U.S. patent application number 16/655945 was filed with the patent office on 2020-03-05 for dialysis membrane and method for its production.
The applicant listed for this patent is B. BRAUN AVITUM AG. Invention is credited to ANGELA BAIER-GOSCHUTZ, ALEXANDER FRIEBE, JULIANE GABLER, ROLAND NAPIERALA, MATHIAS ULBRICHT, CLELIA JADE ELEONORE VICTORIA EMIN.
Application Number | 20200070106 16/655945 |
Document ID | / |
Family ID | 58098494 |
Filed Date | 2020-03-05 |
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United States Patent
Application |
20200070106 |
Kind Code |
A1 |
FRIEBE; ALEXANDER ; et
al. |
March 5, 2020 |
DIALYSIS MEMBRANE AND METHOD FOR ITS PRODUCTION
Abstract
A method for producing a dialysis membrane in hollow-fiber
membrane or flat membrane geometry includes: a) making a casting or
spinning solution for production of a base membrane for the
dialysis membrane out of at least one polysulfone and at least one
pore-forming hydrophilic additive in at least one organic solvent,
b) bringing the casting or spinning solution into contact with a
precipitating agent to form the base membrane, and c) rinsing out
the at least one organic solvent after precipitation of the casting
or spinning solution in flat or hollow-fiber form.
Inventors: |
FRIEBE; ALEXANDER; (FREITAL,
DE) ; NAPIERALA; ROLAND; (WERTHER, DE) ;
BAIER-GOSCHUTZ; ANGELA; (BAD-GOTTLEUBA - BERGGIESSHUBEL,
DE) ; GABLER; JULIANE; (PULSNITZ, DE) ;
ULBRICHT; MATHIAS; (ESSEN, DE) ; VICTORIA EMIN;
CLELIA JADE ELEONORE; (BOCHUM, DE) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
B. BRAUN AVITUM AG |
Melsungen |
|
DE |
|
|
Family ID: |
58098494 |
Appl. No.: |
16/655945 |
Filed: |
October 17, 2019 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
15436135 |
Feb 17, 2017 |
10500549 |
|
|
16655945 |
|
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
B01D 69/02 20130101;
B01D 69/08 20130101; B01J 41/13 20170101; B01D 2325/14 20130101;
B01D 2325/04 20130101; B01D 61/243 20130101; B01D 63/02 20130101;
B01D 69/06 20130101; B01D 71/68 20130101; B01D 71/12 20130101; B01D
69/10 20130101; B01D 2323/02 20130101; B01D 63/08 20130101; B01D
67/0009 20130101; B01D 69/12 20130101; B01D 71/60 20130101; B01D
2323/36 20130101; B01D 2325/36 20130101; A61M 1/16 20130101; B01D
2325/16 20130101; B32B 27/286 20130101; B01D 67/0013 20130101; B01D
67/0093 20130101 |
International
Class: |
B01D 71/68 20060101
B01D071/68; B01J 41/13 20060101 B01J041/13; B01D 67/00 20060101
B01D067/00; B01D 69/06 20060101 B01D069/06; B01D 69/08 20060101
B01D069/08; B01D 69/12 20060101 B01D069/12; B01D 71/12 20060101
B01D071/12; B01D 71/60 20060101 B01D071/60; B32B 27/28 20060101
B32B027/28; B01D 69/10 20060101 B01D069/10; B01D 69/02 20060101
B01D069/02 |
Foreign Application Data
Date |
Code |
Application Number |
Feb 17, 2016 |
DE |
10 2016 102 782.0 |
Claims
1. A method for producing a dialysis membrane in hollow-fiber
membrane or flat membrane geometry, the method comprising the steps
of: a) making a casting or spinning solution for production of a
base membrane for the dialysis membrane out of: i.) at least one
polysulfone, which is selected from the group consisting of: a
polysulfone, a sulfonated polysulfone, a polyethersulfone, a
sulfonated polyethersulfone, a polyphenylsulfone, a sulfonated
polyphenylsulfone, and mixtures thereof; and ii.) at least one
pore-forming hydrophilic additive in at least one organic solvent,
selected from the group consisting of: N,N-dimethylacetamide and
N-Methyl-2-pyrrolidone; b) bringing the casting or spinning
solution into contact with a precipitating agent to form the base
membrane; and c) rinsing out the at least one organic solvent after
precipitation of the casting or spinning solution in flat or
hollow-fiber form, wherein: the base membrane produced in step b)
is subjected to a surface modification to create a functional
surface on the base membrane by carrying out at least one
layer-by-layer deposition on a surface of the base membrane so as
to preserve the dialysis membrane, at least one polymeric
polycationic bonding agent is applied as a first layer on the
surface of the base membrane and at least one polymeric polyanion
is applied on the polycationic layer as a second layer, the at
least one polymeric polycationic bonding agent is selected from the
group consisting of: polyethylenimine chitosan, polylysine,
polyarginine, polyornithine, and mixtures thereof, a carboxylated
polysaccharide or a sulfated polysaccharide is used as the at least
one polymeric polyanion, and which is selected from the group
consisting of: a dextran sulfate with a molecular mass (M.sub.w) of
15 kDa to 1 MDa, a sulfated chitosan with a molecular mass
(M.sub.w) of 30 kDa to 750 kDa, a cellulose sulfate with a
molecular mass (M.sub.w) between 20 kDa and 1 MDa, and mixtures
thereof; and the pore-forming hydrophilic additive is selected from
the group consisting of: polyvinylpyrrolidone [PVP], a short-chain
glycol with 2 to 10 C atoms, triethylene glycol, propylene glycol,
polyethylene glycol, polyethylene oxide, and mixtures thereof.
2. The method according to claim 1, wherein net charge of the
surface of the base membrane can be adjusted by amounts of
sulfonated polymer or polyelectrolyte applied.
3. The method according to claim 1, wherein the pore-forming
hydrophilic additive is at least one of: polyethylene glycol or
polyethylene oxide exhibiting molecular mass of 600 Da to 500 kDa
(M.sub.w); and PVP exhibiting a molecular mass (M.sub.w) of lkDa to
2.2 MDa.
4. The method according to claim 1, wherein the at least one
polymeric polycationic bonding agent is a polyethylenimine with a
molecular mass (M.sub.w) of 1 kDa to 2 MDa.
5. The method according to claim 1, wherein the carboxylated
polysaccharide or sulfated polysaccharide comprises at least one of
a dextran sulfate with a molecular mass (M.sub.w) of approximately
500 kDa or a sulfonated chitosan with a molecular mass (M.sub.w) of
30 kDa to 750 kDa.
6. The method according to claim 1, wherein the at least one
polymeric polyanion is cellulose sulfate having a molecular mass
(M.sub.w) of approximately 100 kDa.
7. A dialysis membrane produced by the method according to claim 1.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a divisional under 35 U.S.C. .sctn. 120
of U.S. application Ser. No. 15/436,135, filed Feb. 17, 2017, which
claims priority to German Application No. 10 2016 102 782.0, filed
Feb. 17, 2016. The contents of U.S. application Ser. No. 15/436,135
and German Application No. 10 2016 102 782.0 are incorporated by
reference herein in their entireties.
FIELD
[0002] The present disclosure concerns a dialysis membrane, a
method for the production of the same and a dialysis membrane
module.
[0003] The following polymer abbreviations are used in the context
of the present disclosure:
TABLE-US-00001 Abbreviation Polymer DEXS Dextran sulphate PA
Polyamide PAA Polyacrylic acid PAN Polyacrylonitrile PC
Polycarbonate PEG* Polyethylene glycol PEI Polyethylenimine PEO*
Polyethylene oxide PES Polyphenylsulfone PMMA Polymethyl
methacrylate PPSU Polyphenylsulfone PUR Polyurethane PSU
Polysulfone PVP Polyvinylpyrrolidone SPES Sulfonated
polyethersulfone SPSU Sulfonated polysulfone SPPSU Sulfonated
polyphenylsulfone *PEG and PEO are essentially the same molecule.
For the purposes of the present disclosure, PEG is regarded as a
polymer with a molar mass of less than 100 kDa. A polymer with a
molar mass from 100 kDa is referred to as PEO.
BACKGROUND
[0004] Dialysis for the treatment of patients after kidney failure
was carried out successfully for the first time in the 1940s.
Dialysis membranes have advanced rapidly since then. In particular,
it was possible to achieve miniaturization from the rotating-drum
kidney to the plate dialyzer and on to today's modern hollow-fibre
dialyzer.
[0005] Nowadays membranes for hollow-fibre dialyzers are produced
on an industrial scale in large numbers and in high, reproducible
quality; they are generally offered as disposable systems in the
form of dialysis membrane modules. In particular, nano-controlled
spinning technologies have resulted in a considerable improvement.
Dialysis membranes made of plastics are now the standard for
low-cost therapy. Further development of dialysis membranes aim to
approach the natural function of the glomerular membrane of the
human kidney even further so as to ensure optimum treatment in the
event of renal insufficiency or complete renal failure in order to
compensate for the lack of kidneys as a result of surgery or
trauma.
[0006] In the advancement of membranes suitable for dialysis, the
focus is on a high degree of biocompatibility and high or
configurable water permeability, while at the same time achieving
the therapeutically desired separation effect. From the clinical
point of view, dialysis treatment continues to be of growing
importance since the number of patients to be treated worldwide is
increasing constantly, firstly as a result of an ageing population
and secondly due to the economic possibilities and availability of
treatment for renal insufficiency, which will likewise increase in
the developing countries in the future.
[0007] In addition to this, the aim is to achieve a downscaling of
dialyzers, which would mean the long-term objective of achieving
complete miniaturization of dialysis membranes down to a kidney
implant consuming very little energy [see Stefan Heinrich, H.
Oliver Pfirrmann, Nanotechnologie fur die Gesundheit,
Gesundheitsvorsorge im Wandel, 2, 12 (2010)].
[0008] The state of the art describes a wide range of membranes,
partly for ultrafiltration and partly for hemodialysis.
[0009] For example, US 2013/0 277 878 A1 describes a method for
producing a hollow-fibre dialysis membrane with a spinning
technique with phase inversion.
[0010] Such membranes are structured from at least one hydrophilic
and at least one hydrophobic polymer. US 2013/0 277 878 A1
discloses as suitable hydrophilic polymers polyvinylpyrrolidone
(PVP), polyethylene glycol, polyglycol monoester, water-soluble
cellulose derivatives, polysorbate and polyethylene
oxide/polypropylene oxide copolymers.
[0011] The hydrophobic polymers can be the following according to
US 2013/0 277 878 A1: polyamides (PA), polyacrylic acids (PAA),
polyarylethersulfones (PAES), polyethersulfones (PES), polysulfones
(PSU), polyarylsulfone (PASU), polycarbonates (PC), polyurethanes
(PUR).
[0012] Document DE 10 2004 008 220 B4 discloses hydrophilic
hollow-fibre membranes for hemodialysis. The material named is a
first synthetic polymer which can be a hydrophobic polymer,
including PSU and/or PES. The composite membranes of DE 10 2004 008
220 B4 contain a hydrophilic second polymer which can be selected
from the group: PVP, PEG, polyvinyl alcohol, polyglycol monoester,
polysorbate, carboxymethyl cellulose or a mixture or copolymer of
these polymers.
[0013] Furthermore, for the so-called high-flux dialysis membranes
of DE 10 2004 008 220 B4, an ultrafiltration rate in albumin
solution is disclosed in the range of 25 to 60
ml/(h.times.m.sup.2.times.mm Hg) and a sieving coefficient for
cytochrome c of at least 0.8 in combination with a sieving
coefficient for albumin of maximum 0.005, whereby the hollow-fibre
membranes of DE 10 2004 008 220 B4 are free of glycerine and other
additives which stabilize the pores in the membrane wall.
[0014] Furthermore, U.S. Pat. No. 6,042,783 A discloses a
hollow-fibre membrane made of a PSU resin for which the permeation
ratio--not described in further detail--is 5 1% for all
proteins.
[0015] Furthermore, document EP 1 634 611 B1 discloses a blood
purifier with a hollow-fibre membrane made of a polymer of the
polysulfone type and PVP, wherein a maximum of 10 ppm PVP is
aqueous elutable out of one gram of hollow-fibre membrane. The
polymers described of the polysulfone type are polysulfone and
polyethersulfone.
[0016] Furthermore, CN 201 669 064 U discloses a base membrane made
of a polysulfone with a "polyose" film for medical purposes which
is not further characterized.
[0017] Furthermore, WO 2013/156 598 A1, for example, discloses
ultrafiltration membranes which contain at least one substrate
layer based on a partially sulfonated polyethersulfone as a
polymer. The polysulfones used in the state of the art are solely
polyethersulfones which can be partially sulfonated.
[0018] Furthermore, WO 2013/156 597 A1 discloses nanofiltration
membranes made of a composite of a substrate layer, at least a
partially sulfonated polyethersulfone and at least a film layer
made of a cationic polymer, whereby cationic polymers are disclosed
which contain trimethyl ammonium salts as side groups.
[0019] In addition to the patent literature listed above, there is
also a range of scientific literature dealing with membranes and in
particular with membranes suitable for hemodialysis.
[0020] For example, Blanco et al. (2002): J Appl Polymer Sci 84,
2461 describes the broad use of polysulfones to make asymmetrical
membranes for ultrafiltration and nanofiltration. In concrete
terms, the use of polysulfone as a medium and polyamide as a
functional layer for asymmetrical membranes is described. Blanco et
al. also show that sulfonating can increase the hydrophily of the
PSU polymers which are in themselves hydrophobic.
[0021] Furthermore, Li et al. (2008): J Membrane Sci 309, 45
describe dual-layer hollow-fibre membranes for protein separation
using the example of BSA/Hb. Polyethersulfone is used for the
porous inner supporting layer and the outer layer is made of
sulfone, whereby the polyethersulfone layer was stable enough to
support the sulfonated polyethersulfone layer so that it was
possible to use the membranes successfully for protein
separation.
[0022] Mahlicli et al. (2013): J Mater Sci: Med 24, 533 disclose a
surface modification of dialysis membranes based on polysulfones
using layer-by-layer (LbL) self-assembly of
polyethylenimine/alginate-heparin layers According to Mahlicli et
al., a polysulfone is initially sulfonated and then a blend of
polysulfone and sulfonated polysulfone is poured out on a glass
plate to form a flat supporting membrane, whereby the solvent is
specified as N-Methyl-2-pyrrolidone.
[0023] The LbL assembly is carried out according to Mahlicli et al.
on the PSU/SPSU membrane which is negatively charged by the
SO.sub.3 groups introduced. For this purpose the membrane was
immersed in a solution of polyethylenimine [PEI] and incubated for
10 minutes. After setting the pH value to a sufficient level so as
to create the protonated form of the PEI, surplus PEI is rinsed out
and the membrane is immersed in an alginate solution where it is
incubated for 10 minutes. Surplus alginate is removed with rinsing
The alternating PEI/alginate immersion is repeated several times so
as to produce a multi-layer assembly. As the final layer, the
support membrane thus coated with PEI-alginate complexes is then
either immersed in a pure heparin solution or else immersed in
alginate/heparin solution so as to obtain as the final layer a pure
heparin layer or a mixed layer of alginate and heparin. According
to Mahlicli et al. the permeation properties of the membranes
produced by the authors for urea, vitamin B12 and lysozyme are
comparable with those of industrial AN69 dialysis membranes. The
plasma protein adsorption of the membranes was significantly
reduced. Likewise, thrombocyte activation as a consequence of the
anticoagulative coating was considerably reduced.
[0024] In addition, Malaisamy et al. (2005): Langmuir 21, 10587
describe nanofiltration membranes with polyethersulfone as the
support and an LbL coating with polystyrene sulfonate [PSS] and
protonated poly(allylamine) [PAH] and/or
poly(diallydimethylammonium chloride) [PDADMAC].
[0025] Kopec et al. (2011): J Membrane Sci 369, 59 describe the
process of designing membrane surface charges with LbL technique
taking the example of support membranes made of polyimides and
coatings made of sulfonated poly(ether ketone)
[0026] [SPEEK] and supports made of PSU with SPEEK coating. The
membranes are configured as hollow-fibre membranes for
ultrafiltration.
[0027] Finally, Kochan et al. (2010): Desalination 250, 1008
describe hollow-fibre membranes made of polyethersulfones whose
surface is modified with the LbL method with a polyelectrolyte, in
particular polyethylenimine and polystyrene sulfonate. The PEI used
is a commercial PEI with a molar mass of 57 kDa. The membranes of
this state of the art can be used for waste water treatment. When
the molecular weight cut-off value was tested with dextran, it
transpired according to Kochan et al. that a considerable increase
in the retention for dextran was observed in the coated membranes
while at the same time permeability was reduced.
SUMMARY
[0028] The present disclosure concerns, for example, a dialysis
membrane in hollow-fibre membrane or flat membrane geometry made of
a composite assembled from at least one base membrane based on at
least one polysulfone with at least one pore-forming hydrophilic
additive and at least one functional layer arranged on the base
membrane, whereby the functional layer is formed from at least one
polymeric polycationic bonding agent and at least one polymeric
polyanion, wherein the base membrane is formed from a material
which is selected from: a polysulfone [PSU], a sulfonated
polysulfone [SPSU], a polyethersulfone [PES], a sulfonated
polyethersulfone [SPES], a polyphenylsulfone [PPSU], a sulfonated
polyphenylsulfone [SPPSU]; and mixtures of these; the polycationic
bonding agent is a polyethylenimine [PEI], for example with a
molecular mass of between 1 kDa and 2 MDa (M.sub.w), in particular
approx. 2.0 kDa, approx. 25 kDa or approx. 750 kDa (M.sub.w),
chitosan, e.g. with a molecular mass of between 30 kDa and 750 kDa
(M.sub.w), polylysine, e.g. with a molecular mass of between 15 kDa
and 300 kDa (M.sub.w) (e.g. poly L-lysine sigma), polyarginine e.g.
with a molecular mass of between 1.9 kDa and 38.5 kDa (M.sub.w)
(for example n-butyl-poly-L-arginine hydrochloride) or
polyornithine, for example with a molecular mass of between 1.5 kDa
and 30.1 kDa (M.sub.w); the polyanion is a sulfated polysaccharide
which is selected from: a dextran sulfate [DEXS], for example with
a molecular mass of 15 kDa to 1 MDa (M.sub.w), in particular
approx. 500 kDa (M.sub.w), a sulfated chitosan, e.g. with a
molecular mass of 30 kDa to 750 kDa (M.sub.w); a cellulose sulfate,
e.g. with a molecular mass of between 20 kDa and 1 MDa (M.sub.w),
preferably approx. 100 kDa (M.sub.w); or mixtures of these; and
whereby the pore-forming hydrophilic additive is selected from:
polyvinylpyrrolidone
[0029] [PVP], e.g. with a molecular mass of between 1 kDa and 2,2
MDa (M.sub.w), in particular approx. 1.1 MDa (M.sub.w), a
short-chain glycol with 2 to 10 C atoms, triethylene glycol,
propylene glycol, polyethylene glycol [PEG]/polyethylene oxide
[PEO], for example with a molecular mass of between 600 Da and 500
kDa (M.sub.w), in particular approx. 8 kDa (M.sub.w) or approx. 10
kDa (M.sub.n); and mixtures of these.
[0030] Typically, the polysulfones used according to aspects of the
disclosure exhibit the following number average (M.sub.n) and
weight average (M.sub.w) molecular mass range:
[0031] polysulfone [PSU]: M.sub.n 16-22 kDa, M.sub.w 40-85 kDa,
[0032] sulfonated polysulfone [SPSU]: M.sub.n 27-32 kDa, M.sub.w
50-55 kDa,
[0033] polyethersulfone [PES]: M.sub.n 16-22 kDa, M.sub.w 30-75
kDa,
[0034] sulfonated polyethersulfone [SPES]: M.sub.n 18-22 kDa,
M.sub.w 30-35 kDa,
[0035] polyphenylsulfone [PPSU]: M.sub.n 22 kDa, M.sub.w 52-55 kDa,
and
[0036] sulfonated polyphenylsulfone [SPPSU]: M.sub.n 17-21 kDa,
M.sub.w 47-53 kDa.
[0037] A preferred embodiment of the present disclosure is a
dialysis membrane in which the SPSU exhibits sulfonation degree of
0.1 to 20 weight %, in relation to the weight of the unsulfonated
PSU; and/or the SPES exhibits a sulfonation degree of 0.1 to 20
weight %, in relation to the weight of the unsulfonated PES; and/or
the SPPSU exhibits a sulfonation degree of 0.1 to 20 weight %, in
relation to the weight of the unsulfonated PPSU.
[0038] The weight percentages are calculated for sulfonated SPES
and SPSU from NMR analyses. The samples for this purpose were
dissolved in deuterated dimethyl sulfoxide or deuterated chloroform
and the NMR spectra were measured using a 300 MHz or a 500 MHz NMR
device (Bruker). Based on the results, the molar ratios between
non-sulfonated and sulfonated repetition units (M.sub.PES=232
g/mol; MSPES=312 g/mol), the sulfonation degrees of SPES3, SPES2
and SPES4 were determined at 1.1; 3,6 and 14.1 weight %
respectively (specification range from 0.1 to 20 weight %).
[0039] SPSUA, SPSUB with 9.3 and 13.4 weight % (unit: M.sub.PSU=442
g/mol; M.sub.SPSU=522 g/mol); specification range of 0.1 to 20
weight %
[0040] Furthermore the specification for sPPSU is related to the
mass content of the sulfonated monomer 4,4.degree. Dichlordiphenyl
sulfone [sDCDPS].
[0041] The present disclosure involves the capability to produce
advantageous dialysis membranes, whereby the SPSU exhibits a
sulfonation degree of 9.3 or 13.4 weight %, in relation to the
weight of the unsulfonated PSU.
[0042] Such dialysis membranes are likewise preferable in which the
SPES exhibits a sulfonation degree of 1.1; 3.6 or 14.1 weight %, in
relation to the weight of the unsulfonated PES.
[0043] In terms of dialysis membranes which contain SPPSU,
preference is given to those which exhibit a sulfonation degree of
1.0, 2.0, 10.1 or 14.7 weight %, in relation to the weight of the
unsulfonated PPSU.
[0044] Preferred additives have been shown to be polyethylene
glycol with a molecular mass of 600 Da to 500 kDa (M.sub.w), in
particular approx. 8 kDa (M.sub.w) or 10 kDa (M.sub.n) and/or a PVP
with a molecular mass of 1 kDa to 2.2 MDa (M.sub.w), in particular
approx. 1.1 MDa (M.sub.w).
[0045] The preferred bonding agent for use in connection with the
present disclosure is a PEI with a molecular mass of between 1 kDa
and 2 MDa (M.sub.w), in particular approx. 2 kDa, preferably
approx. 25 kDa, preferably approx. 750 kDa (M.sub.w) or a C2 to
C8-dialkanal cross-linked, in particular 1,5-pentanedial
cross-linked, high-molecular PEI. In particular, PEI with a molar
mass of 750 kDa is commercially available, while the specially
synthetically cross-linked PEI polymers can be configured in terms
of their properties, in particular their molecule size, for example
via the degree of polymerization and the choice of cross-linking
agent.
[0046] For the purpose of LbL coating, the preferred polysaccharide
for use in connection with the present disclosure is a dextran
sulfate with a molecular mass (M.sub.w) of 15 kDa to 1 MDa, in
particular approx. 500 kDa and/or a sulfated chitosan with a
molecular mass of 30 kDa to 750 kDa; or mixtures of these.
[0047] In the preferred embodiments of the present disclosure, such
dialysis membranes are used in which the pore-forming additive is
selected from: a PVP with a molecular mass of approx. 1.1 MDa,
glycerine, a PEG/polyethylene oxide [PEO] with a molecular mass of
600 Da to 500 kDa (M.sub.w), in particular approx. 10 kDa (M.sub.n)
or 8 kDa (M.sub.w) or a 3-component mixture of these.
[0048] The preferred dialysis membranes exhibit a water
permeability of 10 to 2,000 L/bar*h*m.sup.2 and a sieving
coefficient (@22.+-.2.degree. C.) for bovine serum albumin [BSA] in
the range of 0.5 to 0.0001 and a molecular mass cut-off value of 20
to 50 kDa.
[0049] A further preferred embodiment of the dialysis membrane
according to aspects of the disclosure is characterized in that the
polyethylene glycol/polyethylene oxide exhibits a molecular mass of
600 Da to 500 kDa (M.sub.w), in particular approx. 8 kDa (M.sub.w)
or approx. 10 kDa (Me), and/or the PVP exhibits a molecular mass of
1 kDa to 2.2 MDa (M.sub.w), in particular approx. 1.1 MDa
(M.sub.w).
[0050] Another preferred embodiment of the dialysis membrane
according to aspects of the disclosure is characterized in that the
bonding agent is:
[0051] a polyethylenimine [PEI] with a molecular mass (M.sub.w) of
1 kDa to 2 MDa, a
[0052] chitosan with a molecular mass (M.sub.w) of 40 to 220
kDa,
[0053] a polylysine with a molecular mass (M.sub.w) of 15 to 300
kDa,
[0054] a polyarginine with a molecular mass (M.sub.w) of 1.9 to
38.5 kDa,
[0055] a polyornithine with a molecular mass (M.sub.w) of 1.5 kDa
to 30.1 kDa, or a mixture of these.
[0056] The above-mentioned dialysis membrane is furthermore
preferably characterized in that the bonding agent PEI has a
molecular mass (M.sub.w) of approx. 2 kDa, in particular approx. 25
kDa, preferably approx. 750 kDa, or is a C2 to C8-dialkanal
cross-linked, in particular 1.5-pentanedial cross-linked,
high-molecular PEI.
[0057] Another preferred embodiment of the dialysis membrane
according to aspects of the disclosure is characterized in that the
polysaccharide is a dextran sulfate with a molecular mass (M.sub.w)
of approx. 500 kDa and/or a sulfated chitosan with a molecular mass
(M.sub.w) of 30 kDa to 750 kDa.
[0058] Another preferred embodiment of the dialysis membrane
according to aspects of the disclosure is wherein the pore-forming
additive is selected from: a PVP with a molecular mass (M.sub.w) of
1 kDa to 2,2 MDa, in particular approx. 1.1 MDa, glycerine,
propylene glycol, triethylene glycol, a PEG/PEO with a molecular
mass (M.sub.w) of 600 Da to 500 kDa, in particular 8 to 10 kDa or a
multi-component mixture of these.
[0059] Another preferred embodiment of the dialysis membrane
according to aspects of the disclosure is wherein the contact angle
exhibits a value of 20 to 70.degree., thereby ensuring very good
wettability of the membranes (hydrophily).
[0060] The present disclosure likewise discloses a method for
producing a dialysis membrane in hollow-fibre or flat-membrane
geometry, whereby a) a casting or spinning solution is made for the
production of a dialysis membrane out of at least one polysulfone,
which is selected from: a polysulfone [PSU], a sulfonated
polysulfone SPSU], a polyethersulfone [PES], a sulfonated
polyethersulfone [SPES], a polyphenylsulfone [PPSU], a sulfonated
polyphenylsulfone [SPPSU]; and mixtures of these; and at least one
a pore-forming hydrophilic additive in at least one organic
solvent, selected from N,N-dimethylacetamide, dimethyl sulfoxide,
N-Methyl-2-pyrrolidone or N-Ethyl-2-pyrrolidone; and
[0061] b) the polymer mixture solution thus produced is brought
into contact with a precipitating agent to form the base membrane,
and the organic solvent is rinsed out after precipitation of the
polymer mixture in flat or hollow-fibre form; and
[0062] c) the base membrane produced in step b) is subjected to a
surface modification in order to create a functional surface on it
by carrying out at least one layer-by-layer [LbL] deposition on the
surface of the base membrane so as to preserve the dialysis
membrane, whereby at least one polymeric polycationic bonding agent
is applied as the first layer on the surface of the base membrane
and at least one polymeric polyanion is applied on the polycationic
layer as the second layer; and whereby [0063] d) the polycationic
bonding agent is selected from the group consisting of
polyethylenimine [PEI] chitosan, polylysine, polyarginine and
polyornithine, and mixtures of these; and
[0064] a carboxylated polysaccharide or a sulfated polysaccharide
is used as a polyanion, which is selected from the group consisting
of: a dextran sulfate with a molecular mass (M.sub.w) of 15 kDa to
300 MDa, a sulfated chitosan with a molecular mass (M.sub.w) of 30
kDa to 750 kDa; a cellulose sulfate with a molecular mass (M.sub.w)
between 20 kDa and 1 MDa, preferably approx. 100 kDa; or mixtures
of these; and whereby the pore-forming hydrophilic additive is
selected from: polyvinylpyrrolidone [PVP], a short-chain glycol
with 2 to 10 C atoms, triethylene glycol, propylene glycol,
polyethylene glycol [PEG]/polyethylene oxide [PEO] and mixtures of
these.
[0065] For the purposes of the present disclosure, the term
"surface of the base membrane" is understood to include both the
outer and the lumen surface.
[0066] A suitable precipitating agent for step b) in the above
method is a mixture of the organic solvent and water with a solvent
content of 5 to 85 weight %.
[0067] For production using the method according to aspects of the
disclosure, the polyethylene glycol/polyethylene oxide can exhibit
a molecular mass (M.sub.w) of 600 Da to 500 kDa, in particular
approx. 8 to 10 kDa and/or the PVP a molecular mass (M.sub.w) of 1
kDa to 2.2 MDa.
[0068] Typically, the method according to aspects of the disclosure
uses PEI as a bonding agent, whereby preference is given to a PEI
with a molecular mass of 1 kDa-2 MDa, in particular approx. 750
kDa, or a C2 to C8-dialkanal cross-linked, in particular
1,5-pentanedial cross-linked, high-molecular PEI, preferably one
which can be made from a PEI with a molecular mass of approx. 1.8
kDa by cross-linking with 1,5-pentanedial.
[0069] The polysaccharides used in the method according to aspects
of the disclosure are preferably a dextran sulfate with a molecular
mass (M.sub.w) of 15 kDa to 1 MDa, in particular approx. 500 kDa
and/or a sulfated chitosan with a molecular mass (M.sub.w) of 30
kDa to 750 kDa; or mixtures of these.
[0070] In the method described, the pore-forming additive is
selected from: a PVP with a molecular mass of approx. 1.1 MDa,
glycerine, a PEG/PEO with a molecular mass of 600 Da to 500 kDa, in
particular 8 to 10 kDa, or a 3-component mixture of these.
[0071] It is further preferred that the polymeric polycationic
bonding agent, in particular PEI, is applied to the finished base
membrane by spraying or by addition to the precipitating agent to
the surface of the base membrane.
[0072] Both the polycationic bonding agent and the polyanionic
functional layer can particularly preferably be applied by flushing
into the lumen of a capillary membrane at a flushing station.
[0073] A further preferred embodiment of the method according to
aspects of the disclosure is wherein the components of the casting
or spinning solution are fully dissolved at 20 to 70.degree. C. for
2 to 18 h and the homogeneous casting or spinning solution is
evacuated at 100 to 800 mbar for 5 to 45 mins to remove air
bubbles.
[0074] Another preferred embodiment of the method according to
aspects of the disclosure is wherein the casting or spinning
solution exhibits a viscosity of 0.2 to 5.0 Pa*s (@20.degree.
C.).
[0075] Another preferred embodiment of the method according to
aspects of the disclosure is wherein pore-forming additive is
selected from: a PVP with a molecular mass (M.sub.w) of 1.1 kDa to
2.2 MDa, glycerine, a PEG/PEO with a molecular mass of 600 Da to
500 kDa (M.sub.w), in particular approx. 8 kDa (M.sub.w) or a
3-component mixture of these.
[0076] Another preferred embodiment of the method according to
aspects of the disclosure is wherein the polymeric polycationic
bonding agent, in particular PEI, is applied by spraying onto the
finished base membrane or by addition to the precipitating agent
onto the surface of the base membrane or by flushing onto the
surface of the base membrane at a flushing station.
[0077] Another preferred embodiment of the method according to
aspects of the disclosure is wherein the polymeric polycationic
bonding agent, in particular PEI, is applied according to a ratio
of 1 to 4000 .mu.g /cm.sup.2 of membrane surface.
[0078] Another preferred embodiment of the method according to
aspects of the disclosure is wherein the polymeric polyanionic
polysaccharide, in particular DEXS, is applied according to a ratio
of 1 to 1500 .mu.g/cm.sup.2 of membrane surface.
[0079] Another preferred embodiment of the method according to
aspects of the disclosure is wherein the polymeric polyanionic
polysaccharide, in particular DEXS, is applied in a 0.01 to 1 M
NaCl solution.
[0080] Another preferred embodiment of the method according to
aspects of the disclosure is wherein the polymeric polyanionic
polysaccharide, in particular DEXS, is applied by flushing onto the
lumen surface of the base membrane at a flushing station, thereby
selectively configuring the separation properties of the resulting
composite membrane.
[0081] Another preferred embodiment of the method according to
aspects of the disclosure is wherein the polymeric polycationic
bonding agent, in particular PEI, and the polymeric polyanionic
polysaccharide, in particular DEXS, are applied with a
transmembrane pressure (TMP) of 10 to 250 mbar and a coating time
of 2 to 900 s respectively.
BRIEF DESCRIPTION OF THE DRAWING FIGURES
[0082] The disclosure is best understood from the following
detailed description when read in connection with the accompanying
drawings. Included in the drawings are the following figures:
[0083] FIG. 1 is a series of graphs depicting the water
permeability and sieving coefficients of five different sets of
base membranes prior to their LbL modification;
[0084] FIG. 2 is a series of graphs depicting the effect of LbL
deposition on water permeability and the sieving coefficient for
BSA at 22.+-.2.degree. C. for the polymers of the five different
sets of membranes;
[0085] FIG. 3 is a graph depicting the contact angle of
non-modified membranes of set 1 as a measurement of
wettability;
[0086] FIG. 4 is a pair of graphs depicting the zeta potential for
the membranes of set 1 before and after LbL coating;
[0087] FIG. 5 is a graph depicting the molecular size cut-off limit
for set 3, example P25, before and after LbL modification vs.
commercial high-flux xevonta B.Braun membrane;
[0088] FIG. 6 is a pair of graphs depicting the molar mass
distribution of the polymeric bonding agent PEI 2 kDa and 750 kDa
(M.sub.w) and the polysaccharides DEXS 15 kDa and 500 kDa,
calculated using GPC.
DETAILED DESCRIPTION
[0089] I. General Description of the Production of Base Membranes
With Different Polymers.
[0090] Casting or spinning solutions made of base
membrane-polymer/additive/solvent were produced as follows: First
of all, the selected additive and the desired polymer/polymer blend
is slowly dissolved in N,N-dimethylacetamide [DMAc] and an
appropriate amount of water (solution 1).
[0091] The following compounds were used as membrane polymers:
polysulfone [PSU] (Mn 16-22 kDa, M.sub.w 40-85 kDa), sulfonated
polysulfone [SPSU] (M.sub.w 50-55 kDa, Mn 27-32 kDa),
polyethersulfone [PES] (M.sub.w 30-75 kDa, M.sub.n 16-22 kDa),
sulfonated polyethersulfone [SPES] (M.sub.w 30-35 kDa, M.sub.n
18-22 kDa), polyphenylsulfone [PPSU] (M.sub.w 52-55 kDa, M.sub.n 22
kDa), sulfonated polyphenylsulfone [SPPSU] (M.sub.w 47-53 kDa,
M.sub.n 17-21 kDa); and mixtures (blends) of these.
[0092] The modification of the polymers PSU and PES was realized
with post-sulfonation. The polymer was dissolved in dichlormethane
under inert gas (concentration 3 to 10 weight %). Chlorosulfonic
acid was used as a reagent. 3 to 10 g of polymer (PSU or PES) was
used. The amount of chlorosulfonic acid (0.1 to 20 ml) and the
reaction time (addition within 5 to 45 minutes; then 1 to 5 hours
reaction time) were varied so as to adjust the sulfonation degree.
The reaction was carried out at room temperature. After this, the
polymer solution was transferred to ice-cold water as a
precipitation bath and the solid polymer was rinsed until a pH
value of 6-7 was reached. Finally, the modified polymer was dried
in a vacuum drying chamber at 40.degree. C.
[0093] Sulfonated polyphenylsulfone [SPPSU] can be produced by
copolymerization, according to the literature, e.g. Wang et al.:
Macromol. Symp. 175, 387-395 (2001) and/or the dissertation by
Jeffrey B. Mecham, Faculty of Chemistry at the Virginia Polytechnic
Institute and State University, Blacksburg, Va., USA, 23 Apr.
2001.
[0094] Here the monomers used were commercially available
4,4'-dihydroxybiphenyl (BP), 4,4'-dichlorodiphenyl sulfone (DCDPS)
and disodium-3,3'-disulfonate-4,4'-dichlorodiphenyl sulfone
(sDCDPS). All reactions were carried out in N-Methylpyrrolidone
(NMP). The base used was potassium carbonate.
[0095] The following describes one way to produce sPPSU as an
example:
[0096] In a 2 I HWS flask with stirrer, Dean-Stark apparatus,
nitrogen inlet and temperature control, the following were
suspended under nitrogen atmosphere in 1000 ml NMP: 258.37 g
4,4'-dichlorodiphenyl sulfone (DCDPS), 186.21 g
4,4'-dihydroxybiphenyl (BP), 49.12 g 3,3'-disodium
disulfate-4,4'-dichlorodiphenyl sulfone and 146.5 g potassium
carbonate (average particle size 50 .mu.m). The mixture was stirred
and heated to 190.degree. C. The mixture was gassed with 20 l/h of
nitrogen and kept at 190.degree. C. for 6 h. After this, 500 ml NMP
was added so as to cool the mixture. The mixture was cooled under
nitrogen to below 60.degree. C. After filtration, the mixture was
precipitated in water containing 50 ml 2 m HCl. The precipitated
product was extracted for 20 h at 85.degree. C. with hot water and
dried for 24 h under reduced pressure at 120.degree. C.
[0097] The molecular weight distribution was determined with GPC
using DMAc/LiBr as a solvent and PMMA samples with close molecular
weight distribution as standards so as to calibrate the system.
[0098] As described above, the desired polymer/polymer blend was
then slowly dissolved in N,N-dimethylacetamide [DMAc] and an
appropriate amount of water (solution 1). This solution 1 was
continuously stirred at 40.degree. C., when polyethylene glycol
with an M.sub.n of 10,000 Da was added. If PVP was used, stirring
was carried out at 70.degree. C., whereby a poly(vinylpyrrolidone)
with a weight average molar mass M.sub.w of approx. 1.1 MDa was
used. In order to achieve full dissolution of the polymer
components, the mixtures were stirred for at least 3 to 12 h. If by
this time no full dissolution had been achieved, stirring was
continued for further hours.
[0099] The finished homogeneous casting or spinning solution was
degassed at 100 mbar for 15 mins in order to remove air
bubbles.
[0100] Unless stated otherwise, all percentages are shown in weight
% and the term "molar mass", unless stated otherwise, refers to the
weight average molar mass Mw or the number average molar mass
M.sub.n, both of which can be measured with gel permeation
chromatography with the relevant molecular mass standards. The
reason for this is that the weight average molar mass is of greater
importance for the property correlations of plastics in practice
than the number and viscosity averages (see Saechtling,
Kunststofftaschenbuch, 31st edition, Carl Hanser Verlag, Munich
2013).
TABLE-US-00002 TABLE 1 Parameters for the characterization of molar
masses with GPC PSU, PES, PPSU, SPSU, PEI DEXS SPES, SPPSU Column
NOVEMA SUPREMA GRAM pre-column + 2x 10000 A, 10 .mu.m (PSS) 10000
A, 10 .mu.m (PSS) GRAM, 10 .mu.m (PSS) Eluent 0.1M NaCl 0.4M NaCl
DMAc 0.25% HCOOH 0.1M NaNO3 0.01M LiBr 0.01% NaN3 0.01% NaN3
Volumetric 1 flow rate [ml/mins] Concentration 2.5 1.0 4.0 Polymer
[g/L] Detector RI RI ETA 2010 RI/VIS Standard PVP 900 Da-1 MDa
Pullulan 180 Da-780 kDa PMMA 0.1-1000 kg/mol
[0101] To produce flat membranes, these are made according to the
non-solvent-induced phase separation method [NIPS]. The polymer
solution is extruded in a Coatmaster 509 MC (Erichsen GmbH &
CO. KG, Hemer) on a glass plate at a constant squeegee speed of 25
mm/s with a stainless steel squeegee with a gap height of 200 .mu.m
to form the protomembrane in a controlled atmosphere with a
relative air humidity of <30% at room temperature. The
temperature of membrane production--casting solution, glass plate,
stainless steel squeegee, precipitation bath--was varied from room
temperature to 60.degree. C.
[0102] The cast film thereby obtained is subsequently immersed for
5 mins in a precipitation bath, which contains as the precipitating
agent 500 ml of a mixture of 50 vol. % DMAc/50 vol. % H.sub.2O.
[0103] After precipitation, the membrane is transferred to water,
whereby the water is changed three times, after 20 mins in each
case. For so-called wet variants (see Table 2) the membranes are
cut to the final size and samples are kept at room temperature in
an aqueous solution of 10 mM sodium azide for characterization or
LbL modification. In the case of dry variants, the membranes are
dried for 6 mins at 100.degree. C. after rinsing and prior to
further stages.
[0104] In order to make hollow-fibre membranes, the finished
polymer spinning solution described above is introduced into the
annular gap of a hollow-filament nozzle which is maintained at a
temperature of approx. 60.degree. C. At the same time, for the
formation of lumen and induction of the precipitation process, a
mixture of 50 vol. % DMAc/50 vol. % H.sub.2O is fed through the jet
needle of the hollow-filament nozzle. The fully-formed hollow-fibre
membrane was guided through a channel in which the temperature was
50.degree. C. and the relative air humidity was 90%, precipitated
in warm precipitating agent which was at a temperature of approx.
70.degree. C. (50 vol. % DMAc/50 vol. % H.sub.2O) fixed and
subsequently rinsed and preserved as was the case for the flat
membranes.
[0105] After drying, hollow-fibre membranes had formed with a lumen
diameter of 200 .mu.m and a wall thickness of 30 .mu.m.
[0106] I.1. Modification of the Base Membrane: Layer-By-Layer
Deposition
[0107] The surface modification of the flat membranes produced
according to the above description was carried out with an
Amicon.RTM. ultrafiltration measuring cell or in a cell replicated
in analogue form and dimensions. First of all, a solution of a
commercially available polyethylenimine (750 kDa) was filtered in a
ratio of 3.7 mg/cm.sup.2 of membrane surface through the membrane
for 5 mins at 50 mbar in order to apply an initial layer of a
polymeric cationic bonding agent onto the membrane surface. Then
the membrane surface was rinsed with water and water was
subsequently filtered through the membrane for 5 mins at 50 mbar.
After this, a 1 M NaCl solution was filtered for 2 mins at 50 mbar
through the membrane. The membrane was then coated with filtration
with a dextran sulfate solution (DEXS solution, 500 kDa in 1 M
NaCl) in a ratio of 1.5 mg/cm.sup.2 of membrane surface for 5 mins
at 50 mbar to create the second layer containing the polymeric
polyanion. The membrane was then rinsed as described above so as to
remove surplus dextran sulfate.
[0108] If necessary the LbL coatings described above can be
repeated several times so as to finally obtain a functional layer
with the desired properties.
[0109] For the LbL coating of the hollow-fibre membranes produced
as part of the present disclosure, the hollow fibres were first
introduced to a dialysis module, then they were loosely packed, and
subsequently the LbL coating was carried out as described for the
flat membranes.
[0110] I.2. Permeability and Retention Studies
[0111] I.2.1. Characterization of the Base Membranes
[0112] The filtration experiments were carried out in the so-called
dead-end configuration model using an Amicon.RTM. ultrafiltration
measuring cell or an self-constructed cell with a stirring device.
In all experiments, a PP fleece was placed under the membranes to
be tested so as to prevent the cell floor from mechanically
altering the membrane.
[0113] First the membranes were subjected to a compaction. This is
an alternating pressure load whose effects lead to changes in the
membrane structure, resulting in a loss of water permeability. The
membranes were first compacted for at least 30 mins with
filtrations of ultrapure water at 0.5 bar until a quasi-constant
flow was achieved. Then the pressure was relieved for 10 mins and
the water permeability was measured for a pressure difference of
0.1 to 0.5 bar. The existing water permeability Lp, expressed in L
h.sup.-1m.sup.-2bar.sup.-1, was standardized to a temperature of
20.degree. C.
[0114] The loss in permeability as a result of compaction was
determined from these experiments based on the following equation
1:
Lp compactionloss ( % ) = ( 1 - Lp after compaction @ 0.5 bar Lp
before compaction @ 0.5 bar ) .times. 100 ( 1 ) ##EQU00001##
[0115] The membranes produced were tested with bovine serum albumin
(BSA, Probumin, Millipore) with ultrafiltration. First of all, the
membranes for testing were conditioned for two minutes by
filtration of a phosphate buffer solution (8 g/L NaCl, 1,182 g/L
Na.sub.2HPO.sub.4.2H.sub.2O, 0.9 g/L KH.sub.2PO.sub.4) at 50 mbar.
After this, a known volume of a BSA solution was filtered through
the membrane as a feed with a concentration of 30 g/L BSA in
phosphate buffer--in a ratio of 2.4 ml/cm.sup.2 of the membrane at
30 mbar, and permeate and retentate samples were collected in a
ratio of 1:5. The concentrations in the feed solution, retentate
and permeate were measured at 278.5-279.5 nm (after the relevant
calibration). The sieving coefficient S for BSA was calculated
according to equation 2:
S = 2 .times. Cpermeate Cfeed + Cretentate ( 2 ) ##EQU00002##
[0116] C.sub.permeate, C.sub.feed and C.sub.retentate are the
relevant BSA concentrations in the permeate, feed and
retentate.
[0117] After this, the membranes were carefully rinsed and stirred
for 15 minutes with ultrapure water in the Amicon.RTM. cell so as
to remove the weakly bound fouling layer. Then the permeability was
measured once again and fouling resistance R.sub.f was calculated
as follows:
R f = Lp * Lp ( 3 ) ##EQU00003##
[0118] whereby Lp and Lp* are the permeabilities before and after
BSA filtration.
[0119] For the purposes of the present application, the term
"molecular weight cut-off" (MWCO) is deemed to be the molecular
mass which is 90% retained by a membrane. The unit is Da.
[0120] Determining the molecular weight cut-off was carried out
with a dextran wide band mixture (feed) with a concentration of 1.1
g/l (mass distribution/litre: 0.20 g 1 kDa, 0.25 g 4 kDa, 0.15 g 8
kDa, 0.07 g 15 kDa, 0.10 g 35 kDa, 0.15 g 70 kDa, 0.05 g 110 kDa,
0.13 g 250 kDa) in water with 0.01% sodium azide. The feed was
filtered through the membrane in a ratio of o2.4 ml/cm.sup.2 of the
membrane at 30 mbar @ room temperature, and permeate and retentate
samples were collected in a ratio of 1:5. The concentrations in the
feed solution, retentate and permeate were then analyzed with gel
permeation chromatography (PL-GPC 50 Plus, Varian). The column used
was a PROTEEMA 300A (PSS), PL aquagel-OH Mixed 8 .mu.m (Agilent)
and 0.01% NaN.sub.3 in H.sub.2O with a flow rate of 1 ml/min was
used an eluent. 100 .mu.l of each sample was injected. The analysis
was carried out based on a calibration using the polysaccharide
standard.
[0121] The sieving coefficient for each molar mass is calculated
from the data with software:
S = 2 c permeate c feed + c retentate ( 4 ) ##EQU00004##
[0122] The sieving curve is obtained for each membrane by showing
the sieving coefficient in relation to molar mass (logarithmic
application). The sieving curve is then used to determine the
cut-off for a sieving coefficient of 0.1. The term "molecular
weight cut-off" (MWCO) is deemed to be the molecular mass which is
90% retained by the membrane. The unit is Dalton [Da].
[0123] I.2.2.Characterization of the LbL-Modified Membranes
[0124] In order to characterize the LbL-modified membranes, the
measurements were carried out in the same way as described above
for the base membranes. First of all the unmodified membranes were
compacted and permeability was measured (at a pressure difference
of 0.1 to 0.5 bar). Then the LbL coating was carried out as
described in Section 1.2. After the LbL coating, the new
permeability was measured and the permeability loss due to LbL
deposition Lp.sub.LbL loss was calculated according to equation
4:
Lp LbLloss ( % ) = ( 1 - Lp after LbL deposition Lp before LbL
deposition ) .times. 100 ( 5 ) ##EQU00005##
[0125] The new membrane capacity was also measured based on BSA
retention using the same method as for the base membranes. Finally
the membranes were once again carefully rinsed and stirred for 15
minutes using ultrapure water and then again rinsed for 5 mins at a
pressure of 0.1 bar. After this, the permeability was once again
measured and the MWCO and fouling resistance R.sub.f-LbL were
calculated.
[0126] 1.3. Contact Angle Measurements
[0127] The contact angle in ".degree." was determined using an
optical contact angle measuring device. The measurements were
carried out using a static captive bubble method (air bubble
volume: 5 .mu.l). For each sample, at least five measurements were
carried out in different positions and then the average was
calculated.
[0128] I.4. Zeta Potential Measurements
[0129] In order to determine the surface charge of the lumen
surface of the membranes produced, the zeta potential was measured
using the commercial electrokinetic analyzer SurPASS (Anton Paar).
Prior to each experiment, the membranes to be measured were
equilibrated for one hour in an electrolyte solution of 1 mM KCl.
The experiments were then carried out at room temperature from a pH
value of 3, set with an HCl solution, up to final pH value of 11.5,
gradually increased by the addition of a KOH solution.
[0130] I.5. Rheological Measurements
[0131] The viscosity of the casting and spinning solutions produced
was measured using a rheometer fitted with a Peltier element for
the purpose of temperature control. The experiments were carried
out at a constant shear rate (125 1/s) and at a temperature
difference (between 20 and 60.degree. C.) using a measurement
system with a cone plate (CP25-2/TG).
[0132] II. Results
[0133] The composition of the casting solutions to produce flat
membranes as model membranes and the production temperature are
shown in Table 2.
[0134] In the table, PSU is polysulfone, while SPPSU1, SPPSU2,
SPPSU10, SPPSU14 indicate the respectively specified sulfonation
degree of the sulfated polyphenylsulfones used in weight %;
according to this the following sulfonation degrees apply to the
above-specified sulfonated polyphenylsulfones: 1.1; 3.6 and 14.1
weight %.
[0135] For the sulfonated polysulfonethers used, the same applies
to them in terms of their respective sulfonation degree in the same
way as for the nomenclature set out above for the sulfonated
polysulfones, namely SPES3, SPES2 and SPES4. These sulfonated
polyethersulfones thus exhibit a sulfonation degree of 1.1; 3.6 and
14.1 weight %.
[0136] Five different sets of casting solutions were selected for
the experiments:
[0137] Set 1:15% polymer content in the casting solution using
different proportions of SPPSU and PVP as an additive.
[0138] Set 2:17% polymer content in the casting solution using
different proportions of SPPSU and PVP as an additive.
[0139] Set 3:16% polymer content in the casting solution using
different proportions of SPPSU and PEG/PEO as an additive.
[0140] Set 4:15% polymer content in the casting solution using
different proportions of SPES and PVP as an additive.
[0141] A summary of the experimental data obtained for the
membranes tested is shown in Table 3.
TABLE-US-00003 TABLE 2 Compositions for the solutions and casting
conditions used for membrane production Set 1 Set 1 Set 1 Set 1 Set
1 Set 2 Set 2 Polymer solutions S0-PVP-B S1-PVP-B S2-PVP-B
S10-PVP-B S14-PVP-B S2-PVP-D S10-PVP-5D PSU/SPPSU* 15/0 13.5/1.5
13.5/1.5 13.5/1.5 13.5/1.5 15.3/1.7 16.2/0.8 PVP/DMAc/H.sub.20
3.7/80.8/0.5 3.7/80.8/0.5 3.7/80.8/0.5 3.7/80.8/0.5 3.7/80.8/0.5
3.7/78.8/0.5 3.7/78.8/0.5 Production temperature (.degree. C.) 60
60 60 60 60 60 60 Set 3 Set 3 Set 3 Set 3 Set 3 Polymer solutions
S2-PEG-A S2-PEG-A-25 S10-PEG-A S14-PEG-A P25 PSU/SPPSU* 14.4/1.6
14.4/1.6 14.4/1.6 14.4/1.6 PEG/DMAc 5/79 5/79 5/79 5/79
PSU/PEG/DMAc 16/5/79 Production temperature (.degree. C.) 40 25 40
40 23 .+-. 3 Set 4 Set 4 Set 4 Set 5 Polymer solutions SPES2-PVP-B
SPES3-PVP-B SPES4-PVP-B P29 PSU/SPES 13.5/1.5 13.5/1.5 13.5/1.5
PVP/DMAc/H.sub.20 3.7/80.8/0.5 3.7/80.8/0.5 37/80.8/0.5
PPSU/PEG/DMAc 14.3/5.1/80.6 Production temperature (.degree. C.) 60
60 60 23 .+-. 3 *The sulfonated polymers used are contained in the
names of the polymer solution; S1, S2, S10 and S14 correspond to
SPPSU1, SPPSU2, SPPSU10, SPPSU14 respectively.
TABLE-US-00004 TABLE 3 Summary of the experimental data of the
membranes tested Polymer solution** S0-PVP-B S1-PVP-B S2-PVP-B
S10-PVP-B S14-PVP-B Membrane state wet wet wet wet wet Lp before
compaction 674 .+-. 78.sup.6 746 .+-. 21.sup.3 741 .+-. 121.sup.7
1432 .+-. 137.sup.5 1720 .+-. 446.sup.8 @0.5 bar (L
h.sup.-1m.sup.-2bar.sup.-1) Lp after compaction 578 .+-. 31.sup.6
709 .+-. 16.sup.3 675 .+-. 122.sup.7 1376 .+-. 161.sup.5 1505 .+-.
482.sup.8 @0.5 bar (L h.sup.-1m.sup.-2bar.sup.-1) Lp compaction
loss (%) 13 .+-. 10.sup.6 2 .+-. 2.sup.3 9 .+-. 5.sup.7 4 .+-.
2.sup.5 14 .+-. 8.sup.8 Lp (L h.sup.-1m.sup.-2bar.sup.-1) 509 .+-.
55.sup.6 652 .+-. 16.sup.3 597 .+-. 92.sup.7 1231 .+-. 204.sup.5
1292 .+-. 412.sup.8 Lp BSA (L h.sup.-1m.sup.-2bar.sup.-1) 105 .+-.
9.sup.3 138 .+-. 8.sup.3 83 207 .+-. 26.sup.3 278 .+-. 76.sup.4 Lp
after BSA (L h.sup.-1m.sup.-2bar.sup.-1) 239 .+-. 37.sup.3 277 .+-.
37.sup.3 268 274 .+-. 20.sup.3 349 .+-. 54.sup.4 Fouling resistance
R.sub.f (--) 0.44 .+-. 0.03.sup.3 0.42 .+-. 0.05.sup.3 0.61 0.24
.+-. 0.03.sup.3 0.36 .+-. 0.07.sup.4 Sieving coefficient 0.063 .+-.
0.065.sup.3 0.054 .+-. 0.017.sup.3 0.020 .+-. 0.002.sup.3 0.085
.+-. 0.044.sup.3 0.154 .+-. 0.086.sup.4 Layer by layer Lp LbL 433
.+-. 25.sup.3 -- 432 .+-. 49.sup.3 693 .sup.2 546 .sup.2 @0.5 bar
(L h.sup.-1m.sup.-2bar.sup.-1) Lp LbL (L
h.sup.-1m.sup.-2bar.sup.-1) 408 .+-. 22.sup.3 -- 406 .+-. 46.sup.3
709 .sup.2 514 .sup.2 Lp loss after LbL (%) 15 .+-. 9.sup.3 -- 39
.+-. 4.sup.3 45 .sup.2 62 .sup.2 Lp BSA (L
h.sup.-1m.sup.-2bar.sup.-1) 128 .+-. 23.sup.3 -- 99 .+-. 7.sup.3
153 .sup.2 120 .sup.2 Lp after BSA (L h.sup.-1m.sup.-2bar.sup.-1)
174 .+-. 26.sup.3 -- 164 .+-. 9.sup.3 319 .sup.2 255 .sup.2 Fouling
resistance R.sub.f-LbL (--) 0.43 .+-. 0.05.sup.3 -- 0.41 .+-.
0.04.sup.3 0.45 .sup.2 0.50 .sup.2 Sieving coefficient 0.005 .+-.
0.002.sup.3 -- 0.005 .+-. 0.002.sup.3 0.023 .sup.2 0.017 .sup.2
Characterization Contact angle (.degree.) 47 .+-. 1.sup. 34 .+-.
2.sup. 39 .+-. 1 .sup. 38 .+-. 3.sup. 41 .+-. 4.sup. Viscosity (Pa
s, 20.degree. C.) 3.4 3.4 3 2.7 2.3 **The sulfonated polymers used
are contained in the names of the polymer solution; S1, S2, S10 and
S14 correspond to SPPSU1, SPPSU2, SPPSU10, SPPSU14 respectively.
Polymer solution SPES3-PVP-B SPES2-PVP-B SPES4-PVP-B S2-PVP-D
S10-PVP-5D Membrane state wet wet wet Wet wet Lp before compaction
713 .+-. 126.sup.5 744 .+-. 49.sup.4 1335 .+-. 256.sup.3 631 .+-.
81.sup.7 931 .+-. 214.sup.5 @0.5 bar (L h.sup.-1m.sup.-2bar.sup.-1)
Lp after compaction 625 .+-. 125.sup.5 659 .+-. 66.sup.4 1292 .+-.
228.sup.3 564 .+-. 76.sup.7 891 .+-. 202.sup.5 @0.5 bar (L
h.sup.-1m.sup.-2bar.sup.-1) Lp compaction loss (%) 13 .+-. 5.sup.5
11 .+-. 6.sup.4 3 .+-. 2.sup.3 10 .+-. 7.sup.7 4 .+-. 1.sup.5 Lp (L
h.sup.-1m.sup.-2bar.sup.-1) 593 .+-. 104.sup.5 630 .+-. 45.sup.4
1206 .+-. 176.sup.3 533 .+-. 97.sup.7 774 .+-. 159.sup.5 Lp BSA (L
h.sup.-1m.sup.-2bar.sup.-1) 117 .+-. 21.sup.3 154 .+-. 30.sup.3 208
154 .+-. 13.sup.4 397 .+-. 97.sup.3 Lp after BSA (L
h.sup.-1m.sup.-2bar.sup.-1) 243 .+-. 16.sup.3 339 .+-. 30.sup.3 247
193 .+-. 17.sup.4 254 .+-. 34.sup.3 Fouling resistance R.sub.f (--)
0.48 .+-. 0.08.sup.3 0.52 .+-. 0.06.sup.3 0.21 0.32 .+-. 0.02.sup.4
0.32 .+-. 0.04.sup.3 Sieving coefficient 0.146 .+-. 0.071.sup.3
0.360 .+-. 0.197.sup.3 0.893 0.067 .+-. 0.056.sup.4 0.063 .+-.
0.032.sup.3 Layer by layer Lp LbL 520 .sup.2 455 768 .sup.2 287
.+-. 74.sup.3 487 .sup.2 @0.5 bar (L h.sup.-1m.sup.-2bar.sup.-1) Lp
LbL (L h.sup.-1m.sup.-2bar.sup.-1) 491 .sup.2 463 739 .sup.2 266
.+-. 72.sup.3 457 .sup.2 LP loss after LbL (%) 30 .sup.2 16 38
.sup.2 39 .+-. 13.sup.3 35 .sup.2 Lp BSA (L
h.sup.-1m.sup.-2bar.sup.-1) 124 .sup.2 88 233 .sup.2 103 .+-.
13.sup.3 105 .sup.2 Lp after BSA (L h.sup.-1m.sup.-2bar.sup.-1) 183
.sup.2 242 307 .sup.2 124 .+-. 18.sup.3 166 .sup.2 Fouling
resistance R.sub.f-LbL (--) 0.37 .sup.2 0.52 0.41 .sup.2 0.49 .+-.
0.08.sup.3 0.36 .sup.2 Sieving coefficient 0.030 .sup.2 0.047 0.219
.sup.2 0.002 .sup.2 0.002 .sup.2 Characterization Contact angle
(.degree.) 35 .+-. 1 .sup. 36 .+-. 3.sup. 44 .+-. 6.sup. 39 .+-.
5.sup. 44 .+-. 6 .sup. Viscosity (Pa s, 20.degree. C.) 2.3 2.6 2.2
4.4 4.2 Polymer solution S2-PEG-A S10-PEG-A S14-PEG-A S2-PEG-A-25
Membrane state wet wet Wet wet Lp before compaction 2723 .+-.
335.sup.6 3063 .+-. 219.sup.6 3625 .+-. 340.sup.3 2670 @0.5 bar (L
h.sup.-1m.sup.-2bar.sup.-1) Lp after compaction 2507 .+-. 273.sup.6
2824 .+-. 159.sup.6 2888 .+-. 318.sup.3 2316 @0.5 bar (L
h.sup.-1m.sup.-2bar.sup.-1) Lp compaction loss (%) 8 .+-. 4.sup.6 8
.+-. 4.sup.6 20 .+-. 9.sup.3 13 Lp (L h.sup.-1m.sup.-2bar.sup.-1)
2266 .+-. 286.sup.6 2272 .+-. 114.sup.6 2651 .+-. 260.sup.3 2126 Lp
BSA (L h.sup.-1m.sup.-2bar.sup.-1) 535 .+-. 64.sup.3 478 .+-.
22.sup.3 720.sup. -- Lp after BSA (L h.sup.-1m.sup.-2bar.sup.-1)
805 .+-. 132.sup.3 921 .+-. 68.sup.3 1181 .sup. -- Fouling
resistance R.sub.f (--) 0.38 .+-. 0.02.sup.3 0.42 .+-. 0.03.sup.3
0.49 -- Sieving coefficient 0.193 .+-. 0.055.sup.3 0.293 .+-.
0.036.sup.3 0.647 -- Layer by layer Lp LbL 1142 .+-. 166.sup.3 853
.+-. 36.sup.3 1270 .sup.2 1042 @0.5 bar (L
h.sup.-1m.sup.-2bar.sup.-1) Lp LbL (L h.sup.-1m.sup.-2bar.sup.-1)
1102 .+-. 144.sup.3 793 .+-. 26.sup.3 1220 .sup.2 974 LP loss after
LbL (%) 54 .+-. 5.sup.3 66 .+-. 1.sup.3 56 .sup.2 54 Lp BSA (L
h.sup.-1m.sup.-2bar.sup.-1) 161 .+-. 39.sup.3 283 .+-. 15.sup.3 215
.sup.2 186 Lp after BSA (L h.sup.-1m.sup.-2bar.sup.-1) 448 384 .+-.
28.sup.3 526.sup. -- Fouling resistance R.sub.f-LbL (--) 0.34 0.48
.+-. 0.02.sup.3 0.42 -- Sieving coefficient 0.012 .+-. 0.004.sup.3
0.006 .+-. 0.003.sup.3 0.032 .sup.2 0.007 Characterization Contact
angle (.degree.) -- -- -- -- Viscosity (Pa s, 20.degree. C.) 0.8
0.7 0.7 0.8 Polymer solution P25* P29* P29_limA** P29_limB** P29
limB** Membrane state wet Dry dry Dry wet Lp before compaction
.sup. 2423 .+-. 325.sup.18 1208 .+-. 252.sup.27 1208 .+-.
252.sup.27 1208 .+-. 252.sup.27 3638 .+-. 1241.sup.4 @0.5 bar (L
h.sup.-1m.sup.-2bar.sup.-1) Lp after compaction .sup. 1899 .+-.
320.sup.18 .sup. 690 .+-. 284.sup.27 .sup. 690 .+-. 284.sup.27
.sup. 690 .+-. 284.sup.27 1985 .+-. 298.sup.4 @0.5 bar (L
h.sup.-1m.sup.-2bar.sup.-1) Lp compaction loss (%) .sup. 21 .+-.
10.sup.18 .sup. 44 .+-. 18.sup.27 .sup. 44 .+-. 18.sup.27 .sup. 44
.+-. 18.sup.27 56 .+-. 29.sup.4 Lp (L h.sup.-1m.sup.-2bar.sup.-1)
-- -- -- -- -- Lp BSA (L h.sup.-1m.sup.-2bar.sup.-1) -- -- -- --
356.sup.1 Lp after BSA (L h.sup.-1m.sup.-2bar.sup.-1) -- 300 .+-.
80.sup.4 300 .+-. 80.sup.4 300 .+-. 80.sup.4 1103.sup.1 Fouling
resistance R.sub.f (--) -- 0.69 .+-. 0.09.sup.4 0.69 .+-.
0.09.sup.4 0.69 .+-. 0.09.sup.4 0.48.sup.1 Sieving coefficient
0.0640.sup.2 0.247 .+-. 0.078.sup.5 0.247 .+-. 0.078.sup.5 0.247
.+-. 0.078.sup.5 0.3542.sup.1 MWCO (kDa) 113 .+-. 61.sup.8 97 .+-.
36.sup.2 97 .+-. 36.sup.2 97 .+-. 36.sup.2 122.sup.1 Layer by layer
Lp LbL (L h.sup.-1m.sup.-2bar.sup.-1) .sup. 720 .+-. 193.sup.11 65
.+-. 22.sup.3 228 .+-. 39.sup.3 138 .+-. 82.sup.9 456.sup.2 LP loss
after LbL (%) .sup. 58 .+-. 12 84 .+-. 11.sup.3 64 .+-. 15.sup.3 79
.+-. 15.sup.9 71.sup.2 Lp BSA (L h.sup.-1m.sup.-2bar.sup.-1) 167
.+-. 32.sup.7 -- 60.sup.1 36 .+-. 16.sup.3 113.sup.2 Lp after BSA
(L h.sup.-1m.sup.-2bar.sup.-1) 428 .+-. 117.sup.7 -- 147.sup.1 107
.+-. 41.sup.3 118.sup.2 Fouling resistance R.sub.f-LbL (--) -- --
0.65.sup.1 0.56 .+-. 0.12.sup.3 0.26.sup.2 Sieving coefficient
0.0013 .+-. 0.0005.sup.7 -- 0.0083.sup.1 0.0045 .+-. 0.0009.sup.3
0.01215.sup.2 MWCO (kDa) 34 .+-. 2.sup.5 29.sup.1 50.sup.2 -- --
*LbL modification was carried out according to 1.1 **LbL
modification with limited quantities of polyelectrolyte: 112
.mu.g/cm.sup.2 PEI (750 kDa, 50 mbar, 5 mins), 21 .mu.g/cm.sup.2
DEXS (500 kDa, 50 mbar, 5 mins) for limA; 3.7 mg/cm.sup.2 PEI (750
kDa, 50 mbar, 5 mins), 21 .mu.g/cm.sup.2 DEXS (500 kDa, 50 mbar, 5
mins) for limB
[0142] In order to illustrate the properties of the membranes
according to aspects of the disclosure more clearly, FIG. 1 shows
the water permeabilities and sieving coefficients of five different
membrane types measured prior to modification (see Table 2 and 3).
The hydraulic permeabilities of the base membranes are between 10
and 5,000 L/bar*h*m.sup.2 and exhibit a sieving coefficient
(@22.+-.2.degree. C.) for BSA in the range of 0.9 to 0.001 and an
MWCO of 3 kDa to 250 kDa. In the case of membranes with moderate
flux, which correspond to the membranes with PVP as the additive,
the results show clearly that the use of sulfonated polymers leads
to a drastic increase in water permeability, which is presumably
mainly due to a higher membrane hydrophily of such membranes.
[0143] For the high-flux membranes--corresponding to the membranes
with PEG/PEO as the additive--the effect is less marked, however.
Nonetheless, high permeabilities are obtained in all cases at the
expense of size retention properties. An assumed increase in pore
size is probably the reason for this. Low viscosities are obtained
for those casting solutions which were produced using polymers with
a higher sulfonation degree. This induces a change in membrane
formation during the phase inversion process.
[0144] FIG. 2 shows the effect of LbL deposition on water
permeability and the BSA sieving coefficient for four different
sets of membranes, as well as the induced reduction in permeability
due to LbL deposition.
[0145] After LbL coating with the polyelectrolytes, a drop in
permeability is observed of up to 84%. In particular for set 1 with
PVP as the additive, a direct correlation is observed between the
sulfonation degree of the polymer and the permeability; the use of
a sulfonated polymer with a higher sulfonation degree in the
mixture solution results in a greater reduction in permeability
through the coating.
[0146] Without being bound to this, it is possible that on the one
hand the presence of a higher charge density on the membrane
surface results in better bonding of the polyelectrolytes during
deposition. On the other hand, the same quantity of
polyelectrolytes could have been deposited and the greater
reduction in permeability could have been caused by the existence
of larger pores at the beginning of the LbL process, whereby the
pores could have been narrowed or blocked during the deposition of
the polyelectrolytes as a result of modification.
[0147] Furthermore, FIG. 2 shows that high permeabilities and low
sieving coefficients are obtained for the membranes produced with
PEG/PEO as the additive after modification.
[0148] S2-PEG-A, S2-PEG-A25, S10-PEG-A and P25 show respective
water permeabilities of 1102.+-.144 L*bar*h-1*m-2, 974
L*bar*h-1*m-2, 793.+-.26 L*bar*h-1*m-2, 720.+-.193 L*bar*h-1*m-2
and sieving coefficients for BSA at 22.+-.2.degree. C. of
0.012.+-.0.004, 0.007, 0.006.+-.0.003 and 0.0013.+-.0.0005.
[0149] Membranes modified according to aspects of the disclosure
from set 2, consisting of a polymer solution containing 17% polymer
and PVP as the additive show a high performance. Water
permeabilities were achieved of 266.+-.72 L*bar*h-1*m-2 and 457
L*bar*h-1*m-2, and BSA sieving coefficients were obtained for
S2-PVP-D and S10-PVP-5D of 0.002 in each case
[0150] Composite membranes from set 4, produced from a polymer
solution with 14.3% polymer and PEG as the additive, show water
permeabilities of 65.+-.22 to 456 L*bar*h-1*m-2 and BSA sieving
coefficients of 0.0083 to 0.01215, depending on the coating
quantity and the conditions at modification.
[0151] The result obtained was a wide range of membranes with a
medium to high level of water permeability. Furthermore, the
results show that the LbL coating has the dominating influence on
water permeability and the sieving coefficient for BSA, resulting
in the fact that the membranes obtained with LbL coating are
suitable for dialysis application.
[0152] In particular, in the context of the present disclosure it
was possible to achieve control over the membrane surface charge by
adjusting the content and sulfonation degree of the polymer
used.
[0153] Using the present disclosure, therefore, it is possible to
produce membranes suitable for purifying blood (or dialysis) which
exhibit a water permeability in the range of 10 to 2000
L*bar*h-1*m-2 and a sieving coefficient @22.+-.2.degree. C. for BSA
in the range of 0.0001 to 0.5.
[0154] A supplementary analysis relating to the hydrophily of the
membranes (in particular set 1) is shown in FIG. 3: this shows
contact angle measurements on a PSU/PVP base membrane (SO-PVP-B)
and on membranes made from sulfonated polymer blends (mixtures). As
shown in FIG. 3, the introduction of sulfonated groups to a
polysulfone also results in a reduction of the contact angle and
therefore to improved wettability of the membranes.
[0155] The membranes according to aspects of the disclosure were
also characterized with an analysis of the surface charge (in
particulars set 1) using zeta potential measurements, as shown in
FIG. 4. FIG. 4 shows that a membrane made from a polymer with a
higher sulfonation degree also results in an increase in the
absolute zeta potential value as compared to reference membranes
without sulfonated polymer or containing a polymer with a lower
sulfonation degree. A higher sulfonation degree induces an increase
in the negative net charge of the surface. As such, the presence of
a higher charge density on the membrane surface understandably also
results in the deposition of greater quantities of polyelectrolytes
(at least for PEI, as shown in FIG. 4). Alternatively, a higher
adsorbed PEI quantity--per area with a greater sulfonic acid
density--could also result in a higher proportion of unbound amino
groups (more loops).
[0156] FIG. 5 additionally shows the dextran sieving curve before
and after LbL modification of membrane P25 from set 4. As a result
of LbL modification, the sieving curve clearly shifts into a
smaller molar mass range. The curve apparently steepens up to a
clear cut-off point. This suggests that the pore sizes are more
narrowly distributed after modification. With a MWCO of 35.+-.6
kDa, this shows a better performance for application in dialysis
than a state-of-the-art xevonta Hi membrane, also in terms of water
permeability (720.+-.193 L*bar*h-1*m-2 vs. 163.+-.4 L*bar*h-1*m-2)
and sieving coefficient with BSA @22.+-.2.degree. C.
(0.0013.+-.0.0005 vs. <0.006). The base membrane is not suitable
for application in dialysis, however (see FIG. 5).
[0157] Additionally, FIG. 6 shows molar mass distribution for PEI
with 2.0 kDa and 750 kDa and DEXS with 15 kDa and 500 kDa, which
are used for LbL modification. For PEI with 2.0 kDa, the molar mass
is relatively narrowly distributed. In contrast to this, the molar
mass for PEI with 750 kDa is broadly distributed with fractions
across virtually the entire range, so that the distribution curves
of PEI 750 kDa overlap with those of 2.0 kDa. This means that there
are large proportions of small fractions. For DEXS, the
distribution for 15 kDa is relatively narrow. A similar picture
emerges for 500 kDa, with molar masses likewise relatively narrowly
distributed. All in all, however, there is a low level of overlap
compared with PEI.
[0158] The results also show that the water permeability, the MWCO
and the sieving coefficient for BSA of the composite membranes can
be adjusted selectively with the LbL coating. The membranes
according to aspects of the disclosure obtained by LbL coating are
therefore suitable for blood purification or dialysis.
[0159] For the purposes of the present disclosure it should be
noted that the molecular mass measurements using gel permeation
chromatography [GPC] were calibrated using PMMA standards for the
molar mass range of 0.1 to 1200 kDa. With the GPC columns used, an
approximately linear calibration function is obtained in the molar
mass range of 0.5 to 1000 kDa, which is also very good for the
analysis of oligomers.
* * * * *