U.S. patent application number 12/053929 was filed with the patent office on 2009-03-19 for methods of making and using filtering unit for a virucide substance.
Invention is credited to Francis Goudaliez, Thierry Verpoort.
Application Number | 20090071905 12/053929 |
Document ID | / |
Family ID | 9551138 |
Filed Date | 2009-03-19 |
United States Patent
Application |
20090071905 |
Kind Code |
A1 |
Goudaliez; Francis ; et
al. |
March 19, 2009 |
Methods of Making and Using Filtering Unit for a Virucide
Substance
Abstract
A filtering unit for removing a virucidal substance from a
biological fluid including an outer casing having at least one
input aperture and at least one output aperture. The outer casing
including a filter medium, which separates the filtration unit into
an input compartment and an output compartment. The filter medium
includes at least one hydrophilic material able to absorb or adsorb
the virucidal substance. The at least one hydrophilic material
includes either porous non-woven material or a porous membrane.
Inventors: |
Goudaliez; Francis;
(Faches-Thumesnil, FR) ; Verpoort; Thierry;
(Mouvaux, FR) |
Correspondence
Address: |
Baker Botts L.L.P.;One Shell Plaza
910 Louisiana Street
Houston
TX
77002-4995
US
|
Family ID: |
9551138 |
Appl. No.: |
12/053929 |
Filed: |
March 24, 2008 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10111143 |
Apr 19, 2002 |
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PCT/FR00/02900 |
Oct 18, 2000 |
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12053929 |
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Current U.S.
Class: |
210/651 ;
210/679; 525/384; 525/386; 525/418 |
Current CPC
Class: |
Y10T 29/49826 20150115;
A61M 1/3686 20140204; B01D 39/1623 20130101; A61L 2/0017
20130101 |
Class at
Publication: |
210/651 ;
210/679; 525/384; 525/386; 525/418 |
International
Class: |
B01D 61/14 20060101
B01D061/14; B01D 15/00 20060101 B01D015/00; C08F 8/00 20060101
C08F008/00 |
Foreign Application Data
Date |
Code |
Application Number |
Oct 20, 1999 |
FR |
FR 99/13089 |
Claims
1-20. (canceled)
21. A method for eliminating a virucidal substance from a
biological fluid comprising: passing the biological fluid through a
filter medium produced from a treate, hydrophilic polymer or
copolymer capable of absorbing or adsorbing the virucidal substance
and having a porosity that allows passage of the biological fluid
through the filter medium; wherein the polymer or copolymer
comprises polyester, acrylonitrile, or polyvinylidene fluoride.
22. The method according to claim 21, wherein the biological fluid
comprises blood, serum or plasma.
23. The method according to claim 21, wherein the virucidal
substance comprises methylene blue.
24. The method according to claim 22, wherein the methylene blue
has a concentration of 1 .mu.M.
25. The method according to claim 21, wherein the treated,
hydrophilic polymer or copolymer comprises treated, hydrophilic
polyester.
26. The method according to claim 21, wherein the treated,
hydrophilic polymer or copolymer comprises treated, hydrophilic
acrylonitrile.
27. The method according to claim 21, wherein the treated,
hydrophilic polymer or copolymer comprises treated, hydrophilic
polyvinylidene fluoride.
28. A method of forming a filter medium comprising: treating a
polymer or copolymer to render it hydrophilic and capable of
absorbing or adsorbing a virucidal substance, said polymer or
copolymer comprising polyester, acrylonitrile or polyvinylidene
fluoride; and forming a filter medium containing the polymer or
copolymer, wherein the filter medium has a mean porosity of between
1 .mu.m and 15 .mu.m.
29. The method according to claim 28, wherein treating comprises
grafting a hydrophilic substituent to the polymer or copolymer to
render it hydrophilic and capable of absorbing or adsorbing a
virucidal substance.
30. The method according to claim 29, wherein the hydrophilic
substituent comprises a hydroxyl or a carboxylic group.
31. (canceled)
32. A method of forming a filtration unit comprising: treating a
polymer or copolymer to render it hydrophilic and capable of
absorbing or adsorbing a virucidal substance, said polymer or
copolymer comprising polyester, acrylonitrile or polyvinylidene
fluoride; forming a filter medium containing the polymer or
coplymer, wherein the filter medium has a mean porosity of between
1 .mu.m and 15 .mu.m; placing the filter medium in a casing having
an inlet aperture and an outlet aperture to form a filtration
unit.
33. The method according to claim 32 wherein treating comprises
grafting a hydrophilic substituent to the polymer or copolymer to
render it hydrophilic and capable of absorbing or adsorbing a
virucidal substance.
34. The method according to claim 33, wherein the hydrophilic
substituent comprises a hydroxyl or a carboxylic group.
35. The method according to claim 32, wherein the polymer or
copolymer comprises polyester.
36. The method according to claim 32, wherein the polymer or
copolymer comprises acrylonitrile.
37. The method according to claim 32, wherein the polymer or
coplymer comprises polyvinylidene fluoride.
38. The method according to claim 32, wherein the filter medium has
a thickness between 1 and 10 millimeters.
39. The method according to claim 32, wherein the filter medium
comprises non-woven fibers having a mean diameter of between 0.5
.mu.m and 5 .mu.m.
40. The method according to claim 32, wherein the casing comprises
an inlet aperture and an outlet aperture.
41. The method according to claim 21, wherein the filter medium has
a mean porosity of between 1 .mu.m and 15 .mu.m.
42. The method according to claim 21, wherein the treated,
hydrophilic polymer or copolymer is in the form or a membrane.
43. The method according to claim 21, wherein the treated,
hydrophilic polymer or copolymer is in the form of non-woven
fibers.
44. The method according to claim 21, wherein the treated,
hydrophilic polymer or copolymer is in the form of a porous
non-woven material and one or more porous membranes.
Description
[0001] The invention relates to a filtration unit intended to
remove a virucidal substance present in a biological fluid.
[0002] It typically applies to the case where the virucidal
substance has previously been added to a biological fluid, in
particular blood plasma, intended to be transfused into a patient.
The aim of this addition is to subject the biological fluid to a
viral inactivation treatment prior to its transfusion into the
patient, so as to inactivate any viruses infecting the biological
fluid.
[0003] A conventional technique for viral inactivation of plasma
uses a colouring substance as a virucidal substance, for example
methylene blue or one of its derivatives.
[0004] The principle of this technique is based on photochemical
reactions between the colouring substance and the viral DNA or RNA
which may be present in the biological fluid.
[0005] Exposure of the colouring substance to light brings about a
photochemical reaction which transmits energy to the DNA and RNA
molecules so that the virus is inactivated.
[0006] During these photochemical reactions, the colouring
substance is not removed so that it remains in the biological fluid
after exposure to light.
[0007] After the use of this viral inactivation technique, a very
small amount of the colouring substance may be left in the
biological fluid and thus be transfused into the patient at the
same time as the biological fluid.
[0008] However, recent studies seem to show the possible toxicity
of certain colouring substances used, and in particular methylene
blue, when they are injected into the patient.
[0009] So much so that many countries are demanding the systematic
removal of colouring substances prior to injection of the
biological fluid into the patient.
[0010] The invention therefore aims to propose a filtration unit
which makes it possible to remove substantially all the virucidal
substance present in the biological fluid while leaving the
composition of the biological fluid substantially unchanged during
the filtration.
[0011] To that end, the object of the invention is a filtration
unit intended to remove a virucidal substance present in a
biological fluid, comprising an outer casing provided with at least
one input aperture and at least one output aperture, the casing
containing a filter medium which delimits two compartments,
respectively input and output, of the filtration unit, in which the
filter medium is produced from at least one hydrophilic material in
the form of a porous non-woven material and/or a porous membrane
capable of absorbing and/or adsorbing the virucidal substance.
[0012] According to one embodiment, the mean porosity of the filter
medium is defined so that the contact area between the biological
fluid and the filter medium is sufficient to remove substantially
all the virucidal substance while leaving the composition of the
biological fluid substantially unchanged during its passage through
the filter medium, namely being between 1 .mu.m and 15 .mu.m.
[0013] In a variant, the mean diameter of the fibres of the porous
non-woven material is between 0.5 .mu.m and 5 .mu.m.
[0014] The input compartment and/or the output compartment
communicate with the outside of the filtration unit by means of an
input, respectively output, tube.
[0015] The hydrophilic material of the filter medium is chosen in
particular from amongst the naturally hydrophilic materials or the
materials, in particular based on plastic material, made
hydrophilic, for example from amongst the polymers and/or the
copolymers based on polyester, acrylonitrile or polyvinylidene
fluoride.
[0016] According to one embodiment, the filter medium comprises a
number of layers of hydrophilic material, identical or different in
nature to one another, with a contact area identical or different
to one another.
[0017] The filter medium has for example a thickness between 1 and
10 millimetres.
[0018] According to one embodiment, the outer casing of the
filtration unit is rigid.
[0019] According to another embodiment, the outer casing of the
filtration unit is flexible.
[0020] FIG. 3 depicts, in top view and transverse section, the
embodiment of FIG. 1, showing in particular the assembly of the
frame containing the filter medium in the outer casing.
[0021] FIG. 4 depicts, in front view and partial longitudinal
section, the filtration unit of FIG. 3 in which the spacing rods
appear.
[0022] A filtration unit 1 intended to remove a virucidal substance
present in a biological fluid comprises typically an outer casing 2
provided with at least one input aperture 3 and at least one output
aperture 4, the casing containing a filter medium 5 which delimits
two compartments, respectively input 6 and output 7, of the
filtration unit 1.
[0023] In the description, the words "input" and "output" are
defined with respect to the direction of movement of the biological
fluid in the filtration unit 1 (see the arrows shown in FIG.
1).
[0024] According to one particular embodiment, the biological fluid
is blood or a blood compound, in particular blood plasma, and the
virucidal substance is methylene blue or one of its
derivatives.
[0025] Prior to its passage into the filtration unit 1, the
biological fluid has undergone a viral inactivation treatment by
means of the virucidal substance which was added to the biological
fluid.
[0026] This treatment, generally used at the blood transfusion
centre, will not be described further here.
[0027] The filtration unit 1 is intended to be integrated, in
particular by means of tubes, respectively input 8 and output 9,
into a system comprising for example bags for medical use, tubes,
clamps or other filters (for example to remove leukocytes from the
biological fluid).
[0028] In such a system, the filtration unit 1 is disposed on the
flow path of the biological fluid so that the biological fluid with
the virucidal substance added enters the filtration unit 1 by the
input aperture 3 and the biological fluid free from the virucidal
substance is delivered by means of the output aperture 4.
[0029] One particular example of such a system is a transfusion
line of a bag containing a biological fluid to be transfused into a
patient. In such a line, the filtration unit 1 is connected by its
input 3 to the bag containing the biological fluid with the
virucidal substance added and by its output 4 to means of
transfusion of the biological fluid free from virucidal
substance.
[0030] These various systems are not described further inasmuch as
they comprise the filtration unit 1 according to the structure
described here.
[0031] A description is now given of a first embodiment of the
filtration unit 1 comprising a flexible outer casing 2 formed by
the assembly of two sheets of flexible plastic material 10, 11
connected to one another, for example by welding, on their
periphery (FIG. 1).
[0032] This outer casing contains a filter medium designated
generally by the reference 5, the structure of which will be
described in more detail below.
[0033] The filter medium 5 is held in a flexible and impervious
support frame 12 and delimits two compartments, respectively input
6 and output 7, of the filtration unit 1.
[0034] The input compartment 6 communicates with the outside of the
filtration unit 1 by means of an input tube 8 which is used to fill
it with the biological fluid with the virucidal substance
added.
[0035] The output compartment 7 communicates with the outside of
the filtration unit 1 by means of an output tube 9 which delivers
the biological fluid free from virucidal substance.
[0036] The structure of the filtration unit 1 thus allows the
biological fluid with the virucidal substance added to be received
in the input compartment 6 via the input aperture 3, to pass
through the filter medium 5 so that the virucidal substance is
absorbed and/or adsorbed thereby, and then the biological fluid
free from virucidal substance is received in the output compartment
7 in order to be delivered via the output aperture 4.
[0037] According to one embodiment, the input tubes 8 and/or output
tubes 9 are flexible, and can be cut and welded.
[0038] Where a collecting bag is associated with the output tube 9,
this embodiment makes it possible, after separation of the
filtration unit 1 by cutting and welding of the output tube 9, to
obtain a bag full of biological fluid free from virucidal
substance. Such a bag can then be used conventionally, for example
for transfusion into a patient.
[0039] A first level of sealing of the filtration unit 1 is
provided between the filter medium 5 and the flexible frame 12
where no tube passes.
[0040] A second level of sealing is provided at the periphery of
the filtration unit 1 where the two outer sheets 10, 11, the
periphery of the flexible frame 12 and the passage of the input
tube 8 and output tube 9 come together.
[0041] This second level of sealing can be provided by the known
techniques for connecting plastic materials, for example by
high-frequency welding.
[0042] The implementation of the assembly of the filtration unit 1
is now described with reference to FIGS. 2 to 4.
[0043] The flexible frame 12 is formed by an assembly of two sheets
13, 14, for example plasticised sheets, between which the filter
medium 5 is placed.
[0044] These two sheets 13, 14 are perforated in their central part
and each have at least one opening 15, 16 allowing passage of the
biological fluid to be filtered.
[0045] The two sheets 13, 14 are fixed to one another preferably in
the region of the periphery of the filter medium 5, for example by
a weld seam 17, made through the filter medium 5, providing both
the fixing of the filter medium 5 and also the sealing of the unit
1.
[0046] The welding of the sheets 13, 14 through the filter medium 5
causes a compression 18, forming an impervious seam around the
filter medium 5.
[0047] The periphery 19 of the flexible frame 12 is also welded
with the outer sheets 10, 11 forming the outer casing 2 of the
filtration unit 1, these being welded to one another over their
entire circumference and in the region of their periphery, thus
providing the sealing of the unit 1.
[0048] In order to avoid the filter medium 5 sticking against the
outer casing 2, and thus interfering with the flow of the
biological fluid into the output compartment 7, two spacing rods
20, 21 are placed inside the output compartment 7, between the
filter medium 5 and the outer casing 2.
[0049] These two rods 20, 21 keep the output compartment 7 clear of
the filter medium 5 and thus avoid the filter medium 5 being
flattened against the inner wall of the outer sheet 2.
[0050] The rods 20, 21 can be produced from flexible tubes welded
for example at the inner wall of the sheet of the outer casing 2,
for example in the region of the peripheral weld 19 of the
filtration unit 1.
[0051] It is self-evident that the number of spacing rods can vary,
depending for example on the dimensions of the filtration unit
1.
[0052] For example, provision of a single spacing rod folded so as
to form a loop inside the output compartment 7 can be
envisaged.
[0053] Preferably, flexible rods are used, in order not to
interfere with the possibilities of folding the filtration unit
1.
[0054] In a second embodiment (not depicted), the filtration unit 1
comprises a rigid outer casing 2, for example made of a rigid
plastic material such as polycarbonate.
[0055] There will now be described in more detail the structure and
implementation of the filter medium 5 capable of removing
substantially all the virucidal substance while leaving the
composition of the biological fluid substantially unchanged during
the filtration.
[0056] In a first embodiment, the filter medium 5 is produced from
at least one hydrophilic material in the form of a porous non-woven
material.
[0057] In a second embodiment, the filter medium 5 is produced from
at least one hydrophilic material in the form of a porous
membrane.
[0058] In a third embodiment, the filter medium 5 is produced from
a hydrophilic material in the form of at least one porous membrane
which is inserted between a number of layers of hydrophilic
material in the form of a non-woven material.
[0059] In these three embodiments, the hydrophilic material is
capable of absorbing and/or adsorbing the virucidal substance, in
particular by affinity between the virucidal substance and the
hydrophilic material.
[0060] Various materials can be used for producing the filter
medium depending on the nature of the fluid to be filtered and that
of the biological fluid.
[0061] The choice of materials usable in the filtration unit
according to the invention is however limited by the fact that they
must not prevent, in particular by affinity, the passage of the
cellular or non-cellular constituents of the biological fluid.
[0062] In other words, the material forming the filter medium must
be capable of absorbing and/or adsorbing the virucidal substance
but not the constituents of the biological fluid.
[0063] In the case of treatment of a blood plasma containing
methylene blue, the following can be cited amongst the possible
materials: the polymers and/or the copolymers based on polyester,
acrylonitrile or polyvinylidene fluoride.
[0064] These polymeric products are generally not naturally
hydrophilic and must be treated by physical and/or chemical
methods, in order to give them said hydrophilic properties.
[0065] These treatments consist for example in grafting hydrophilic
substituents, for example hydroxyl or carboxylic type groups, onto
the polymer, according to known methods.
[0066] Such polymers made hydrophilic by physical and/or chemical
treatment are available on the market.
[0067] The hydrophilic nature of the material forming the filter
medium 5 allows a good wettability of the filter medium during
passage of the biological fluid, which allows in particular a
better flow of the biological fluid through the filtration unit 1
but also an improvement in the filtration efficiency.
[0068] The porosity characteristics of the filter medium allow the
passage of the biological fluid through the filtration unit while
leaving the composition of the biological fluid substantially
unchanged.
[0069] To that end, the mean size of the pores of the filter medium
is chosen according to the biological fluid to be treated. For
example, for the filtration unit 1 to allow the constituents of
whole blood to pass, the mean size of the pores can be of the order
of or greater than 7 .mu.m. In the case of blood plasma, the mean
size of the pores can be smaller, for example of the order of 4
.mu.m, on account of the absence of cellular constituents in the
plasma.
[0070] During passage of the biological fluid with the virucidal
substance added through the filter medium 5, the contact area
between the biological fluid and the filter medium must be
sufficient to remove substantially all the virucidal substance
while leaving the composition of the biological fluid substantially
unchanged.
[0071] In the first embodiment, this characteristic is
advantageously obtained by means of the use of a non-woven material
which has, through its structure, a large contact area for a small
volume.
[0072] Contact area between the biological fluid and the filter
medium means the area over which the absorption and/or adsorption
of the virucidal substance by the porous material can take place.
It is self-evident that this area is a function in particular of
the area of the filter medium, its porosity, its thickness and the
diameter of the fibres of the non-woven material.
[0073] Thus, by changing the diameter of the fibres, the porosity
of the non-woven material and the thickness of the filter medium 5
it composes, access can be obtained to a wide range of contact
areas which makes it possible to remove substantially all the
virucidal substance while leaving the composition of the biological
fluid substantially unchanged.
[0074] By way of example, there can be cited a filter medium 5
formed from a non-woven material made of polyester having a
thickness of the order of 5 mm, a mean porosity of the order of 8
.mu.m and a mean fibre diameter of the order of 2 .mu.m, allowing
the removal of a concentration of 1 .mu.M of methylene blue in 250
ml of blood plasma.
[0075] It should be noted however that these values can vary to a
great extent, in particular according to the time of contact
between the filter medium and the biological fluid, that is to say
the filtration speed.
[0076] In the second embodiment, a porous membrane is used as the
filter medium 5 to absorb and/or adsorb the virucidal substance
present in the biological fluid.
[0077] In one particular example, such a membrane is made of
polyvinylidene fluoride and with a pore size calibrated to a value
between 1 and 15 .mu.m.
[0078] In the third embodiment, the filter medium 5 can combine the
two materials used in the preceding embodiments, namely comprise a
number of layers of hydrophilic material in the form of a porous
non-woven material and one or more porous membranes. The material
and/or the structure of the material forming these layers can then
be identical or different to one another.
[0079] The layers are then disposed, for example contiguously, next
to one another in the filtration unit so that the biological fluid
passes through them successively during the filtration.
[0080] In one particular example, there can be cited a filter
medium 5 formed from a superposition of layers formed respectively
of a "spunbond" type polyester non-woven material, a "meltblown"
type polyester non-woven material, one or more polyvinylidene
fluoride membranes, a "meltblown" type polyester non-woven material
and a "spunbond" type polyester non-woven material.
[0081] The words "spunbond" and "meltblown" mean two of the
conventional methods of forming a layer of non-woven material
directly from the polymer, namely respectively either by forming
continuous monofilaments or by blowing the polymer in the molten
state into irregular filaments.
[0082] As these techniques are conventional, they will not be
detailed further here.
[0083] In this embodiment, the two outer layers of "spunbond"
non-woven material are identical and serve respectively as a pre-
and post-filter. Furthermore, they have the function of improving
the weldability of the filter medium 5 onto the casing 2 of the
filtration unit 1.
[0084] The two layers of "meltblown" non-woven material and the
membrane or membranes placed between them form more particularly
the filter medium 5 capable of absorbing and/or adsorbing the
virucidal substance.
[0085] Furthermore, the two layers of "meltblown" non-woven
material are identical and have the function of protecting the
membrane or membranes.
* * * * *