MEMBRANES POREUSES D'ALDEHYDE RETICULE

ALDEHYDE CROSS-LINKED POROUS MEMBRANES

Abrégé anglais

ABSTRACT
A polymeric porous membrane having a matrix made from
an aliphatic thermoplastic polyamide or from an aliphatic
thermoplastic polyamide/polyimide copolymer which has both
relatively non-crystalline and relatively crystalline portions is
provided. A method for preparing such a membrane comprises
dissolution of an aliphatic thermoplastic polyamide or
polyamide/polyimide copolymer having crystalline and non-
crystalline portions such that the non-crystalline portions
dissolve. At least some of the crystalline portions form a
colloidal dispersion which is formed into a film. Dissolved
non-crystalline portions are subsequently precipitated to form the porous
membrane matrix. The pores in the membrane are defined by spaces
between the relatively crystalline portions and at least some of
the relatively crystalline portions are linked together by the
reaction of a bis-aldehyde with the membrane matrix.

Revendications

- 22 -
The embodiments of the invention in which an exclusive
property or privilege is claimed are defined as follows:-
1. A polymeric porous membrane comprising a membrane
matrix made from an aliphatic thermoplastic polyamide
or from an aliphatic thermoplastic
polyamide/polyimide copolymer which has both
relatively non-crystalline and relatively crystalline
portions joined together by relatively non-
crystalline portions with pores in the membrane being
defined by spaces between the relatively crystalline
portions characterised in that at least some of the
relatively crystalline portions have been linked together
by the reaction of a polyfunctional aldehyde with the
membrane matrix.
2. A membrane according to claim 1 wherein the aldehyde
is a bis-aldehyde.
3. A membrane according to claim 2 wherein the bis-
aldehyde is glutaraldehyde.
4. A membrane according to claim 3 wherein the thermo-
plastic material is polyamide 6 and each polyamide
chain has a number of amide groups spaced apart along
the chain and wherein the glutaraldehyde has
displaced the hydrogen atom of the amide group with
its end carbon atom becoming bonded to a nitrogen
atom in the polyamide chain at least in part as
follows:-
<IMG>
5. A membrane according to claim 1 modified in that from
10 to 25% of the aldehyde chains are not linked at
each end to a polyamide chain but one end is
unattached to leave the CH = O in a more reactive
form group.
6. A membrane according to claim 5 wherein the free end
of the single-link aldehyde chains have been reacted

- 23 -
with a phenol so that the free end of the aldehyde is
a bis (phenylol) methane as follows:-
-CH = O ? - <IMG>
7. A membrane according to claim 6 wherein the phenol is
selected from resorcinol, diphenylolpropane, tannic
acid, pyrogallol, hydroquinone, meta-cresol and
naphthol as well as derivatives or mixtures thereof.
8. A membrane according to claim 3 modified in that
formaldehyde is used as an additional linking
reagent.
9. A membrane according to claim a wherein the free ends
of the formaldehyde link have been reacted with
resorcinol.
10. A membrane according to claim 2, wherein the bis-
aldehyde is selected from the group comprising
glutaraldehyde, glyoxal, succinic dialdehyde, alpha-
hydroxyadipic aldehyde, terephthalic dialdehyde or
phthalic dialdehyde or mixtures thereof.
11. A membrane according to any one of claims 1, 4 and 5
wherein the membrane contains reactive aldehyde
groups and wherein the membrane has been modified by sodium
bisulphite, hydroxylamine - 0 - sulphonic acid or
phenylhydrazinesulphonic acid to form a cation
exchange membrane.
12. A membrane according to claim 6 wherein the phenol is
resorcinol and the membrane was further reacted with
sodium monochloroacetate in aqueous solution.
13. A membrane according to claim 6 wherein the membrane
wherein free aldehyde groups were reacted with
14. A membrane according to any one of claims 1, 4 and 5
wherein free aldehyde groups are reacted with
proteins or polyhydric colloids to form hydrophilic

- 24 -
membranes.
15. A membrane according to any one of claims 6, 7 or 9
wherein:-
(i) traces of the remaining reactive aldehyde
groups have been reacted with hydrazine,
(ii) the phenolic hydroxyl groups have been
reacted with epichlorohydrin,
(iii) the resultant epoxides have been reacted with
diamines to fix a pre-determined concentration
of amine groups and excess epoxide has been
hydrolysed to hydroxyls, and,
(iv) the amine groups have been reacted with excess
bis(isothiocyanate)
to produce a reactive substrate suitable for
combining with the free -NH2 groups of biological
substances by forming covalent thiourea linkages to
provide immobilized proteins or affinity
chromatographic media.
16. A membrane according to claim 2 wherein the bis-
aldehyde is derived from a bis-aldehyde polymer, an
acetal or an acetal ester.
17. A membrane according to claim 5 wherein at least some
of the free ends of the single-link aldehyde chain
were reacted with gelatin or hydroxyethylcellulose.
18. A method of preparing a porous membrane comprising
the steps of:-
(i) dissolving an aliphatic thermoplastic
polyamide or an aliphatic thermoplastic
polyamide/polyimide copolymer which has both
relatively non-crystalline and relatively
crystalline portions into a solvent
under conditions of temperature and time which
cause the relatively non-crystalline portions
of the polyamide or copolymer to dissolve

- 25 -
while at least a part of the relatively
crystalline portions of the polyamide or
copolymer do not dissolve, but form a
colloidal dispersion in said solvent,
(ii) forming said colloidal dispersion
into a film and thereafter causing
precipitation of at least part of the
dissolved non-crystalline portions in the film
to form a porous membrane matrix in which the
pores are defined by spaces between the
relatively crystalline portions, and,
(iii) reacting the membrane matrix with a polyfunctional
aldehyde to link at least some of the relatively
crystalline portions with the aldehyde.
19. A method according to claim 18 wherein the aldehyde
is a bis-aldehyde.
20. A method according to claim 19, wherein the aldehyde is
glutaraldehyde, glyoxal, succinic dialdehyde, alpha-
hydroxyadipic aldehyde, terephthalic dialdehyde,
phthalic dialdehyde and mixtures thereof.
21. A method according to claim 18 wherein the aldehyde
is derived from a bis-aldehyde polymer, an acetal or
an acetal ester.
22. A method according to claim 19 wherein aldehyde
reaction step is so controlled that from 10% to 25%
of the aldehyde chains are not linked at one end.
23. A method according to claim 22 including the step of
reacting at least some of the free ends of the
single-link aldehyde chains with a phenol.
24. A method according to claim 23 wherein the phenol is
selected from the group comprising resorcinol,
diphenylol propane, tannic acid, pyrogallol,
hydroquinone, meta-cresol and naphthol as well as
derivatives or mixtures thereof.
25. A method according to claim 22 including the step of

- 26 -
reacting at least some of the free ends of the
single-link chains with a protein or polyhydric
colloid.
26. A method according to claim 22 including the steps of
reacting at least some of the free ends of the
single-link chains with gelatin or hydroxyethyl
cellulose.
27. A method according to claim 23 including the step of
reacting the phenol modified chain with sodium mono-
chloroacetate in aqueous solution.
28. A method according to claim 23 including the step of
reacting the phenol modified chain with aqueous
diazonium salts.
29. A method according to claim 23 including the steps
of:-
(a) reacting at least some of the remaining
reactive single-link aldehyde chains with
hydrazine,
(b) reacting the phenolic hydroxyl groups with
epichlorohydrin,
(c) reacting the resultant epoxides with diamine
to fix a pre-determined concentration of amine
groups and hydrolysing excess epoxide to
hydroxyls, and,
(d) reacting the amine groups with excess bis
(isothiocyanate).
30. A method according to claim 23 and including the step
of reacting the phenol modified membrane with a bis-
aldehyde.
31. A method according to claim 18 wherein the
membrane is reacted with sodium bisulphite,
hydroxylamine-o-sulphonic acid or
phenylhydrazinesulphonic acid.

Description

1'28BS~
This invention relates to porous membranes made from
aliphatic thermo-plastic polyamides or aliphatic
polyamide/polyimide copolymers.
Synthetic polymeric membrcmes are used for separation
of species by dialysis, electroclialysis, ultrafiltration,
cross flow filtration, raverse osmosi~ and other similar
techniques. One such synthetic polymeric membrane is
disclosed in Australian Patent Specification No. 505,494 of
Unisearch Limited.
The membrane forming technique disclosed in the
abovementioned Unisearch pat~nt specification is broadly
described as being the controlled uni-directional
coagulation of the polymeric material from a solution which
is coated onto a suitable inert surface. The first step in
the process is the preparation of a "dope" by dissolution
of a polymer. According to the specification, this is said
to be achieved by using a solvent to cut the hydrogen bonds
which link the moleculax chains of the polymer together.
After a period of maturation, the dope is then cast onto a
glass plate and coagulated by immersion in a coagulation
bath which is capable of diluting the solvent and annealing
the depolymerised polymer which has been used. According
to the one example given in this specification, the "dope"
consisted of a polyamide dissolved in a solvent which
comprised hydrochloric acid and ethanol.
In another membrane forming technigue, the liquid
material out of which the membrane is cast is a colloidal
suspension which gives a surface pore density that is
significantly increased over the surface pore density of
prior membranes.
..
.
-

5i6:3
-- 2 --
According to that technique a thermoplastic material
~aving both relatively non-crystalline and relatively
crystalline portions is dissolved in a suitable solvent
under conditions of temperature and tirne which cause the
relatively non-crystalline portions of the thermoplastic
material to dissolve whilst at least a portion of the
relatively crystalline portion does not dissolve but forms
a colloidal dispersion in the solvent. The collQidal
dispersion and solvent (i.e. the "dope") is then coated
onto a surface as a film and thereafter precipitation of
the dissolved thermoplastic portion is effected to form a
porous membrane.
Membranes of both of the above kinds suffer from
disadvantages which limit their commercial usefulness and
applicability. For example, they exhibit dimensional
instability when drying and may shrink by up to 7~. Thus,
it is essential that they be kept moist prior to and after
use. Furthermore, where the membranes are made from
polyamide, it has not been possible to generate
concentrated and varied chemical derivatives of the
membranes and this restricts the situations to which the
membrane may be applied.
Another disadvantage is that such polyamide membranes
are fundamentally unstable and eventually become brittle on
storage. The instability has been carefully investigated
by I.R. Susantor of the Faculty of Science, Universitas
Andalas, Padang, Indonesia with his colleague Bjulia. Their
investigations were reported at the nSecond A~S~EoA~N~ Food
Waste Project Conference", Bangkok, Thailand (1982) and
30 included the following comments regarding brittlenesso
"To anneal a membrane, the thus prepared membrane
~according to Australian Patent NoO 505,494 using
Nylon 6 yarn) is immersed in water at a given
temperature, known as the annealing temperature, T in
degrees Kelvin. It is allowed to stay in the water a
certain length of time, called the annealing time.
For a glven annealing temperature, there is a maximum
.
: ~ :
. .

~8~6~L
annealing time, t(b) in minutes, beyond which further
annealing makes the membrane brittle. Plotting ln
l/t(b) versus l/T gives a straight line. From the
slope of this line it can be concluded that becoming
brittle on prolonged annealing is a process requiring
an activation energy of approximately 10.4
kilocalories/mole. From the magnitude of this
activation energy, which is of the order of van der
Waals forces, the various polymer fragments are
probably held together b~y rather strong van der Waals
forcPs or hydrogen bond(s)."
We have confirmed that the brittleness is due to a
recrystallization of water-solvated amorphous polyamide.
In some cases tsuch as polyamide 6) brittleness
occurs within 48 hours of immersion in distilled water
(p~7) at 80C. Colorimetric ~NH2 end group analysis has
shown that there is no significant hydrolysis of the amide
groups during this time. As would be expected, the rate of
embrittlement is catalysed by dilute acids (eg: pH of 1.0)
due to nitrogen protonation and subsequent solvation. This
~ effect explains the apparently low "acid resistance" of the
-~ polyamide membranes. However colorimetric determination o
both -~2 end groups and -COOH end groups has shown that
the effect is due to crystallization rather than acid
~5 catalysed hydrolysis.
~ Th~re is a potential source of confusion in the use
of words such as "acid-resistance~ in the context of this
specification. That most of the brittleness is due to
physical effects rather than chemical decomposition or
chemical solvation (at least for dilute acids) is shown by
- the extreme embrittlement caused on standing 5 minutes in
absolute ethanol. The ethanol removes the plasticizing
water tenaciously held by non-crystalline nylon as will
hereinafter be described in relation to Example 2.
.
:,.
,

s~
-- 4
Acc~rdingly, the following definitions apply in this
specification:-
(a) "Embrittlement resi~stance" means hindrance or
prevention of the physical recrystallization
mechanism of the amorphous polymer matrix~
(b) "~cid-catalysed embrittlement resistance"
means prevention of embrittlement of type (a)
even in the presence of dilute acids (pH 1 to
7).
(c) "Acid solubility" means the rapid dissolution
of polyamide in strong acids (100~ formic acid
or 6 N hydrochloric acid).
(d) "A~id catalysed hydrolysis" means the scission
of amide bonds (such scission is much faster in
l; an amorphous polyamide than in a crystalline
polyamide.)
As well as "embrittlement" the prior art me~branes
show the normal chemical defects of the parent nylon
polyamides in that they possess only modera~e oxidation
resistance and bio-resistance.
It is an object of this invPntion to provide
Rolymeric porous membranes composed of thermoplastic
aliphatic polyamides ~including polyamide/polyimide
copolymers) which have greater resistance properties and
2~ improved mechanical stabilîty than prior art membranes. It
is a further object of the invention to provide polymeric
porous membranes which readily lend themselves to the
preparation of chemical derivatives thereof for particular
uses.
.. .
; .. . . -
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:. . . :,
: : , :

~2~3~35~i~
~ ccordlng to one aspe~t of the invention there i~
provided a method o~ prepar ing a porc~ membrane compr is ing
the ~tep3 o~ :-
1 i ) di~solving an aliphatic polyamide or an
aliphatic polyamide/polyimide copolymer which
h~ both relatively non-crystallin0 and
relatively crystalline portion8 into a ~olvent
under conditions of temperature and time which
cau~ the r~latively non-crystalline portion~
of thls polyamide or copoly~r to di3~01~e while
. at le~st a part of the r~lat~v~ly crystalline
portion~ o~ th~ polyamide or ~opolymer do ~IOt
di3~01v~, but form a colloidal di~persion in
aid ~olvent,
( i i ) forming said ~olloldal di~per~ion and ~olvsnt
into z~ filan ~i~d thereafter causing
pr~cipitation of at least part of the di ~olved
non-cry~t~lline porl:iolls in the ~ilm to form a
poro~3 r~embralle in which th~s pores are def ined
by ~pace~ b~tween the relatively c:rystalline
portiona~ nd~
( iii ) reacting the membr2~ne with ~ polyfunctional aldehyde
~ as herein defined to llnk ~t least some of the
relatively crystalline portions with the aldehyde.
In the context of this spscificatlon the term "a
polyunctional aldahyd~ as herein de~ined" means an aldehyde or
aldehydc yieldln~ ~i~ture in which the ald~hyd~ functionality
exceeds one -- C~ ~ O per molecule.
Preerably, the polyfunctional aldehyde is a bis-aldehyde
and is selscl:ed from the group comprising glutaraldehyde,
glyoxal, succinic dlaldehyde, alpha-hydroxyadipic aldehyde,
terephthalic dialdehyde and phthalic dialdehyde as well as
~ ., .
. .
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s~
-- 6
mixtures thereof. Furthermore, the aldehyde may be derived
from a bis-aldehyde polymer, an acetal or an acetal ester.
The aldehyde reaction step may be controlled so that
from 10% to 25~ of the aldehyde chains are not linked at
one end. In which case, the invention can include any one
of the following steps of reacting at least some of the
free ends of the single-link aldehyde chains with:-
(i~ a phenol that may be selected from the group
comprising resorcinol, diphenylolpropane,
tannic acid, pyrogallol, hydroquinone, meta-
cresol and naphthol as well as derivatives or
mixtures thexeof~
(ii) a protein such as gelatin,
(iii~ a polyhydric colloid such as
hydroxyethylcellulose, or
(iv) an amine such as melamine.
The phenol modified chains may be further reacted
with:-
(a3 sodium monochloroacetate in agueous solution,
or
(b) aqueous diazonium salts
Also, the phenol modified chains may be subjected to
further processing including the steps of:-
(a~ reacting at least some of the remaining
reactive single-link aldehyde chains with
hydra~ine,
(b) reacting the phenolic hydroxyl groups
with epichlorohydrin,
(c) reacting the resultant epoxides with a diamine
to fix a pre-determined concentration of amine
groups, hydrolysing excess epoxide groups to
hydroxyls and r
- :' ' ' , ' :
-
. . ~ - .

-- 7 --
(d) reacting the amine groups with excess bis
(isothiocyanate).
A membrane made in accordance with the method of the
invention may be further treatecl by reacting it with sodium
bisulphite, hydroxylamine-O-sulphonic acid or
phenylhydrazinesulphonic acid. A phenol-modified membrane
may be further reacted with a bis-aldehyde.
The invention also provides a polymeric porous
membrane comprising a membrane matrix made from an
aliphatic thermoplastic polyamicle or from an aliphatic
thermoplastic polyamide/polyimicle copolymer which has both
relatively non-crystalline and relatively crystalline
portions and in which the relatively crystalline portions
are joined together by relatively non-crystalline portions
with pores in the membrane being defined by spaces between
the relatively crystalline portions characterised in that
at least some of the relatively crystalline portions are
linked together by the reaction cf an aldehyde as herein
defined with the porous membrane matrix.
A particularly preferred bis-aldehyde is the five
carbon atom glutaraldehyde which has the following
formula:-
C) C--CE~2--- CH2--CH2-- C-- ' ' '
H H
~ When polyamide 6 is used as the polymeric membrane,
each low or relatively crystalline chain has a number of
amide groups spaced apart alor,g the chain and the bis- :
aldehyde (such as glutaraldehyde) displaces the hydrogen
atom of the amide groups with their end carbon atom
becoming bonded to the nitrogen atom in the polyamide chain
as follows:-
N -~CH - CH2 ~ CH2 CH2 - CH - N
OH 1H
:

:~L2~
-- 8 --
The glutaraldehyde provides a true cross link between
the polyamide chains and this increases the membrane's bio-
resistance as well as its embrittlement resistance.
In a modification of the invention, from 10 to 25% of
the glutaraldehyde chains are not linked at each end to a
polyamide chain but rather one end is unattached to leave
the CH = o group in a more react:ive form. This
mcdifi~ation further improves the dimensional stability of
the membrane and allows extensive chemical modification.
Steric effects ensure that there are always some detectable
singly linked glutaraldehyde molecules but the proportion
can be increased by using conditions which favour rapid
reaction and by high glutaraldehyde concentration~.
A feature of the glutaraldehyde type of cross-linking
is that the permeability of the original polyamide membrane
to water is unexpectedly only ~lightly and controllably
affected as will be hereinafter apparent from example 2,
although (as expected) the permeability of many dissolved
solutes is greatly affected.
Further reaction with a phenol provides a membrane
having acid-catalyzed embrittlement resistanceO The
resultant polyamide/phenol~aldehyde block copolymer is
particularly useful in the treatment of effluent from food
processing plants where alkaline mixtures are used as a
cleaning agent, often after an acidic enzymatic cleaning
treatment.
When the free end of the single-link aldehyde chain
is reacted with a phenol (such as resorcinol) the free end
of the aldehyde chain is transformed to bis (phenylol)
methane:-
QH
~ OH
- CH=O ~ CH ~
~ OH
OH
In addition to glutaraldehyde (or other bis-aldehyde)
a small amoun~ of formaldehyde may be used as the link
particularly if free ends are reacted with resorcinol.
All or part of the glutaraldehyde can be replaced by
,: . : . . : . .
-' . : ' . , - . ~ :
.
,, : :
: . :: - ' '. . -
: ,
:

~8563~
g
equivalent amounts of many commercially available
bisaldehydes 3uch as glyoxal, ~uccinlc dialdehyde, alpha-
hydroxyadipic aldehyde, terephthalic dialdehyde and
phthalic dialdehyde with very ~imilar results including the
preparation of chemical derivatives of the membrane arising from
a proportion of end groups reacting as an aldehyde. Choice
of bis-aldehyde dep~nd~ largely on economic, ~afs-handlinq
and aldehyde storage stability factors rathex than chemical
reactivity for mo~t applications. Nevertheles~ ~ome quite
~ubtl~ differences ~uch as ab~orp~ion of colloid~ which can
be important in commercial u~age of the membrane may affect
the choice of aldehyde.
The aromatic aldehydes are ~lower reacting, giving
lighter-coloured products and are harder but ~ore
lS brittle. They also ~how the usual difference~ ~hat
aromatic aldehyde~ ~how from aliphat.ic aldeh~des, eg:
slower.reaction with bi3ulphite.
Any de~ired properties likely to be needed in
ultrafilters, ion-e~change re9ins, ion-specific resins,
dyeing colour (by reaction with diazonium salts) or
intermediates for highly active enzyme immobilization or
affinity chromatographiG ~urfaces can be obtained by
choosing a cheap glyoxal, glutaraldehyde, succinic dialdehyde
or terephthalic dialdehyde and combining with a cheap reactive
2~ phenol ~uch a~ r~oxcinol, diphenylolpropan~, hydr~guinone,
pyrogallol, tanni~ acid or naphthol as well as mixtures or
derivatives thereof. For speci$ic purpo~e~, specific
phenolic derivatives can be u~ed or the pra erred
glutar~ldehyde/re~orcinol treatment can be modified by
simple ~oaking proceduxe~ in appropriate reagent~.
A ~table, ~terilizable, controll~bly porou3
structur~ can b~ made by sequential reaction a~ in Example
6 with hydrazine, epichlorohydrin, h~xamethylene diamine
and 1,4 - phenylenebisi~othiocyanate. This is excellent
for reaction with the -N~2 end grcup~ of many proteins,
whil~t still ~llowing bioactivity and aff inity
, ,~, ., `.
:

-- 10 --
chromatography for harvesting anti-bodies. The protein
bond is covalent and stable but on a suitably long arm on
an extended controllable interior structure.
In contrast thereto, a glutaraldehyde treated
polyamide may be made electrically conductive by treatment
with 4-phenylhydrazine-sulphonic acid to provide an
electrodialysis membrane when the porosity is almost zero
to a hydraulic pressure difference as in Example 3.
The reactivity of products containing highly reactive
aldehyde groups is not restricted to phenols, although the
latter are preferred for long-lived and aggressive
environments. For example, prot:ein, gelatin or
hydxoxyethylcellulose can be reacted with the membrane to
give products which are very elastic and rubbery in
ethanol. Furthermore, the preferred properties of the
glutaraldehyde/resorcinol treated membranes can be combined
with free aldehyde group reaction versatility by reacting
once again with a bis-aldehyde to give an enhanced free
aldehyde content. The product is then a
polyamide/glutaraldehyde/resorcinol/bis-aldehyde which can
form more concentrated and more stable derivatives. There
is some advantage in using glyoxal for the last bis-
aldehyde to give highest concentrations of -CHO. However,
glutaraldehyde seems best for initial reaction with the
polyamide, presumably for steric reasons of cross-linking.
Of course it is possible to involve the use of small
quantities of the cheap mono aldehyde, formaldehyde, at
various stages to dilute the bis-aldehydes. However for
steric reasons formaldehyde is undesirable for cross-
linking in the initial polyamide reaction. Formaldehydecan have some use for a -further diluent reaction with
phenols. However, it is preferable to condense the
~ormaldehyde separately with the phenols to make controlled
pure reagents or condensation products and then to condense
these with the polyamide/glutaraldehyde precursor.
''' '- ' . ' ' '' . ~ -:
,
' ' ' . '
: - :

EX~MPLE 1
A solvent (A) was prepared by mixing 225ml of 6.67N
hydrochloric acid with 15ml of anhydrous ethanol. 90 grams
of 55 dtex 17 filament polyamide 6 with ~ero twist (which
constitutes the polyamide starting material) was added to
solvent A held at a temperature of 22C over a period of
less than 15 minutes.
The dope of the polyamide 6 and solvent A was then
left to mature for 24 hours at a temperature of 22C during
which the relatively non-crystalline portions of the
polyamide dissolved as did no more than 50% of the
relatively crystalline portions of the polyamide 6 with the
remaining relatively crystalline portion dispersing in the
solvent.
After maturation, the dope was then spread as a film
of about 120 micron thick on a clean glass plate. The
coated plate was placed in a water bath where precipitation
of the dissolved portions of the polyamide was effected
; 20 within 3 minutes. The membrane was then reacted with 5~ of
glutaraldehyde tbased on the dry membrane weight~ at a pH
of 3 to 6 at a temperature of 60C overnight. It was found
that 50~ to 80~ of the glutaraldehyde had reacted depending
upon the pH and that of these percentages 10% to 25% of the
glutaraldehyde had one aldehyde free for further reaction.
EXAMPLE 2
.
The polyamide 6 membrane made according to Example 1 had a
water permeability of 339 litres/square metre/hour and
rejected 81% of the protein in a standard edible gelatin.
60 grams o this membrane were treated with 2.24 grams of
glutaraldehyde in 138 grams of water at p~ 5.5 and at a
temperature of 20C for 1 week followed by water washing.
It was found that the membrane had reacted with 2.7% of its
dry weight of glutaraldehyde. Of this 2.7%, about 0.6~%
:
.. . . . ..
- :
.. : . :
.. - .. . : - .. , . ~ :.. . . :
- , : ...... . .

5~
- 12 -
(ie: 23% of glutaraldehyde reacted) was still reactive as
an aldehyde. The water permeability was now 384
litres/square metre/hour and the gelatin rejection was
82~. These differences from the original permeability and
gelatin rejection figures are very slight ~or any practical
use.
The cross-linked membrane was not "acid-catalysed
embrittlement resistant" as it became brittle in 6 days at
60C at pH l but was unaffect2d in 35 days at 60c at pH 13
(alkaline). There was a complete absence of traces o~
terminal -NH2 groups, originally present in the polyamide 6
membrane of Example l, as shown by the disappearance of the
original yellow reaction with D.A.~.I.T.C. reagent, 4-
dimethyl-aminophenylazobenzene - isothiocyanate. The
slowed "acid-catalysed embrittlement" is due to the slow
reversible reactions which yield glutaraldehyde and the
starting polyamide 6. Such reactions are due to the acid~
labile group,
,, I
N - CH ~ NH + O _ CH
OH
Also there will be present some proportion of acid-
~abile glutaraldehyde polymers. Confirmation of this
reversibility was shown by the reaction of the membrane of
this Example 2 with M/400 2,4-dinitrophenylhydrazine tDNP~
in N/100 HCl at 22C. In 21 hour 15% o the total
glutaraldehyde had reacted with and removed from solution
an equivalent of DNP; in 37 hour 17~4% and after 48 hour at
60C, 23%. The reaction of glutaraldehyde with primary
amides -CO -NH2 has been well studied and the products are
said to be stable reactive gels for affinity
chromatography;see P. Monsan, G. Puzo and H. Mazarguil,
Biochemie, 57, pl281 tl975). Reaction of polyamides
containing secondary amide -CO-MH with glutaraldehyde could
be expected to give less stable products.
~
: : .

s~
- 13 -
Despite the low "acid catalysed embrittlement
resistance" of the abovP polyamide 6/glutaraldehyde
reaction product it was found to be a key intermediate in
the preparation of preferred stable, tough, rubbery
ultrafilter membranes by reaction with resorcinol (see
Example 5) and of stable tough, rubbery oil and detergent
repelling ultrafilters by reaction with gelatin or
hydroxyethylcellulose (see Example 7). The reaction with
gelatin in Example 7 illustrates the method of immobilizing
an enzyme and for preparing absorbents for affinity
chromatography. Many useful chemical derivatives can be
prepared by known procedurPs and are described in examples
below.
The brittleness of the membranes of examples one and
two air dry ~70% Relative Humidity) wet and in ethanol are
indicated by the extension to break on stretching and by
behaviour on rubbing in the following tables:-
MEMBRANE - EXAMPLE 1.
_ , _ . . _
Air Dry ~et Ethanol
. .. _ . __ -
Extension
to Break 10% 60~ ~0
_ _ _ _
Behaviour
on rubbing Rubbery Rubbery Powdered
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MEMBRANE - EXAMPLE 2
Air Dry Wet Ethanol
Extenslon .
to Break 6~ 60% 20
. _ _
Behaviour
on rubbiny Rubbery Rubbery Powdered
Thus, the glutaraldehyde to this stage has altered
the chemical rather than the elastic properties (which
appear identical). The large elastic improvement on
further reaction is shown in later examples.
EXAMPLE 3
5g. of polyamide 6 yarn was dissolved in 15g. of 98%
formic acid to form a "dope" which was cast at 22C onto a
sheet of high density polyethylene and dried at 60C for 10
hours to give a translucent film which was impermeable to
water at 200 kpa at a thickness of 120 microns. The sheet
was washed for 48 hours in distilled water and cut to a
disc of 45mm diameter. Wedging between metal plates showed
a resistance of 200,U00 ohms and only traces of weakly
acidic groups, COOH, by methylene blue absorption.
Heating with 25~ weight/volume glutaraldehyde at
100C for 48 hGurs and washing gave a translucent brown
disc, with an unchanged resistance of 200,000 ohms but
staining an intense purple in Schiff's fuchsin reagent,
indicating the presence of many -CHO yroupsO
Heating at 60C in 2% sodium 4 -
phenylhydrazinesulphonate and long washing gave a brown
disc of lowered electrical resistance, 20,000 ohms showing
the presence of conducting ionic groups. Methylene blue
then gave an intense blue stain which would not wash out,
showing large amounts of SO3 ~ groups. The produc~ was
satisfactory for an electrodialysis membrane~ permeable to
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~L2~8~i6~
- 15
cations. Although ion-exchange properties were shown, the
capacity and exchange rates were too low for commercial
use. Similar results were obtained using films formed by
precipitating a 98% formic acid "dope" by immersion in
water. Contrary to the hydrochloric acid "dopes", a porous
ultrafilter was not formed, as the 98~ formic acid had
dispersed the polyamide 6 molecularly, including the
crystallites.
EX~MPL~ ~
To 90g. of the dry polyarnide 6 yarn used in Example 1
were added O.9g of isophthaloy;Lchloride in 180ml of
cyclohexane and 3g. of anhydrous potassium carbonate at
22C for 36 hours when 93% of the acid chloride had reacted
as determined by the fall in UV absorption at 290
nanometres and the content of chloride reactable with
boiling ethanolic silver nitrate in the cyclohexane. The
cyclohexane was allowed to evaporate, the fibre washed in
water for 1 hour, soaked to pH 3 in dilute HCl, washed
overnight and dried at 60C. The isophthaloyl chloride had
largely converted some of the amide groups to imide groups
with very little -COO~ as determined by comparison of
methylene blue absorption with the original yarn.
A "dope" was made up according to Example 1. The
dope" was slightly more turbid than that of ExamplQ 1
which indicated some yreater content sf colloidal
crystallite or some cross-linking of amorphous polyamide.
The "dope" was cast in parallel with the "dope" of Example
1. ~ comparison of the porous membranes formed showed that
the permeabilities to water at 100 kPa for the unmodified
polyamide 6 was 117 litre/square metre/hour whereas the
imide modified membrane was 97 litre/square metre/hour
The polyamide 6/isophthaloylimide-modified membrane
above was reacted with glutaraldehyde as in Example 2 with
little significant difference from the unmodified polyamide
6 membrane. This similarity extended to the further
reaction wit:h xesorcinol according to Example 5. It is
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clear that the reacting species is the -CO -NH - group and
that the imide group -CO - N = is not reactive and merely
a diluent whose utility is largely restricted to Eorming a
desired physical porous structure. Polyamide 6~6 also
reacted as polyamide 6 but was somewhat less resistant to
oxidation and to biological attack.
EXAMPLE 5
12 gra~s of the glutaraldehyde cross-linked membrane
of Example 2 were heated with 12 millilitres of a 1% aqueous
resorcinol solution at pH 3.0 at a temperature of 60C for
12 hours and then washed. The resultant membrane had
incorporated about 0.2~ of its dry weight of the
resorcinol. It was then dyed with p-nitrobenzenediazonium
fluoroborate solution. It was not ~oluble in 6N
hydrochloric acid in 1 hour whereas such acid rapidly
dissolved precursor membranes. The resultant water
permeability of 299 litre/square metre/hour and gelatin
rejection of 75% showea that this further modification of
the glutaraldehyde membrane occurred without significant
change in permeability.
However the ~embrittlem~nt resistance" was raised to
a high level - no embrittlement occurred even after 6
m~nths at 60C at pH 7 as against 9 days fcr the
embrittlement of the membrane before raaction with
resorcinola The ~xtension to break (dry~ was raised from
6~ to 10% and the behaviour to rubbing remaining very
rubbery; the extension to break (wet) was raised from 60%
to 70% and the behaviour to rubbing was extremely rubbery
whilst the extension to break in ethanol was raised from
20% to 30% with full rubber-like resistance to rubbing.
This membrane made by sequential glutaraldehyde then
resorcinol treatment was apparently unaffected by two bio-
resistance tests:-
a~ Enzymatic. A commercial mixture of papain
~5 and amylase was renewed weekly at 25C to
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35C for 13 months and a prior art membrane
stored therein remained intact but tore
easily. In this respect it behaved better
than one stored in water since
"crystalli~ation embrittlement" was hindered
by the contained proteins, presumably
because proteins are strongly absorbed and
could be expected to hinder
crystallization. The treated membrane
remained very strong, tcugh and rubbery for
the 13 months.
b. Compost Burial. The membranes were soaked
in a commercial compost con~aining added
commercial "Organic Compo~t Accelerator~ for
13 months at 25C. The untreated polyamide
6 membrane still showed reasonable streny~h
but was not comparable to the apparently
unchanged tough rubbery nature o~ the
Example 5 membrane. A membrane made from
polyamide 6,6 rather than polyamide 6 but
otherwise treated according to Example~ 2
and 5 showed poor bio-reslstance to compost
and easily broke up. Outstandingly good
bio-resistance ~to enzymes and compost) was
also shown by membranes treated with
glutaralaehyde according to ~xample 2 and
then:-
~a) reacted with hydrazine at
pH 5.0 for 10 hours and
washed or
(b) reacted with excess 2~4-
dinitrophenylhydrazine in
N/100 HCl overnight, then
washed.
The glutaraldehyde/resorcinol treated membranes of
Examples 5 are preferred for ultrafiltration purposes and
as a stable matrix of controllable porosity from which
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chemical derivatives for ion-exchange or enzyme
immobilization or affinity chromatography can readily be
made as described in Example 6.
Repetition of the reactions but substituting
hydroquinone, tannic acid or 2 - naphthol - 3,6-
disulphonic acid or resorcinol gave analogous products
showing expected properties. For example, the tannic acid
product formed dark blue-black ferric derivatives; the
naphthol-disulphonic acid derivative showed cation-exchange
properties. None was physically superior, nor more
convenient in ultrafilter manufacture than resorcinol. It
is relatively certain that any commercial
bisaldehyde/reactive phenol sequence will cross-link and
stabilize against "embrittlemant" due to amorphous
polyamide recrystallization but glutaraldehyde has overall
advantages as a reactant, although further reaction will
provide tough, or more rubbery products.
EXAMPLE 6
The membrane of Example 5 ~lg) was freed of trace
-CHO groups by reaction with dilute hydra~ine at pH 3.5 at
80C for 15 minutes and washed well. The resultant
membrane wa~ treated with 0.45g epichlorohydrin in 10ml 95%
ethanol at pH 10 to 12 by adding 0.5ml 2N NaOH at 80C and
then washing well. The presence of combined epoxy-groups
was demonstrated by slow precipitation of AgI03 on adding
AgIo4 in 2N HNO3. The epoxide was reacted with L~ aqueous
hexamethylenediamine or 1~ diethylenetriamine by heating to
80C for 30 minutes and then washed well. The presence in
both cases of bound -NH2 groups was shown by colorimetric
estimation with p~dimethylaminophenylazobenzene-4-
isothiocyante. The products were then heated to 80C with
excess 1% alcoholic 1,4-phenylenebisisothio-cyanate when
the -~H2 groups were converted to the yellow 4-
, -, . :
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~IL21~
- lg -
isothiocyanotophenylthioureas (1). The isothiocyanato- end
groups were estimated colorimetrically by reaction with 5-
aminofluorescein to give the salmon-coloured derivative.
Throughout the entire sequence the membranes retained their
desirable ultrafiltration characteristics. The desirable
isothiocyanate intermediates (1) may be regarded as
polyamide/(imide)/aldehyde/polyphenol/epoxy/diamine/thio-
ureaphenylisothiocyanates. They are dimensionally stable~
controllable-porosity structures with ability to be heat
sterilizedO They are especially preferred for reaction
with the free -NM2 groups of proteins to give immobilized
enzymes or affinity chromatographic column supports.
The membrane of this Example is sterile and ready for
use whereas prior art membranes require reaction with a
variety of multifunctional reagents before they can be used
as is explained in Canadian Patent 1,083,057.
A membrane of this example was treated with an
immunoglobulin at 25C with the pH in the range of 7 to 9
to ensure optimal reaction. The binding was unaffected by
the addition of sodium chloride of up to 3 Molar. At pH 9
in a 0.01 M phosphate buffered saline solution at 25C, the
reaction exhibited diffusion limitations as expected
because the membrane pores would not pass the
immunoglobulin as its molecular weight of 156~000 is close
to the molecular weight cut off of the membrane. The
immunoglobulin was applied at 500 microgram/millilitre and
the membrane surface took up 512 micrograms/s~uare
centimetre. The membrane was then washed to remove non-
combined immunoglobulin. Ethanolamine was then added to
block off the unreacted isothiocyanate and the membrane was
then washed. Incubation with protein and further washing
did not lead to takeup of the protein.
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- 20 -
EXAMPLE 7
.. . , . _
The polyamide 6/glutaraldehyde membrane of Example 2
after drying at 60C reacted readily with 0~5% aqueous
gelatin, draining, then heating in an oven at 60C for 15
hours. The product was fully "embrittlement resistant~ and
had an extension to break of over 50% in absolute ethanol
(versus 20~ without gelatin) and was fully rubbery. The
membrane showed some utility in rejecting fine oil droplets
when used as a cross-flow ultrafilter on oil emulsions in
water. Similarly substitution of high molecular weight
hydroxyethylcellulose for gelatin gave equivalent membranes
which were "embrittl~ment resistant" and rubbery in ethanol
with much the same utility in filtering oil emulsions.
EXAMPLE 8
The glutaraldehyde in Examples 2,3,5,6 and 7 was
replaced with glyoxal, succindialdehyde, phthaldialdehyde
and terephthaldehyde. There was little difference in
behaviour but the products ~rom terephthaldehyde tended to
be too hard for ultrafilters, although the hardness could
be turned to useful account when powdered high-pressure
liquid affinity chromatographic packings were needed. The
aromatic bis-aldehydes tended to be rather slow in reaction
but always gave lighter-coloured products. The reactivity
Qf all intermediates was in line with the properties of the
parent aldehydes eg: polyamide 6/aliphatic bis-aldehydes
gave membranes which contained -CHO groups readily reacting
with NaHSO3 (stained by Schiff's reagent) whereas the
aromatic bis-aldehydes reacted slower. However, all formed
2,4 - dinitro - phenylhydrazones, as expected.
The use of the cheap glyoxal~ glutaraldehyde and
terephthaldehyde (if desired by mixing these and, if
desired, including a very limited am~unt of formaldehyde)
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- 21 -
can meet all likely needs in serving as a vital
intermediate step in the conversion of the desirably
structured known polyamide/(imide) membranes into
"embrittlement resistant" membranes by further reaction
with reactive phenols, proteins or other aldehyde-reactive
substances. These can further form desirable derivatives
for ultrafiltration~ cross-flow filtration, ion-exchange,
protein immobilization or packings for affinity
chromatography. The vital point is t~at all of thi~ can be
done by immersion in suitable reagents whilst still
retaining the carefully controlled initial porous
structure.
EXAMPLE 9
lOOg. of a 60C dried polyamide 6 based membrane made
according to Example 1 and containing 4% of reacted
~lutaraldehyde and 4% of reacted resorcinol based on the
dry weight of polyamid membrane was heated 24 hours at
60C with 400ml of a solution of 75ml of 25% weight/volume
glutaraldehyde and 40g. of sodium benzoate buffer per
litre. The original polyamide/glutaraldehyde reaction
product contained only the equivalent of 1% of
glutaraldehyde with a reactive single -CHO group as judged
by rapid reaction with 2~4-dinitrophenylhydrazine.
Furthermore the product was not stable to dilute acids,
gradually releasing more aldehyde. However, by the present
~example it was possible to obtain the equivalent of 2% of
single-linked glutaraldehyde which was now linked to a much
more stable rubbery matrix. This doubling of the capacity
to form derivatives is very important for ion-exchangers
and ion-specific ultrafilters, eg: rejecting anionic
detergents after treatment with bisulphite.
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