibility, does not risk damaging the bag 1.

in one particular example, the ratio of the volume of extracted blood to the total volume of the bag is less than 1/2, in particular equal to 1/3. Thus, the layer of blood contained in the bag 1 laid flat is thin and the surface of contact -between-the-blood and the textile element 9 is extensive.

According to one embodiment, the second tube 13 is divisible and weldable so as to make it possible to separate, from the bag system, the secondary bag 12 containing the defibrinated blood or serum.

Where in the foregoing description, reference has been made to specific components or integers of the invention having known equivalent, then such equivalents are herein incorporated as if individually set forth.

Although the invention has been described by way of example and with reference to possible embodiments thereof, it is to be understood that modifications or improvements may be made thereto without departing from the scope of the attached claims.

Although the invention has been described with reference to specific examples it will be appreciated by those skilled in the art that the invention may be embodied in many other forms.

Claims

1. A bag intended for the defibrination of a biological fluid such as blood or blood plasma, of the type comprising an-outer envelope forming an internal volume for said fluid, said envelope being provided with at least one input and/or output orifice for the fluid, characterised in that at least one textile element able to fix the fibrin in the fluid is disposed in the internal volume, without partitioning said internal volume.

2. A bag according to Claim 1, characterised in that the textile element comprises at least one layer of knitted fabric, woven material and/or non-woven material.

3. A bag according to Claim 1 or 2, characterised in that the textile element is produced from a polymer or a copolymer based on polyethylene, polypropylene, polyester, polyamide, polyurethane and their derivatives.

4. A bag according to any one of Claims 1 to 3, characterised in that the outer envelope is formed from two sheets of flexible plastic material which are assembled on their periphery.

A bag according to any one of Claims 1 to 4, characterised in that the textile element is fixed locally on part of the periphery of the internal volume.

6. A bag system intended for the extraction and defibrination of a biological fluid such as blood or blood plasma; of the type comprising a primary bag for collecting the fluid comprising an outer envelope forming an internal volume for said fluid, said envelope being provided with at least one input orifice to which means of extracting the fluid are connected by means of a first tube, said system being characterised in that at least one textile element able to fix the fibrin in the fluid is disposed in the internal volume.

7. A system according to Claim 6, characterised in that it also comprises at least one second bag for collecting the defibrinated fluid which is connected to an output orifice of said bag by means of a second tube.

8. A bag system according to Claim 7, characterised in that a filter capable of retaining micro-clots is provided on the second tube.

9. A method of defibrination of a biological fluid such as blood or blood plasma, in which the fluid is collected in the internal volume of a bag inside which at least one textile element able to fix the fibrin in the fluid is disposed, said bag being agitated for a duration making it possible to eliminate substantially all the fibrin from the fluid.

A method of extraction and defibrination of a biological fluid such as blood or blood plasma, in which the fluid is extracted and collected in the internal volume of a bag inside which at least one textile element able to fix the fibrin in the fluid is disposed, said volume not containing any anticoagulant solution and said bag being agitated for a duration making it possible to eliminate substantially all the fibrin from the fluid.

11. A method according to Claim 10. in which the defibrinated fluid is next transferred in closed circuit into a second bag which is connected in a sealed and sterile manner to the bag.

12. A method according to Claim 10, in which the fluid is blood and, after defibrination of the blood, the agitation of the bag is interrupted so as to let the defibrinated blood in said bag settle until separation of the blood serum and the cellular elements of the blood.

13. A method according to Claim 12, in which the serum is next transferred in closed circuit into a second bag which is connected in a sealed and sterile manner-to the bag,-- DATED this 25th Day of March, 2003 BALDWIN SHELSTON WATERS Attorneys for: MACO PHARMA